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Sample records for treatment-resistant mania case

  1. Electroconvulsive therapy in treatment-resistant mania: case reports A Eletroconvulsoterapia no tratamento da mania resistente: relatos de casos

    Directory of Open Access Journals (Sweden)

    Marcia Britto de Macedo Soares

    2002-02-01

    Full Text Available Electroconvulsive therapy is known to be effective in the treatment of mood disorders, more specifically for depression and mania. Although a large body of evidence confirms the efficacy of electroconvulsive therapy in the treatment of mania, few prospective studies have been done to assess its effectiveness in treatment-resistant manic episodes. These case reports describe the initial results of a study that is being conducted to evaluate the efficacy of Electroconvulsive therapy among treatment-resistant bipolar patients. METHODS: Three manic patients (according to DSM-IV criteria who were considered treatment-resistant underwent a series of 12 bilateral Electroconvulsive therapy sessions. Before the treatment and then weekly, they were evaluated with the following rating scales: Young Mania Rating Scale, Hamilton Rating Scale for Depression, Brief Psychiatric Rating Scale, and Clinical Global Impressions-Bipolar Version. RESULTS: The 3 patients showed a satisfactory response to Electroconvulsive therapy, although some differences in the course of response were observed. CONCLUSION: These case reports suggest that Electroconvulsive therapy needs further evaluation for the treatment of resistant bipolar patients.A Eletroconvulsoterapia é uma alternativa reconhecidamente eficaz no tratamento dos transtornos do humor. Embora vários estudos tenham confirmado a eficácia desta modalidade terapêutica no tratamento da mania aguda, poucos estudos foram realizados em pacientes maníacos resistentes à farmacoterapia. Esses relatos de casos descrevem resultados preliminares de um projeto de pesquisa que tem por objetivo avaliar a eficácia da Eletroconvulsoterapia no tratamento de transtornos bipolares resistentes. MÉTODOS: Três pacientes com diagnóstico de mania (de acordo com os critérios do DSM-IV, considerados resistentes ao tratamento medicamentoso, foram submetidos a 12 aplicações bilaterais de Eletroconvulsoterapia. Antes do tratamento e

  2. 5. CASE SERIES OF MANIA SECONDARY

    African Journals Online (AJOL)

    Esem

    meeting the criteria for DSM IV- TR is increasing. What is not clear with this increase is whether it is primary mania or secondary mania linked with HIV. METHODS. This study design was a case series in which patients with acute manic episodes were admitted to. Chainama Hills College Hospital and University. Teaching ...

  3. Mania associated with paliperidone treatment in schizophrenia: A case report

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    Süleyman Demir

    2015-09-01

    Full Text Available Paliperidone is an atypical antipsychotic drug used to treat schizophrenia. Paliperidone can cause some rare side effects during treatment. Despite many publications of mania and hypomania induced by antipsychotics, mania cases induced by paliperidone are few in the literature. In this case a schizophrenia patient showing symptoms of mania during usage of paliperidone with a dose of 9 mg/day in which the symptoms rapidly disappeared after discontinuation of paliperidone and initiation of aripiprazole was reported. Clinicians should be aware of that Paliperidone treatment may trigger mania symptoms. J Clin Exp Invest 2015; 6 (3: 321-323

  4. A case report on very late onset mania

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    Manjunadh Muraleedharan

    2017-06-01

    Full Text Available Diagnosing primary psychiatric disorder in elderly is a challenge considering the high prevalence of neurological and other medical diseases presenting with psychiatric manifestation. The first episode of mania occurring after the age of 80 years is extremely rare. We report a case of an 88-year-old married Hindu male educated up to fifth standard from rural background and lower socioeconomic status presenting with first episode mania, diagnosed using the tenth revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10 criteria. Secondary causes were ruled out and successfully treated with low dose olanzapine.

  5. Olanzapine-Induced Mania in Bipolar Spectrum Disorder:A Case Report

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    Mehrdad Eftekhar

    2006-07-01

    Full Text Available Objective: To report the case of a 46-year old male with major depressive disorder, who represented manic symptoms, when olanzapine was added to his treatment. Method: A 46-year old female, with a diagnosis of treatment resistant depression was referred to the authors. He had past history of depression for more than 20 years. The symptoms were present nearly every day since 1981, without any distinct period of remission, nor any noticeable fluctuation. His irritability had been disruptive to his family all these years. His doctor had prescribed maprotiline 25 mg/day, and lorazepam, 2mg/day, in addition to fluoxetine for the last 5 months. He is also a father of two children with methylphenidateresistant and sodium valproate-responsive attention-deficit hyperactivity disorder. Considering the antidepressant effects of olanzapine and its positive effects on irritability, the authors added olanzapine, to the patient’s previous medications. Results: After one week, he showed new problems such as talkativeness and beginning to smoke for the first time in his life, elevated mood, grandiosity about his intelligence and abilities, talkativeness, and shopping sprees. The score on the mania rating scale was 14. Fluoxetine was discontinued and sodium valproate, were prescribed. It took around 2 months to completely control the manic symptoms. Conclusions: In the patients with depression who show bipolar spectrum disorder features, adding mood stabilizers may be preferred to the drugs as olanzapine which could induce mania.

  6. A Case of Mania Presenting with Hypersexual Behavior and Gender Dysphoria that Resolved with Valproic Acid

    OpenAIRE

    Heare, Michelle R.; Barsky, Maria; Faziola, Lawrence R.

    2016-01-01

    Hypersexuality and gender dysphoria have both been described in the literature as symptoms of mania. Hypersexuality is listed in the Diagnostic and Statistical Manual of Mental Disorders 5 as part of the diagnostic criteria for bipolar disorder. Gender dysphoria is less often described and its relation to mania remains unclear. This case report describes a young homosexual man presenting in a manic episode with co-morbid amphetamine abuse whose mania was marked by hypersexuality and the new o...

  7. A case of mania presenting with hypersexual behavior and gender dysphoria that resolved with valproic acid

    Directory of Open Access Journals (Sweden)

    Michelle R. Heare

    2016-11-01

    Full Text Available Hypersexuality and gender dysphoria have both been described in the literature as symptoms of mania. Hypersexuality is listed in the Diagnostic and Statistical Manual of Mental Disorders 5 as part of the diagnostic criteria for bipolar disorder. Gender dysphoria is less often described and its relation to mania remains unclear. This case report describes a young homosexual man presenting in a manic episode with co-morbid amphetamine abuse whose mania was marked by hypersexuality and the new onset desire to be a woman. Both of these symptoms resolved with the addition of valproic acid to antipsychotics. This case report presents the existing literature on hypersexuality and gender dysphoria in mania and describes a treatment option that has not been previously reported.

  8. Recognizing thyrotoxicosis in a patient with bipolar mania: a case report

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    Lee Catherine

    2008-02-01

    Full Text Available Abstract Background A thyroid stimulating hormone level is commonly measured in patients presenting with symptoms of mania in order to rule out an underlying general medical condition such as hyperthyroidism or thyrotoxicosis. Indeed, many cases have been reported in which a patient is initially treated for bipolar mania, but is later found to have a thyroid condition. Several case reports have noted the development of a thyroid condition in bipolar patients either on lithium maintenance treatment or recently on lithium treatment. Case presentation We review a case in which a patient with a long history of bipolar disorder presents with comorbid hyperthyroidism and bipolar mania after recent discontinuation of lithium treatment. Conclusion Physicians should consider a comorbid hyperthyroidism in bipolar manic patients only partially responsive to standard care treatment with a mood stabilizer and antipsychotic.

  9. A Case of Probable Amisulpride Induced Mania after Eight Months of Therapy

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    Prakash Thapa

    2017-01-01

    Full Text Available Development of manic symptoms during treatment with atypical antipsychotics can be a troublesome side effect that has been described with most atypical antipsychotics. However, reports of amisulpride induced mania have been rare. Here, we report the case of an 18-year-old male patient diagnosed with schizophrenia, who developed manic symptoms while on treatment with amisulpride. While previous reports have described occurrence of mania within days to three months of treatment with amisulpride, we report a case where manic symptoms occurred after around eight months of therapy. We have also attempted to describe the possible risk factors based on the available case studies.

  10. Mania as complication of HIV infection: case reports | Sulyman ...

    African Journals Online (AJOL)

    These case reports highlight the fact that organic mood disorder, manic episode, in HIV infection AIDS might not be uncommon in this part of the world. Patients present with irritable mood rather than euphoria and they respond rapidly to psychotropic medications. Key words: Manic episode, HIV infection; Acquired immune ...

  11. Elevated midbrain serotonin transporter availability in mixed mania: a case report

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    Kuikka Jyrki

    2004-09-01

    Full Text Available Abstract Background Results obtained from brain imaging studies indicate that serotonin transporter (SERT and dopamine transporter (DAT densities are altered in major depression. However, no such studies have been published on current mania or hypomania. Case presentation In this single photon emission computed tomography (SPECT study with [123I]nor-β-CIT we present a case with simultaneous symptoms of major depression and hypomania. She had an elevated serotonin transporter availability (SERT in the midbrain and elevated dopamine transporter availability (DAT in the striatum, which normalised in a one-year follow-up period during which she received eight months of psychodynamic psychotherapy. Conclusions To our knowledge, this is the first report on SERT and DAT associated with mania. In our case the availability of both SERT in the midbrain and DAT in the striatum were elevated at baseline and declined during psychotherapy, while the SERT and DAT of the depressed controls increased during psychotherapy. Symptoms of hypomania in the case were alleviated during psychotherapy. Clinical recovery was also reflected in the Hamilton Depression Rating Scale (HDRS scores.

  12. "MOOC Mania"

    Science.gov (United States)

    Meisenhelder, Susan

    2013-01-01

    The push for increased use of online teaching in colleges and universities has been gaining momentum for some time, but even in that context the recent enthusiasm for MOOCs (Massive Open Online Courses), free online courses that often enroll tens of thousands of students, is remarkable and rightly dubbed "MOOC Mania." As with so many…

  13. A Case Report of Mania and Psychosis Five Months after Traumatic Brain Injury Successfully Treated Using Olanzapine

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    Giordano F. Cittolin-Santos

    2017-01-01

    Full Text Available Background. There are few published pharmacologic trials for the treatment of acute mania following traumatic brain injury (TBI. To our knowledge, we present the first case report of an individual being treated and stabilized with olanzapine monotherapy for this condition. Case Presentation. We describe the case of a 53-year-old African American male admitted to an inpatient psychiatric hospital with one month of behavioral changes including irritability, decreased need for sleep, hyperverbal speech, hypergraphia, and paranoia five months after TBI. Using Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5 criteria, he was diagnosed with bipolar disorder due to traumatic brain injury, with manic features. He was serially evaluated with clinical rating scales to measure symptom severity. The Young Mania Rating Scale (YMRS score upon admission was 31, and the Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS score was initially 9. After eight days of milieu treatment and gradual titration of olanzapine to 15 mg nightly, his symptoms completely abated, with YMRS and CRDPSS scores at zero on the day of discharge. Conclusion. Olanzapine was effective and well tolerated for the treatment of mania following TBI.

  14. A Case of Treatment- resistant Depression and Body Dysmorphic Disorder: The Role of Electroconvulsive Therapy Revisited.

    Science.gov (United States)

    Mahato, Ram S; San Gabriel, Maria Chona P; Longshore, Carrol T; Schnur, David B

    2016-01-01

    Body dysmorphic disorder is a common, often disabling condition, and is frequently comorbid with major depressive disorder. Selective serotonin reuptake inhibitors constitute first line set of somatic interventions but the management of refractory patients remains challenging. Electroconvulsive therapy, an often highly beneficial treatment for medication resistant-depression, is not considered an effective therapeutic alternative for treatment refractory body dysmorphic disorder. Here we present a 50-year-old woman with body dysmorphic disorder and comorbid major depressive disorder who remained incapacitated and suicidal despite several trials with selective serotonin reuptake inhibitors and antipsychotic medication. Depressive and dysmorphic symptoms appeared to resolve with electroconvulsive therapy, and remission was sustained for two months. Electroconvulsive therapy has an important place in the management of treatment- resistant depression associated with body dysmorphic disorder, and, in select cases, may be effective for dysmorphic symptoms as well.

  15. Treatment-resistant neuromyelitis optica spectrum disorders associated with Toxocara canis infection: A case report.

    Science.gov (United States)

    Kambe, Daisuke; Takeoka, Kayo; Ogawa, Kenta; Doi, Kosuke; Maruyama, Haruhiko; Yoshida, Ayako; Suenaga, Toshihiko; Kageyama, Takashi

    2017-04-01

    A 53-year-old woman was admitted to the department of neurology in Tenri Hospital because of progressive thoracic myelitis a month after she had eaten uncooked bovine liver. A previous episode of right optic neuritis and a positive test for serum anti-aquaporin-4 antibodies indicated a diagnosis of neuromyelitis optica spectrum disorders. Although the patient initially recovered with the reduction of anti-aquaporin-4 antibodies during treatment with intravenous methylprednisolone infusion and plasma exchange, her neurological symptoms deteriorated soon after the completion of plasma exchange. Western blotting analysis detected anti-Toxocara canis antibodies in the serum; thus, the patient underwent oral albendazole treatment. This resulted in the alleviation of her symptoms. We therefore consider that rigorous investigation should be encouraged to detect rare pathogens including parasites in cases of treatment-resistant neuromyelitis optica spectrum disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Do antidepressants increase the risk of mania and bipolar disorder in people with depression? A retrospective electronic case register cohort study

    NARCIS (Netherlands)

    Patel, Rashmi; Reiss, Peter; Shetty, Hitesh; Broadbent, Matthew; Stewart, Robert; McGuire, Philip; Taylor, Matthew

    2015-01-01

    Objectives To investigate the association between antidepressant therapy and the later onset of mania/bipolar disorder. Design Retrospective cohort study using an anonymised electronic health record case register. Setting South London and Maudsley National Health Service (NHS) Trust (SLaM), a large

  17. Treatment resistant adolescent depression with upper airway resistance syndrome treated with rapid palatal expansion: a case report

    Directory of Open Access Journals (Sweden)

    Miller Paul

    2012-12-01

    Full Text Available Abstract Introduction To the best of our knowledge, this is the first report of a case of treatment-resistant depression in which the patient was evaluated for sleep disordered breathing as the cause and in which rapid palatal expansion to permanently treat the sleep disordered breathing produced a prolonged symptom-free period off medication. Case presentation An 18-year-old Caucasian man presented to our sleep disorders center with chronic severe depression that was no longer responsive to medication but that had recently responded to electroconvulsive therapy. Ancillary, persistent symptoms included mild insomnia, moderate to severe fatigue, mild sleepiness and severe anxiety treated with medication. Our patient had no history of snoring or witnessed apnea, but polysomnography was consistent with upper airway resistance syndrome. Although our patient did not have an orthodontic indication for rapid palatal expansion, rapid palatal expansion was performed as a treatment of his upper airway resistance syndrome. Following rapid palatal expansion, our patient experienced a marked improvement of his sleep quality, anxiety, fatigue and sleepiness. His improvement has been maintained off all psychotropic medication and his depression has remained in remission for approximately two years following his electroconvulsive therapy. Conclusions This case report introduces the possibility that unrecognized sleep disordered breathing may play a role in adolescent treatment-resistant depression. The symptoms of upper airway resistance syndrome are non-specific enough that every adolescent with depression, even those responding to medication, may have underlying sleep disordered breathing. In such patients, rapid palatal expansion, by widening the upper airway and improving airflow during sleep, may produce a prolonged improvement of symptoms and a tapering of medication. Psychiatrists treating adolescents may benefit from having another treatment option for

  18. Do antidepressants increase the risk of mania and bipolar disorder in people with depression? A retrospective electronic case register cohort study

    OpenAIRE

    Patel, Rashmi; Reiss, Peter; Shetty, Hitesh; Broadbent, Matthew; Stewart, Robert; McGuire, Philip; Taylor, Matthew

    2015-01-01

    Objectives To investigate the association between antidepressant therapy and the later onset of mania/bipolar disorder.Design Retrospective cohort study using an anonymised electronic health record case register.Setting South London and Maudsley National Health Service (NHS) Trust (SLaM), a large provider of inpatient and community mental healthcare in the UK.Participants 21 012 adults presenting to SLaM between 1 April 2006 and 31 March 2013 with unipolar depression.Exposure Prior antidepres...

  19. Mixed mania associated with cessation of breastfeeding

    OpenAIRE

    Schmidt, Kristen A.; Palmer, Brian A.; Frye, Mark A.

    2016-01-01

    Background This case chronicles the unique presentation of psychotic mixed mania in a female 5?months after parturition and 1?week following breastfeeding discontinuation, highlighting a rarely recognized mania risk factor that is temporally delayed from parturition: breastfeeding discontinuation. Case presentation A 25-year-old G1P1 female with a past psychiatric history of a depressive episode in adolescence presented to the Emergency Department with her 5-month-old daughter, fianc?e, and f...

  20. Ketamine Therapy for Treatment-resistant Depression in a Patient with Multiple Sclerosis: A Case Report.

    Science.gov (United States)

    Messer, Michael M; Haller, Irina V

    2017-01-01

    Objective: Depression is a common condition among patients with multiple sclerosis and often becomes resistant to oral antidepressants. We report a patient with multiple sclerosis who developed severe treatment-resistant depression and who was successfully treated with intravenous ketamine over the period of two years. Methods: Ketamine treatment protocol included an initial series of six treatments administered every other day, followed by a maintenance schedule. Ketamine was administered intravenously at 0.5mg/kg of ideal body weight over 40 minutes. Depression symptoms were measured using Beck Depression Index. Results: The patient's Beck Depression Index score prior to initiating ketamine treatment was 38, corresponding to severe depression. Response to treatment, defined as 50-percent reduction in Beck Depression Index score, was observed after five treatments. For this patient, the maintenance schedule ranged from a weekly treatment to one treatment every three weeks. During the two-year observation period, this patient was able to maintain a stable non-depressed mood and had no worsening of her MS symptoms. Conclusion: Ketamine may be an alternative treatment for resistant depression and may have a special use in patients with multiple sclerosis.

  1. Case Report: Valproic Acid and Risperidone Treatment Leading to Development of Hyperammonemia and Mania

    Science.gov (United States)

    Carlson, Teri; Reynolds, Charles A.; Caplan, Rochelle

    2007-01-01

    This case report describes two children who developed hyperammonemia together with frank manic behavior during treatment with a combination of valproic acid and risperidone. One child had been maintained on valproic acid for years and risperidone was added. In the second case, valproic acid was introduced to a child who had been treated with…

  2. A Case of ChroniC Mania in a Patient with A Double Diagnosis of Bipolar I and Delusional Disorders

    Directory of Open Access Journals (Sweden)

    Marina Teles Martins

    2013-12-01

    Full Text Available The authors describe the case of a 62 year old woman without any significant personal or family psychiatric history prior to being 52, when after a minor head trauma occurring during worktime, she started showing delusional ideas of hypochondri- ac and somatic content believing to have developed a “problem in the head”. Two years later she was admitted to a Psychiatric inpatient unit and diagnosed with a delusional disorder of the somatic subtype. At discharge she maintained the delusional ideas, which, however, were encapsulated from her personality and quiescent, while exhibiting no insight into her psychopatho- logical state. Very shortly thereafter, at follow-up in the outpatient clinic, she stopped all drug therapy (oral antipsychotic drugs. One year later, she was readmitted to the inpatient unit upon worsening of the hypochondriac and somatic delusional ideas. The prescribed medication was switched to depot injection, which she also stopped shortly thereafter. Three years later, being 58 years of age, she began to show manic symptoms of crescendo severity (grandiose delusion-like ideas, elated mood, overactivity, disinhibition, acceleration of thinking, reduced need for sleep and increased pres- sure of speech. This clinical condition gets worse, with persecutory delusional ideas and complex auditory hallucinations and she was admitted to the inpatient unit once more. This time she presents a full manic episode and a Bipolar I affective disorder diagnosis was made. She had a hyperthymic pre-morbid temperament. For the next 4 years, the patient remained somewhat stable with elation of mood, grandiose ideas, increased pressure of speech, eccen- tric clothing and lack of insight to her psychopathological state. Since the beginning of follow up, the patient always kept poor treatment compliance. The authors discuss the evolution and clinical significance of a particular and infrequent type of Bipolar Disorder, chronic mania.

  3. Experiment-o-mania

    Science.gov (United States)

    Drndarski, Marina

    2015-04-01

    Every 21st century student is expected to develop science literacy skills. As this is not part of Serbian national curriculum yet, we decided to introduce it with this project. Experiment-o-mania provides students to experience science in different and exciting way. It makes opportunity for personalized learning offering space and time to ask (why, where, how, what if) and to try. Therefore, we empower young people with skills of experimenting, and they love science back. They ask questions, make hypothesis, make problems and solve them, make mistakes, discuss about the results. Subsequently this raises the students' interest for school curriculum. This vision of science teaching is associated with inquiry-based learning. Experiment-o-mania is the unique and recognizable teaching methodology for the elementary school Drinka Pavlović, Belgrade, Serbia. Experiment-o-mania implies activities throughout the school year. They are held on extra class sessions, through science experiments, science projects or preparations for School's Days of science. Students learn to ask questions, make observations, classify data, communicate ideas, conduct experiments, analyse results and make conclusions. All science teachers participate in designing activities and experiments for students in Experiment-o-mania teaching method. But they are not alone. Teacher of fine arts, English teachers and others also take part. Students have their representatives in this team, too. This is a good way to blend knowledge among different school subject and popularize science in general. All the experiments are age appropriate and related to real life situations, local community, society and the world. We explore Fibonacci's arrays, saving energy, solar power, climate change, environmental problems, pollution, daily life situations in the country or worldwide. We introduce great scientists as Nikola Tesla, Milutin Milanković and sir Isaac Newton. We celebrate all relevant international days, weeks

  4. Treatment-Resistant Schizophrenia

    DEFF Research Database (Denmark)

    Howes, Oliver D; McCutcheon, Rob; Agid, Ofer

    2017-01-01

    OBJECTIVE: Research and clinical translation in schizophrenia is limited by inconsistent definitions of treatment resistance and response. To address this issue, the authors evaluated current approaches and then developed consensus criteria and guidelines. METHOD: A systematic review of randomize...

  5. Mania associated with complicated hereditary spastic paraparesis

    Directory of Open Access Journals (Sweden)

    Raghavendra B Nayak

    2011-01-01

    Full Text Available Hereditary spastic paraparesis (HSP is an inherited group of neurological disorders with progressive lower limb spasticity. HSP can be clinically grouped into pure and complicated forms. Pure HSP is one without any associated neurological/psychiatric comorbidity. Depression is the most common psychiatric comorbidity. Presence of mania or bipolar affective illness with HSP is a rare phenomenon. We report a case of a 17-year-old boy who presented with classical features of HSP with complaints of excessive happiness, irritability, increased self-esteem and decreased sleep since 1 month. The patient also had complex partial seizure ever since he had features of HSP. The patient′s father and younger sister suffer from pure HSP. The patient was diagnosed to have first episode mania with complicated HSP. The details of treatment and possible neurobiology are discussed in this case report.

  6. Mania associated with complicated hereditary spastic paraparesis.

    Science.gov (United States)

    Nayak, Raghavendra B; Bhogale, Govind S; Patil, Nanasaheb M; Pandurangi, Aditya A

    2011-07-01

    Hereditary spastic paraparesis (HSP) is an inherited group of neurological disorders with progressive lower limb spasticity. HSP can be clinically grouped into pure and complicated forms. Pure HSP is one without any associated neurological/psychiatric comorbidity. Depression is the most common psychiatric comorbidity. Presence of mania or bipolar affective illness with HSP is a rare phenomenon. We report a case of a 17-year-old boy who presented with classical features of HSP with complaints of excessive happiness, irritability, increased self-esteem and decreased sleep since 1 month. The patient also had complex partial seizure ever since he had features of HSP. The patient's father and younger sister suffer from pure HSP. The patient was diagnosed to have first episode mania with complicated HSP. The details of treatment and possible neurobiology are discussed in this case report.

  7. Mania associated with complicated hereditary spastic paraparesis

    OpenAIRE

    Raghavendra B Nayak; Govind S Bhogale; Nanasaheb M Patil; Aditya A Pandurangi

    2011-01-01

    Hereditary spastic paraparesis (HSP) is an inherited group of neurological disorders with progressive lower limb spasticity. HSP can be clinically grouped into pure and complicated forms. Pure HSP is one without any associated neurological/psychiatric comorbidity. Depression is the most common psychiatric comorbidity. Presence of mania or bipolar affective illness with HSP is a rare phenomenon. We report a case of a 17-year-old boy who presented with classical features of HSP with complaints ...

  8. Pharmacological Hypotension as a Cause of Delirious Mania in a Patient with Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Manuel Glauco Carbone

    2017-01-01

    Full Text Available Delirious mania is a severe but often underrecognized syndrome characterized by rapid onset of delirium, mania, and psychosis, not associated with a prior toxicity, physical illness, or mental disorder. We discuss the case of a delirious mania potentially triggered and maintained by a systemic hypotension induced by antihypertensive drugs. Symptoms recovered completely after the discontinuation of antihypertensive medications and the normalization of blood pressure levels.

  9. Major stressful life events and other risk factors for first admission with mania

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Agerbo, Esben; Mortensen, Preben Bo

    2004-01-01

    OBJECTIVES: To investigate whether first admission with mania is associated with the occurrence of death in the family or with major stressful life events and to explore whether the associations change with age. METHODS: Case register study with linkage of the Danish Psychiatric Central Research ...... disorder. The susceptibility to major life stressors of inducing mania does not seem to change throughout life....

  10. Acute mania after thyroxin supplementation in hypothyroid state

    Directory of Open Access Journals (Sweden)

    Rohit Verma

    2013-01-01

    Full Text Available The current literature variedly ascribes depressive and manic symptoms to hypo- and hyperthyroid state, respectively, reporting mania in hypothyroidism as an unusual entity. More unusual is precipitation of manic state in hypothyroid subjects after thyroxine supplementation for which studies report otherwise treating manic symptoms in hypothyroid state with thyroxine. We report a case of a patient whose acute mania appears to have been precipitated by thyroxine supplementation in hypothyroidism state. This case underscores the importance of thyroid screening in patients with mood and psychotic disorders, as well as the potency of thyroxine in producing manic symptoms.

  11. Targeting treatment-resistant auditory verbal hallucinations in schizophrenia with fMRI-based neurofeedback – exploring different cases of schizophrenia

    Directory of Open Access Journals (Sweden)

    Miriam S. Dyck

    2016-03-01

    Full Text Available Auditory verbal hallucinations (AVHs are a hallmark of schizophrenia and can significantly impair patients’ emotional, social, and occupational functioning. Despite progress in psychopharmacology, over 25% of schizophrenia patients suffer from treatment-resistant hallucinations. In the search for alternative treatment methods, neurofeedback (NF emerges as a promising therapy tool. NF based on real-time functional magnetic resonance imaging (rt-fMRI allows voluntarily change of the activity in a selected brain region – even in patients with schizophrenia. This study explored effects of NF on ongoing AVHs. The selected participants were trained in the self-regulation of activity in the anterior cingulate cortex (ACC, a key monitoring region involved in generation and intensity modulation of AVHs. Using rt-fMRI, three right-handed patients, suffering from schizophrenia and ongoing, treatment-resistant AVHs, learned control over ACC activity on three separate days. The effect of NF training on hallucinations’ severity was assessed with the Auditory Vocal Hallucination Rating Scale (AVHRS and on the affective state – with the Positive and Negative Affect Schedule (PANAS.All patients yielded significant up-regulation of the ACC and reported subjective improvement in some aspects of AVHs (AVHRS such as disturbance and suffering from the voices. In general, mood (PANAS improved during NF training, though two patients reported worse mood after NF on the third day. ACC and reward system activity during NF learning and specific effects on mood and symptoms varied across the participants. None of them profited from the last training set in the prolonged 3-session training. Moreover, individual differences emerged in brain networks activated with NF and in symptom changes, which were related to the patients’ symptomatology and disease history.NF based on rt-fMRI seems a promising tool in therapy of AVHs. The patients, who suffered from continuous

  12. Family influences on mania-relevant cognitions and beliefs: a cognitive model of mania and reward.

    Science.gov (United States)

    Chen, Stephen H; Johnson, Sheri L

    2012-07-01

    The present study proposed and tested a cognitive model of mania and reward. Undergraduates (N = 284; 68.4% female; mean age = 20.99 years, standard deviation ± 3.37) completed measures of family goal setting and achievement values, personal reward-related beliefs, cognitive symptoms of mania, and risk for mania. Correlational analyses and structural equation modeling supported two distinct, but related facets of mania-relevant cognition: stably present reward-related beliefs and state-dependent cognitive symptoms in response to success and positive emotion. Results also indicated that family emphasis on achievement and highly ambitious extrinsic goals were associated with these mania-relevant cognitions. Finally, controlling for other factors, cognitive symptoms in response to success and positive emotion were uniquely associated with lifetime propensity towards mania symptoms. Results support the merit of distinguishing between facets of mania-relevant cognition and the importance of the family in shaping both aspects of cognition. © 2012 Wiley Periodicals, Inc.

  13. Sofa dermatitis presenting as a chronic treatment resistant dermatitis.

    LENUS (Irish Health Repository)

    Lynch, M

    2010-04-01

    There is now a well publicised increase in cases of sofa dermatitis since 2007. These have been linked to allergic contact sensitization to dimethlylfumarate, a novel contact allergen. We report on a case associated with a two year history of a treatment resistant dermatitis.

  14. Novel antipsychotics in bipolar and schizoaffective mania

    NARCIS (Netherlands)

    Slooff, CJ

    Objective: Novel antipsychotics are increasingly used in the treatment of bipolar and schizoaffective mania. This paper presents an overview of the controlled studies in this field. Method: Using cross-references, a computerized search was performed on MEDLINE and EMBASE psychiatry covering the

  15. Major stressful life events and other risk factors for first admission with mania

    DEFF Research Database (Denmark)

    Kessing, L.V.; Agerbo, E.; Mortensen, P.B.

    2004-01-01

    OBJECTIVES: To investigate whether first admission with mania is associated with the occurrence of death in the family or with major stressful life events and to explore whether the associations change with age. METHODS: Case register study with linkage of the Danish Psychiatric Central Research...... was found on the association between life events and the first admission with mania, totally, or for men or women, separately regarding ageing. CONCLUSIONS: The occurrence of death in the family and the experience of major life events are associated with increased risk of first admission with bipolar...

  16. Neuromodulation therapies and treatment-resistant depression

    Directory of Open Access Journals (Sweden)

    Al-Harbi KS

    2012-07-01

    Full Text Available Khalid Saad Al-Harbi,1 Naseem Akhtar Qureshi21National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia; 2General Administration for Research and Studies and Mental Health and Social Services, Riyadh, Saudi ArabiaBackground: Patients with treatment-resistant depression (TRD who showed partial response to pharmacological and psychotherapeutic interventions need a trial of neuromodulation therapies (NTs.Objective: This paper aims to review evidence-based data on the use of NTs in TRD.Method: Using keywords and combined-word strategy, multiple computer searches of PubMed, Google Scholar, Quertle(R, and Medline were conducted for retrieving relevant articles published in English-language peer-reviewed journals (2000–2012. Those papers that addressed NTs in TRD were retained for extensive review.Results: Despite methodological challenges, a range of 30%–93% of TRD patients showed substantial improvement to one of the NTs. One hundred–percent improvement was reported in two single-case studies on deep brain stimulation. Some studies reported no benefits from transcranial direct current stimulation. NTs were reported to have good clinical efficacy, better safety margin, and benign side-effect profile. Data are limited regarding randomized clinical trials, long-term efficacy, and cost-effectiveness of these approaches. Both modified electroconvulsive therapy and magnetic seizure therapy were associated with reversible but disturbing neurocognitive adverse effects. Besides clinical utility, NTs including approaches on the horizon may unlock the biological basis underlying mood disorders including TRD.Conclusion: NTs are promising in patients with TRD, as the majority of them show good clinical response measured by standardized depression scales. NTs need further technological refinements and optimization together with continuing well-designed studies that recruit larger numbers of participants with TRD.Keywords: treatment-resistant

  17. Unipolar Mania: Recent Updates and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Shubham Mehta

    2014-01-01

    Full Text Available Introduction. Unipolar mania (UM has received less than the expected attention, when compared to its contemporary mood disorders, unipolar depression (UD and bipolar disorder (BD. Method. The literature search included PUBMED and PSYCINFO databases. Cross-searches of key references were made to identify other articles of importance. Results. There seems to be a bipolar subgroup with a stable, unipolar recurrent manic course. Although UM does not have significant differences from bipolar mania in terms of sociodemographic variables, there are certain significant differences in clinical features. UM is reported to have more grandiosity, psychotic symptoms, and premorbid hyperthymic temperament, but less rapid cycling, suicidality, seasonality, and comorbid anxiety disorders. It seems to have a better course of illness with better social and professional adjustment. However, its response to lithium prophylaxis is found to be poor as compared to classical BD and valproate could be a better choice in this case. Conclusion. The available literature suggests that UM has certain differences from classical BD. The evidence, however, is insufficient to categorize it as separate diagnostic entity. However, considering UM as a course specifier of BD would be a reasonable step.

  18. Aripiprazole for acute mania in an elderly person

    Directory of Open Access Journals (Sweden)

    Balaji Bharadwaj

    2011-01-01

    Full Text Available New-onset bipolar disorder is rare in the elderly. Symptom profile is similar to that in young adults but the elderly are more likely to have neurological co-morbidities. There are no case reports of elderly mania being treated with aripiprazole, an atypical antipsychotic. A 78-year-old gentleman presented to us with symptoms suggestive of mania of 1 month′s duration. He had similar history 3 years ago and a family history of postpartum psychosis in his mother. There were no neurological signs on examination and work-up for an organic etiology was negative except for age-related cerebral atrophy. He improved with aripiprazole and tolerated the medications well. The use of psychotropic medications in the elderly is associated with side-effects of sedation, increased cardiovascular risk, and greater risk of extra-pyramidal side-effects. The use of partial dopaminergic antagonists like aripiprazole may be useful in the balancing of effects and side-effects.

  19. Kraepelin’s description of chronic mania: a clinical picture that meets the behavioral variant frontotemporal dementia phenotype

    Directory of Open Access Journals (Sweden)

    Leandro Boson Gambogi

    Full Text Available ABSTRACT Chronic mania is an under-investigated condition and few reports have associated this disorder with an organic background. The present work examines Kraepelin’s reliable description of chronic mania from a current behavioral neurology viewpoint. Kraepelin had described a cluster of symptoms that are now recognized as core manifestations of the behavioral variant frontotemporal dementia (bvFTD clinical phenotype. We also carried out additional reviews of original manuscripts from Kraepelin’s peers, in order to find any case reports that might fulfill the current diagnostic proposal for bvFTD. Even though we failed to find an ideal case, we found some scholars who seemed to agree that chronic mania should be considered a special form of dementia. The present work highlights, through historical data, the possible overlapping features between primary psychiatric disorders and neuropsychiatric symptoms secondary to neurodegenerative conditions.

  20. Management of treatment resistant schizophrenia | Jones | African ...

    African Journals Online (AJOL)

    Whilst gains have been made in recent years in the pharmacological treatment of schizophrenia, a number of patients still have residual symptoms and disabilities, or simply do not show response to antipsychotic medications. For such 'treatment resistant' patients, there is little by way of randomised controlled data to ...

  1. The Dancing Manias: Psychogenic Illness as a Social Phenomenon.

    Science.gov (United States)

    Lanska, Douglas J

    2018-01-01

    The dancing mania erupted in the 14th century in the wake of the Black Death, and recurred for centuries in central Europe - particularly Germany, the Netherlands, and Belgium - finally abating in the early 17th century. The term "dancing mania" was derived from "choreomania," a concatenation of choros (dance) and mania (madness). A variant, tarantism, was prevalent in southern Italy from the 15th to the 17th centuries, and was attributed at the time to bites from the tarantula spider. Affected individuals participated in continuous, prolonged, erratic, often frenzied and sometimes erotic, dancing. In the 14th century, the dancing mania was linked to a corruption of the festival of St. John's Day by ancient pagan customs, but by the 16th century it was commonly considered an ordeal sent by a saint, or a punishment from God for people's sins. Consequently, during outbreaks in the 14th and 15th centuries, the dancing mania was considered an issue for magistrates and priests, not physicians, even though the disorder proved intractable to decrees and exorcisms. However, in the 16th century Paracelsus discounted the idea that the saints caused or interceded in the cure of the dancing mania; he instead suggested a psychogenic or malingered etiology, and this reformulation brought the dancing mania within the purview of physicians. Paracelsus advocated various mystical, psychological, and pharmacological approaches, depending on the presumptive etiologic factors with individual patients. Only music provided any relief for tarantism. Later authors suggested that the dancing mania was a mass stress-induced psychosis, a mass psychogenic illness, a culturally determined form of ritualized behavior, a manifestation of religious ecstasy, or even the result of food poisoning caused by the toxic and psychoactive chemical products of ergot fungi. In reality, dancing manias did not have a single cause, but component causes likely included psychogenic illness, malingering, and

  2. Acute mania induced by hypothyroidism in a male patient after thyroidectomy

    OpenAIRE

    Morgado, Pedro; Gonçalves, Carla Marina Mendonça

    2016-01-01

    Hypothyroidism is a common hormone deficiency, associated with multiple causes and presenting with diverse clinical manifestations including neuropsychiatric disease. Hypothyroidism is commonly associated with depressive symptoms, and thyroid hormone screening is indicated in patients with a history of depression. Although other neuropsychiatric disorders could be induced by hypothyroidism, only 14 reports present clinical cases of mania related with this hormone deficiency.1,2 Autoimmune thy...

  3. [The concept of mania in Greek medical and philosophical literature].

    Science.gov (United States)

    Corleto, L M

    1992-01-01

    Coverage of the concept of mania in late archaic Greek culture displays a clear difference between its use in medical and philosophical works. Medical literature uses the terms [Greek] and [Greek] to describe mania, with the condition seen largely associated with physical illness. Specific treatment for this attered psychic state is not advanced. The philosophical view sees mania as a divine folly and thus possessing positive as well as negative aspects. Plate identifies four types of mania and treatment is closely associated with the divinity seen as responsible for that particular type. The radical rationalism found in the medical literature is a counterpoint to moderation as shown by Plato with his interest on regulations of society.

  4. A combined marker of inflammation in individuals with mania.

    Directory of Open Access Journals (Sweden)

    Faith Dickerson

    Full Text Available BACKGROUND: Markers of immune activation have been associated with mania but have not been examined in combination. We studied the association between mania and an inflammation score based on four immune markers. METHODS: A total of 57 individuals with mania were assessed at up to three time points: the day of hospital admission, evaluation several days later, and six-month follow-up. Also assessed were 207 non-psychiatric controls and 330 individuals with recent onset psychosis, multi-episode schizophrenia, or bipolar disorder depression. A combined inflammation score was calculated by factor analysis of the levels of class-specific antibodies to the NR peptide of the NMDA receptor; gliadin; Mason-Pfizer monkey virus protein 24; and Toxoplasma gondii. Inflammation scores among groups were compared by multivariate analyses. The inflammation score of the mania group at evaluation was studied as a predictor of re-hospitalization in the follow-up period. RESULTS: The combined inflammation score of the mania group at hospital admission and at evaluation differed significantly from that of the non-psychiatric controls (t=3.95, 4.10, p<.001. The inflammation score was significantly decreased at six month follow-up (F=5.85, p=0.004. There were not any significant differences in the inflammation scores of any of the other psychiatric groups and that of the controls. Within the mania group, an elevated inflammation score at evaluation predicted re-hospitalization (Hazard ratio=7.12, p=.005. CONCLUSIONS: Hospitalization for mania is associated with immune activation. The level of this activation is predictive of subsequent re-hospitalization. Interventions for the modulation of inflammation should be evaluated for the therapy of individuals with mania.

  5. Pediatric Mania: The Controversy between Euphoria and Irritability.

    Science.gov (United States)

    Serra, Giulia; Uchida, Mai; Battaglia, Claudia; Casini, Maria Pia; De Chiara, Lavinia; Biederman, Joseph; Vicari, Stefano; Wozniak, Janet

    2017-04-01

    Pediatric Bipolar Disorder (BD) is a highly morbid pediatric psychiatric disease, consistently associated with family psychiatric history of mood disorders and associated with high levels of morbidity and disability and with a great risk of suicide. While there is a general consensus on the symptomatology of depression in childhood, the phenomenology of pediatric mania is still highly debated and the course and long-term outcome of pediatric BD still need to be clarified. We reviewed the available studies on the phenomenology of pediatric mania with the aim of summarizing the prevalence, demographics, clinical correlates and course of these two types of pediatric mania. Eighteen studies reported the number of subjects presenting with either irritable or elated mood during mania. Irritability has been reported to be the most frequent clinical feature of pediatric mania reaching a sensitivity of 95-100% in several samples. Only half the studies reviewed reported on number of episodes or cycling patterns and the described course was mostly chronic and ultra-rapid whereas the classical episodic presentation was less common. Few long-term outcome studies have reported a diagnostic stability of mania from childhood to young adult age. Future research should focus on the heterogeneity of irritability aiming at differentiating distinct subtypes of pediatric psychiatric disorders with distinct phenomenology, course, outcome and biomarkers. Longitudinal studies of samples attending to mood presentation, irritable versus elated, and course, chronic versus episodic, may help clarify whether these are meaningful distinctions in the course, treatment and outcome of pediatric onset bipolar disorder.

  6. Adjunctive Treatment of Acute Mania with Risperidone versus Typical Antipsychotics: A Retrospective Study

    Directory of Open Access Journals (Sweden)

    Jui-Hsiu Tsai

    2005-12-01

    Full Text Available Few studies have directly compared atypical antipsychotics (e.g. risperidone with typical antipsychotics as adjunctive therapy in patients hospitalized for acute mania, especially during a lengthy hospital stay. Our retrospective, case-controlled study is a chart review of 64 patients with Diagnostic and Statistical Manual of Mental Disorders, 4th edition, defined bipolar I disorder (current episode, mania. Patients were divided into two groups according to the adjunctive medications used: the risperidone group (mood stabilizers plus risperidone and the control group (mood stabilizers plus typical antipsychotics. Outcome at discharge, medications, adverse drug effects, and length of hospital stay were compared between groups, controlling for gender, age, number of prior admissions, and duration of illness. Results indicated no statistically significant differences between groups in the controlled factors, Global Assessment of Functioning and Clinical Global Impression-Improvement scores, and adverse drug events. Patients in the risperidone group used significantly lower doses of trihexyphenidyl than those in the control group (p < 0.05. Patients treated with risperidone had a shorter hospital stay than those treated with typical antipsychotics (p < 0.01. In conclusion, antipsychotics are effective as adjunctive agents in the treatment of acute mania. The use of risperidone, in particular, decreases the need for anticholinergics and may lead to a shorter hospital stay compared with typical antipsychotics.

  7. Pharmacotherapy for treatment-resistant schizophrenia

    Directory of Open Access Journals (Sweden)

    Meghan E Mcilwain

    2011-03-01

    Full Text Available Meghan E Mcilwain1,2, Jeff Harrison1, Amanda J Wheeler1,3, Bruce R Russell1,21School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; 2Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; 3School of Human Services, Griffith University, Queensland, AustraliaAbstract: Schizophrenia is a disabling mental illness with a lifetime prevalence of 0.7% worldwide and significant, often devastating, consequences on social and occupational functioning. A range of antipsychotic medications are available; however, suboptimal therapeutic response in terms of psychotic symptoms is common and affects up to one-third of people with schizophrenia. Negative symptoms are generally less amenable to treatment. Because of the consequences of inadequate symptom control, effective treatment strategies are required for people with treatment-resistant schizophrenia. Clozapine has been shown to be more effective than other antipsychotics in treatment-resistant populations in several studies; however, the occurrence of adverse effects, some of which are potentially life-threatening, are important limitations. In addition to those who are intolerant to clozapine, only 30% to 50% experience clinically significant symptom improvement. This review describes the recent evidence for treatment strategies for people not responding to nonclozapine antipsychotic agents and people not responding or only partially responding to clozapine.Keywords: antipsychotic, refractory, clozapine

  8. Contact high: Mania proneness and positive perception of emotional touches.

    Science.gov (United States)

    Piff, Paul K; Purcell, Amanda; Gruber, June; Hertenstein, Matthew J; Keltner, Dacher

    2012-01-01

    How do extreme degrees of positive emotion-such as those characteristic of mania-influence emotion perception? The present study investigated how mania proneness, assessed using the Hypomanic Personality Scale, influences the perception of emotion via touch. Using a validated dyadic interaction paradigm for communicating emotion through touch (Hertenstein, Keltner, App, Bulleit, & Jaskolka, 2006), participants (N=53) received eight different touches to their forearm from a stranger and then identified the emotion via forced-choice methodology. Mania proneness predicted increased overall accuracy in touch perception, particularly for positive emotion touches, as well as the over-attribution of positive and under-attribution of negative emotions across all touches. These findings highlight the effects of positive emotion extremes on the perception of emotion in social interactions.

  9. Pediatric Mania: The Controversy between Euphoria and Irritability

    Science.gov (United States)

    Serra, Giulia; Uchida, Mai; Battaglia, Claudia; Casini, Maria Pia; De Chiara, Lavinia; Biederman, Joseph; Vicari, Stefano; Wozniak, Janet

    2017-01-01

    Abstract: Pediatric Bipolar Disorder (BD) is a highly morbid pediatric psychiatric disease, consistently associated with family psychiatric history of mood disorders and associated with high levels of morbidity and disability and with a great risk of suicide. While there is a general consensus on the symptomatology of depression in childhood, the phenomenology of pediatric mania is still highly debated and the course and long-term outcome of pediatric BD still need to be clarified. We reviewed the available studies on the phenomenology of pediatric mania with the aim of summarizing the prevalence, demographics, clinical correlates and course of these two types of pediatric mania. Eighteen studies reported the number of subjects presenting with either irritable or elated mood during mania. Irritability has been reported to be the most frequent clinical feature of pediatric mania reaching a sensitivity of 95–100% in several samples. Only half the studies reviewed reported on number of episodes or cycling patterns and the described course was mostly chronic and ultra-rapid whereas the classical episodic presentation was less common. Few long-term outcome studies have reported a diagnostic stability of mania from childhood to young adult age. Future research should focus on the heterogeneity of irritability aiming at differentiating distinct subtypes of pediatric psychiatric disorders with distinct phenomenology, course, outcome and biomarkers. Longitudinal studies of samples attending to mood presentation, irritable versus elated, and course, chronic versus episodic, may help clarify whether these are meaningful distinctions in the course, treatment and outcome of pediatric onset bipolar disorder. PMID:28503110

  10. Pharmacological Approaches for Treatment-resistant Bipolar Disorder

    Science.gov (United States)

    Poon, Shi Hui; Sim, Kang; Baldessarini, Ross J.

    2015-01-01

    Bipolar disorder is prevalent, with high risks of disability, substance abuse and premature mortality. Treatment responses typically are incomplete, especially for depressive components, so that many cases can be considered “treatment resistant.” We reviewed reports on experimental treatments for such patients: there is a striking paucity of such research, mainly involving small incompletely controlled trials of add-on treatment, and findings remain preliminary. Encouraging results have been reported by adding aripiprazole, bupropion, clozapine, ketamine, memantine, pramipexole, pregabalin, and perhaps tri-iodothyronine in resistant manic or depressive phases. The urgency of incomplete responses in such a severe illness underscores the need for more systematic, simpler, and better controlled studies in more homogeneous samples of patients. PMID:26467409

  11. naturalistic study of olanzapine in treatment-resistant schizophrenia

    African Journals Online (AJOL)

    hi-tech

    2000-02-02

    Feb 2, 2000 ... of some 800,000 mixed race people, of whom the indigenous race ... severity of mania, depression, anxiety and OCD; (ii) the Clinical. Global Impression ... schizophrenia (36 or 56.3%), Bipolar I disorder, manic phase (8 or ...

  12. Recombinant Human Erythropoietin for Treating Treatment-Resistant Depression

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla W; Vinberg, Maj; Christensen, Ellen M

    2014-01-01

    improves mood and memory in treatment-resistant depression. Forty treatment-resistant depressed unipolar patients with Hamilton Depression Rating Scale-17 (HDRS-17) score ≥ 17 were randomized to eight weekly EPO (Eprex; 40,000 IU) or saline infusions in a double-blind, placebo-controlled, parallel...

  13. Ketamine for Treatment-Resistant Unipolar Depression

    Science.gov (United States)

    Mathew, Sanjay J.; Shah, Asim; Lapidus, Kyle; Clark, Crystal; Jarun, Noor; Ostermeyer, Britta; Murrough, James W.

    2013-01-01

    Currently available drugs for unipolar major depressive disorder (MDD), which target monoaminergic systems, have a delayed onset of action and significant limitations in efficacy. Antidepressants with primary pharmacological targets outside the monoamine system may offer the potential for more rapid activity with improved therapeutic benefit. The glutamate system has been scrutinized as a target for antidepressant drug discovery. The purpose of this article is to review emerging literature on the potential rapid-onset antidepressant properties of the glutamate NMDA receptor antagonist ketamine, an established anaesthetic agent. The pharmacology of ketamine and its enantiomer S-ketamine is reviewed, followed by examples of its clinical application in chronic, refractory pain conditions, which are commonly co-morbid with depression. The first generation of studies in patients with treatment-resistant depression (TRD) reported the safety and acute efficacy of a single subanaesthetic dose (0.5 mg/kg) of intravenous ketamine. A second generation of ketamine studies is focused on testing alternate routes of drug delivery, identifying methods to prevent relapse following resolution of depressive symptoms and understanding the neural basis for the putative antidepressant actions of ketamine. In addition to traditional depression rating endpoints, ongoing research is examining the impact of ketamine on neurocognition. Although the first clinical report in MDD was published in 2000, there is a paucity of adequately controlled double-blind trials, and limited clinical experience outside of research settings. Given the potential risks of ketamine, safety considerations will ultimately determine whether this old drug is successfully repositioned as a new therapy for TRD. PMID:22303887

  14. Treatment-resistant depression and suicidality.

    Science.gov (United States)

    Bergfeld, Isidoor O; Mantione, Mariska; Figee, Martijn; Schuurman, P Richard; Lok, Anja; Denys, Damiaan

    2018-08-01

    Thirty percent of patients with treatment-resistant depression (TRD) attempt suicide at least once during their lifetime. However, it is unclear what the attempted and completed suicide incidences are in TRD patients after initiating a treatment, and whether specific treatments increase or decrease these incidences. We searched PubMed systematically for studies of depressed patients who failed at least two antidepressant therapies and were followed for at least three months after initiating a treatment. We estimated attempted and completed suicide incidences using a Poisson meta-analysis. Given the lack of controlled comparisons, we used a meta-regression to estimate whether these incidences differed between treatments. We included 30 studies investigating suicidality in 32 TRD samples, undergoing deep brain stimulation (DBS, n = 9), vagal nerve stimulation (VNS, n = 9), electroconvulsive therapy (ECT, n = 5), treatment-as-usual (n = 3), capsulotomy (n = 2), cognitive behavioral therapy (n = 2), ketamine (n = 1), and epidural cortical stimulation (n = 1). The overall incidence of completed suicides was 0.47 per 100 patient years (95% CI: 0.22-1.00), and of attempted suicides 4.66 per 100 patient years (95% CI: 3.53-6.23). No differences were found in incidences following DBS, VNS or ECT. Suicidality is poorly recorded in many studies limiting the number of studies available. The completed and attempted suicide incidences are high (0.47 and 4.66 per 100 patient years respectively), but these incidences did not differ between three end of the line treatments (DBS, VNS or ECT). Given the high suicide risk in TRD patients, clinical trials should consider suicidality as an explicit outcome measure. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Olanzapine monotherapy and olanzapine combination therapy in the treatment of mania: 12-week results from the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) observational study.

    Science.gov (United States)

    Vieta, Eduard; Panicali, Francesco; Goetz, Iris; Reed, Catherine; Comes, Merce; Tohen, Mauricio

    2008-02-01

    To evaluate the 12-week outcomes (effectiveness, tolerability, and patterns of medication use) of olanzapine (either in antimanic monotherapy or in combination with other antipsychotics, anticonvulsants, and/or lithium) in patients with bipolar mania or mixed mania. EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 24-month prospective observational study of in- and outpatients with acute mania/mixed mania conducted in 14 European countries. Primary outcome measures included Clinical Global Impressions-Bipolar Disorder scale (overall, mania, and depression); 5-item Hamilton Depression Rating Scale; and Young Mania Rating Scale. Tolerability measures included a questionnaire to assess patients' symptomatic complaints. Overall, 2004 patients received olanzapine (olanzapine monotherapy, n=673; olanzapine combination, n=1331). Concomitant therapy with antidepressants and/or anxiolytics was possible in both groups. The countries significantly differed in the use of olanzapine monotherapy versus olanzapine combination (pEMBLEM results suggest that in naturalistic settings, olanzapine (both as monotherapy and combination) may be effective in treating patients with bipolar mania. The use of olanzapine monotherapy or combination varies significantly across countries, but combination is generally the rule, rather than the exception.

  16. MANIA (276-3/4/5). Nuclear analysis

    International Nuclear Information System (INIS)

    Sciolla, C.M.

    1993-11-01

    This report contains the results of the nuclear calculations performed for the MANIA-276 experiment, sample holders 3, 4 and 5. The codes MICROFLUX-2, GAM, HFR-TEDDI and ORIGEN-S have been used for this analysis. Nuclear constants, dpa, reactivity effect and activity of the samples and of the structural materials have been calculated. The results are given in the tables and appendices of the present report. (orig.)

  17. Clozapine Can Be the Good Option in Resistant Mania

    Directory of Open Access Journals (Sweden)

    S. M. Yasir Arafat

    2016-01-01

    Full Text Available Bipolar mood disorder is a mental disorder with a lifetime prevalence rate of about 1% in the general population and there are still a proportion of individuals who suffer from bipolar mood disorders that are resistant to standard treatment. Reporting clozapine responsive mania that was not responding to two previous consecutive atypical antipsychotics and one typical antipsychotic was aimed at. A 17-year-old male manic patient was admitted into the psychiatry inpatient department and was nonresponsive to Risperidone 12 mg daily for 4 weeks, Olanzapine 30 mg daily for 3 weeks, and Haloperidol 30 mg daily for 3 weeks, along with valproate preparation 1500 mg daily. He was started on clozapine as he was nonresponsive to Lithium in previous episodes and did not consent to starting Electroconvulsive Therapy (ECT. He responded adequately to 100 mg clozapine and 1500 mg valproate preparation and remission happened within 2 weeks of starting clozapine. Clozapine can be a good option for resistant mania and further RCT based evidences will strengthen the options in treating resistant mania.

  18. Subacute sclerosing panencephalitis presenting as mania

    Directory of Open Access Journals (Sweden)

    Aggarwal Ashish

    2011-01-01

    Full Text Available Subacute sclerosing panencephalitis (SSPE is a rare, invariably fatal degenerative disease of the central nervous system developing after measles infection. Besides neurological symptoms as initial presenting symptoms, rare reports of its presentation with pure psychiatric symptoms have been reported. We here report a case of 14 year old male who initially presented with manic symptoms and then subsequently diagnosed to be suffering from SSPE. Improtance of ruling our organic conditions is emphasized.

  19. An Integrative Approach to Treatment-Resistant Obsessive-Compulsive Disorder.

    Science.gov (United States)

    Woon, Luke Sy-Cherng; Kanapathy, Anita; Zakaria, Hazli; Alfonso, César A

    2017-01-01

    Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder that often runs a chronic unremitting course. Treatment outcomes can be unsatisfactory despite the availability of various somatic and psychological therapies. Psychodynamic psychotherapy in combination with cognitive behavioral therapy (CBT) with exposure and response prevention (ERP) could help patients with treatment-resistant OCD achieve better outcomes. An integrative approach can help patients gain insight, strengthen the therapeutic alliance, improve treatment adherence, and provide symptomatic relief when other treatments seem insufficient or have failed. We describe the treatment process of a person with treatment-resistant OCD who received pharmacotherapy, concurrent CBT/ERP, and a brief course of psychodynamic psychotherapy. Case formulations from cognitive behavioral and psychodynamic perspectives are presented. The authors discuss the advantages of doing a psychodynamic assessment and formulation in treatment refractory cases and the wisdom of integrating psychotherapy interventions for OCD, as well as the unique clinical features of cases that warrant a multimodal treatment approach.

  20. Use of Ketamine in Elderly Patients with Treatment-Resistant Depression.

    Science.gov (United States)

    Medeiros da Frota Ribeiro, Carolina; Riva-Posse, Patricio

    2017-11-15

    The purpose of this paper is to provide a review of the use of ketamine as an antidepressant for treatment-resistant depression (TRD) in the geriatric population. Available treatment options for late-life treatment-resistant depression are limited and include electroconvulsive therapy and transcranial magnetic stimulation as well as possible pharmacologic augmentation. Ketamine has been shown to be a promising treatment in TRD; however, data regarding the use of ketamine in the elderly includes only five case reports. We discuss the use of ketamine for late-life TRD and present two cases where ketamine led to a significant and sustained improvement in depressive symptoms. Ketamine is a promising treatment for geriatric patients with TRD. Further studies in the elderly will provide valuable insights into the use of ketamine for a population much in need of safe and effective treatments for TRD.

  1. Predictors of switching from mania to depression in a large observational study across Europe (EMBLEM)

    NARCIS (Netherlands)

    Vieta, Eduard; Angst, Jules; Reed, Catherine; Bertsch, Jordan; Maria Haro, Josep

    Background: The risk of switching from mania to depression in bipolar disorder has been poorly studied. Large observational studies may be useful in identifying variables that predict switch to depression after mania and provide data on medication use and outcomes in "real world" patients. Method:

  2. Gender differences in subtypes of late-onset depression and mania

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel

    2006-01-01

    illness. No gender differences were found in the prevalence of depression with or without melancholic or psychotic symptoms. Men more often presented with mania/bipolar disorder with comorbid substance abuse. CONCLUSIONS: The distributions of the subtypes of a single depressive episode or mania...

  3. Predictors of switching from mania to depression in a large observational study across Europe (EMBLEM)

    NARCIS (Netherlands)

    Vieta, Eduard; Angst, Jules; Reed, Catherine; Bertsch, Jordan; Maria Haro, Josep

    2009-01-01

    Background: The risk of switching from mania to depression in bipolar disorder has been poorly studied. Large observational studies may be useful in identifying variables that predict switch to depression after mania and provide data on medication use and outcomes in "real world" patients. Method:

  4. Mania after termination of epilepsy treatment: a case report

    African Journals Online (AJOL)

    animal model can adequately match the mood swings.9,10. Understanding the ... and Children's Health and Diseases Training and Research Hospital,. Altindag, Ankara ... American Psychiatric Association: Diagnostic and statistical manual of.

  5. Return of the psychedelics: Psilocybin for treatment resistant depression.

    Science.gov (United States)

    Patra, Suravi

    2016-12-01

    Psilocybin, the clinically most researched classic psychedelic has recently been tested for its safety and efficacy in a clinical population of treatment resistant depression. The efficacy of psilocybin in clinical depression previously demonstrated in the elecrophysiologic and neuroimaging findings as also in neuropsychological assessments is further validated by the findings of this rigorously conducted randomized trial. Mechanism of action of psilocybin and efficacy in treatment resistant depression are discussed in this paper. Ethical issues of conducting clinical trials with psychedelics are also discussed with particular emphasis on their relative safety and absence of addiction potential. Implications of these issues for conduct of larger trials for establishing risk benefit ratio in treatment resistant depression are further suggested. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Response after Infection-Associated Rise in Clozapine Levels in Treatment-Resistant Schizoaffective Disorder

    Directory of Open Access Journals (Sweden)

    Nina H. Grootendorst-van Mil

    2018-01-01

    Full Text Available The clinical management of patients with treatment-resistant psychotic disorders is still challenging despite years of extensive research. If first-line antipsychotic treatment proves ineffective, clozapine is considered golden standard. Herein, we report on a patient with schizoaffective disorder that initially showed no response to treatment with clozapine and ECT and therefore reached a therapeutic dead end. After an unintentional exposure to supratherapeutic clozapine levels, related to a pneumonia, a significant and persistent reduction of psychotic symptoms occurred. The report suggests a careful reevaluation of the clozapine dose in cases of treatment-resistant psychotic disorders with failed trials of clozapine. Further increase of dose may prove efficacious, although side effects should be closely monitored. Research to determine the upper threshold of clozapine for antipsychotic efficacy is warranted.

  7. Reduced dorso-lateral prefrontal cortex in treatment resistant schizophrenia.

    Science.gov (United States)

    Zugman, André; Gadelha, Ary; Assunção, Idaiane; Sato, João; Ota, Vanessa K; Rocha, Deyvis L; Mari, Jair J; Belangero, Sintia I; Bressan, Rodrigo A; Brietzke, Elisa; Jackowski, Andrea P

    2013-08-01

    Treatment resistance affects up to one third of patients with schizophrenia (SCZ). A better understanding of its biological underlying processes could improve treatment. The aim of this study was to compare cortical thickness between non-resistant SCZ (NR-SCZ), treatment-resistant SCZ (TR-SCZ) patients and healthy controls (HC). Structural MRI scans were obtained from 3 groups of individuals: 61 treatment resistant SCZ individuals, 67 non-resistant SCZ and 80 healthy controls. Images were analyzed using cortical surface modelling (implemented in freesurfer package) to identify group differences in cortical thickness. Statistical significant differences were identified using Monte-Carlo simulation method with a corrected p-cluster<0.01. Patients in the TR-SCZ group showed a widespread reduction in cortical thickness in frontal, parietal, temporal and occipital regions bilaterally. NR-SCZ group had reduced cortex in two regions (left superior frontal cortex and left caudal middle frontal cortex). TR-SCZ group also showed decreased thickness in the left dorsolateral prefrontal cortex (DLPFC) when compared with patients from NR-SCZ group. The reduction in cortical thickness in DLPFC indicates a more severe form of the disease or a specific finding for this group. Alterations in this region should be explored as a putative marker for treatment resistance. Prospective studies, with individuals being followed from first episode psychosis until refractoriness is diagnosed, are needed to clarify these hypotheses. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Treatment resistance and psychodynamic psychiatry: concepts psychiatry needs from psychoanalysis.

    Science.gov (United States)

    Plakun, Eric

    2012-06-01

    Over the last 30 years psychiatry and psychoanalysis have moved in substantially divergent directions. Psychiatry has become rich in methodology but conceptually limited, with a drift toward biological reductionism. Psychoanalysis has remained relatively limited in methodology, but conceptually rich. The rich methodology of psychiatry has led to major contributions in discovering gene by environment interactions, the importance of early adversity, and to recognition of the serious problem posed by treatment resistance. However, psychiatry's biologically reductionistic conceptual focus interferes with the development of a nuanced clinical perspective based on emerging knowledge that might help more treatment resistant patients become treatment responders. This article argues that recognition of the problem of treatment resistance in psychiatry creates a need for it to reconnect with the conceptual richness of psychoanalysis in order to improve patient care. Psychodynamic psychiatry is defined as the relevant intersection of psychiatry and psychoanalysis where this reconnection can occur. I will suggest selected aspects of psychoanalysis that are especially relevant to psychiatry in improving outcomes in work with treatment resistant patients.

  9. Indução de mania durante o tratamento com antidepressivos no transtorno bipolar

    Directory of Open Access Journals (Sweden)

    Tamada Renata S

    2003-01-01

    Full Text Available OBJETIVOS: Realizar uma revisão da literatura sobre a mania induzida por antidepressivos, sua incidência, quadro clínico, fatores de risco e tratamento. MÉTODOS: Foi realizado um levantamento no Medline dos artigos publicados entre 1970 e 2001. Foram incluídos estudos abertos e controlados bem como relatos de caso com casuística maior que cinco pacientes. RESULTADOS: Mania induzida e mania espontânea parecem ter apresentações clínicas distintas, sendo a mania induzida mais leve e breve. Os fatores de risco para mania induzida ainda não estão bem estabelecidos. CONCLUSÃO: Existe um número muito limitado de estudos controlados e prospectivos sobre a mania induzida. Os antidepressivos estão associados a um aumento no risco de indução de mania. Este risco pode variar dependendo da droga utilizada. Portanto, os antidepressivos devem ser utilizados em pacientes bipolares considerado-se tanto a eficácia clínica como os potenciais efeitos sobre o curso da doença.

  10. Social phobia, panic disorder and suicidality in subjects with pure and depressive mania.

    Science.gov (United States)

    Dilsaver, Steven C; Chen, Yuan-Who

    2003-11-01

    The objective of this study is to ascertain the rates of social phobia, panic disorder and suicidality in the midst of the manic state among subjects with pure and depressive mania. Subjects received evaluations entailing the use of serial standard clinical interviews, the Schedule for Affective Disorders and Schizophrenia (SADS) and a structured interview to determine whether they met the criteria for intra-episode social phobia (IESP) and panic disorder (IEPD). The diagnoses of major depressive disorder and mania were rendered using the Research Diagnostic Criteria. The diagnoses of IESP and IEPD were rendered using DSM-III-R criteria. Categorization as being suicidal was based on the SADS suicide subscale score. Twenty-five (56.8%) subjects had pure and 19 (43.2%) subjects had depressive mania. None of the subjects with pure and 13 (68.4%) with depressive mania had IESP (Pdepressive mania had IEPD (Pdepressive were suicidal. Twelve of 13 (92.3%) subjects with depressive mania met the criteria for IESP and IEPD concurrently (Pdepressive but not pure mania exhibited high rates of both IESP and IEPD. Concurrence of the disorders is the rule. The findings suggest that databases disclosing a relationship between panic disorder and suicidality merit, where possible, reanalysis directed at controlling for the effect of social phobia.

  11. GANGGUAN AFEKTIF BIPOLAR MANIA DENGAN PSIKOTIK: SEBUAH LAPORAN KASUS

    Directory of Open Access Journals (Sweden)

    Hendrikus Gede Surya Adhi Putra

    2015-05-01

    Full Text Available Gangguan bipolar merupakan gangguan yang terdiri dari afek yang meningkat, dan jugaaktivitas yang berlebih (mania atau hipomania, dan dalam jangka waktu yang berbedaterjadi penurunan afek yang disertai dengan penurunan aktivitas (depresi. Kejadianpada  gangguan  bipolar  berkisar  antara  0,3-1,5%.  Prevalensi  serupa  pada  pria  danwanita.Gejala gangguan bipolar episode manik meliputi perasaan sensitif, kurangistirahat, harga diri melonjak naik, dan pada episode depresi meliputi kehilanganminat, tidur lebih atau kurang dari normal, gelisah, merasa tidak berharga, dan kurangkonsentrasi. Laporan ini membahas kasus gangguan bipolar episode kini manik yangterjadi pada seorang laki-laki berusia 45 tahun. Pasien ini mendapatkan psikoterapi,haloperidol 1 x 5 mg, dan trihexyphenidyl 1 x 2 mg per oral.

  12. Regulation of glycogen synthase kinase-3 during bipolar mania treatment.

    Science.gov (United States)

    Li, Xiaohong; Liu, Min; Cai, Zhuoji; Wang, Gang; Li, Xiaohua

    2010-11-01

    Bipolar disorder is a debilitating psychiatric illness presenting with recurrent mania and depression. The pathophysiology of bipolar disorder is poorly understood, and molecular targets in the treatment of bipolar disorder remain to be identified. Preclinical studies have suggested that glycogen synthase kinase-3 (GSK3) is a potential therapeutic target in bipolar disorder, but evidence of abnormal GSK3 in human bipolar disorder and its response to treatment is still lacking. This study was conducted in acutely ill type I bipolar disorder subjects who were hospitalized for a manic episode. The protein level and the inhibitory serine phosphorylation of GSK3 in peripheral blood mononuclear cells of bipolar manic and healthy control subjects were compared, and the response of GSK3 to antimanic treatment was evaluated. The levels of GSK3α and GSK3β in this group of bipolar manic subjects were higher than healthy controls. Symptom improvement during an eight-week antimanic treatment with lithium, valproate, and atypical antipsychotics was accompanied by a significant increase in the inhibitory serine phosphorylation of GSK3, but not the total level of GSK3, whereas concomitant electroconvulsive therapy treatment during a manic episode appeared to dampen the response of GSK3 to pharmacological treatment. Results of this study suggest that GSK3 can be modified during the treatment of bipolar mania. This finding in human bipolar disorder is in agreement with preclinical data suggesting that inhibition of GSK3 by increasing serine phosphorylation is a response of GSK3 to psychotropics used in bipolar disorder, supporting the notion that GSK3 is a promising molecular target in the pharmacological treatment of bipolar disorder. © 2010 John Wiley and Sons A/S.

  13. Recognizing mania in children and adolescents-age does not matter, but decreased need for sleep does.

    Science.gov (United States)

    Meyer, Thomas D; Fuhr, Kristina; Hautzinger, Martin; Schlarb, Angelika A

    2011-01-01

    The diagnosis of pediatric bipolar disorders is a controversial topic. If this is mainly due to a bias against a diagnosis in younger children, then just changing the information about the age of a patient should influence the likelihood of a diagnosis despite otherwise identical symptoms. Therefore, we designed a study to test if the age of a patient will influence diagnostic decisions. We further attempted to replicate an earlier result with regard to "decreased need for sleep" as a salient symptom for mania. We randomly sent 1 of 4 case vignettes describing a person with current mania to child/adolescents psychiatrists in Germany. This vignette was systematically varied with respect to age of the patient (6 vs 16 years) and the presence/absence of decreased need for sleep but always included sufficient criteria to diagnose a mania. One hundred sixteen responded and, overall, 63.8% of the respondents diagnosed a bipolar disorder in the person described in the vignette. Although age did not affect the likelihood of a bipolar diagnosis, the presence of decreased need for sleep did increase its likelihood. Furthermore, the number of core symptoms identified by the clinicians was closely linked to the likelihood of assigning a bipolar diagnosis. Certain symptoms such as the decreased need for sleep, and also elated mood and grandiosity, seem to be salient for some clinicians and influence their diagnoses. Biological age of the patient, however, does not seem to cause a systematic bias against a diagnosis of bipolar disorder in children. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Differentiating risk for mania and borderline personality disorder: The nature of goal regulation and impulsivity.

    Science.gov (United States)

    Fulford, Daniel; Eisner, Lori R; Johnson, Sheri L

    2015-06-30

    Researchers and clinicians have long noted the overlap among features and high comorbidity of bipolar disorder and borderline personality disorder. The shared features of impulsivity and labile mood in both disorders make them challenging to distinguish. We tested the hypothesis that variables related to goal dysregulation would be uniquely related to risk for mania, while emotion-relevant impulsivity would be related to risk for both disorders. We administered a broad range of measures related to goal regulation traits and impulsivity to 214 undergraduates. Findings confirmed that risk for mania, but not for borderline personality disorder, was related to higher sensitivity to reward and intense pursuit of goals. In contrast, borderline personality disorder symptoms related more strongly than did mania risk with threat sensitivity and with impulsivity in the context of negative affect. Results highlight potential differences and commonalities in mania risk versus borderline personality disorder risk. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Sodium valproate for the treatment of mania in a patient with Charcot ...

    African Journals Online (AJOL)

    and the treatment thereof with sodium valproate. Mr. L, a 28 ... prolonged distal latencies, decreased compound muscle action ... 1000mg per day for treatment of mania. ... dystrophy, facio-scapulo-humeral dystrophy, and hereditary motor and.

  16. Risk for Mania and Positive Emotional Responding: Too Much of a Good Thing?

    OpenAIRE

    Gruber, June; Oveis, Christopher; Keltner, Dacher; Johnson, Sheri L.

    2008-01-01

    Although positive emotion research has begun to flourish, the extremes of positive emotion remain understudied. The present research used a multimethod approach to examine positive emotional disturbance by comparing participants at high and low risk for episodes of mania, which involves elevations in positive emotionality. Ninety participants were recruited into a high or low mania risk group according to responses on the Hypomanic Personality Scale. Participants’ subjective, expressive, and ...

  17. A twin study of schizoaffective-mania, schizoaffective-depression, and other psychotic syndromes.

    Science.gov (United States)

    Cardno, Alastair G; Rijsdijk, Frühling V; West, Robert M; Gottesman, Irving I; Craddock, Nick; Murray, Robin M; McGuffin, Peter

    2012-03-01

    The nosological status of schizoaffective disorders remains controversial. Twin studies are potentially valuable for investigating relationships between schizoaffective-mania, schizoaffective-depression, and other psychotic syndromes, but no such study has yet been reported. We ascertained 224 probandwise twin pairs [106 monozygotic (MZ), 118 same-sex dizygotic (DZ)], where probands had psychotic or manic symptoms, from the Maudsley Twin Register in London (1948-1993). We investigated Research Diagnostic Criteria schizoaffective-mania, schizoaffective-depression, schizophrenia, mania and depressive psychosis primarily using a non-hierarchical classification, and additionally using hierarchical and data-derived classifications, and a classification featuring broad schizophrenic and manic syndromes without separate schizoaffective syndromes. We investigated inter-rater reliability and co-occurrence of syndromes within twin probands and twin pairs. The schizoaffective syndromes showed only moderate inter-rater reliability. There was general significant co-occurrence between syndromes within twin probands and MZ pairs, and a trend for schizoaffective-mania and mania to have the greatest co-occurrence. Schizoaffective syndromes in MZ probands were associated with relatively high risk of a psychotic syndrome occurring in their co-twins. The classification of broad schizophrenic and manic syndromes without separate schizoaffective syndromes showed improved inter-rater reliability, but high genetic and environmental correlations between the two broad syndromes. The results are consistent with regarding schizoaffective-mania as due to co-occurring elevated liability to schizophrenia, mania, and depression; and schizoaffective-depression as due to co-occurring elevated liability to schizophrenia and depression, but with less elevation of liability to mania. If in due course schizoaffective syndromes show satisfactory inter-rater reliability and some specific etiological

  18. Renal denervation in moderate treatment-resistant hypertension.

    Science.gov (United States)

    Ott, Christian; Mahfoud, Felix; Schmid, Axel; Ditting, Tilmann; Sobotka, Paul A; Veelken, Roland; Spies, Aline; Ukena, Christian; Laufs, Ulrich; Uder, Michael; Böhm, Michael; Schmieder, Roland E

    2013-11-12

    This study sought to investigate the effect of renal denervation (RDN) in patients with treatment-resistant hypertension according to the established definition (Joint National Committee VII and European Society of Hypertension/European Society of Cardiology guidelines), that is, office blood pressure (BP) ≥140/90 mm Hg (with at least three antihypertensive drugs, including a diuretic, in adequate doses) and confirmed by 24-h ambulatory BP monitoring (ABPM). RDN emerged as an innovative interventional antihypertensive therapy. However, so far, only patients with severe hypertension (systolic BP ≥160 mm Hg or ≥150 mm Hg for patients with type 2 diabetes) have been investigated. In this study, there were 54 patients with moderate treatment-resistant hypertension (office BP ≥140/90 mm Hg and who underwent catheter-based RDN using the Symplicity catheter (Medtronic Inc., Mountain View, California). Patients were treated with 5.1 ± 1.4 antihypertensive drugs on average. Office BP was significantly reduced by 13/7 mm Hg 6 months after RDN (systolic: 151 ± 6 mm Hg vs. 138 ± 21 mm Hg, p who underwent ABPM 6 months after treatment, there was a reduction in average 24-h ABPM by 14/7 mm Hg (systolic: 150 ± 16 mm Hg vs. 136 ± 16 mm Hg, p hypertension. (Renal Denervation in Treatment Resistant Hypertension; NCT01687725). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. Maintenance Electroconvulsive Therapy in a Patient with Treatment-Resistant Paranoid Schizophrenia and Comorbid Epilepsy

    Directory of Open Access Journals (Sweden)

    Beppe Micallef-Trigona

    2012-01-01

    Full Text Available The treatment of choice for acute schizophrenia is antipsychotic drug treatment and electroconvulsive therapy (ECT and should only be considered as an option for treatment-resistant schizophrenia, where treatment with clozapine has already proven ineffective or intolerable. The use of ECT as a maintenance treatment for patients with schizophrenia and comorbid epilepsy is uncommon as scant evidence exists to support this. We describe a patient with a serious case of paranoid schizophrenia and comorbid epilepsy who had not responded to typical and atypical antipsychotic medication, but responded remarkably to acute ECT and required maintenance ECT to sustain a positive therapeutic response.

  20. An evolutionary approach to mania studying Sardinian immigrants to Argentina.

    Science.gov (United States)

    Carta, Mauro G; Perra, Alessandra; Atzeni, Michela; D'Oca, Silvia; Moro, Maria F; Kurotschka, Peter K; Moro, Daniela; Sancassiani, Federica; Minerba, Luigi; Brasesco, Maria V; Mausel, Gustavo; Nardi, Antonio E; Tondo, Leonardo

    2017-01-01

    To ascertain lifetime prevalence of positivity to a screening questionnaire for bipolar disorders (BD) in Sardinian immigrants to Argentina and residents of Sardinia and assess whether such positivity affects quality of life (QoL) in either group. Our hypothesis is that screen positivity for BD may be more frequent in immigrants. Observational study. Subjects were randomly selected from the membership lists of associations of Sardinian immigrants in Argentina. A study carried out in Sardinia using the same methodology was used for comparison. The Mood Disorder Questionnaire was used to screen for mania/hypomania and the Short-Form Health Survey-12 to measure QoL. A higher prevalence of manic/hypomanic episodes was found in Sardinian immigrants to Argentina (p immigrants to Argentina and in residents of Sardinia. To the best of our knowledge, this is the first study to show a higher lifetime prevalence of manic/hypomanic episodes in a general-population sample of individuals who migrated to a foreign country. Our results are in agreement with the hypothesis that hyperactive/novelty-seeking features may represent an adaptive substrate in certain conditions of social change.

  1. The Role of Electroconvulsive Therapy (ECT) in Bipolar Disorder: Effectiveness in 522 Patients with Bipolar Depression, Mixed-state, Mania and Catatonic Features.

    Science.gov (United States)

    Perugi, Giulio; Medda, Pierpaolo; Toni, Cristina; Mariani, Michela Giorgi; Socci, Chiara; Mauri, Mauro

    2017-04-01

    We evaluated the effectiveness of Electroconvulsive Therapy (ECT) in the treatment of Bipolar Disorder (BD) in a large sample of bipolar patients with drug resistant depression, mania, mixed state and catatonic features. 522 consecutive patients with DSM-IV-TR BD were evaluated prior to and after the ECT course. Responders and nonresponders were compared in subsamples of depressed and mixed patients. Descriptive analyses were reported for patients with mania and with catatonic features. Of the original sample only 22 patients were excluded for the occurrence of side effects or consent withdrawal. After the ECT course, 344 (68.8%) patients were considered responders (final CGIi score ≤2) and 156 (31.2%) nonresponders. Response rates were respectively 68.1% for BD depression, 72.9% for mixed state, 75% for mania and 80.8% for catatonic features. Length of current episode and global severity of the illness were the only statistically significant predictors of nonresponse. ECT resulted to be an effective and safe treatment for all the phases of severe and drug-resistant BD. Positive response was observed in approximately two-thirds of the cases and in 80% of the catatonic patients. The duration of the current episode was the major predictor of nonresponse. The risk of ECT-induced mania is virtually absent and mood destabilization very unlikely. Our results clearly indicate that current algorithms for the treatment of depressive, mixed, manic and catatonic states should be modified and, at least for the most severe patients, ECT should not be considered as a "last resort".

  2. The Risk of Treatment-Emergent Mania With Methylphenidate in Bipolar Disorder.

    Science.gov (United States)

    Viktorin, Alexander; Rydén, Eleonore; Thase, Michael E; Chang, Zheng; Lundholm, Cecilia; D'Onofrio, Brian M; Almqvist, Catarina; Magnusson, Patrik K E; Lichtenstein, Paul; Larsson, Henrik; Landén, Mikael

    2017-04-01

    The authors sought to determine the risk of treatment-emergent mania associated with methylphenidate, used in monotherapy or with a concomitant mood-stabilizing medication, in patients with bipolar disorder. Using linked Swedish national registries, the authors identified 2,307 adults with bipolar disorder who initiated therapy with methylphenidate between 2006 and 2014. The cohort was divided into two groups: those with and those without concomitant mood-stabilizing treatment. To adjust for individual-specific confounders, including disorder severity, genetic makeup, and early environmental factors, Cox regression analyses were used, conditioning on individual to compare the rate of mania (defined as hospitalization for mania or a new dispensation of stabilizing medication) 0-3 months and 3-6 months after medication start following nontreated periods. Patients on methylphenidate monotherapy displayed an increased rate of manic episodes within 3 months of medication initiation (hazard ratio=6.7, 95% CI=2.0-22.4), with similar results for the subsequent 3 months. By contrast, for patients taking mood stabilizers, the risk of mania was lower after starting methylphenidate (hazard ratio=0.6, 95% CI=0.4-0.9). Comparable results were observed when only hospitalizations for mania were counted. No evidence was found for a positive association between methylphenidate and treatment-emergent mania among patients with bipolar disorder who were concomitantly receiving a mood-stabilizing medication. This is clinically important given that up to 20% of people with bipolar disorder suffer from comorbid ADHD. Given the markedly increased hazard ratio of mania following methylphenidate initiation in bipolar patients not taking mood stabilizers, careful assessment to rule out bipolar disorder is indicated before initiating monotherapy with psychostimulants.

  3. Psychopharmacological treatment of psychotic mania and psychotic bipolar depression compared to non-psychotic mania and non-psychotic bipolar depression.

    Science.gov (United States)

    Bjørklund, Louise B; Horsdal, Henriette T; Mors, Ole; Gasse, Christiane; Østergaard, Søren D

    2017-09-01

    An evidence base for the treatment of mania and bipolar depression with psychotic symptoms is lacking. Nevertheless, clinicians may have a preference for treating episodes of bipolar disorder with or without psychotic symptoms in different ways, which is likely to reflect notions of differential efficacy of treatments between these subtypes. This study aimed to investigate whether the psychopharmacological treatment of psychotic and non-psychotic episodes of mania and bipolar depression, respectively, differs in clinical practice. We conducted a register-based study assessing the psychopharmacological treatment of all individuals receiving their first diagnosis of mania or bipolar depression between 2010 and 2012. The psychopharmacological treatment within 3 months following the time of diagnosis was considered. Potential differences in psychopharmacological treatment between the psychotic and non-psychotic subtypes of mania and bipolar depression, respectively, were investigated by means of Pearson's χ 2 test and logistic regression adjusted for sex and age at diagnosis of bipolar disorder. A total of 827 patients were included in the analyses. The adjusted odds ratio (aOR) for treatment with an antipsychotic was 1.71 (95% confidence interval [CI]: 1.18-2.48, Pbipolar depression. The aOR for treatment with the combination of an antipsychotic and an anticonvulsant was 1.60 (95% CI: 1.06-2.43, Pbipolar psychotic depression. It would be of interest to conduct studies evaluating whether antipsychotics represent the superior pharmacological treatment for psychotic mania and psychotic bipolar depression. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. The enduring psychosocial consequences of mania and depression.

    Science.gov (United States)

    Coryell, W; Scheftner, W; Keller, M; Endicott, J; Maser, J; Klerman, G L

    1993-05-01

    The authors sought to determine the scope, severity, and persistence of psychosocial impairment arising from bipolar and unipolar affective disorder. Patients with bipolar (N = 148) or unipolar (N = 240) major affective disorder were assessed as they sought treatment and again after a 5-year follow-up. Concurrently, parents, siblings, and adult children underwent similar assessments and were followed for 6 years. To quantify the impact of affective disorder, probands were individually matched to relatives who had no lifetime history of affective disorder. Sixty-nine relatives who were depressed at intake constituted a separate, nonclinical study group and were also matched to relatives who were well. Both unipolar and bipolar patients began follow-up with deficits in annual income. Relative to comparison subjects, affective disorder groups were significantly more likely to report declines in job status and income at the end of follow-up and significantly less likely to report improvements. Similarly, both bipolar and unipolar patients showed significant deficits in nearly all other areas of psychosocial functioning measured at follow-up. Except for relationships with spouses, deficits did not differ significantly by polarity. Surprisingly, probands with recovery sustained throughout the final 2 years of follow-up also showed severe and widespread impairment. Relatives with major depression exhibited substantial deficits on follow-up, but job status and income were not significantly affected. The psychosocial impairment associated with mania and major depression extends to essentially all areas of functioning and persists for years, even among individuals who experience sustained resolution of clinical symptoms.

  5. Treatment resistance in urothelial carcinoma: an evolutionary perspective.

    Science.gov (United States)

    Vlachostergios, Panagiotis J; Faltas, Bishoy M

    2018-05-02

    The emergence of treatment-resistant clones is a critical barrier to cure in patients with urothelial carcinoma. Setting the stage for the evolution of resistance, urothelial carcinoma is characterized by extensive mutational heterogeneity, which is detectable even in patients with early stage disease. Chemotherapy and immunotherapy both act as selective pressures that shape the evolutionary trajectory of urothelial carcinoma throughout the course of the disease. A detailed understanding of the dynamics of evolutionary drivers is required for the rational development of curative therapies. Herein, we describe the molecular basis of the clonal evolution of urothelial carcinomas and the use of genomic approaches to predict treatment responses. We discuss various mechanisms of resistance to chemotherapy with a focus on the mutagenic effects of the DNA dC->dU-editing enzymes APOBEC3 family of proteins. We also review the evolutionary mechanisms underlying resistance to immunotherapy, such as the loss of clonal tumour neoantigens. By dissecting treatment resistance through an evolutionary lens, the field will advance towards true precision medicine for urothelial carcinoma.

  6. Mechanisms Underlying the Antidepressant Response and Treatment Resistance

    Directory of Open Access Journals (Sweden)

    Marjorie Rose Levinstein

    2014-06-01

    Full Text Available Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance.

  7. Primary Sjogren’s Syndrome Associated With Treatment-Resistant Obsessive–Compulsive Disorder

    Directory of Open Access Journals (Sweden)

    Lawrence T. C. Ong

    2017-07-01

    Full Text Available There is an increasing awareness that autoimmune diseases can present with neuropsychiatric manifestations. We present the case of a 17-year-old female requiring psychiatric hospitalization for obsessive–compulsive disorder and major depressive disorder with mixed affective features, who was subsequently diagnosed with primary Sjogren’s syndrome. Treatment with potent immunosuppression resulted in remission of psychiatric illness. Due to a lack of awareness and/or the lack of specific biomarkers, clinicians may not associate psychiatric symptoms with autoimmune disease, including primary Sjogren’s syndrome. This case demonstrates that Sjogren’s syndrome may be a causative or aggravating factor in mental disorders and that autoimmune diseases should be carefully considered in the differential diagnosis of psychiatric illness especially in cases of concurrent physical symptomatology and severity or treatment resistance of psychiatric disease.

  8. Decreased plasma neurotrophin-4/5 levels in bipolar disorder patients in mania.

    Science.gov (United States)

    Barbosa, Izabela G; Morato, Isabela B; Huguet, Rodrigo B; Rocha, Fabio L; Machado-Vieira, Rodrigo; Teixeira, Antônio L

    2014-01-01

    To evaluate two poorly explored neurotrophins (NT), NT-3 and NT-4/5, in bipolar disorder (BD). Forty patients with type I BD (18 in remission and 22 in mania) and 25 healthy controls matched for age, gender, and educational attainment were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatric Interview; the Young Mania Rating Scale and the Hamilton Depression Rating Scale were used to evaluate severity of symptoms in BD patients. Plasma levels of NT-3 and NT-4/5 were measured by enzyme-linked immunosorbent assay (ELISA). BD patients in mania presented decreased NT-4/5 plasma levels in comparison with controls (p neurotrophin dysfunction is associated with mood states in patients with BD.

  9. Enduring increased risk of developing depression and mania in patients with dementia

    DEFF Research Database (Denmark)

    Nilsson, Flemming Mørkeberg; Kessing, Lars Vedel; Sørensen, Tine Møller

    2002-01-01

    OBJECTIVE: To investigate the time relation between dementia and major affective disorders (major depression and mania). METHODS: Register linkage study of the Danish Hospital Register and the Danish Psychiatric Central Research Register, to establish study cohorts of patients with dementia...... and control groups (osteoarthritis or diabetes) on first discharge from hospital. Follow up of cohorts was for up to 21 years. Hazard of death was allowed for by the use of competing risks models. RESULTS: Patients with dementia had an increased risk of being admitted to hospital for major depression or mania...... during the course of the illness. The incidence remained elevated throughout the rest of the patient's life. CONCLUSIONS: Patients with dementia have an increased risk of developing depression or mania. Proper treatment of affective disorders in patients with dementia is important in reducing suffering...

  10. Risk for mania and positive emotional responding: too much of a good thing?

    Science.gov (United States)

    Gruber, June; Johnson, Sheri L; Oveis, Christopher; Keltner, Dacher

    2008-02-01

    Although positive emotion research has begun to flourish, the extremes of positive emotion remain understudied. The present research used a multimethod approach to examine positive emotional disturbance by comparing participants at high and low risk for episodes of mania, which involves elevations in positive emotionality. Ninety participants were recruited into a high or low mania risk group according to responses on the Hypomanic Personality Scale. Participants' subjective, expressive, and physiological emotional responses were gathered while they watched two positive, two negative, and one neutral film clip. Results suggested that participants at high risk for mania reported elevated positive emotion and irritability and also exhibited elevated cardiac vagal tone across positive, negative, and neutral films. Discussion focuses on the implications these findings have for the diagnosis and prevention of bipolar disorder, as well as for the general study of positive emotion.

  11. Predictors of switching from mania to depression in a large observational study across Europe (EMBLEM)

    DEFF Research Database (Denmark)

    Vieta, Eduard; Angst, Jules; Reed, Catherine

    2009-01-01

    BACKGROUND: The risk of switching from mania to depression in bipolar disorder has been poorly studied. Large observational studies may be useful in identifying variables that predict switch to depression after mania and provide data on medication use and outcomes in "real world" patients. METHOD...... Depression Rating Scale. Switching was defined using CGI-BP mania and depression such that patients changed from manic and not depressed to depressed but not manic over two consecutive observations within the first 12 weeks of follow-up. Cox proportional hazards models identified baseline variables...... independently associated with switch to depression. RESULTS: Of 2390 patients who participated in the maintenance phase (i.e. up to 24 months), 120 (5.0%) switched to depression within the first 12 weeks. Factors associated with greater switching to depression include previous depressive episodes, substance...

  12. Decreased medial prefrontal cortex activation during self-referential processing in bipolar mania.

    Science.gov (United States)

    Herold, Dorrit; Usnich, Tatiana; Spengler, Stephanie; Sajonz, Bastian; Bauer, Michael; Bermpohl, Felix

    2017-09-01

    Patients with bipolar disorder in mania exhibit symptoms pointing towards altered self-referential processing, such as decreased self-focus, flight of ideas and high distractibility. In depression, the opposite pattern of symptoms has been connected to increased activation of medial prefrontal cortex (mPFC) during self-referential processing. In this study, we hypothesized that (1) patients with mania will exhibit decreased activation in the mPFC during self-referential processing and (2) will be more alexithymic and that levels of alexithymia will correlate negatively with mPFC activation. The neural response to standardized pictures was compared in 14 patients with bipolar I disorder in mania to 14 healthy controls using blood oxygen level dependent contrast magnetic resonance imaging. Participants were asked to indicate with button press during the scanning session for each picture whether the pictures personally related to them or not. Toronto alexithymia scale (TAS) scores were recorded from all participants. In the group analysis, patients with mania exhibited decreased activation in a predefined region of interest in the mPFC during self-referential processing compared to healthy controls. Patients with mania showed significantly higher levels of alexithymia, attributable to difficulties in identifying and describing emotions. Activation in the mPFC correlated negatively with levels of alexithymia. Results presented here should be replicated in a larger group, potentially including unmedicated patients. The finding of decreased mPFC activation during self-referential processing in mania may reflect decreased self-focus and high distractibility. Support for this view comes from the negative correlation between higher alexithymia scores and decreased mPFC activation. These findings represent an opposite clinical and neuroimaging pattern to findings in depression. Copyright © 2017. Published by Elsevier B.V.

  13. Predictors of switching from mania to depression in a large observational study across Europe (EMBLEM).

    Science.gov (United States)

    Vieta, Eduard; Angst, Jules; Reed, Catherine; Bertsch, Jordan; Haro, Josep Maria

    2009-11-01

    The risk of switching from mania to depression in bipolar disorder has been poorly studied. Large observational studies may be useful in identifying variables that predict switch to depression after mania and provide data on medication use and outcomes in "real world" patients. EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 2-year, prospective, observational study of patients with a manic/mixed episode. Symptom severity measures included Clinical Global Impression-Bipolar Disorder scale (CGI-BP), Young Mania Rating Scale (YMRS) and 5-item Hamilton Depression Rating Scale. Switching was defined using CGI-BP mania and depression such that patients changed from manic and not depressed to depressed but not manic over two consecutive observations within the first 12 weeks of follow-up. Cox proportional hazards models identified baseline variables independently associated with switch to depression. Of 2390 patients who participated in the maintenance phase (i.e. up to 24 months), 120 (5.0%) switched to depression within the first 12 weeks. Factors associated with greater switching to depression include previous depressive episodes, substance abuse, greater CGI-BP overall severity and benzodiazepine use. Factors associated with lower switching rates were greater CGI-BP depression, lower YMRS severity and atypical antipsychotic use. The definition of switching biased against patients with mixed episodes being likely to switch. Strictly defined, switch to depression from mania occurs in a small proportion of bipolar patients. Clinical history, illness severity, co-morbidities and treatment patterns are associated with switching to depression. Atypical antipsychotics may protect against switch to depression.

  14. Validity of the Mania Subscale of the Diagnostic Assessment for the Severely Handicapped-II (DASH-II).

    Science.gov (United States)

    Matson, Johnny L.; Smiroldo, Brandi B.

    1997-01-01

    A study tested the validity of the Diagnostic Assessment for the Severely Handicapped-II (DASH-II) for determining the presence of mania (bipolar disorder) in 22 individuals with severe mental retardation. Results found the mania subscale to be internally consistent and able to be used to classify manic and control subjects accurately. (Author/CR)

  15. Predictors of treatment resistance in patients with schizophrenia

    DEFF Research Database (Denmark)

    Wimberley, Theresa; Støvring, Henrik; Sørensen, Holger J

    2016-01-01

    ·13-1·37]), comorbid personality disorder (1·24 [1·11-1·39]), psychotropic drug use (antipsychotics 1·51 [1·35-1·69], antidepressants 1·15 [1·03-1·29], and benzodiazepines 1·22 [1·10-1·37]), and previous suicide attempt (1·21 [1·07-1·39]) were all significantly associated with treatment-resistant schizophrenia...... (provincial 1·38 [1·23-1·56], rural 1·44 [1·25-1·65]), primary education level (0·88 [0·79-0·98]), more than 30 bed-days in psychiatric hospital in the year before first schizophrenia diagnosis (1·54 [1·35-1·75]), inpatient at first schizophrenia diagnosis (2·07 [1·87-2·29]), paranoid subtype (1·24 [1...

  16. Mania in the Nordic countries: patients and treatment in the acute phase of the EMBLEM study

    DEFF Research Database (Denmark)

    Larsen, Jens Knud; Porsdal, Vibeke; Aarre, Trond F

    2009-01-01

    countries with other European countries during the first 12 weeks of the EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) study. Adult patients with bipolar disorder were enrolled within standard course of care as in/outpatients if they initiated/changed oral medication...... status, functional status and pharmacological treatment. Psychiatric status at inclusion measured by the Young Mania Rating Scale (YMRS) and the Clinical Global Impression-Bipolar Disorder (CGI-BP) were similar in the Nordic and European patient groups, which is surprising as 73% of the Nordic patients...

  17. An overview of mice models: a key for understanding subtypes of mania

    Directory of Open Access Journals (Sweden)

    Jorge Mauricio Cuartas Arias

    2016-09-01

    Full Text Available Animal models have been broadly used in the study of pathophysiology and molecular and neurochemical pathways in neuropsychiatric diseases. Different approaches have used both consanguineous and non-consanguineous mice models to model behavioral patterns associated with the maniac spectrum. However, the disadvantages of validating clinical and experimental protocols have hindered the replication of these studies. In this article, the advantages and disadvantages of using consanguineous lines and non-consanguineous stocks in mice animal models for the study of mania and its subtypes are discussed. Additionally, new experimental alternatives to advance the pathogenesis and pharmacogenetics of mania using animal models are proposed and analyzed.

  18. Pattern of adult psychiatric emergency cases presenting at a ...

    African Journals Online (AJOL)

    , current episode manic without psychotic symptoms constituted 17.2% of the cases, while 9.4% were cases of Mental and Behavioural Disorder due to Psychoactive Substance Use. Other cases included depressive illness, mania and delirium.

  19. IS TREATMENT-RESISTANCE IN PSYCHIATRIC DISORDERS A TRAP FOR POLYPHARMACY?

    OpenAIRE

    Jašović-Gašić, Miroslava

    2015-01-01

    Background: Nowadays, more and more mental health professionals manage patients who fail treatment for major psychiatric disorders. There is not a consensus on how to deal with treatment-resistance patients, but usually psychiatrists result to polypharmacy. Method: In reviewing the evidence based clinical research we will try to answer some questions about treatment-resistant psychiatric disorders. Treatment-resistant symptoms complicate the clinical course of all psychiatric diso...

  20. Pharmacoeconomics of quetiapine for the management of acute mania in bipolar I disorder

    NARCIS (Netherlands)

    Klok, Rogier M; Al Hadithy, Asmar Fy; van Schayk, Nathalie Pjt; Antonisse, Ad Jj; Caro, Jaime J; Brouwers, Jacobus Rbj; Postma, Maarten J

    2007-01-01

    Bipolar disorder (or manic depression) is a lifelong, severe and complex psychiatric illness characterized by recurrent episodes of depression and mania. The aim of this study is to explore the cost-effectiveness of quetiapine compared with other alternatives for the treatment of acute manic

  1. Mania Symptoms and HIV-Risk Behavior among Adolescents in Mental Health Treatment

    Science.gov (United States)

    Stewart, Angela J.; Theodore-Oklota, Christina; Hadley, Wendy; Brown, Larry K.; Donenberg, Geri; DiClemente, Ralph

    2012-01-01

    This study explored whether adolescents with elevated symptoms of mania (ESM+) engage in more HIV risk behaviors than those with other psychiatric disorders and examined factors associated with HIV risk behavior among ESM+ adolescents. Eight hundred forty adolescents (56% female, 58% African American, "M" age = 14.9 years) who received mental…

  2. Early warning signs checklists for relapse in bipolar depression and mania: utility, reliability and validity.

    Science.gov (United States)

    Lobban, Fiona; Solis-Trapala, Ivonne; Symes, Wendy; Morriss, Richard

    2011-10-01

    Recognising early warning signs (EWS) of mood changes is a key part of many effective interventions for people with Bipolar Disorder (BD). This study describes the development of valid and reliable checklists required to assess these signs of depression and mania. Checklists of EWS based on previous research and participant feedback were designed for depression and mania and compared with spontaneous reporting of EWS. Psychometric properties and utility were examined in 96 participants with BD. The majority of participants did not spontaneously monitor EWS regularly prior to use of the checklists. The checklists identified most spontaneously generated EWS and led to a ten fold increase in the identification of EWS for depression and an eight fold increase for mania. The scales were generally reliable over time and responses were not associated with current mood. Frequency of monitoring for EWS correlated positively with social and occupational functioning for depression (beta=3.80, p=0.015) and mania (beta=3.92, p=0.008). The study is limited by a small sample size and the fact that raters were not blind to measures of mood and function. EWS checklists are useful and reliable clinical and research tools helping to generate enough EWS for an effective EWS intervention. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Tertiary work-up of apparent treatment-resistant hypertension.

    Science.gov (United States)

    Heimark, Sondre; Eskås, Per Anders; Mariampillai, Julian Eek; Larstorp, Anne Cecilie K; Høieggen, Aud; Fadl Elmula, Fadl Elmula M

    2016-10-01

    Treatment-resistant hypertension (TRH) has regained attention with development of new methods for treatment. However, the prevalence of TRH varies considerably from primary to secondary and tertiary care. We aimed to assess the prevalence of true TRH in a population of patients with apparent TRH in a university hospital setting of tertiary work-up and also investigate reasons for poor BP control and evaluate how work-up can be performed in general practice and secondary care. In this cohort study, we characterize a study population from Oslo Renal Denervation (RDN) Study. Patients (n = 83) were referred for RDN from secondary care. All patients underwent thorough medical investigation and 24-h ambulatory blood pressure measurements (24ABPM) after directly observed therapy (DOT). We then assessed reasons for lack of BP control. Fifty-three of 83 patients did not have true TRH. Main reasons for non-TRH were poor drug adherence (32%), secondary hypertension (30%) and white coat hypertension (15%). Forty-seven percent achieved blood pressure control after DOT with subsequent 24ABPM. There were otherwise no statistically significant differences in patient characteristics between the true TRH and the non-TRH group. Despite being a highly selected cohort referred for tertiary work-up of apparent TRH, BP control was achieved or secondary causes were identified in almost two thirds of the patients. Thorough investigation according to guidelines and DOT with subsequent 24ABPM is needed in work-up of apparent TRH.

  4. Clinical and psychometric characterization of depression in mixed mania: a report from the French National Cohort of 1090 manic patients.

    Science.gov (United States)

    Hantouche, E G; Akiskal, H S; Azorin, J M; Châtenet-Duchêne, L; Lancrenon, S

    2006-12-01

    Despite extensive research recently focused on mixed mania, it is uncertain as how best to define it clinically, psychometrically (which has major bearing on its prevalence), and the methodology needed for future research. This topic is also of historical interest, because Magnan (1890) [Magnan, V., 1890. La Folie Intermittente. G Masson, Paris.] suggested that "combined [mixed] states" linked Falret's "circular insanity" with Baillarger's "dual insanity" (both described in 1854). This work eventually led to the Kraepelinian synthesis of all manic, mixed, and depressive states into the unitary rubric of "manic-depressive insanity (1899/1921). EPIMAN-II Thousand" (EPIMAN-II MILLE) is a French national collaborative study, which involved training 317 psychiatrists working in different sites representative of psychiatric practice in France. We recruited 1090 patients hospitalized for acute DSM-IV mania. assessed at index admission by the following measures: the Mania Rating Scale (MRS), the Beigel-Murphy Scale (MSRS), a newly derived checklist of depressive symptoms least contaminated by mania, MADRS for severity of depression, and the SAPS for psychotic features. The rate of mixed mania, as defined by at least 2 depressive symptoms, was 30%. Even with this broad definition, we found significantly higher female representation. This clinical sub-type of mania was characterized by high frequency of past diagnostic errors, particularly those of anxiety and personality disorders. Refined definition of co-exiting depression was obtained from an abbreviated version of the MADRS (6 items), with distinct "emotional-cognitive" symptoms, and "psychomotor inhibition" factors, both of which were separable from an "irritable" factor linked to lability and poor judgment. Mixed mania was psychometrically best identified by a MADRS score of 6 (80% sensitivity, 94% specificity) and validated by a mixed polarity of first episodes, a higher rate of recurrence, psychotic features, and

  5. Evidence-based treatment strategies for treatment-resistant bipolar depression: a systematic review

    NARCIS (Netherlands)

    Sienaert, P.; Lambrichts, L.; Dols, A.; De Fruyt, J.

    2013-01-01

    Objectives: Treatment resistance in bipolar depression is a common clinical problem that constitutes a major challenge for the treating clinician as there is a paucity of treatment options. The objective of this paper was to review the evidence for treatment options in treatment-resistant bipolar

  6. Anhedonia Predicts Poorer Recovery among Youth with Selective Serotonin Reuptake Inhibitor Treatment-Resistant Depression

    Science.gov (United States)

    McMakin, Dana L.; Olino, Thomas M.; Porta, Giovanna; Dietz, Laura J.; Emslie, Graham; Clarke, Gregory; Wagner, Karen Dineen; Asarnow, Joan R.; Ryan, Neal D.; Birmaher, Boris; Shamseddeen, Wael; Mayes, Taryn; Kennard, Betsy; Spirito, Anthony; Keller, Martin; Lynch, Frances L.; Dickerson, John F.; Brent, David A.

    2012-01-01

    Objective: To identify symptom dimensions of depression that predict recovery among selective serotonin reuptake inhibitor (SSRI) treatment-resistant adolescents undergoing second-step treatment. Method: The Treatment of Resistant Depression in Adolescents (TORDIA) trial included 334 SSRI treatment-resistant youth randomized to a medication…

  7. A New Prediction Model for Evaluating Treatment-Resistant Depression.

    Science.gov (United States)

    Kautzky, Alexander; Baldinger-Melich, Pia; Kranz, Georg S; Vanicek, Thomas; Souery, Daniel; Montgomery, Stuart; Mendlewicz, Julien; Zohar, Joseph; Serretti, Alessandro; Lanzenberger, Rupert; Kasper, Siegfried

    2017-02-01

    Despite a broad arsenal of antidepressants, about a third of patients suffering from major depressive disorder (MDD) do not respond sufficiently to adequate treatment. Using the data pool of the Group for the Study of Resistant Depression and machine learning, we intended to draw new insights featuring 48 clinical, sociodemographic, and psychosocial predictors for treatment outcome. Patients were enrolled starting from January 2000 and diagnosed according to DSM-IV. Treatment-resistant depression (TRD) was defined by a 17-item Hamilton Depression Rating Scale (HDRS) score ≥ 17 after at least 2 antidepressant trials of adequate dosage and length. Remission was defined by an HDRS score depressive episode, age at first antidepressant treatment, response to first antidepressant treatment, severity, suicidality, melancholia, number of lifetime depressive episodes, patients' admittance type, education, occupation, and comorbid diabetes, panic, and thyroid disorder. While single predictors could not reach a prediction accuracy much different from random guessing, by combining all predictors, we could detect resistance with an accuracy of 0.737 and remission with an accuracy of 0.850. Consequently, 65.5% of predictions for TRD and 77.7% for remission can be expected to be accurate. Using machine learning algorithms, we could demonstrate success rates of 0.737 for predicting TRD and 0.850 for predicting remission, surpassing predictive capabilities of clinicians. Our results strengthen data mining and suggest the benefit of focus on interaction-based statistics. Considering that all predictors can easily be obtained in a clinical setting, we hope that our model can be tested by other research groups. © Copyright 2017 Physicians Postgraduate Press, Inc.

  8. Validation of an algorithm-based definition of treatment resistance in patients with schizophrenia.

    Science.gov (United States)

    Ajnakina, Olesya; Horsdal, Henriette Thisted; Lally, John; MacCabe, James H; Murray, Robin M; Gasse, Christiane; Wimberley, Theresa

    2018-02-19

    Large-scale pharmacoepidemiological research on treatment resistance relies on accurate identification of people with treatment-resistant schizophrenia (TRS) based on data that are retrievable from administrative registers. This is usually approached by operationalising clinical treatment guidelines by using prescription and hospital admission information. We examined the accuracy of an algorithm-based definition of TRS based on clozapine prescription and/or meeting algorithm-based eligibility criteria for clozapine against a gold standard definition using case notes. We additionally validated a definition entirely based on clozapine prescription. 139 schizophrenia patients aged 18-65years were followed for a mean of 5years after first presentation to psychiatric services in South-London, UK. The diagnostic accuracy of the algorithm-based measure against the gold standard was measured with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). A total of 45 (32.4%) schizophrenia patients met the criteria for the gold standard definition of TRS; applying the algorithm-based definition to the same cohort led to 44 (31.7%) patients fulfilling criteria for TRS with sensitivity, specificity, PPV and NPV of 62.2%, 83.0%, 63.6% and 82.1%, respectively. The definition based on lifetime clozapine prescription had sensitivity, specificity, PPV and NPV of 40.0%, 94.7%, 78.3% and 76.7%, respectively. Although a perfect definition of TRS cannot be derived from available prescription and hospital registers, these results indicate that researchers can confidently use registries to identify individuals with TRS for research and clinical practices. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. A randomized, 4-week double-blind placebo control study on the efficacy of donepezil augmentation of lithium for treatment of acute mania

    Directory of Open Access Journals (Sweden)

    Chen J

    2013-06-01

    Full Text Available Jing Chen,1 Zheng Lu,1,2 Mingyuan Zhang,1 Jie Zhang,1 Xiaodong Ni,1 Xuefeng Jiang,1 Heding Xu,1 Anisha Heeramun-Aubeeluck,2 Qiaoyan Hu,3 Hua Jin,4 John M Davis31Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Psychiatry, Tongji Hospital of Tongji University, Shanghai, People’s Republic of China; 3University of Illinois at Chicago, Chicago, IL, USA; 4University of California at San Diego, San Diego, CA, USAIntroduction: A significant number of mania patients fail to respond to current pharmacotherapy, thereby there is need for novel augmentation strategies. The results of some early studies showed the effectiveness of cholinomimetics in the treatment of mania. One open case series suggested the efficacy of donepezil in the treatment of bipolar disorder. Our aim was to explore whether an oral cholinesterase inhibitor, donepezil, administered during a 4-week treatment period,would benefit patients with acute mania.Methods: We conducted a 4-week double-blind, placebo-controlled trial of donepezil as an adjunctive treatment to lithium in patients with acute mania. Eligible subjects were randomly assigned to receive donepezil or placebo in addition to lithium. Donepezil was started at 5 mg/day, and increased to 10 mg/day in the first week. Patients were rated with the Young Mania Rating Scale (YMRS and Brief Psychiatric Rating Scale (BPRS at baseline, day 1, week 1, week 2, and week 4.Results: Out of the 30 patients who were enrolled, 15 were on donepezil and 15 were on placebo. All patients completed the 4-week trial. On the first day, there was a difference of 1.97 units on the psychomotor symptoms scale of the YMRS in the donepezil group as compared to the placebo group (t = 2.39, P = 0.02. There was a difference of 0.57 units (t = 2.09, P = 0.04 in the speech item and a difference of 0.29 units in the sexual interest item (t = 2.11, P = 0.04 in the donepezil

  10. Diagnosis and characterization of mania: Quantifying increased energy and activity in the human behavioral pattern monitor

    OpenAIRE

    Perry, William; McIlwain, Meghan; Kloezeman, Karen; Henry, Brook L.; Minassian, Arpi

    2016-01-01

    Increased energy or activity is now an essential feature of the mania of Bipolar Disorder (BD) according to DSM-5. This study examined whether objective measures of increased energy can differentiate manic BD individuals and provide greater diagnostic accuracy compared to rating scales, extending the work of previous studies with smaller samples. We also tested the relationship between objective measures of energy and rating scales. 50 hospitalized manic BD patients were compared to healthy s...

  11. The psychopharmacology algorithm project at the Harvard South Shore Program: an algorithm for acute mania.

    Science.gov (United States)

    Mohammad, Othman; Osser, David N

    2014-01-01

    This new algorithm for the pharmacotherapy of acute mania was developed by the Psychopharmacology Algorithm Project at the Harvard South Shore Program. The authors conducted a literature search in PubMed and reviewed key studies, other algorithms and guidelines, and their references. Treatments were prioritized considering three main considerations: (1) effectiveness in treating the current episode, (2) preventing potential relapses to depression, and (3) minimizing side effects over the short and long term. The algorithm presupposes that clinicians have made an accurate diagnosis, decided how to manage contributing medical causes (including substance misuse), discontinued antidepressants, and considered the patient's childbearing potential. We propose different algorithms for mixed and nonmixed mania. Patients with mixed mania may be treated first with a second-generation antipsychotic, of which the first choice is quetiapine because of its greater efficacy for depressive symptoms and episodes in bipolar disorder. Valproate and then either lithium or carbamazepine may be added. For nonmixed mania, lithium is the first-line recommendation. A second-generation antipsychotic can be added. Again, quetiapine is favored, but if quetiapine is unacceptable, risperidone is the next choice. Olanzapine is not considered a first-line treatment due to its long-term side effects, but it could be second-line. If the patient, whether mixed or nonmixed, is still refractory to the above medications, then depending on what has already been tried, consider carbamazepine, haloperidol, olanzapine, risperidone, and valproate first tier; aripiprazole, asenapine, and ziprasidone second tier; and clozapine third tier (because of its weaker evidence base and greater side effects). Electroconvulsive therapy may be considered at any point in the algorithm if the patient has a history of positive response or is intolerant of medications.

  12. Assessment of white matter abnormalities in paranoid schizophrenia and bipolar mania patients.

    Science.gov (United States)

    Cui, Liqian; Chen, Zhuangfei; Deng, Wei; Huang, Xiaoqi; Li, Mingli; Ma, Xiaohong; Huang, Chaohua; Jiang, Lijun; Wang, Yingcheng; Wang, Qiang; Collier, David A; Gong, Qiyong; Li, Tao

    2011-12-30

    White matter abnormalities have been repeatedly reported in both schizophrenia and bipolar disorder (BD) in diffusion tensor imaging (DTI) studies, but the empirical evidence about the diagnostic specificity of white matter abnormalities in these disorders is still limited. This study sought to investigate the alterations in fractional anisotropy (FA) in white matter throughout the entire brain of patients from Chengdu, China with paranoid schizophrenia and bipolar mania. For this purpose, DTI was used to assess white matter integrity in patients with paranoid schizophrenia (n=25) and psychotic bipolar mania (n=18) who had been treated with standard pharmacotherapy for fewer than 5 days at the time of study, as well as in normal controls (n=30). The differences in FA were measured by use of voxel-based analysis. The results show that reduced FA was found in the left posterior corona radiata (PCR) in patients with psychotic bipolar mania and paranoid schizophrenia compared to the controls. Patients with psychotic bipolar mania also showed a significant reduction in FA in right posterior corona radiata and in right anterior thalamic radiation (ATR). A direct comparison between the two patient groups found no significant differences in any regions, and none of the findings were associated with illness duration. Correlation analysis indicated that FA values showed a significant negative correlation with positive symptom scores on the Positive and Negative Syndrome Scale in the left frontal-parietal lobe in the paranoid schizophrenia. It was concluded that common abnormalities in the left PCR might imply an overlap in white matter pathology in the two disorders and might be related to shared risk factors for the two disorders. 2011 Elsevier Ireland Ltd. All rights reserved.

  13. A TWIN STUDY OF SCHIZOAFFECTIVE-MANIA, SCHIZOAFFECTIVE-DEPRESSION AND OTHER PSYCHOTIC SYNDROMES

    OpenAIRE

    Cardno, Alastair G; Rijsdijk, Frühling V; West, Robert M; Gottesman, Irving I; Craddock, Nick; Murray, Robin M; McGuffin, Peter

    2011-01-01

    The nosological status of schizoaffective disorders remains controversial. Twin studies are potentially valuable for investigating relationships between schizoaffective-mania, schizoaffective-depression and other psychotic syndromes, but no such study has yet been reported. We ascertained 224 probandwise twin pairs (106 monozygotic, 118 same-sex dizygotic), where probands had psychotic or manic symptoms, from the Maudsley Twin Register in London (1948–1993). We investigated Research Diagnosti...

  14. Diagnóstico, tratamento e prevenção da mania e da hipomania no transtorno bipolar Diagnosis, treatment and prevention of mania and hipomania within the bipolar disorder

    Directory of Open Access Journals (Sweden)

    Ricardo Alberto Moreno

    2005-01-01

    Full Text Available Pelo menos 5% (Moreno, 2004 e Angst et al., 2003 da população geral já apresentou mania ou hipomania. A irritabilidade e sintomas depressivos durante episódios de hiperatividade breves e a heterogeneidade de sintomas complicam o diagnóstico. Doenças neurológicas, endócrinas, metabólicas e inflamatórias podem causar uma síndrome maníaca. Às vezes, a hipomania ou a mania são diagnosticadas de forma errada como normalidade, depressão maior, esquizofrenia ou transtornos de personalidade, ansiosos ou de controle de impulsos. O lítio é a primeira escolha no tratamento da mania, mas ácido valpróico, carbamazepina e antipsicóticos atípicos são também freqüentemente utilizados. A eletroconvulsoterapia está indicada na mania grave, psicótica ou gestacional. A maioria dos estudos controlados para a profilaxia de episódios maníacos foi realizada com lítio e mais estudos são necessários para investigar a eficácia profilática do valproato, da olanzapina e de outras medicações. O tratamento e a profilaxia da hipomania foram pouco estudados e, de modo geral, seguem as mesmas diretrizes usadas para a mania.At least 5% (Moreno, 2004 e Angst et al., 2003 of the general population have presented mania or hypomania. Irritability and depressive symptoms during brief hyperactivity episodes and the heterogeneity of symptoms complicate the diagnosis. Neurological, metabolic, endocrine, inflammatory diseases, besides drugs intoxication and abstinence can cause a manic syndrome. Sometimes hypomania or mania are misdiagnosed as normality, major depression, schizophrenia, personality, anxiety and impulse control disorders. Lithium is the first treatment choice for episodes of mania. Valproic acid, carbamazepine and atypical antipsychotics are frequently used as well. Electroconvulsive therapy should be used in severe, psychotic or gestational mania. For the prophylaxy of manic episodes, lithium is the medication with most controlled

  15. The acute mania of King George III: A computational linguistic analysis.

    Directory of Open Access Journals (Sweden)

    Vassiliki Rentoumi

    Full Text Available We used a computational linguistic approach, exploiting machine learning techniques, to examine the letters written by King George III during mentally healthy and apparently mentally ill periods of his life. The aims of the study were: first, to establish the existence of alterations in the King's written language at the onset of his first manic episode; and secondly to identify salient sources of variation contributing to the changes. Effects on language were sought in two control conditions (politically stressful vs. politically tranquil periods and seasonal variation. We found clear differences in the letter corpus, across a range of different features, in association with the onset of mental derangement, which were driven by a combination of linguistic and information theory features that appeared to be specific to the contrast between acute mania and mental stability. The paucity of existing data relevant to changes in written language in the presence of acute mania suggests that lexical, syntactic and stylometric descriptions of written discourse produced by a cohort of patients with a diagnosis of acute mania will be necessary to support the diagnosis independently and to look for other periods of mental illness of the course of the King's life, and in other historically significant figures with similarly large archives of handwritten documents.

  16. Insight in bipolar mania: evaluation of its heterogeneity and correlation with clinical symptoms.

    Science.gov (United States)

    Silva, Rafael de Assis da; Mograbi, Daniel C; Bifano, Jaqueline; Santana, Cristina M T; Cheniaux, Elie

    2016-07-15

    Studies on insight in bipolar mania are not numerous and usually consider insight as a unitary construct. Evaluate how different facets of insight are affected in bipolar mania and investigate correlations between insight for each specific object in bipolar disorder and manic symptomatology. A group of 165 bipolar patients were followed during a year, with 51 patients having manic episodes according to DSM-IV-TR criteria. Patients underwent a clinical assessment and insight was evaluated through the Insight Scale for Affective Disorders. The study found that insight regarding symptoms is worse than insight of having bipolar disorder, social relationships and self esteem. Moreover, poor global insight (total ISAD) correlates with more severe changes in mood, speech and thought structure, with worse insight about symptoms correlating with the same alterations and also with more severe symptoms of agitation/energy. Although a large sample of bipolar patients was followed up, the final sample composed of patients with at least one manic episode was relatively smaller. Moreover, the fact that the study was performed in a university hospital may have led to selection biases. Results suggest that patients with BD are reasonably capable of identifying that their condition implies consequences but have more impaired awareness of their energy and activity levels. A lower level of insight specifically about symptoms correlates with more severe symptoms of agitation/energy, which suggests a psychomotor nucleus able to impair insight in mania. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Reserpine for the treatment of refractory mania | Eloff | South African ...

    African Journals Online (AJOL)

    Reserpine is a centrally acting antihypertensive with anti-adrenergic properties. It has been found to reduce the duration of a manic episode rapidly in a small group of studies. This proved to be the case with this patient. Reserpine used in conjunction with other psychotropic medication may be considered in the treatment of ...

  18. Conversion (dissociative) symptoms as a presenting feature in early onset bipolar disorder: a case series

    OpenAIRE

    Ghosal, Malay Kumar; Guha, Prathama; Sinha, Mausumi; Majumdar, Debabrata; Sengupta, Payel

    2009-01-01

    We present three cases of early onset bipolar disorder where dissociative (conversion) symptoms preceded the onset of mania. This case series underscores the significance of dissociative/conversion symptoms as an early atypical presentation in juvenile bipolar disorder.

  19. Modulating affect, cognition and behavior – prospects of deep brain stimulation for treatment resistant psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Thomas E. Schlaepfer

    2011-06-01

    Full Text Available Most patients suffering from psychiatric disorders respond to combina-tions of psycho- and psychopharmacotherapy, however there are patients who profit little if anything even after many years of treatment. Since about a decade different modalities of targeted neuromodulation – among them most prominently – Deep Brain Stimulation (DBS - are being actively researched as putative approaches to very treatment resistant forms of those disorders. Recently, promising pilot data have been re-ported both for Major Depression (MD and Obsessive-Compulsive Disor-der (OCD. Given the fact that patients studied had been treated unsuc-cessfully for many years renders these findings remarkable. Remarkable is the fact, that in case of the long-term studies underway for MD, patients show a stable response. This gives hope to a substantial percentage of therapy-resistant psychiatric patients requiring new therapy approaches. There are no fundamental ethic objections to its use in psychiatric disor-ders, but until substantial clinical data is available, mandatory standards are needed. DBS is a unique and very promising method for the treat-ment of therapy-resistant psychiatric patients. The method allows ma-nipulating pathological neuronal networks in a very precise way.

  20. CRANIOPHARYNGIOMA PRESENTING AS ‘MANIA’—CASE REPORT

    Science.gov (United States)

    Prusty, Gouri K.; Subramanya; Hemalatha, V.; Narayanan, H.S.

    1982-01-01

    SUMMARY We are reporting a case of craniopharyngioma presenting with features of mania. To our knowledge, this is the first reported case of craniopharyngioma with presenting features of mania- The patient is a six years old child with history of maniac behaviour of six months duration. There is no significant family history. During the course in the hospital he was found to be having craniopharyngioma. The patient recovered completely following the surgical intervention without any aid of antipsychotics. PMID:21965929

  1. Effect of the new antiepileptic drug retigabine in a rodent model of mania

    DEFF Research Database (Denmark)

    Dencker, Ditte; Dias, Rebecca; Pedersen, Mette Lund

    2008-01-01

    Bipolar spectrum disorders are severe chronic mood disorders that are characterized by episodes of mania or hypomania and depression. Because patients with manic symptoms often experience clinical benefit from treatment with anticonvulsant drugs, it was hypothesized that retigabine, a novel...... compound with anticonvulsant efficacy, may also possess antimanic activity. The amphetamine (AMPH)+chlordiazepoxide (CDP)-induced hyperactivity model has been proposed as a suitable model for studying antimanic-like activity of novel compounds in mice and rats. The aims of the present study in rats were...

  2. New approaches for the management of bipolar disorder: role of sublingual asenapine in the treatment of mania

    Directory of Open Access Journals (Sweden)

    Warren CG

    2013-05-01

    Full Text Available Calvert G Warren,1 Steven L Dubovsky1,21Department of Psychiatry, State University of New York at Buffalo, Buffalo, NY, USA; 2Departments of Psychiatry and Medicine, University of Colorado, Boulder, CO, USAAbstract: Bipolar disorder is a prevalent disorder that tends to become progressive without treatment and with inadequate treatment. Second generation (atypical antipsychotic drugs have increasingly been used as adjunctive treatment or monotherapy for mania, but they have the potential for significant adverse effects and their role in maintenance treatment remains unclear. Asenapine is a new atypical antipsychotic medication formulated in a sublingual preparation that has been studied for mania but not maintenance therapy. Evidence indicating efficacy, adverse effects, and potential benefits and drawbacks of using asenapine in the treatment of bipolar disorder based on currently available published data are summarized.Keywords: bipolar disorder, antipsychotic drug, mania, maintenance, sublingual

  3. Prevalence, predictors, and outcomes in treatment-resistant hypertension in patients with coronary disease.

    Science.gov (United States)

    Bangalore, Sripal; Fayyad, Rana; Laskey, Rachel; Demicco, David A; Deedwania, Prakash; Kostis, John B; Messerli, Franz H

    2014-01-01

    Increasingly, apparent treatment-resistant hypertension has been recognized. However, much of the prevalence, predictors, and outcomes are largely unknown, especially in patients with coronary artery disease. We evaluated 10,001 patients with coronary artery disease who were enrolled in the Treating to New Targets trial. Apparent treatment-resistant hypertension was defined as blood pressure ≥ 140 mm Hg despite 3 antihypertensive agents or hypertension. In a multivariable model adjusting for baseline differences, the treatment-resistant hypertension group had a 64% increase in primary outcome (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.39-1.94; P hypertension group. In addition, patients with apparent treatment-resistant hypertension had a 71% increase in major coronary event (P hypertension group. Results were largely similar whether the definition of apparent treatment-resistant hypertension was based on a blood pressure ≥ 140 mm Hg despite 3 agents or a blood pressure hypertension is associated with a marked increase in the risk of cardiovascular morbidity and mortality, including an increase in all-cause death. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. An interprofessional approach to managing children with treatment-resistant enuresis: an educational review.

    Science.gov (United States)

    Caldwell, Patrina H Y; Lim, Melissa; Nankivell, Gail

    2017-11-06

    Enuresis (intermittent urinary incontinence during sleep in a child aged ≥ 5 years) is commonly seen in paediatric practice. Despite the availability of effective interventions, treatment resistance is encountered in up to 50% of children. In this educational review we attempt to provide insight into the causes of treatment resistance, and offer practical suggestions for addressing this condition using an interprofessional approach. We explore the pathophysiology of and standard treatments for enuresis and discuss why standard treatments may fail. An interprofessional approach to treatment resistance is proposed which utilises the expertise of professionals from different disciplines to address the problems and barriers to treatment. The two interprofessional approaches include a multidisciplinary approach that involves the patient being sent to experts in different disciplines at different times to address their treatment resistance utilising the skills of the respective experts, and an interdisciplinary approach that involves a patient being managed by members of interdisciplinary team who integrate their separate discipline perspectives into a single treatment plan. Although an interdisciplinary approach is ideal, interdisciplinary teams may not be available in all circumstances. Understanding the roles of other disciplines and engaging clinicians from other disciplines when appropriate can still be helpful when treatment resistance is encountered.

  5. Clinical and psychopathological features associated with treatment-emergent mania in bipolar-II depressed outpatients exposed to antidepressants.

    Science.gov (United States)

    Fornaro, Michele; Anastasia, Annalisa; Monaco, Francesco; Novello, Stefano; Fusco, Andrea; Iasevoli, Felice; De Berardis, Domenico; Veronese, Nicola; Solmi, Marco; de Bartolomeis, Andrea

    2018-07-01

    Treatment-emergent affective switch (TEAS), including treatment-emergent mania (TEM), carry significant burden in the clinical management of bipolar depression, whereas the use of antidepressants raises both efficacy, safety and tolerability concerns. The present study assesses the prevalence and clinical correlates of TEM in selected sample of Bipolar Disorder (BD) Type-II (BD-II) acute depression outpatients. Post-hoc analysis of the clinical and psychopathological features associated with TEM among 91 BD-II depressed outpatients exposed to antidepressants. Second-generation antipsychotics (SGA) (p = .005), lithium (≤ .001), cyclothymic/irritable/hyperthymic temperaments (p = ≤ .001; p = .001; p = .003, respectively), rapid-cycling (p = .005) and depressive mixed features (p = .003) differed between TEM + cases vs. TEM - controls. Upon multinomial logistic regression, the accounted psychopathological features correctly classified as much as 88.6% of TEM + cases (35/91 overall sample, or 38.46% of the sample), yet not statistically significantly [Exp(B) = .032; p = ns]. Specifically, lithium [B = - 2.385; p = .001], SGAs [B = - 2.354; p = .002] predicted lower rates of TEM + in contrast to the number of lifetime previous psychiatric hospitalizations [B = 2.380; p = .002], whereas mixed features did not [B = 1.267; p = ns]. Post-hoc analysis. Lack of systematic pharmacological history record; chance of recall bias and Berkson's biases. Permissive operational criterion for TEM. Relatively small sample size. Cyclothymic temperament and mixed depression discriminated TEM + between TEM - cases, although only lithium and the SGAs reliably predicted TEM +/- grouping. Larger-sampled/powered longitudinal replication studies are warranted to allow firm conclusions on the matter, ideally contributing to the identification of clear-cut sub-phenotypes of BD towards patient-tailored-pharmacotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Is disorganized schizophrenia a predictor of treatment resistance? Evidence from an observational study

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    Bruno Bertolucci Ortiz

    2013-12-01

    Full Text Available Objective: To investigate whether inpatients with disorganized schizophrenia are more resistant to treatment. Method: Eighty-five inpatients were assessed at admission and at discharge for schizophrenia subtype, symptom severity, and treatment resistance criteria. Results: Disorganized patients were significantly more treatment-resistant than paranoid patients (60%, p = 0.001, and presented worse scores on the Positive and Negative Syndrome Scale (PANSS, the Clinical Global Impression Scale (CGI-S, and the Global Assessment of Functioning Scale (GAF (p < 0.001. Although the difference was not significant, 80% of treatment-resistant patients with disorganized schizophrenia responded to clozapine. Conclusion: Patients with the disorganized subtype of schizophrenia should benefit from clozapine as a second-line agent.

  7. [Lithium and anticonvulsants in the treatment of mania and in the prophylaxis of recurrences].

    Science.gov (United States)

    Salvi, Virginio; Cat Berro, Alberto; Bechon, Elisa; Bogetto, Filippo; Maina, Giuseppe

    2011-01-01

    A mood stabilizer is an agent effective in treating both poles of the illness and at the same time being able to prevent both manic and depressive episodes in bipolar disorder. According to a broader definition, a mood stabilizer should be effective in decreasing the frequency or severity of any type of episode in bipolar disorder, without worsening the frequency or severity of episodes of opposite polarity. According to this, anticonvulsants and atypical antipsychotics can be considered as mood stabilizers. In this paper we review the use of lithium and other anticonvulsants that have proved effective in randomized controlled trials of the treatment of manic episodes and prevention of recurrences of bipolar disorder. Lithium and valproate are considered as first-line treatment options for acute mania while evidence regarding carbamazepine is insufficient to consider it as a first-line agent. Patients who fail to respond to first-line treatments may benefit from the adjunct of an atypical antipsychotic such as olanzapine, quetiapine, risperidone or aripiprazole. Lithium retains the strongest evidence of efficacy in the prophylaxis of manic episodes, lamotrigine in the prevention of depressive episodes. Valproate and carbamazepine have no indication for long-term treatment of bipolar disorder. Lithium can still be considered a gold standard in the treatment of manic episodes as well as in the prophylaxis of recurrences. Other anticonvulsants should be employed in particular situations, such as valproic acid in the treatment of mania and lamotrigine in the prevention of depressive recurrences.

  8. Mania risk and creativity: a multi-method study of the role of motivation.

    Science.gov (United States)

    Ruiter, Margina; Johnson, Sheri L

    2015-01-01

    Substantial literature has linked bipolar disorder and risk for bipolar disorder with creative accomplishment, but few multimodal studies of creativity are available, and little is known about mechanisms. We use a multi-method approach to test the association of bipolar risk with several creativity measures, including creative accomplishments, creative personality traits, and a laboratory index of insight. We also examined whether multiple facets of motivation accounted for the links of bipolar risk with creativity. Among 297 undergraduates, mania risk, as measured with the Hypomanic Personality Scale was related to lifetime creativity and creative personality, but not to performance on the insight task. Motivational traits appeared to mediate the links of mania risk with both lifetime creative accomplishments and self-rated creativity. The study relied on a cross-sectional design and a convenience sample. Future studies would benefit from exploring motivation as a positive aspect of manic vulnerability that may foster greater creativity. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Strain-specific battery of tests for domains of mania: effects of valproate, lithium and imipramine

    Directory of Open Access Journals (Sweden)

    Shlomit Flaisher-Grinberg

    2010-04-01

    Full Text Available The lack of efficient animal models for bipolar disorder (BPD, especially for the manic pole, is a major factor hindering the research of its pathophysiology and the development of improved drug treatments. The present study was designed to identify an appropriate mouse strain for modeling some behavioral domains of mania and to evaluate the effects of drugs using this strain. The study compared the behavior of four strains: Black Swiss, C57Bl/6, CBA/J and A/J mice in a battery of tests that included spontaneous activity; sweet solution preference; light/dark box; resident-intruder; forced-swim and amphetamine-induced hyperactivity. Based on the ‘manic-like’ behavior demonstrated by the Black Swiss strain, the study evaluated the effects of the mood stabilizers valproate and lithium and of the antidepressant imipramine in the same tests using this strain. Results indicated that lithium and valproate attenuate the ‘manic-like’ behavior of Black Swiss mice whereas imipramine had no effects. These findings suggest that Black Swiss mice might be a good choice for modeling several domains of mania and distinguishing the effects of drugs on these specific domains. However, the relevance of the behavioral phenotype of Black Swiss mice to the biology of BPD is unknown at this time and future studies will investigate molecular differences between Black Swiss mice and other strains and asess the interaction between strain and mood stabilizing treatment.

  10. Mood self-assessment in bipolar disorder: a comparison between patients in mania, depression, and euthymia

    Directory of Open Access Journals (Sweden)

    Rafael de Assis da Silva

    2013-01-01

    Full Text Available BACKGROUND: Some studies indicate that mood self-assessment is more severely impaired in patients with bipolar disorder in a manic episode than in depression. OBJECTIVES: To investigate variations in mood self-assessment in relation to current affective state in a group of individuals with bipolar disorder. METHODS: A total of 165 patients with a diagnosis of bipolar disorder type I or type II had their affective state assessed using the Clinical Global Impressions Scale for use in bipolar illness (CGI-BP, the Positive and Negative Syndrome Scale (PANSS, and the Global Assessment of Functioning (GAF. In addition, participants completed a self-report visual analog mood scale (VAMS. Patients were divided into three groups (euthymia, mania, and depression and compared with regard to VAMS results. RESULTS: Manic patients rated their mood similarly to patients in euthymia in 14 out of 16 items in the VAMS. By contrast, depressed patients rated only two items similarly to euthymic patients. CONCLUSION: Patients with bipolar disorder in mania, but not those in depression, poorly evaluate their affective state, reinforcing the occurrence of insight impairment in the manic syndrome.

  11. Mixed states vs. pure mania in the french sample of the EMBLEM study: results at baseline and 24 months – European mania in bipolar longitudinal evaluation of medication

    Directory of Open Access Journals (Sweden)

    Azorin Jean-Michel

    2009-06-01

    Full Text Available Abstract Background To describe the clinical course and treatment patterns over 24 months of patients experiencing an acute manic/mixed episode within the standard course of care. Methods EMBLEM was a 2-year European prospective, observational study on outcomes of patients experiencing a manic/mixed episode. Adults with bipolar disorder were enrolled within the standard course of care as in/outpatients if they initiated or changed oral medication for treatment of acute mania. After completing 12 weeks of acute phase, patients were assessed every 3–6 months during the maintenance phase. We present the 24 month results, with subgroup analysis for mixed states (MS and pure mania (PM. These subgroup analyses are driven by the high proportion of antidepressants prescribed in this cohort. Results In France, 771 patients were eligible for the maintenance phase. 69% of patients completed the follow up over 24 months. The mean age was 45.5 years (sd = 13.6 with 57% of women. 504 (66% patients were experiencing a PM and 262 (34% a MS at baseline. The main significant differences in MS vs. PM at baseline were: a higher rate of women, and in the previous 12 months, a higher frequency of episodes (manic/mixed and depressive, more suicide attempts, more rapid cycling, fewer social activities and more work impairment. Over the 24 months of follow-up the MS group had a significantly lower recovery than PM (36% vs. 46%, p = 0.006. Overall, 42% of all patients were started on monotherapy and 58% on combination therapy; of those 35% and 30% respectively remained on their initial medication throughout the 24 months. At baseline, 36% were treated with an antidepressant, this proportion remains high throughout the follow-up period, with a significantly higher rate for MS vs. PM at 24 months (55% vs. 27%, p Conclusion In this large sample, MS occur frequently (34%, they are more severe at baseline and have a worse functional prognosis than PM. Although

  12. Manga Mania.

    Science.gov (United States)

    Kan, Katherine

    1996-01-01

    "Manga," or Japanese comics, differ from American comics by their lack of color, the attitude of their audience, and their acceptance of nudity. Several science fictional and action-oriented "manga" for young adult and general audiences are described. (AEF)

  13. Deep brain stimulation and treatment-resistant obsessive-compulsive disorder: A systematic review.

    Science.gov (United States)

    Vázquez-Bourgon, Javier; Martino, Juan; Sierra Peña, María; Infante Ceberio, Jon; Martínez Martínez, M Ángeles; Ocón, Roberto; Menchón, José Manuel; Crespo Facorro, Benedicto; Vázquez-Barquero, Alfonso

    2017-07-01

    At least 10% of patients with Obsessive-compulsive Disorder (OCD) are refractory to psychopharmacological treatment. The emergence of new technologies for the modulation of altered neuronal activity in Neurosurgery, deep brain stimulation (DBS), has enabled its use in severe and refractory OCD cases. The objective of this article is to review the current scientific evidence on the effectiveness and applicability of this technique to refractory OCD. We systematically reviewed the literature to identify the main characteristics of deep brain stimulation, its use and applicability as treatment for obsessive-compulsive disorder. Therefore, we reviewed PubMed/Medline, Embase and PsycINFO databases, combining the key-words 'Deep brain stimulation', 'DBS' and 'Obsessive-compulsive disorder' 'OCS'. The articles were selected by two of the authors independently, based on the abstracts, and if they described any of the main characteristics of the therapy referring to OCD: applicability; mechanism of action; brain therapeutic targets; efficacy; side-effects; co-therapies. All the information was subsequently extracted and analysed. The critical analysis of the evidence shows that the use of DBS in treatment-resistant OCD is providing satisfactory results regarding efficacy, with assumable side-effects. However, there is insufficient evidence to support the use of any single brain target over another. Patient selection has to be done following analyses of risks/benefits, being advisable to individualize the decision of continuing with concomitant psychopharmacological and psychological treatments. The use of DBS is still considered to be in the field of research, although it is increasingly used in refractory-OCD, producing in the majority of studies significant improvements in symptomatology, and in functionality and quality of life. It is essential to implement random and controlled studies regarding its long-term efficacy, cost-risk analyses and cost/benefit. Copyright

  14. Discrepancies between explicit and implicit self-esteem and their relationship to symptoms of depression and mania.

    Science.gov (United States)

    Pavlickova, Hana; Turnbull, Oliver H; Bentall, Richard P

    2014-09-01

    Self-esteem is a key feature of bipolar symptomatology. However, so far no study has examined the interaction between explicit and implicit self-esteem in individuals vulnerable to bipolar disorder. Cross-sectional design was employed. Thirty children of parents with bipolar disorder and 30 offspring of control parents completed Hamilton Rating Scale for Depression, the Bech-Rafaelson Mania Scale, the Self-esteem Rating Scale and the Implicit Association Test. No differences between groups were revealed in levels of explicit or implicit self-esteem. However, bipolar offspring showed increased levels of symptoms of depression and mania. Furthermore, depressive symptoms were associated with low explicit self-esteem, whilst symptoms of mania were associated with low implicit self-esteem. When self-esteem discrepancies were examined, damaged self-esteem (i.e., low explicit but high implicit self-esteem) was associated with depression, whilst no associations between mania and self-esteem discrepancies were found. Not only explicit, but also implicit self-esteem, and the interactions between the two are of relevance in bipolar symptoms. Clinical implications and future research directions are discussed. Explicit as well as implicit SE, and particularly their relationship, are relevant for mental health. Fluctuations in implicit SE may serve as an early indicator for risk of bipolarity. Psychotherapeutic approaches may be more suitable for one kind of SE challenge than the other. © 2013 The British Psychological Society.

  15. What Symptoms Predict the Diagnosis of Mania in Persons with Severe/Profound Intellectual Disability In Clinical Practice?

    Science.gov (United States)

    Matson, J. L.; Gonzalez, M. L.; Terlonge, C.; Thorson, R. T.; Laud, R. B.

    2007-01-01

    Background: While researchers have attempted to address the difficulties of diagnosing affective disorders in the intellectually disabled population, diagnosing bipolar disorder in an individual with severe intellectual disability (ID) remains a challenge. The aim of this study was to identify what symptoms can predict a diagnosis of mania in the…

  16. Does Insight Affect the Efficacy of Antipsychotics in Acute Mania?: An Individual Patient Data Regression Meta-Analysis.

    Science.gov (United States)

    Welten, Carlijn C M; Koeter, Maarten W J; Wohlfarth, Tamar D; Storosum, Jitschak G; van den Brink, Wim; Gispen-de Wied, Christine C; Leufkens, Hubert G M; Denys, Damiaan A J P

    2016-02-01

    Patients having an acute manic episode of bipolar disorder often lack insight into their condition. Because little is known about the possible effect of insight on treatment efficacy, we examined whether insight at the start of treatment affects the efficacy of antipsychotic treatment in patients with acute mania. We used individual patient data from 7 randomized, double-blind, placebo-controlled registration studies of 4 antipsychotics in patients with acute mania (N = 1904). Insight was measured with item 11 of the Young Mania Rating Scale (YMRS) at baseline and study endpoint 3 weeks later. Treatment outcome was defined by (a) mean change score, (b) response defined as 50% or more improvement on YMRS, and (c) remission defined as YMRS score less than 8 at study endpoint. We used multilevel mixed effect linear (or logistic) regression analyses of individual patient data to assess the interaction between baseline insight and treatment outcomes. At treatment initiation, 1207 (63.5%) patients had impaired or no insight into their condition. Level of insight significantly modified the efficacy of treatment by mean change score (P = 0.039), response rate (P = 0.033), and remission rate (P = 0.043), with greater improvement in patients with more impaired insight. We therefore recommend that patients experiencing acute mania should be treated immediately and not be delayed until patients regain insight.

  17. Developing Community Reinforcement and Family Training (CRAFT) for Parents of Treatment-Resistant Adolescents

    Science.gov (United States)

    Kirby, Kimberly C.; Versek, Brian; Kerwin, MaryLouise E.; Meyers, Kathleen; Benishek, Lois A.; Bresani, Elena; Washio, Yukiko; Arria, Amelia; Meyers, Robert J.

    2015-01-01

    We describe a project focused on training parents to facilitate their treatment-resistant adolescent's treatment entry and to manage their child after entry into community-based treatment. Controlled studies show that Community Reinforcement and Family Training (CRAFT) is a unilateral treatment that fosters treatment entry of adults; however,…

  18. Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia

    Directory of Open Access Journals (Sweden)

    Makoto Kinoshita

    2017-03-01

    Full Text Available Clozapine is an atypical antipsychotic, that is established as the treatment of choice for treatment-resistant schizophrenia (SCZ. To date, no study investigating comprehensive DNA methylation changes in SCZ patients treated with chronic clozapine has been reported. The purpose of the present study is to reveal the effects of clozapine on DNA methylation in treatment-resistant SCZ. We conducted a genome-wide DNA methylation profiling in peripheral leukocytes (485,764 CpG dinucleotides from treatment-resistant SCZ patients treated with clozapine (n = 21 in a longitudinal study. Significant changes in DNA methylation were observed at 29,134 sites after one year of treatment with clozapine, and these genes were enriched for “cell substrate adhesion” and “cell matrix adhesion” gene ontology (GO terms. Furthermore, DNA methylation changes in the CREBBP (CREB binding protein gene were significantly correlated with the clinical improvements. Our findings provide insights into the action of clozapine in treatment-resistant SCZ.

  19. Evaluating depressive symptoms in mania: a naturalistic study of patients with bipolar disorder

    Directory of Open Access Journals (Sweden)

    Young AH

    2015-04-01

    Full Text Available Allan H Young,1 Jonas Eberhard1,21Institute of Psychiatry, King’s College London, London, UK; 2Corporate Medical Affairs, H. Lundbeck A/S, Copenhagen, DenmarkObjective: This study aimed to evaluate patients with bipolar I disorder (BD-I who have mania with depressive symptoms and who meet the new “with mixed features” specifier of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5.Method: This prospective, multinational, naturalistic study surveyed psychiatrists and their patients with BD-I from October 2013 to March 2014. Eligible patients had BD-I, had a (current manic episode, and had experienced onset of a manic episode within the previous 3 months. Psychiatrists provided patient information on depressive symptoms (DSM-5 criteria; symptoms of anxiety, irritability, and agitation; suicide attempts; and physician satisfaction with treatment response. Data were stratified according to whether patients met the criteria for the BD-I “with mixed features” specifier of DSM-5 (≥3 depressive symptoms or not, and characteristics were compared between the two subgroups. Patients also self-reported on depressive symptoms using the Mini-International Neuropsychiatric Interview module questionnaire.Results: Overall, 34% of 1,035 patients met the criteria for BD-I “with mixed features,” exhibiting ≥3 depressive symptoms during their current manic episode. This correlated with the matched patient self-reports of depressive symptoms. During their current manic episode, BD-I patients “with mixed features” had more severe symptoms of anxiety, irritability, and agitation (average composite severity score of 4.1 vs 3.4, a higher incidence of suicide attempts (38% vs 9%, and more physician dissatisfaction with treatment response (22% vs 14%, compared to patients with 0–2 depressive symptoms (all P<0.05.Conclusion: This study found that patients with BD-I “with mixed features” (ie, ≥3 depressive symptoms

  20. The management of bipolar mania: a national survey of baseline data from the EMBLEM study in Italy

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    Barraco Alessandra

    2007-07-01

    Full Text Available Abstract Background Although a number of studies have assessed the management of mania in routine clinical practice, no studies have so far evaluated the short- and long-term management and outcome of patients affected by bipolar mania in different European countries. The objective of the study is to present, in the context of a large multicenter survey (EMBLEM study, an overview of the baseline data on the acute management of a representative sample of manic bipolar patients treated in the Italian psychiatric hospital and community settings. EMBLEM is a 2-year observational longitudinal study that evaluates across 14 European countries the patterns of the drug prescribed in patients with bipolar mania, their socio-demographic and clinical features and the outcomes of the treatment. Methods The study consists of a 12-week acute phase and a ≤ 24-month maintenance phase. Bipolar patients were included into the study as in- or out-patients, if they initiated or changed, according to the decision of their psychiatrist, oral antipsychotics, anticonvulsants and/or lithium for the treatment of an episode of mania. Data concerning socio-demographic characteristics, psychiatric and medical history, severity of mania, prescribed medications, functional status and quality of life were collected at baseline and during the follow-up period. Results In Italy, 563 patients were recruited in 56 sites: 376 were outpatients and 187 inpatients. The mean age was 45.8 years. The mean CGI-BP was 4.4 (± 0.9 for overall score and mania, 1.9 (± 1.2 for depression and 2.6 (± 1.6 for hallucinations/delusions. The YMRS showed that 14.4% had a total score Conclusion Data collected at baseline in the Italian cohort of the EMBLEM study represent a relevant source of information to start addressing the short and long-term therapeutic strategies for improving the clinical as well as the socio-economic outcomes of patients affected by bipolar mania. Although it's not an

  1. Early treatment resistance in a Latin-American cohort of patients with schizophrenia.

    Science.gov (United States)

    Mena, Cristian; Gonzalez-Valderrama, Alfonso; Iruretagoyena, Barbara; Undurraga, Juan; Crossley, Nicolas A

    2018-03-08

    Failure to respond to antipsychotic medication in schizophrenia is a common clinical scenario with significant morbidity. Recent studies have highlighted that many patients present treatment-resistance from disease onset. We here present an analysis of clozapine prescription patterns, used as a real-world proxy marker for treatment-resistance, in a cohort of 1195 patients with schizophrenia from a Latin-American cohort, to explore the timing of emergence of treatment resistance and possible subgroup differences. Survival analysis from national databases of clozapine monitoring system, national disease notification registers, and discharges from an early intervention ward. Echoing previous studies, we found that around 1 in 5 patients diagnosed with schizophrenia were eventually prescribed clozapine, with an over-representation of males and those with a younger onset of psychosis. The annual probability of being prescribed clozapine was highest within the first year (probability of 0.11, 95% confidence interval of 0.093-0.13), compared to 0.018 (0.012-0.024) between years 1 and 5, and 0.006 (0-0.019) after 5years. Age at psychosis onset, gender, dose of clozapine used, and compliance with hematological monitoring at 12months, was not related to the onset of treatment resistance. A similar pattern was observed in a subgroup of 230 patients discharged from an early intervention ward with a diagnosis of non-affective first episode of psychosis. Our results highlight that treatment resistance is frequently present from the onset of psychosis. Future studies will shed light on the possible different clinical and neurobiological characteristics of this subtype of psychosis. Copyright © 2018. Published by Elsevier B.V.

  2. Comparison of mania patients suitable for treatment trials versus clinical treatment.

    Science.gov (United States)

    Talamo, Alessandra; Baldessarini, Ross J; Centorrino, Franca

    2008-08-01

    It remains uncertain whether bipolar disorder (BPD) patients in randomized-controlled trials (RCTs) are sufficiently representative of clinically encountered patients as to guide clinical-therapeutic practice. We complied inclusion/exclusion criteria by frequency from reports of 21 RCTs for mania, and applied them in a pilot study of patients hospitalized for DSM-IV BPD manic/mixed states to compare characteristics and clinical responses of patients who did versus did not meet exclusion criteria. From 27 initially identified inclusion/exclusion criteria ranked by citation frequency, we derived six inclusion, and 10 non-redundant-exclusion factors. Of 67 consecutive patients meeting inclusion criteria, 15 (22.4%) potential "research subjects" met all 10 exclusion criteria. The remaining 52 "clinical patients" differed markedly on exclusion criteria, including more psychiatric co-morbidity, substance abuse, involuntary hospitalization, and suicide attempts or violence, but were otherwise similar. In both groups responses to clinically determined inpatient treatments were similar, including improvement in mania ratings. Based on applying reported inclusion/exclusion criteria for RCTs to a pilot sample of hospitalized-manic patients, those likely to be included in modern RCTs were similar to patients who would be excluded, most notably in short-term antimanic-treatment responses. The findings encourage further comparisons of subjects included/excluded from RCTs to test potential clinical generalizability of research findings. The pilot study is limited in numbers and exposure times with which to test for the minor differences between "research subjects" and "clinical patients." (c) 2008 John Wiley & Sons, Ltd.

  3. Evaluating depressive symptoms in mania: a naturalistic study of patients with bipolar disorder

    Science.gov (United States)

    Young, Allan H; Eberhard, Jonas

    2015-01-01

    Objective This study aimed to evaluate patients with bipolar I disorder (BD-I) who have mania with depressive symptoms and who meet the new “with mixed features” specifier of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). Method This prospective, multinational, naturalistic study surveyed psychiatrists and their patients with BD-I from October 2013 to March 2014. Eligible patients had BD-I, had a (current) manic episode, and had experienced onset of a manic episode within the previous 3 months. Psychiatrists provided patient information on depressive symptoms (DSM-5 criteria); symptoms of anxiety, irritability, and agitation; suicide attempts; and physician satisfaction with treatment response. Data were stratified according to whether patients met the criteria for the BD-I “with mixed features” specifier of DSM-5 (≥3 depressive symptoms) or not, and characteristics were compared between the two subgroups. Patients also self-reported on depressive symptoms using the Mini-International Neuropsychiatric Interview module questionnaire. Results Overall, 34% of 1,035 patients met the criteria for BD-I “with mixed features,” exhibiting ≥3 depressive symptoms during their current manic episode. This correlated with the matched patient self-reports of depressive symptoms. During their current manic episode, BD-I patients “with mixed features” had more severe symptoms of anxiety, irritability, and agitation (average composite severity score of 4.1 vs 3.4), a higher incidence of suicide attempts (38% vs 9%), and more physician dissatisfaction with treatment response (22% vs 14%), compared to patients with 0–2 depressive symptoms (all P<0.05). Conclusion This study found that patients with BD-I “with mixed features” (ie, ≥3 depressive symptoms during a manic episode), suffered, on average, from a greater burden of disease than patients with pure mania. Improved identification of these patients may help to optimize

  4. Evaluating depressive symptoms in mania: a naturalistic study of patients with bipolar disorder.

    Science.gov (United States)

    Young, Allan H; Eberhard, Jonas

    2015-01-01

    This study aimed to evaluate patients with bipolar I disorder (BD-I) who have mania with depressive symptoms and who meet the new "with mixed features" specifier of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). This prospective, multinational, naturalistic study surveyed psychiatrists and their patients with BD-I from October 2013 to March 2014. Eligible patients had BD-I, had a (current) manic episode, and had experienced onset of a manic episode within the previous 3 months. Psychiatrists provided patient information on depressive symptoms (DSM-5 criteria); symptoms of anxiety, irritability, and agitation; suicide attempts; and physician satisfaction with treatment response. Data were stratified according to whether patients met the criteria for the BD-I "with mixed features" specifier of DSM-5 (≥3 depressive symptoms) or not, and characteristics were compared between the two subgroups. Patients also self-reported on depressive symptoms using the Mini-International Neuropsychiatric Interview module questionnaire. Overall, 34% of 1,035 patients met the criteria for BD-I "with mixed features," exhibiting ≥3 depressive symptoms during their current manic episode. This correlated with the matched patient self-reports of depressive symptoms. During their current manic episode, BD-I patients "with mixed features" had more severe symptoms of anxiety, irritability, and agitation (average composite severity score of 4.1 vs 3.4), a higher incidence of suicide attempts (38% vs 9%), and more physician dissatisfaction with treatment response (22% vs 14%), compared to patients with 0-2 depressive symptoms (all Pmixed features" (ie, ≥3 depressive symptoms during a manic episode), suffered, on average, from a greater burden of disease than patients with pure mania. Improved identification of these patients may help to optimize treatment outcomes.

  5. Kidney Function Decline and Apparent Treatment-Resistant Hypertension in the Elderly.

    Directory of Open Access Journals (Sweden)

    Jean Kaboré

    Full Text Available Cross-sectional studies show a strong association between chronic kidney disease and apparent treatment-resistant hypertension, but the longitudinal association of the rate of kidney function decline with the risk of resistant hypertension is unknown.The population-based Three-City included 8,695 participants older than 65 years, 4265 of them treated for hypertension. We estimated the odds ratios (OR of new-onset apparent treatment-resistant hypertension, defined as blood pressure ≥ 140/90 mmHg despite use of 3 antihypertensive drug classes or ≥ 4 classes regardless of blood pressure, associated with the mean estimated glomerular filtration rate (eGFR level and its rate of decline over 4 years, compared with both controlled hypertension and uncontrolled nonresistant hypertension with ≤ 2 drugs. GFR was estimated with three different equations.Baseline prevalence of apparent treatment-resistant hypertension and of controlled and uncontrolled nonresistant hypertension, were 6.5%, 62.3% and 31.2%, respectively. During follow-up, 162 participants developed apparent treatment-resistant hypertension. Mean eGFR decline with the MDRD equation was 1.5±2.9 mL/min/1.73 m² per year: 27.7% of the participants had an eGFR ≥3 and 10.1% ≥ 5 mL/min/1.73 m² per year. After adjusting for age, sex, obesity, diabetes, and cardiovascular history, the ORs for new-onset apparent treatment-resistant hypertension associated with a mean eGFR level, per 15 mL/min/1.73 m² drop, were 1.23 [95% confidence interval 0.91-1.64] compared to controlled hypertension and 1.10 [0.83-1.45] compared to uncontrolled nonresistant hypertension; ORs associated with a decline rate ≥ 3 mL/min/1.73 m² per year were 1.89 [1.09-3.29] and 1.99 [1.19-3.35], respectively. Similar results were obtained when we estimated GFR with the CKDEPI and the BIS1 equations. ORs tended to be higher for an eGFR decline rate ≥ 5 mL/min/1.73 m² per year.The speed of kidney function decline is

  6. Transcranial low voltage pulsed electromagnetic fields in patients with treatment-resistant depression

    DEFF Research Database (Denmark)

    Martiny, Klaus Per Juul; Lunde, Marianne; Bech, Per

    2010-01-01

    BACKGROUND: Approximately 30% of patients with depression are resistant to antidepressant drugs. Repetitive transcranial magnetic stimulation (rTMS) has been found effective in combination with antidepressants in this patient group. The aim of this study was to evaluate the antidepressant effect...... of a new principle using low-intensity transcranially applied pulsed electromagnetic fields (T-PEMF) in combination with antidepressants in patients with treatment-resistant depression. METHODS: This was a sham-controlled double-blind study comparing 5 weeks of active or sham T-PEMF in patients...... with treatment-resistant major depression. The antidepressant treatment, to which patients had been resistant, was unchanged 4 weeks before and during the study period. Weekly assessments were performed using both clinician-rated and patient-rated scales. The T-PEMF equipment was designed as a helmet containing...

  7. Mortality and Self-Harm in Association With Clozapine in Treatment-Resistant Schizophrenia

    DEFF Research Database (Denmark)

    Wimberley, Theresa; Maccabe, James H; Laursen, Thomas M

    2017-01-01

    Objective: This study evaluated rates of all-cause mortality and self-harm in association with clozapine treatment in individuals with treatment-resistant schizophrenia. Method: A population-based cohort of 2,370 individuals with treatment-resistant schizophrenia after Jan. 1, 1996, was followed...... until death, first episode of self-harm, emigration, or June 1, 2013. Time to all-cause death and time tofirst episode of self-harm were analyzed in Cox regression models with timevarying treatment, adjusted for clinical and sociodemographic covariates. Results: The rate of all-cause mortality...... with other antipsychotics (hazard ratio: 1.45, 95% CI: 0.86-2.45). Excess mortality was observed in the year after clozapine discontinuation (hazard ratio: 2.65, 95% CI: 1.47-4.78). The rate of self-harm was higher for nonclozapine antipsychotics than for clozapine (hazard ratio: 1.36, 95% CI: 1...

  8. Treatment Resistant Epilepsy in Autism Spectrum Disorder: Increased Risk for Females.

    Science.gov (United States)

    Blackmon, Karen; Bluvstein, Judith; MacAllister, William S; Avallone, Jennifer; Misajon, Jade; Hedlund, Julie; Goldberg, Rina; Bojko, Aviva; Mitra, Nirmala; Giridharan, Radha; Sultan, Richard; Keller, Seth; Devinsky, Orrin

    2016-02-01

    The male:female ratio in autism spectrum disorder (ASD) averages greater than 4:1 while the male:female ratio of ASD with epilepsy averages less than 3:1. This indicates an elevated risk of epilepsy in females with ASD; yet, it is unknown whether phenotypic features of epilepsy and ASD differ between males and females with this comorbidity. The goal of this study is to investigate sex differences in phenotypic features of epilepsy and ASD in a prospective sample of 130 children and young adults with an initial ASD diagnosis and subsequent epilepsy diagnosis. All participants were characterized by standardized diagnostic inventories, parent/caregiver completed questionnaires, and medical/academic record review. Diagnostic classifications of epilepsy, ASD, and intellectual disability were performed by board certified neurologists and a pediatric neuropsychologist. Results demonstrated a lower male:female ratio (1.8:1) in individuals with ASD and treatment-resistant epilepsy relative to those with ASD and treatment-responsive epilepsy (4.9:1), indicating a higher risk of treatment-resistant epilepsy in females. Mild neuroimaging abnormalities were more common in females than males and this was associated with increased risk of treatment-resistance. In contrast, ASD symptom severity was lower in females compared with males. Findings distinguish females with ASD and epilepsy as a distinct subgroup at higher risk for a more severe epilepsy phenotype in the context of a less severe ASD phenotype. Increased risk of anti-epileptic treatment resistance in females with ASD and epilepsy suggests that comprehensive genetic, imaging, and neurologic screening and enhanced treatment monitoring may be indicated for this subgroup. Autism Res 2016, 9: 311-320. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  9. Blockade of dopamine D1-family receptors attenuates the mania-like hyperactive, risk-preferring, and high motivation behavioral profile of mice with low dopamine transporter levels

    NARCIS (Netherlands)

    Milienne-Petiot, Morgane; Groenink, Lucianne; Minassian, Arpi; Young, Jared W

    2017-01-01

    Background: Patients with bipolar disorder mania exhibit poor cognition, impulsivity, risk-taking, and goal-directed activity that negatively impact their quality of life. To date, existing treatments for bipolar disorder do not adequately remediate cognitive dysfunction. Reducing dopamine

  10. Pindolol augmentation in treatment-resistant obsessive compulsive disorder: a double-blind placebo controlled trial.

    Science.gov (United States)

    Dannon, P N; Sasson, Y; Hirschmann, S; Iancu, I; Grunhaus, L J; Zohar, J

    2000-05-01

    To evaluate the efficacy of pindolol augmentation in treatment-resistant obsessive compulsive disorder (OCD) patients who were unsuccessfully treated with serotonin reuptake inhibitors. Fourteen treatment-resistant OCD patients were treated with paroxetine for 17.4+/-2.1 weeks up to 60 mg/d after they failed at least two other serotonin reuptake inhibitor trials. The patients, who did not respond to open-label paroxetine treatment, were assigned to a double-blind, placebo-controlled pindolol (2.5 mgx3/d) augmentation. All the subjects were evaluated biweekly for a six-week period with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Anxiety Scale (HAM-Anx), and Montgomery Asberg Depression Rating Scale (MADRS). Data was analyzed by paired t-test, and ANOVA with repeated measures. Pindolol augmentation to paroxetine (n=8) as compared to placebo augmentation (n=6), was associated with a significant (P<0.01) improvement in Y-BOCS as measured by paired t-test after the fourth week of the treatment and by ANOVA with repeated measures (df: 4.9, f: 3,3, P<0.006). Although no significant differences were found between placebo and pindolol groups on HAM-Anx and MADRS, a trend for improvement in the pindolol group was noted. The results of our study demonstrated that pindolol may augment the therapeutic effect of paroxetine in treatment-resistant OCD patients.

  11. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up.

    Science.gov (United States)

    Carhart-Harris, R L; Bolstridge, M; Day, C M J; Rucker, J; Watts, R; Erritzoe, D E; Kaelen, M; Giribaldi, B; Bloomfield, M; Pilling, S; Rickard, J A; Forbes, B; Feilding, A; Taylor, D; Curran, H V; Nutt, D J

    2018-02-01

    Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy. Here, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression. Twenty patients (six females) with (mostly) severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart) in a supportive setting. Depressive symptoms were assessed from 1 week to 6 months post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure. Treatment was generally well tolerated. Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen's d = 2.2 at week 1 and 2.3 at week 5, both p psilocybin. Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience. Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort. Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind randomised control trials.

  12. Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression.

    Science.gov (United States)

    Stroud, J B; Freeman, T P; Leech, R; Hindocha, C; Lawn, W; Nutt, D J; Curran, H V; Carhart-Harris, R L

    2018-02-01

    Depressed patients robustly exhibit affective biases in emotional processing which are altered by SSRIs and predict clinical outcome. The objective of this study is to investigate whether psilocybin, recently shown to rapidly improve mood in treatment-resistant depression (TRD), alters patients' emotional processing biases. Seventeen patients with treatment-resistant depression completed a dynamic emotional face recognition task at baseline and 1 month later after two doses of psilocybin with psychological support. Sixteen controls completed the emotional recognition task over the same time frame but did not receive psilocybin. We found evidence for a group × time interaction on speed of emotion recognition (p = .035). At baseline, patients were slower at recognising facial emotions compared with controls (p psilocybin, this difference was remediated (p = .208). Emotion recognition was faster at follow-up compared with baseline in patients (p = .004, d = .876) but not controls (p = .263, d = .302). In patients, this change was significantly correlated with a reduction in anhedonia over the same time period (r = .640, p = .010). Psilocybin with psychological support appears to improve processing of emotional faces in treatment-resistant depression, and this correlates with reduced anhedonia. Placebo-controlled studies are warranted to follow up these preliminary findings.

  13. Treatment-resistant, five-year long, postpartum-onset Capgras episode resolving after electroconvulsive therapy.

    Science.gov (United States)

    Rapinesi, Chiara; Kotzalidis, Georgios D; Del Casale, Antonio; Ferri, Vittoria Rachele; Di Pietro, Simone; Scatena, Paola; Serata, Daniele; Danese, Emanuela; Sani, Gabriele; Koukopoulos, Alexia E; Angeletti, Gloria; Girardi, Paolo

    2015-01-01

    Postpartum psychosis, which rarely presents with Capgras syndrome (delusional misidentification), requires rapid symptom resolution. First-line drugs have important drawbacks, such as delayed onset of clinical response and secretion in breast milk. In this report, we report successful treatment of a treatment-resistant woman presenting with treatment-resistant Capgras syndrome, with onset during postpartum. A 36-year-old woman had presented with Capgras syndrome during postpartum. For more than five years, she believed her son and other family members were substituted by impostors. All adequately administrated treatments were unsuccessful. We suggested electroconvulsive therapy to overcome treatment resistance. After six electroconvulsive therapy sessions, delusions of doubles subsided and other symptoms improved. She was discharged two weeks later with a mood stabilizer and low-dose atypical antipychotic combination and is well at the one-and-a-half-year follow-up. Electroconvulsive therapy followed by a mood stabilizer-antipsychotic drug combination showed rapid, permanent, and effective control of long-standing Capgras syndrome in a young woman. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  14. Treatment-resistant depression in adolescents: is the addition of cognitive behavioral therapy of benefit?

    Directory of Open Access Journals (Sweden)

    Hetrick SE

    2011-08-01

    Full Text Available Sarah E Hetrick1, Georgina R Cox1, Sally N Merry21Orygen Youth Health Research Centre, Centre for Youth Mental Health, Melbourne, Parkville, Victoria, Australia; 2Werry Centre for Child and Adolescent Mental Health, Department of Psychological Medicine, The University of Auckland, Auckland, New ZealandBackground: Many young people with major depression fail first-line treatments. Treatment resistant depression has various definitions in the literature but typically assumes nonresponse to medication. In young people, cognitive behavioral therapy (CBT is the recommended firstline intervention, thus the definition of treatment resistance should be expanded. Therefore, our aim was to synthesize the existing evidence of any interventions for treatment-resistant depression, broadly defined, in children and adolescents and to investigate the effectiveness of CBT in this context. Methods: We used Cochrane Collaboration methodology, with electronic searches of Medline, PsycINFO, Embase, and the Cochrane Depression Anxiety and Neurosis Group trials registers. Only randomized controlled trials were included, and were assessed for risk of bias. Meta-analysis was undertaken where possible and appropriate.Results: Of 953 articles retrieved, four trials were eligible for inclusion. For one study, only the trial registration document was available, because the study was never completed. All other studies were well conducted with a low risk of bias, although one study had a high dropout rate. Two studies assessed the effect of adding CBT to medication. While an assertive trial of antidepressants does appear to lead to benefit, when compared with placebo, there was no significant advantage, in either study, or in a meta-analysis of data from these trials, that clearly demonstrated an additional benefit of CBT. The third trial showed little advantage of a tricyclic antidepressant over placebo in the context of an inpatient admission. Conclusion: Few randomized

  15. Splenectomy in a patient with treatment-resistant visceral leishmaniasis: a case report

    Directory of Open Access Journals (Sweden)

    Robson Azevedo Dutra

    2012-02-01

    Full Text Available Visceral leishmaniasis (VL, also known as Kala-azar, is a systemic infection caused by a protozoan (Leishmania and, in its classic form, is a serious illness associated with malnutrition, anemia, hepatosplenomegaly, infectious processes and coagulopathies. The effect of splenectomy in patients with visceral leishmaniasis is not well defined; however, it is known that the spleen is the largest reservoir of infected cells belonging to the reticulo endothelial system. Therefore, the surgical procedure is an option for the debulking of parasites, providing a cure for refractory VL and minimizing the complications of hypersplenism.

  16. Texas Medication Algorithm Project, phase 3 (TMAP-3): clinical results for patients with a history of mania.

    Science.gov (United States)

    Suppes, Trisha; Rush, A John; Dennehy, Ellen B; Crismon, M Lynn; Kashner, T Michael; Toprac, Marcia G; Carmody, Thomas J; Brown, E Sherwood; Biggs, Melanie M; Shores-Wilson, Kathy; Witte, Bradley P; Trivedi, Madhukar H; Miller, Alexander L; Altshuler, Kenneth Z; Shon, Steven P

    2003-04-01

    The Texas Medication Algorithm Project (TMAP) assessed the clinical and economic impact of algorithm-driven treatment (ALGO) as compared with treatment-as-usual (TAU) in patients served in public mental health centers. This report presents clinical outcomes in patients with a history of mania (BD), including bipolar I and schizoaffective disorder, bipolar type, during 12 months of treatment beginning March 1998 and ending with the final active patient visit in April 2000. Patients were diagnosed with bipolar I disorder or schizoaffective disorder, bipolar type, according to DSM-IV criteria. ALGO was comprised of a medication algorithm and manual to guide treatment decisions. Physicians and clinical coordinators received training and expert consultation throughout the project. ALGO also provided a disorder-specific patient and family education package. TAU clinics had no exposure to the medication algorithms. Quarterly outcome evaluations were obtained by independent raters. Hierarchical linear modeling, based on a declining effects model, was used to assess clinical outcome of ALGO versus TAU. ALGO and TAU patients showed significant initial decreases in symptoms (p =.03 and p <.001, respectively) measured by the 24-item Brief Psychiatric Rating Scale (BPRS-24) at the 3-month assessment interval, with significantly greater effects for the ALGO group. Limited catch-up by TAU was observed over the remaining 3 quarters. Differences were also observed in measures of mania and psychosis but not in depression, side-effect burden, or functioning. For patients with a history of mania, relative to TAU, the ALGO intervention package was associated with greater initial and sustained improvement on the primary clinical outcome measure, the BPRS-24, and the secondary outcome measure, the Clinician-Administered Rating Scale for Mania (CARS-M). Further research is planned to clarify which elements of the ALGO package contributed to this between-group difference.

  17. Incidence, prevalence and clinical correlates of antidepressant-emergent mania in bipolar depression: a systematic review and meta-analysis.

    Science.gov (United States)

    Fornaro, Michele; Anastasia, Annalisa; Novello, Stefano; Fusco, Andrea; Solmi, Marco; Monaco, Francesco; Veronese, Nicola; De Berardis, Domenico; de Bartolomeis, Andrea

    2018-05-01

    Treatment-emergent mania (TEM) represents a common phenomenon inconsistently reported across primary studies, warranting further assessment. A systematic review and meta-analysis following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were conducted. Major electronic databases were searched from inception to May 2017 to assess the incidence and prevalence rates and clinical features associated with manic switch among bipolar depressed patients receiving antidepressants, using meta-regression and subgroup analysis. Overall, 10 098 depressed patients with bipolar disorder (BD) across 51 studies/arms were included in the quantitative analysis. The cumulative incidence of cases (TEM + ) among 4767 patients with BD over 15 retrospective studies was 30.9% (95% confidence interval [CI] 19.6-45.0%, I 2  = 97.9%). The cumulative incidence of TEM + among 1929 patients with BD over 12 prospective open studies was 14.4% (95% CI 7.4-26.1%, I 2  = 93.7%). The cumulative incidence of TEM + among 1316 patients with BD over 20 randomized controlled trials (RCTs) was 11.8% (95% CI 8.4-16.34%, I 2  = 73.46%). The pooled prevalence of TEM + among 2086 patients with BD over four cross-sectional studies was 30.9% (95% CI 18.1-47.4%, I 2  = 95.6%). Overall, concurrent lithium therapy predicted the lowest TEM rates. Inconsistent operational definitions of TEM were recorded, and the lack of information about age, sex, co-occurring anxiety, and other clinically relevant moderators precluded further stratification of the results. Rates of TEM vary primarily depending on study setting, which is concordant with the high degree of heterogeneity of the included records. Forthcoming RCT studies should adopt consistent operational definitions of TEM and broaden the number of moderators, in order to contribute most effectively to the identification of clear-cut sub-phenotypes of

  18. [Concordance between hospital prescriptions and recommendations in the treatment of mania].

    Science.gov (United States)

    Laforgue, Edouard-Jules; Bulteau, Samuel; Cholet, Jennyfer; Victorri-Vigneau, Caroline; Guitteny, Marie; Mauduit, Nicolas; Vanelle, Jean-Marie; Sauvaget, Anne

    2017-06-01

    There are differences between recommendations and practice in the pharmacological treatment of acute mania. The objective was to assess conformity of the anti-manic prescription between national recommendations (Haute Autorité de santé [French health authority, HAS] and "résumé des caractéristiques du produit" [product characteristics, RCP]) and clinical practice. We observed the drug prescriptions of in-patients for a manic episode. The main outcome measure was the concordance rate with the recommendations of the drugs prescriptions at the 48th hour. The secondary outcome repeated the same process with the hospital discharge statement of switches, associations, the presence of symptomatic and antidepressant treatments. Sixty-six episodes were included, 40 patients (60%) had a prescription complies with RCP recommendations H48 and 46 patients (70%) to HAS. These rates fall at hospital discharge. Off-label prescriptions, drug combinations and choices of not listed molecules are the most common reasons for non-conformity. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  19. Neuroprotective and antioxidant effects of curcumin in a ketamine-induced model of mania in rats.

    Science.gov (United States)

    Gazal, Marta; Valente, Matheus R; Acosta, Bruna A; Kaufmann, Fernanda N; Braganhol, Elizandra; Lencina, Claiton L; Stefanello, Francieli M; Ghisleni, Gabriele; Kaster, Manuella P

    2014-02-05

    Bipolar disorder (BD) is a chronic and debilitating illness characterized by recurrent manic and depressive episodes. Our research investigates the protective effects of curcumin, the main curcuminoid of the Indian spice turmeric, in a model of mania induced by ketamine administration in rats. Our results indicated that ketamine treatment (25 mg/kg, for 8 days) induced hyperlocomotion in the open-field test and oxidative damage in prefrontal cortex (PFC) and hippocampus (HP), evaluated by increased lipid peroxidation and decreased total thiol content. Moreover, ketamine treatment reduced the activity of the antioxidant enzymes superoxide dismutase and catalase in the HP. Pretreatment of rats with curcumin (20 and 50 mg/kg, for 14 days) or with lithium chloride (45 mg/kg, positive control) prevented behavioral and pro-oxidant effects induced by ketamine. These findings suggest that curcumin might be a good compound for preventive intervention in BD, reducing the episode relapse and the oxidative damage associated with the manic phase of this disorder. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Significant Need for a French Network of Expert Centers Enabling a Better Characterization and Management of Treatment-Resistant Depression (Fondation FondaMental

    Directory of Open Access Journals (Sweden)

    Antoine Yrondi

    2017-11-01

    Full Text Available BackgroundMajor depression is characterized by (i a high lifetime prevalence of 16–17% in the general population; (ii a high frequency of treatment resistance in around 20–30% of cases; (iii a recurrent or chronic course; (iv a negative impact on the general functioning and quality of life; and (v a high level of comorbidity with various psychiatric and non-psychiatric disorders, high occurrence of completed suicide, significant burden along with the personal, societal, and economic costs. In this context, there is an important need for the development of a network of expert centers for treatment-resistant depression (TRD, as performed under the leadership of the Fondation FondaMental.MethodsThe principal mission of this national network is to establish a genuine prevention, screening, and diagnosis policy for TRD to offer a systematic, comprehensive, longitudinal, and multidimensional evaluation of cases. A shared electronic medical file is used referring to a common exhaustive and standardized set of assessment tools exploring psychiatric, non-psychiatric, metabolic, biological, and cognitive dimensions of TRD. This is paralleled by a medico-economic evaluation to examine the global economic burden of the disease and related health-care resource utilization. In addition, an integrated biobank has been built by the collection of serum and DNA samples for the measurement of several biomarkers that could further be associated with the treatment resistance in the recruited depressed patients. A French observational long-term follow-up cohort study is currently in progress enabling the extensive assessment of resistant depressed patients. In those unresponsive cases, each expert center proposes relevant therapeutic options that are classically aligned to the international guidelines referring to recognized scientific societies.DiscussionThis approach is expected to improve the overall clinical assessments and to provide evidence

  1. C-reactive protein levels and treatment resistance in schizophrenia - A Danish population-based cohort study

    DEFF Research Database (Denmark)

    Horsdal, Henriette Thisted; Wimberley, Theresa; Benros, Michael Eriksen

    2017-01-01

    -time schizophrenia diagnosis and a baseline C-reactive protein measurement (a commonly available marker of systemic inflammation) from 2000 to 2012. We defined treatment resistance as the earliest observed instance of either clozapine initiation or hospital admission due to schizophrenia after having received......OBJECTIVE: Schizophrenia is associated with increased levels of inflammatory markers. However, it remains unclear whether inflammatory markers are associated with treatment-resistant schizophrenia. METHODS: We conducted a population-based follow-up study among individuals with a first...... (4.0 vs. 3.1 mg/L, p = .13) was observed among the 52 (13.3%) treatment-resistant individuals. Increased levels of C-reactive protein (above 3 mg/L) at baseline were not associated with treatment resistance (adjusted hazard ratio = 0.99, 95% confidence interval [0.56, 1.73]). CONCLUSIONS: C...

  2. Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma.

    Science.gov (United States)

    Green, Benjamin J; Wiriyachaiporn, Surasa; Grainge, Christopher; Rogers, Geraint B; Kehagia, Valia; Lau, Laurie; Carroll, Mary P; Bruce, Kenneth D; Howarth, Peter H

    2014-01-01

    Molecular microbiological analysis of airway samples in asthma has demonstrated an altered microbiome in comparison to healthy controls. Such changes may have relevance to treatment-resistant severe asthma, particularly those with neutrophilic airway inflammation, as bacteria might be anticipated to activate the innate immune response, a process that is poorly steroid responsive. An understanding of the relationship between airway bacterial presence and dominance in severe asthma may help direct alternative treatment approaches. We aimed to use a culture independent analysis strategy to describe the presence, dominance and abundance of bacterial taxa in induced sputum from treatment resistant severe asthmatics and correlate findings with clinical characteristics and airway inflammatory markers. Induced sputum was obtained from 28 stable treatment-resistant severe asthmatics. The samples were divided for supernatant IL-8 measurement, cytospin preparation for differential cell count and Terminal Restriction Fragment Length Polymorphism (T-RFLP) profiling for bacterial community analysis. In 17/28 patients, the dominant species within the airway bacterial community was Moraxella catarrhalis or a member of the Haemophilus or Streptococcus genera. Colonisation with these species was associated with longer asthma disease duration (mean (SD) 31.8 years (16.7) vs 15.6 years (8.0), p = 0.008), worse post-bronchodilator percent predicted FEV1 (68.0% (24.0) vs 85.5% (19.7), p = 0.025) and higher sputum neutrophil differential cell counts (median (IQR) 80% (67-83) vs 43% (29-67), p = 0.001). Total abundance of these organisms significantly and positively correlated with sputum IL-8 concentration and neutrophil count. Airway colonisation with potentially pathogenic micro-organisms in asthma is associated with more severe airways obstruction and neutrophilic airway inflammation. This altered colonisation may have a role in the development of an asthma phenotype that

  3. A lamotrigina pode induzir virada maníaca? ¿Lamotrigina puede inducir manía? Can lamotrigine induce switch into mania?

    Directory of Open Access Journals (Sweden)

    Elie Cheniaux

    2005-08-01

    Full Text Available Em ensaios clínicos controlados com pacientes bipolares, a lamotrigina tem demonstrado eficácia no tratamento da fase aguda da depressão e, principalmente, na prevenção de novos episódios depressivos. É relatado o caso de um paciente bipolar tipo II, ciclador rápido, que, durante um episódio depressivo, fez uso dessa substância, em monoterapia, e passou a apresentar um quadro maníaco disfórico. Este remitiu logo após a retirada da medicação e foi sucedido por um novo episódio depressivo. Essa ocorrência foi bastante inesperada diante dos dados clínicos da literatura científica, os quais associam a lamotrigina a uma taxa muito baixa de virada para a mania.En los ensayos clínicos controlados con pacientes bipolares, la lamotrigina mostró eficacia en el tratamiento de la fase aguda de la depresión y, principalmente, en la prevención de nuevos episodios depresivos. Describimos un caso de un paciente bipolar de tipo II, con un curso de ciclos rápidos, que, durante un episodio depresivo, tomó lamotrigina en monoterapia, desarrollando un episodio maníaco disfórico. Este episodio remitió pronto después de la suspensión de la medicina y fue seguido por un nuevo episodio depresivo. Esa ocurrencia fue bastante inesperada si comparada a los datos clínicos de la literatura científica, que muestran la lamotrigina con una tasa muy baja de "viraje" para la manía.Controlled clinical trials involving bipolar patients have shown that lamotrigine is effective in acute phase treatment of depression and mainly in the prevention of new depressive episodes. We report the case of a bipolar II, rapid cycling patient who used lamotrigine (in monotherapy during a depressive episode and developed a dysphoric manic episode. This episode resolved soon after discontinuation of the drug and was followed by a new depressive episode. The occurrence of the dysphoric manic episode was much unexpected, based on the clinical data found in the

  4. A study of remitted and treatment-resistant depression using MMPI and including pessimism and optimism scales.

    Science.gov (United States)

    Suzuki, Masatoshi; Takahashi, Michio; Muneoka, Katsumasa; Sato, Koichi; Hashimoto, Kenji; Shirayama, Yukihiko

    2014-01-01

    The psychological aspects of treatment-resistant and remitted depression are not well documented. We administered the Minnesota Multiphasic Personality Inventory (MMPI) to patients with treatment-resistant depression (n = 34), remitted depression (n = 25), acute depression (n = 21), and healthy controls (n = 64). Pessimism and optimism were also evaluated by MMPI. ANOVA and post-hoc tests demonstrated that patients with treatment-resistant and acute depression showed similarly high scores for frequent scale (F), hypochondriasis, depression, conversion hysteria, psychopathic device, paranoia, psychasthenia and schizophrenia on the MMPI compared with normal controls. Patients with treatment-resistant depression, but not acute depression registered high on the scale for cannot say answer. Using Student's t-test, patients with remitted depression registered higher on depression and social introversion scales, compared with normal controls. For pessimism and optimism, patients with treatment-resistant depression demonstrated similar changes to acutely depressed patients. Remitted depression patients showed lower optimism than normal controls by Student's t-test, even though these patients were deemed recovered from depression using HAM-D. The patients with remitted depression and treatment-resistant depression showed subtle alterations on the MMPI, which may explain the hidden psychological features in these cohorts.

  5. A study of remitted and treatment-resistant depression using MMPI and including pessimism and optimism scales.

    Directory of Open Access Journals (Sweden)

    Masatoshi Suzuki

    Full Text Available The psychological aspects of treatment-resistant and remitted depression are not well documented.We administered the Minnesota Multiphasic Personality Inventory (MMPI to patients with treatment-resistant depression (n = 34, remitted depression (n = 25, acute depression (n = 21, and healthy controls (n = 64. Pessimism and optimism were also evaluated by MMPI.ANOVA and post-hoc tests demonstrated that patients with treatment-resistant and acute depression showed similarly high scores for frequent scale (F, hypochondriasis, depression, conversion hysteria, psychopathic device, paranoia, psychasthenia and schizophrenia on the MMPI compared with normal controls. Patients with treatment-resistant depression, but not acute depression registered high on the scale for cannot say answer. Using Student's t-test, patients with remitted depression registered higher on depression and social introversion scales, compared with normal controls. For pessimism and optimism, patients with treatment-resistant depression demonstrated similar changes to acutely depressed patients. Remitted depression patients showed lower optimism than normal controls by Student's t-test, even though these patients were deemed recovered from depression using HAM-D.The patients with remitted depression and treatment-resistant depression showed subtle alterations on the MMPI, which may explain the hidden psychological features in these cohorts.

  6. A Study of Remitted and Treatment-Resistant Depression Using MMPI and Including Pessimism and Optimism Scales

    Science.gov (United States)

    Suzuki, Masatoshi; Takahashi, Michio; Muneoka, Katsumasa; Sato, Koichi; Hashimoto, Kenji; Shirayama, Yukihiko

    2014-01-01

    Background The psychological aspects of treatment-resistant and remitted depression are not well documented. Methods We administered the Minnesota Multiphasic Personality Inventory (MMPI) to patients with treatment-resistant depression (n = 34), remitted depression (n = 25), acute depression (n = 21), and healthy controls (n = 64). Pessimism and optimism were also evaluated by MMPI. Results ANOVA and post-hoc tests demonstrated that patients with treatment-resistant and acute depression showed similarly high scores for frequent scale (F), hypochondriasis, depression, conversion hysteria, psychopathic device, paranoia, psychasthenia and schizophrenia on the MMPI compared with normal controls. Patients with treatment-resistant depression, but not acute depression registered high on the scale for cannot say answer. Using Student's t-test, patients with remitted depression registered higher on depression and social introversion scales, compared with normal controls. For pessimism and optimism, patients with treatment-resistant depression demonstrated similar changes to acutely depressed patients. Remitted depression patients showed lower optimism than normal controls by Student's t-test, even though these patients were deemed recovered from depression using HAM-D. Conclusions The patients with remitted depression and treatment-resistant depression showed subtle alterations on the MMPI, which may explain the hidden psychological features in these cohorts. PMID:25279466

  7. Oral ketamine for the treatment of pain and treatment-resistant depression†.

    Science.gov (United States)

    Schoevers, Robert A; Chaves, Tharcila V; Balukova, Sonya M; Rot, Marije Aan Het; Kortekaas, Rudie

    2016-02-01

    Recent studies with intravenous (i.v.) application of ketamine show remarkable but short-term success in patients with MDD. Studies in patients with chronic pain have used different ketamine applications for longer time periods. This experience may be relevant for psychiatric indications. To review the literature about the dosing regimen, duration, effects and side-effects of oral, intravenous, intranasal and subcutaneous routes of administration of ketamine for treatment-resistant depression and pain. Searches in PubMed with the terms 'oral ketamine', 'depression', 'chronic pain', 'neuropathic pain', 'intravenous ketamine', 'intranasal ketamine' and 'subcutaneous ketamine' yielded 88 articles. We reviewed all papers for information about dosing regimen, number of individuals who received ketamine, number of ketamine days per study, results and side-effects, as well as study quality. Overall, the methodological strength of studies investigating the antidepressant effects of ketamine was considered low, regardless of the route of administration. The doses for depression were in the lower range compared with studies that investigated analgesic use. Studies on pain suggested that oral ketamine may be acceptable for treatment-resistant depression in terms of tolerability and side-effects. Oral ketamine, given for longer time periods in the described doses, appears to be well tolerated, but few studies have systematically examined the longer-term negative consequences. The short- and longer-term depression outcomes as well as side-effects need to be studied with rigorous randomised controlled trials. © The Royal College of Psychiatrists 2016.

  8. Treatment resistance in potentially malignant disorders-'Nature' or 'Nurture'…?

    Science.gov (United States)

    Thomson, P J; Goodson, M L; Smith, D R

    2017-11-01

    Contemporary potentially malignant disorder management is based upon provisional histological diagnosis followed by interventional surgery to excise or ablate 'high-risk' mucosal lesions. Although the majority of patients achieve disease-free status post-treatment, others develop further or persistent disease unresponsive to intervention. A detailed, retrospective clinico-pathological review of treatment resistant potentially malignant lesions, from a 590 patient cohort treated by CO 2 laser surgery and followed for a mean of 7.3 years, was undertaken. Clinical outcome was determined at study census date (31 December 2014). A total of 87 patients (15%) exhibited PMD disease resistant to treatment: 34 (6%) became disease free following further treatment, whilst 53 (9%) had persistent disease despite intervention. Disease-free patients were younger, changed lesion appearance from erythroleukoplakia to leukoplakia (P = .004), developed further lesions at new sites, demonstrated reduction in dysplasia severity with time and required multiple treatments to achieve disease-free status (P = .0005). In contrast, persistent disease patients were older, male, often presented with proliferative verrucous leukoplakia (PVL) on gingival and alveolar sites, displayed less severe dysplasia initially and underwent laser ablation rather than excision (P = .027). Despite clinico-pathological profiling of treatment resistant patients, the precise inter-relationship between the inherent nature of potentially malignant disease and the external influence of treatment intervention remains obscure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Expression of EGFR Under Tumor Hypoxia: Identification of a Subpopulation of Tumor Cells Responsible for Aggressiveness and Treatment Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Hoogsteen, Ilse J., E-mail: i.hoogsteen@rther.umcn.nl [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Marres, Henri A.M.; Hoogen, Franciscus J.A. van den [Department of Otorhinolaryngology/Head-Neck Surgery, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Rijken, Paul F.J.W.; Lok, Jasper; Bussink, Johan; Kaanders, Johannes H.A.M. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

    2012-11-01

    Purpose: Overexpression of epidermal growth factor receptor (EGFR) and tumor hypoxia have been shown to correlate with worse outcome in several types of cancer including head-and-neck squamous cell carcinoma. Little is known about the combination and possible interactions between the two phenomena. Methods and Materials: In this study, 45 cases of histologically confirmed squamous cell carcinomas of the head and neck were analyzed. All patients received intravenous infusions of the exogenous hypoxia marker pimonidazole prior to biopsy. Presence of EGFR, pimonidazole binding, and colocalization between EGFR and tumor hypoxia were examined using immunohistochemistry. Results: Of all biopsies examined, respectively, 91% and 60% demonstrated EGFR- and pimonidazole-positive areas. A weak but significant association was found between the hypoxic fractions of pimonidazole (HFpimo) and EGFR fractions (F-EGFR) and between F-EGFR and relative vascular area. Various degrees of colocalization between hypoxia and EGFR were found, increasing with distance from the vasculature. A high fraction of EGFR was correlated with better disease-free and metastasis-free survival, whereas a high degree of colocalization correlated with poor outcome. Conclusions: Colocalization of hypoxia and EGFR was demonstrated in head-and-neck squamous cell carcinomas, predominantly at longer distances from vessels. A large amount of colocalization was associated with poor outcome, which points to a survival advantage of hypoxic cells that are also able to express EGFR. This subpopulation of tumor cells might be indicative of tumor aggressiveness and be partly responsible for treatment resistance.

  10. Early effects of modern electroconvulsive therapy on subjective memory in patients with mania or depression

    Science.gov (United States)

    Bag, Sevda; Canbek, Ozge; Atagun, Ilhan Murat; Kutlar, Tarik Mehmet

    2016-01-01

    Context: Although electroconvulsive therapy (ECT) is considered a very effective tool for the treatment of psychiatric diseases, memory disturbances are among the most important adverse effects. Aims: This study aimed to assess prospectively early subjective memory complaints in depressive and manic patients due to bilateral, brief-pulse ECT, at different stages of the treatment, compare the associations between psychiatric diagnosis, sociodemographic characteristics, and ECT characteristics. Settings and Design: This prospective study was done with patients undergoing ECT between November 2008 and April 2009 at a tertiary care psychiatry hospital of 2000 beds. Materials and Methods: A total of 140 patients, scheduled for ECT with a diagnosis of bipolar disorder (depressive or manic episode) or unipolar depression according to Diagnostic and Statistical Manual of Mental Disorders IV diagnostic criteria, were included in the study and invited to complete the Squire Subjective Memory Questionnaire (SSMQ) before ECT, after the first and third sessions and end of ECT treatment. Statistical Analysis: Mean values were compared with the Kruskal–Wallis test and comparison of the longitudinal data was performed with a nonparametric longitudinal data analysis method, F1_LD_F1 design. Results: SSMQ scores of the patients before ECT were zero. SSMQ scores showed a decrease after the first and third ECT sessions and before discharge, showing a memory disturbance after ECT and were significantly less severe in patients with mania in comparison to those with depression. Conclusions: These findings suggest an increasing degree of subjective memory complaints with bilateral brief-pulse ECT parallel to the increasing number of ECT sessions. PMID:27385854

  11. A new mouse model for mania shares genetic correlates with human bipolar disorder.

    Directory of Open Access Journals (Sweden)

    Michael C Saul

    Full Text Available Bipolar disorder (BPD is a debilitating heritable psychiatric disorder. Contemporary rodent models for the manic pole of BPD have primarily utilized either single locus transgenics or treatment with psychostimulants. Our lab recently characterized a mouse strain termed Madison (MSN that naturally displays a manic phenotype, exhibiting elevated locomotor activity, increased sexual behavior, and higher forced swimming relative to control strains. Lithium chloride and olanzapine treatments attenuate this phenotype. In this study, we replicated our locomotor activity experiment, showing that MSN mice display generationally-stable mania relative to their outbred ancestral strain, hsd:ICR (ICR. We then performed a gene expression microarray experiment to compare hippocampus of MSN and ICR mice. We found dysregulation of multiple transcripts whose human orthologs are associated with BPD and other psychiatric disorders including schizophrenia and ADHD, including: Epor, Smarca4, Cmklr1, Cat, Tac1, Npsr1, Fhit, and P2rx7. RT-qPCR confirmed dysregulation for all of seven transcripts tested. Using a novel genome enrichment algorithm, we found enrichment in genome regions homologous to human loci implicated in BPD in replicated linkage studies including homologs of human cytobands 1p36, 3p14, 3q29, 6p21-22, 12q24, 16q24, and 17q25. Using a functional network analysis, we found dysregulation of a gene system related to chromatin packaging, a result convergent with recent human findings on BPD. Our findings suggest that MSN mice represent a polygenic model for the manic pole of BPD showing much of the genetic systems complexity of the corresponding human disorder. Further, the high degree of convergence between our findings and the human literature on BPD brings up novel questions about evolution by analogy in mammalian genomes.

  12. Does recent mania affect response to antidepressants in bipolar disorder? A re-analysis of STEP-BD data.

    Science.gov (United States)

    Mousavi, Zahra; Johnson, Sheri; Li, Descartes

    2018-08-15

    One previous study suggested that the presence of a manic episode before bipolar depression is related to worse response to antidepressants. To examine this effect in a larger sample, we used data from the large, multi-site STEP-BD study. We hypothesized that among persons treated with antidepressants for bipolar depression, manic or mixed episodes before depression onset (as compared to euthymia) would predict lower rate of recovery, more sustained depressive symptoms and higher rate of switching into mania/hypomania after antidepressant treatment of bipolar depression. 320 participants were available for analyses (140 male) diagnosed with bipolar I, bipolar II, cyclothymia, bipolar disorder not otherwise specified, or schizoaffective disorder bipolar subtype. Patients were randomly assigned to 3 treatment randomization strata (placebo, bupropion, and paroxetine) as adjuncts to mood stabilizers. Analyses were conducted to examine the effect of episode status before the depressive episode on the degree of change in depressive symptoms at 3 and 6 months, the likelihood of depression recovery and the likelihood of anti-depressant induced switching. Presence of a manic episode before depression in patients with bipolar disorder did not significantly predict response to antidepressants. The study was limited by a high rate of attrition, and consideration of only two antidepressant medications. Our findings are in agreement with other past studies suggesting that mania and depression may operate separately for those with bipolar disorder, with differential predictors of the onset and offset of mania versus depression. Future directions may consider vulnerability for these episodes separately. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Symptom predictors of response to electroconvulsive therapy in older patients with treatment-resistant depression

    Directory of Open Access Journals (Sweden)

    Tominaga K

    2011-07-01

    Full Text Available Keiichiro Tominaga¹, Mioto Okazaki¹, Hisashi Higuchi¹, Itaru Utagawa¹, Etsuko Nakamura², Noboru Yamaguchi¹¹Department of Neuropsychiatry, St Marianna University School of Medicine, Miyamae-ku, Kawasaki City, Kanagawa, ²Tsurukawa Sanatorium Hospital, Machida City, Tokyo, JapanBackground: Electroconvulsive therapy (ECT has been used for treatment-resistant depression. However, predictors of response to ECT have not been adequately studied using the Montgomery and Åsberg Depression Rating Scale, especially in older patients with treatment-resistant depression.Methods: This study included 18 Japanese patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision criteria for a diagnosis of major depressive disorder or bipolar disorder with a current major depressive episode, and met the definition of treatment-resistant depression outlined by Thase and Rush, scoring ≥21 on the Montgomery and Åsberg Depression Rating Scale. The three-factor model of the Montgomery and Åsberg Depression Rating Scale was used for analysis. Factor 1 was defined by three items, factor 2 by four items, and factor 3 by three items, representing dysphoria, retardation, and vegetative symptoms, respectively. ECT was performed twice a week for a total of six sessions using a Thymatron System IV device with the brief pulse technique. Clinical responses were defined on the basis of a ≥50% decrease in total pretreatment Montgomery and Åsberg Depression Rating Scale scores.Results: The mean pretreatment factor 2 score for responders (n = 7 was significantly lower than that for nonresponders (n = 11. Furthermore, a significant difference in mean factor 3 score between responders and nonresponders was observed one week after six sessions of ECT, indicating a time lag of response. No significant differences were observed for age, number of previous episodes, and duration of the current episode between responders and

  14. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.

    Science.gov (United States)

    Carhart-Harris, Robin L; Bolstridge, Mark; Rucker, James; Day, Camilla M J; Erritzoe, David; Kaelen, Mendel; Bloomfield, Michael; Rickard, James A; Forbes, Ben; Feilding, Amanda; Taylor, David; Pilling, Steve; Curran, Valerie H; Nutt, David J

    2016-07-01

    Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression. In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797. Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1

  15. Treatment-Resistant Major Depression: Rationale for NMDA Receptors as Targets and Nitrous Oxide as Therapy

    Science.gov (United States)

    Zorumski, Charles F.; Nagele, Peter; Mennerick, Steven; Conway, Charles R.

    2015-01-01

    Major depressive disorder (MDD) remains a huge personal and societal encumbrance. Particularly burdensome is a virulent subtype of MDD, treatment resistant major depression (TMRD), which afflicts 15–30% of MDD patients. There has been recent interest in N-methyl-d-aspartate receptors (NMDARs) as targets for treatment of MDD and perhaps TMRD. To date, most pre-clinical and clinical studies have focused on ketamine, although psychotomimetic and other side effects may limit ketamine’s utility. These considerations prompted a recent promising pilot clinical trial of nitrous oxide, an NMDAR antagonist that acts through a mechanism distinct from that of ketamine, in patients with severe TRMD. In this paper, we review the clinical picture of TRMD as a subtype of MDD, the evolution of ketamine as a fast-acting antidepressant, and clinical and basic science studies supporting the possible use of nitrous oxide as a rapid antidepressant. PMID:26696909

  16. Pilot Randomized Controlled Trial of Titrated Subcutaneous Ketamine in Older Patients with Treatment-Resistant Depression.

    Science.gov (United States)

    George, Duncan; Gálvez, Verònica; Martin, Donel; Kumar, Divya; Leyden, John; Hadzi-Pavlovic, Dusan; Harper, Simon; Brodaty, Henry; Glue, Paul; Taylor, Rohan; Mitchell, Philip B; Loo, Colleen K

    2017-11-01

    To assess the efficacy and safety of subcutaneous ketamine for geriatric treatment-resistant depression. Secondary aims were to examine if repeated treatments were safe and more effective in inducing or prolonging remission than a single treatment. In this double-blind, controlled, multiple-crossover study with a 6-month follow-up (randomized controlled trial [RCT] phase), 16 participants (≥60 years) with treatment-resistant depression who relapsed after remission or did not remit in the RCT were administered an open-label phase. Up to five subcutaneous doses of ketamine (0.1, 0.2, 0.3, 0.4, and 0.5 mg/kg) were administered in separate sessions (≥1 week apart), with one active control (midazolam) randomly inserted (RCT phase). Twelve ketamine treatments were given in the open-label phase. Mood, hemodynamic, and psychotomimetic outcomes were assessed by blinded raters. Remitters in each phase were followed for 6 months. Seven of 14 RCT-phase completers remitted with ketamine treatment. Five remitted at doses below 0.5 mg/kg. Doses ≥ 0.2 mg/kg were significantly more effective than midazolam. Ketamine was well tolerated. Repeated treatments resulted in higher likelihood of remission or longer time to relapse. Results provide preliminary evidence for the efficacy and safety of ketamine in treating elderly depressed. Dose titration is recommended for optimizing antidepressant and safety outcomes on an individual basis. Subcutaneous injection is a practical method for giving ketamine. Repeated treatments may improve remission rates (clinicaltrials.gov; NCT01441505). Copyright © 2017 American Association for Geriatric Psychiatry. All rights reserved.

  17. Laser acupuncture therapy in patients with treatment-resistant temporomandibular disorders.

    Directory of Open Access Journals (Sweden)

    Wen-Long Hu

    Full Text Available To investigate the clinical effects of laser acupuncture therapy for temporomandibular disorders (TMD after ineffective previous treatments.A retrospective observational study was conducted in 29 treatment-resistant TMD patients (25 women, 4 men; age range, 17-67 years. Subjects were treated 3 times per week for 4 weeks with the Handylaser Trion (GaAlAs laser diode, 810 nm, 150 mW, pulsed waves, which delivered 0.375 J of energy (5 s to ST7, ST6, and LI4 and 3 J (40 s to each Ashi point, 7.5-26.25 J/cm2 in total. The visual analog scale (VAS and maximal mouth opening (MMO were evaluated before and after treatment.VAS analysis showed that the patients were free of pain at rest (endpoint after 5.90±6.08 sessions of laser acupuncture for acute TMD and after 16.21±17.98 sessions for chronic TMD. The VAS score on palpation of the temporomandibular joint reduced to 0.30±0.67 for patients with acute TMD (p = 0.005 and to 0.47±0.84 for those with chronic TMD (p<0.001. The MMO significantly increased in patients with acute TMD (7.80±5.43 mm, p = 0.008 and in patients with chronic TMD (15.58±7.87 mm, p<0.001.Our study shows that laser acupuncture therapy improves the symptoms of treatment-resistant TMD. Further studies with a more appropriate design, involving long-term follow-up examinations in a larger patient sample, are needed to evaluate its efficacy.

  18. Psychosocial functioning in patients with treatment-resistant depression after group cognitive behavioral therapy

    Directory of Open Access Journals (Sweden)

    Kunisato Yoshihiko

    2010-03-01

    Full Text Available Abstract Background Although patients with Treatment Resistant Depression (TRD often have impaired social functioning, few studies have investigated the effectiveness of psychosocial treatment for these patients. We examined whether adding group cognitive behavioral therapy (group-CBT to medication would improve both the depressive symptoms and the social functioning of patient with mild TRD, and whether any improvements would be maintained over one year. Methods Forty-three patients with TRD were treated with 12 weekly sessions of group-CBT. Patients were assessed with the Global Assessment of Functioning scale (GAF, the 36-item Short-Form Health Survey (SF-36, the Hamilton Rating Scale for Depression (HRSD, the Dysfunctional Attitudes Scale (DAS, and the Automatic Thought Questionnaire-Revised (ATQ-R at baseline, at the termination of treatment, and at the 12-month follow-up. Results Thirty-eight patients completed treatment; five dropped out. For the patients who completed treatment, post-treatment scores on the GAF and SF-36 were significantly higher than baseline scores. Scores on the HRSD, DAS, and ATQ-R were significantly lower after the treatment. Thus patients improved on all measurements of psychosocial functioning and mood symptoms. Twenty patients participated in the 12-month follow-up. Their improvements for psychosocial functioning, depressive symptoms, and dysfunctional cognitions were sustained at 12 months following the completion of group-CBT. Conclusions These findings suggest a positive effect that the addition of cognitive behavioural group therapy to medication on depressive symptoms and social functioning of mildly depressed patients, showing treatment resistance.

  19. Cortisol Modulation by Ayahuasca in Patients With Treatment Resistant Depression and Healthy Controls

    Directory of Open Access Journals (Sweden)

    Ana C. de Menezes Galvão

    2018-05-01

    Full Text Available Major depression is a highly prevalent mood disorder, affecting about 350 million people, and around 30% of the patients are resistant to currently available antidepressant medications. Recent evidence from a randomized controlled trial (RCT supports the rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression. The aim of this study was to explore the effect of ayahuasca on plasma cortisol and awakening salivary cortisol response, in the same group of treatment-resistant patients (MD and in healthy volunteers (C. Subjects received a single dose of ayahuasca or placebo (dosing session, and both plasma and awakening salivary cortisol response were measured at baseline (before dosing session and 48 h after the dosing session. Baseline assessment (D0 showed blunted awakening salivary cortisol response and hypocortisolemia in patients, with respect to healthy controls. Salivary cortisol was also measured during dosing session, and we observed higher increases for both C and MD that ingested ayahuasca than placebo. After 48 h from the dosing session with ayahuasca, patients' awakening salivary cortisol response is similar to the ones detected in controls. No significant changes in plasma cortisol levels were observed 48 h after the sessions. Therefore, these findings point to new evidence on the modulation of salivary cortisol levels as a result of an ayahuasca session, both in healthy and depressive volunteers. Considering that cortisol acts in regulation of distinct physiological pathways, emotional and cognitive processes, it is assumed to be critically involved to the etiology of depression and its regulation seems to be important for the treatment and remission of major depression, ayahuasca use as antidepressant should be further investigated. Moreover, this study highlights the importance of psychedelics in the treatment of human mental disorders.

  20. A clinical risk stratification tool for predicting treatment resistance in major depressive disorder.

    Science.gov (United States)

    Perlis, Roy H

    2013-07-01

    Early identification of depressed individuals at high risk for treatment resistance could be helpful in selecting optimal setting and intensity of care. At present, validated tools to facilitate this risk stratification are rarely used in psychiatric practice. Data were drawn from the first two treatment levels of a multicenter antidepressant effectiveness study in major depressive disorder, the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) cohort. This cohort was divided into training, testing, and validation subsets. Only clinical or sociodemographic variables available by or readily amenable to self-report were considered. Multivariate models were developed to discriminate individuals reaching remission with a first or second pharmacological treatment trial from those not reaching remission despite two trials. A logistic regression model achieved an area under the receiver operating characteristic curve exceeding .71 in training, testing, and validation cohorts and maintained good calibration across cohorts. Performance of three alternative models with machine learning approaches--a naïve Bayes classifier and a support vector machine, and a random forest model--was less consistent. Similar performance was observed between more and less severe depression, men and women, and primary versus specialty care sites. A web-based calculator was developed that implements this tool and provides graphical estimates of risk. Risk for treatment resistance among outpatients with major depressive disorder can be estimated with a simple model incorporating baseline sociodemographic and clinical features. Future studies should examine the performance of this model in other clinical populations and its utility in treatment selection or clinical trial design. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Young Mania Rating Scale: how to interpret the numbers? Determination of a severity threshold and of the minimal clinically significant difference in the EMBLEM cohort.

    Science.gov (United States)

    Lukasiewicz, Michael; Gerard, Stephanie; Besnard, Adeline; Falissard, Bruno; Perrin, Elena; Sapin, Helene; Tohen, Mauricio; Reed, Catherine; Azorin, Jean-Michel

    2013-03-01

    The aim of this analysis was to identify Young Mania Rating Scale (YMRS) meaningful benchmarks for clinicians (severity threshold, minimal clinically significant difference [MCSD]) using the Clinical Global Impressions Bipolar (CGI-BP) mania scale, to provide a clinical perspective to randomized clinical trials (RCTs) results. We used the cohort of patients with acute manic/mixed state of bipolar disorders (N = 3459) included in the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) study. A receiver-operating characteristic analysis was performed on randomly selected patients to determine the YMRS optimal severity threshold with CGI-BP mania score ≥ "Markedly ill" defining severity. The MCSD (clinically meaningful change in score relative to one point difference in CGI-BP mania for outcome measures) of YMRS, was assessed with a linear regression on baseline data. At baseline, YMRS mean score was 26.4 (±9.9), CGI-BP mania mean score was 4.8 (±1.0) and 61.7% of patients had a score ≥ 5. The optimal YMRS severity threshold of 25 (positive predictive value [PPV] = 83.0%; negative predictive value [NPV] = 66.0%) was determined. In this cohort, a YMRS score of 20 (typical cutoff for RCTs inclusion criteria) corresponds to a PPV of 74.6% and to a NPV of 77.6%, meaning that the majority of patients included would be classified as severely ill. The YMRS minimal clinically significant difference was 6.6 points. Copyright © 2013 John Wiley & Sons, Ltd.

  2. Comparing premodern melancholy/mania and modern trauma: an argument in favor of historical experiences of trauma.

    Science.gov (United States)

    Trembinski, Donna

    2011-02-01

    Historians and psychiatrists have repeatedly looked to both real and imagined individuals of the past, like Achilles and Samuel Pepys, and found evidence that they were suffering from symptoms of trauma and posttraumatic stress disorder. The assumptions that allow such historical "diagnoses" have, however, recently been called into question by philosophers such as lan Hacking, anthropologists like Allan Young and psychiatrists such as Patrick Bracken. These scholars have all suggested in various ways that experiences of trauma could not have occurred until the diagnosis of trauma and its symptoms had been formalized and the language of trauma had been developed in the late 19th century. This article attempts to resolve this bifurcation of opinion on the universality of the mind and historical experiences of trauma in two ways. First, it argues for the necessity of applying modern categories of analysis to further present understandings of the past. Second, it considers discussions of"melancholia" and "mania" in premodern medical literature and argues that there are enough similarities between the causes and symptoms of these premodern disorders and modern trauma to suggest that experiences of trauma may not be wholly culturally bound to the modern world, as the above scholars have suggested. While melancholy or mania cannot simply be understood as premodern names for trauma, and it is not always correct to "diagnose" a premodern person who exhibits symptoms of these illnesses with trauma, such an assumption is not always ahistorical or incorrect either.

  3. Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression.

    Science.gov (United States)

    Roseman, Leor; Nutt, David J; Carhart-Harris, Robin L

    2017-01-01

    Introduction: It is a basic principle of the "psychedelic" treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED) (similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would have negligible predictive value. Materials and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10 and 25 mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25 mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-Time and DED-by-Time interactions were the primary outcomes of interest. Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each time point compared to baseline were all significant ( p = 0.002 and p = 0.003, respectively, for main effects), confirming our main hypothesis. Furthermore, Pearson's correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions of the ASC ( p

  4. Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression

    Directory of Open Access Journals (Sweden)

    Leor Roseman

    2018-01-01

    Full Text Available Introduction: It is a basic principle of the “psychedelic” treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD. In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN (sharing features with mystical-type experience and Dread of Ego Dissolution (DED (similar to anxiety would predict long-term positive outcomes, whereas sensory perceptual effects would have negligible predictive value.Materials and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10 and 25 mg psilocybin. The Altered States of Consciousness (ASC questionnaire was used to assess the quality of experiences in the 25 mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable, with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-Time and DED-by-Time interactions were the primary outcomes of interest.Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable, the main effect and the effects at each time point compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects, confirming our main hypothesis. Furthermore, Pearson's correlation of OBN with QIDS-SR (5 weeks was specific compared to perceptual dimensions of the

  5. Basal exposure therapy: A new approach for treatment resistant patients with severe and comorbid mental disorders

    Directory of Open Access Journals (Sweden)

    Didrik Heggdal

    2016-12-01

    Full Text Available New treatment approaches are needed for patients with severe and composite mental disorders who appear resistant to conventional treatments. Such treatment resistant patients often have diagnoses of psychotic or bipolar disorders or severe personality disorders and comorbid conditions. Here we evaluate Basal Exposure Therapy (BET, a novel ward-integrated psychotherapeutic approach for these patients. Central to BET is the conceptualization of undifferentiated existential fear as basic to the patients’ problem, exposure to this fear, and the therapeutic platform Complementary External Regulation (CER which integrates and governs the totality of interventions throughout the treatment process. BET is administered at a locked-door ward with six patient beds and 13.5 full time employees, including a psychiatrist and two psychologists. Thirty-eight patients who had completed BET were included, all but two being female, mean age 29.9 years. Fourteen patients had a diagnosis of schizophrenia or schizoaffective disorder (F20/25, eight had bipolar disorder or recurrent depressive disorder (F31/33, eight had diagnoses in the F40-49 domain (anxiety, stress, dissociation, five were diagnosed with emotionally unstable personality disorder (F60.3, and three patients had other diagnoses. Twenty of the patients (53% had more than one ICD-10 diagnosis. Average treatment time in BET was 13 months, ranging from 2 to 72 months. Time-series data show significant improvements in symptoms and functioning from enrolment to discharge, with effect sizes at 0.76 for the Dissociation Experience Scale, 0.93 for the Brief Symptom Inventory, 1.47 for the Avoidance and Action Questionnaire, and 1.42 and 1.56, respectively for the functioning and symptom subscales of the Global Assessment of Functioning Scale. In addition, the patients used significantly less antiepileptic, antipsychotic, anxiolytic and antidepressant medications at discharge than at treatment enrolment

  6. Acute Frontal Lobe Dysfunction Following Prefrontal Low-Frequency Repetitive Transcranial Magnetic Stimulation in a Patient with Treatment-Resistant Depression

    Directory of Open Access Journals (Sweden)

    Guilhem Carle

    2017-05-01

    Full Text Available The potential of repetitive transcranial magnetic stimulation (rTMS to treat numerous neurological and psychiatric disorders has been thoroughly studied for the last two decades. Here, we report for the first time, the case of a 65-year-old woman suffering from treatment-resistant depression who developed an acute frontal lobe syndrome following eight sessions of low-frequency rTMS (LF-rTMS to the right dorsolateral prefrontal cortex while also treated with sertraline and mianserin. The pathophysiological mechanisms underlying such an unexpected acute frontal lobe dysfunction are discussed in relation to the therapeutic use of LF-rTMS in combination with pharmacotherapy in depressed patients.

  7. Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression : a pilot randomized, placebo-controlled continuation trial

    NARCIS (Netherlands)

    Mathew, S.J.; Murrough, J.W.; Aan het Rot, M.; Collins, K.A.; Reich, D.L.; Charney, D.S.

    2010-01-01

    The N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine may have rapid, albeit transient, antidepressant properties. This study in patients with treatment-resistant major depression (TRD) aimed to (1) replicate the acute efficacy of single-close intravenous (i.v.) ketamine; (2) test

  8. Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

    NARCIS (Netherlands)

    Murrough, James W.; Perez, Andrew M.; Pillemer, Sarah; Stern, Jessica; Parides, Michael K.; aan het Rot, Marije; Collins, Katherine A.; Mathew, Sanjay J.; Charney, Dennis S.; Iosifescu, Dan V.

    2013-01-01

    Background: Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine

  9. The Bi-Directional Relationship between Parent-Child Conflict and Treatment Outcome in Treatment-Resistant Adolescent Depression

    Science.gov (United States)

    Rengasamy, Manivel; Mansoor, Brandon M.; Hilton, Robert; Porta, Giovanna; He, Jiayan; Emslie, Graham J.; Mayes, Taryn; Clarke, Gregory N.; Wagner, Karen Dineen; Keller, Martin B.; Ryan, Neal D.; Birmaher, Boris; Shamseddeen, Wael; Asarnow, Joan Rosenbaum; Brent, David A.

    2013-01-01

    Objective: To examine the bidirectional relationship between parent-child discord and treatment outcome for adolescent treatment-resistant depression. Method: Depressed youth who had not responded to an adequate course of a selective serotonin reuptake inhibitor (SSRI) were randomized to either a switch to another SSRI or venlafaxine, with or…

  10. The Dutch Measure for quantification of Treatment Resistance in Depression (DM-TRD) : an extension of the Maudsley Staging Method

    NARCIS (Netherlands)

    Peeters, Frenk P. M. L.; Ruhe, Henricus G.; Wichers, Marieke; Abidi, Latifa; Kaub, Karin; van der Lande, H. Josephine; Spijker, Jan; Huibers, Marcus J. H.; Schene, Aart H.

    2016-01-01

    Background: Treatment resistant depression (TRD) is common in daily practice. An empirical, widely accepted and applicable measure to quantify TRD is lacking. Previously, the Maudsley Staging Method (MSM) showed good validity. We aimed to improve the MSM by refining and extending its items resulting

  11. Annotating MYC Status in Treatment-Resistant Metastatic Castration-Resistant Prostate Cancer With Gallium-68 Citrate PET

    Science.gov (United States)

    2017-09-01

    which avidly binds to circulating transferrin) labeled transferrin (Tf) can detect MYC-positive prostate cancer tumors, since the transferrin receptor ...Castration-Resistant Prostate Cancer with Androgen Receptor - Axis Imaging. Journal of nuclear medicine : official publication, Society of Nuclear...AWARD NUMBER: W81XWH-16-1-0469 TITLE: Annotating MYC Status in Treatment-Resistant Metastatic Castration- Resistant Prostate Cancer With

  12. Risperidone and Divalproex Differentially Engage the Fronto-Striato-Temporal Circuitry in Pediatric Mania: A Pharmacological Functional Magnetic Resonance Imaging Study

    Science.gov (United States)

    Pavuluri, Mani N.; Passarotti, Alessandra M.; Fitzgerald, Jacklynn M.; Wegbreit, Ezra; Sweeney, John A.

    2012-01-01

    Objective: The current study examined the impact of risperidone and divalproex on affective and working memory circuitry in patients with pediatric bipolar disorder (PBD). Method: This was a six-week, double-blind, randomized trial of risperidone plus placebo versus divalproex plus placebo for patients with mania (n = 21; 13.6 [plus or minus] 2.5…

  13. Early Nonresponse in the Antipsychotic Treatment of Acute Mania : A Criterion for Reconsidering Treatment? Results From an Individual Patient Data Meta-Analysis

    NARCIS (Netherlands)

    Welten, Carlijn C M; Koeter, Maarten W J; Wohlfarth, Tamar D; Storosum, Jitschak G; van den Brink, Wim; Gispen-de Wied, Christine C; Leufkens, Hubert G M; Denys, Damiaan A J P

    OBJECTIVE: To investigate whether early nonresponse to antipsychotic treatment of acute mania predicts treatment failure and, if so, to establish the best definition or criterion of an early nonresponse. DATA SOURCES: Short-term efficacy studies assessing antipsychotics that were submitted to the

  14. Selective deficits in semantic verbal fluency in patients with a first affective episode with psychotic symptoms and a positive history of mania.

    LENUS (Irish Health Repository)

    Kravariti, Eugenia

    2009-05-01

    Neurocognitive dysfunction is likely to represent a trait characteristic of bipolar disorder, but the extent to which it comprises \\'core\\' deficits as opposed to those secondary to longstanding illness or intellectual decline is unclear. We investigated neuropsychological performance in an epidemiologically derived sample of patients with a first affective episode with psychotic symptoms and a positive history of mania, compared to community controls.

  15. Three dysconnectivity patterns in treatment-resistant schizophrenia patients and their unaffected siblings.

    Science.gov (United States)

    Wang, Jicai; Cao, Hongbao; Liao, Yanhui; Liu, Weiqing; Tan, Liwen; Tang, Yanqing; Chen, Jindong; Xu, Xiufeng; Li, Haijun; Luo, Chunrong; Liu, Chunyu; Ries Merikangas, Kathleen; Calhoun, Vince; Tang, Jinsong; Shugart, Yin Yao; Chen, Xiaogang

    2015-01-01

    Among individuals diagnosed with schizophrenia, approximately 20%-33% are recognized as treatment-resistant schizophrenia (TRS) patients. These TRS patients suffer more severely from the disease but struggle to benefit from existing antipsychotic treatments. A few recent studies suggested that schizophrenia may be caused by impaired synaptic plasticity that manifests as functional dysconnectivity in the brain, however, few of those studies focused on the functional connectivity changes in the brains of TRS groups. In this study, we compared the whole brain connectivity variations in TRS patients, their unaffected siblings, and healthy controls. Connectivity network features between and within the 116 automated anatomical labeling (AAL) brain regions were calculated and compared using maps created with three contrasts: patient vs. control, patient vs. sibling, and sibling vs. To evaluate the predictive power of the selected features, we performed a multivariate classification approach. We also evaluated the influence of six important clinical measures (e.g. age, education level) on the connectivity features. This study identified abnormal significant connectivity changes of three patterns in TRS patients and their unaffected siblings: 1) 69 patient-specific connectivity (PCN); 2) 102 shared connectivity (SCN); and 3) 457 unshared connectivity (UCN). While the first two patterns were widely reported by previous non-TRS specific studies, we were among the first to report widespread significant connectivity differences between TRS patient groups and their healthy sibling groups. Observations of this study may provide new insights for the understanding of the neurophysiological mechanisms of TRS.

  16. Evaluation of the efficacy of the continuation electroconvulsive therapy in treatment-resistant schizophrenia

    Directory of Open Access Journals (Sweden)

    Isil Gogcegoz Gul

    2014-08-01

    Full Text Available Background : Electroconvulsive therapy (ECT has been reported being a safe and effective treatment in schizophrenia. However, there are a limited number of studies assessing continuation ECT utilization in patients with schizophrenia giving partial response to pharmacological treatment. Objective : The aim of this study is to evaluate the effectiveness of continuation ECT in preventing relapse in patients with treatment-resistant schizophrenia. Methods : In this retrospective analysis, schizophrenia patients (n = 73 were defined in three groups such as patients who received only AP treatment (only AP, patients who received acute ECT only during hospitalization (aECT+AP, patients who received acute ECT and continuation ECT (a-cECT+AP. Three groups were compared according to positive and negative syndrome scale (PANSS and Brief Psychiatric Rating Scale (BPRS scores. Results : As per comparison of only AP group, aECT+AP group and a+cECT+AP groups in terms of after discharge PANSS and after discharge BPRS scores for 1st month, 3rd month and 6th month; 3rd and 6th month’s PANSS scores of a+cECT+AP group were statistically significantly lower than other two groups. Discussion : Although this study suffers the limitations of retrospective medical chart analysis, results suggest that, in patients with a diagnosis of schizophrenia who have responded to an acute course of ECT, continuation ECT in combination with antipsychotics is more effective than antipsychotics alone in preventing relapse.

  17. Predictors of response to combined wake and light therapy in treatment-resistant inpatients with depression

    DEFF Research Database (Denmark)

    Kragh, Mette; Roj Larsen, Erik; Martiny, Klaus

    2018-01-01

    There is growing evidence for combined chronotherapeutic interventions as adjunctive treatments for major depression. However, as the treatments can be demanding, we need to identify predictors of response. This study aimed to describe predictors of response, remission and deterioration in the sh......There is growing evidence for combined chronotherapeutic interventions as adjunctive treatments for major depression. However, as the treatments can be demanding, we need to identify predictors of response. This study aimed to describe predictors of response, remission and deterioration...... in the short-term phase, as well as predictors of long-term response. The predictors investigated were gender, type of depression, severity of depression, treatment resistance, quetiapine use, general self-efficacy, educational level and positive diurnal variation. Follow-up data from 27 inpatients...... with moderate-to-severe depression participating in a chronotherapeutic intervention were analysed. As a supplement to standard treatment, they completed 3 wake therapy sessions in the first week, 30 min daily light treatment and sleep-time stabilisation in the entire 9-week study period. Patients had...

  18. Routine Treatment-Resistant Clostridium difficile Infection during Recovery from Myxedema

    Directory of Open Access Journals (Sweden)

    Jan K. Adamski

    2017-11-01

    Full Text Available Development of the extreme form of hypothyroidism defined as myxedema is very rare. Acute symptoms and their management have been described in detail previously. However, not much attention has been devoted to therapeutic challenges that are faced in the recovery phase of the treatment, especially pertaining to the gastrointestinal system. The link between myxedema and the appearance of severe Clostridium difficile infection (CDI has not been established so far. A 61-year-old woman with no significant medical record was admitted to hospital because of infected heel pressure and thyroid dysfunction. A week later, due to hypothermia, hypotension, and unconsciousness, she was transferred to the intensive care unit. The clinical picture and the results of laboratory tests confirmed diagnosis of myxedema. After the introduction of resuscitative measures and hormonal substitution, patient’s condition stabilized within 10 days. Due to concomitant sepsis, initially piperacillin/tazobactam and later cefuroxime were administered. After 20 days of antibiotic therapy, the patient developed CDI that was resistant to the routine mode of treatment. The clinical recovery was achieved only after a fecal microbiota transplantation procedure. The function of the digestive tract in myxedema is disturbed by gastric achlorydia and reduced peristalsis, which in turn can predispose the small intestine to overgrowth of bacteria. The use of antibiotics can additionally decrease the intestinal bacterial diversity, favoring the overgrowth of Clostridium difficile. The authors conclude that myxedema may increase the likelihood of a treatment-resistant form of CDI that requires the implementation of fecal microbiota transplantation.

  19. Deficits in Regional Cerebral Blood Flow on Brain SPECT Predict Treatment Resistant Depression.

    Science.gov (United States)

    Amen, Daniel G; Taylor, Derek V; Meysami, Somayeh; Raji, Cyrus A

    2018-03-22

    Depression remains an important risk factor for Alzheimer's disease, yet few neuroimaging biomarkers are available to identify treatment response in depression. To analyze and compare functional perfusion neuroimaging in persons with treatment resistant depression (TRD) compared to those experiencing full remission. A total of 951 subjects from a community psychiatry cohort were scanned with perfusion single photon emission computed tomography (SPECT) of the brain in both resting and task related settings. Of these, 78% experienced either full remission (n = 506) or partial remission (n = 237) and 11% were minimally responsive (n = 103) or non-responsive (11%. n = 106). Severity of depression symptoms were used to define these groups with changes in the Beck Depression Inventory prior to and following treatment. Voxel-based analyses of brain SPECT images from full remission compared to the worsening group was conducted with the statistical parametric mapping software, version 8 (SPM 8). Multiple comparisons were accounted for with a false discovery rate (p <  0.001). Persons with depression that worsened following treatment had reduced cerebral perfusion compared to full remission in the multiple regions including the bilateral frontal lobes, right hippocampus, left precuneus, and cerebellar vermis. Such differences were observed on both resting and concentration SPECT scans. Our findings identify imaging-based biomarkers in persons with depression related to treatment response. These findings have implications in understanding both depression to prognosis and its role as a risk factor for dementia.

  20. Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms.

    Science.gov (United States)

    Carhart-Harris, Robin L; Roseman, Leor; Bolstridge, Mark; Demetriou, Lysia; Pannekoek, J Nienke; Wall, Matthew B; Tanner, Mark; Kaelen, Mendel; McGonigle, John; Murphy, Kevin; Leech, Robert; Curran, H Valerie; Nutt, David J

    2017-10-13

    Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other 'psychedelics' yet were related to clinical outcomes. A 'reset' therapeutic mechanism is proposed.

  1. Striatal dopamine D2/3 receptor availability in treatment resistant depression.

    Directory of Open Access Journals (Sweden)

    Bart P de Kwaasteniet

    Full Text Available Several studies demonstrated improvement of depressive symptoms in treatment resistant depression (TRD after administering dopamine agonists which suggest abnormal dopaminergic neurotransmission in TRD. However, the role of dopaminergic signaling through measurement of striatal dopamine D(2/3 receptor (D2/3R binding has not been investigated in TRD subjects. We used [(123I]IBZM single photon emission computed tomography (SPECT to investigate striatal D2/3R binding in TRD. We included 6 severe TRD patients, 11 severe TRD patients on antipsychotics (TRD AP group and 15 matched healthy controls. Results showed no significant difference (p = 0.75 in striatal D2/3R availability was found between TRD patients and healthy controls. In the TRD AP group D2/3R availability was significantly decreased (reflecting occupancy of D2/3Rs by antipsychotics relative to TRD patients and healthy controls (p<0.001 but there were no differences in clinical symptoms between TRD AP and TRD patients. This preliminary study therefore does not provide evidence for large differences in D2/3 availability in severe TRD patients and suggests this TRD subgroup is not characterized by altered dopaminergic transmission. Atypical antipsychotics appear to have no clinical benefit in severe TRD patients who remain depressed, despite their strong occupancy of D2/3Rs.

  2. Effectiveness of electroconvulsive therapy in patients with treatment resistant schizophrenia: A retrospective study.

    Science.gov (United States)

    Grover, Sandeep; Chakrabarti, Subho; Hazari, Nandita; Avasthi, Ajit

    2017-03-01

    This study aimed to evaluate the effectiveness of electroconvulsive therapy (ECT) among patients with treatment resistant schizophrenia (TRS). Records of patients who had received ECT were reviewed to identify patients with TRS who were administered ECT in combination with clozapine. Socio-demographic, clinical data and ECT details were extracted. The most common diagnosis was of paranoid schizophrenia (49%) followed by undifferentiated schizophrenia (36%). A-fifth (22%) of the patients were judged to have poor response to clozapine. The mean number of ECTs given were 13.97 (SD-7.67) and mean clozapine dose was 287.5mgs/day (SD-100.1). About two-thirds (63%) of the patients showed >30% reduction in scores on different symptom-rating scales with combined use of clozapine and ECT. Among clozapine non-responders, approximately 69% responded to the combination. Post-ECT rise in blood pressure was the most common side effect (16.9%) followed by prolonged seizures (7%). Long-term follow-up data was available for 47 out of the 59 patients. More than two-third (N=34; 72%) followed-up for an average of 30 months (SD 32.3; range: 1-120), maintained well with continued clozapine treatment. To conclude, results of this study further endorse the effectiveness, safety and long-term benefits of the clozapine-ECT combination in TRS and clozapine-refractory schizophrenia. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  3. The Change in Facial Emotion Recognition Ability in Inpatients with Treatment Resistant Schizophrenia After Electroconvulsive Therapy.

    Science.gov (United States)

    Dalkıran, Mihriban; Tasdemir, Akif; Salihoglu, Tamer; Emul, Murat; Duran, Alaattin; Ugur, Mufit; Yavuz, Ruhi

    2017-09-01

    People with schizophrenia have impairments in emotion recognition along with other social cognitive deficits. In the current study, we aimed to investigate the immediate benefits of ECT on facial emotion recognition ability. Thirty-two treatment resistant patients with schizophrenia who have been indicated for ECT enrolled in the study. Facial emotion stimuli were a set of 56 photographs that depicted seven basic emotions: sadness, anger, happiness, disgust, surprise, fear, and neutral faces. The average age of the participants was 33.4 ± 10.5 years. The rate of recognizing the disgusted facial expression increased significantly after ECT (p facial expressions (p > 0.05). After the ECT, the time period of responding to the fear and happy facial expressions were significantly shorter (p Facial emotion recognition ability is an important social cognitive skill for social harmony, proper relation and living independently. At least, the ECT sessions do not seem to affect facial emotion recognition ability negatively and seem to improve identifying disgusted facial emotion which is related with dopamine enriched regions in brain.

  4. Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression

    Directory of Open Access Journals (Sweden)

    Alik S. Widge

    2018-03-01

    Full Text Available Major depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial “failures” are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this “valley of disillusionment,” DBS may be nearing a “slope of enlightenment.” Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI, the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care.

  5. Three dysconnectivity patterns in treatment-resistant schizophrenia patients and their unaffected siblings

    Directory of Open Access Journals (Sweden)

    Jicai Wang

    2015-01-01

    Full Text Available Among individuals diagnosed with schizophrenia, approximately 20%–33% are recognized as treatment-resistant schizophrenia (TRS patients. These TRS patients suffer more severely from the disease but struggle to benefit from existing antipsychotic treatments. A few recent studies suggested that schizophrenia may be caused by impaired synaptic plasticity that manifests as functional dysconnectivity in the brain, however, few of those studies focused on the functional connectivity changes in the brains of TRS groups. In this study, we compared the whole brain connectivity variations in TRS patients, their unaffected siblings, and healthy controls. Connectivity network features between and within the 116 automated anatomical labeling (AAL brain regions were calculated and compared using maps created with three contrasts: patient vs. control, patient vs. sibling, and sibling vs. control. To evaluate the predictive power of the selected features, we performed a multivariate classification approach. We also evaluated the influence of six important clinical measures (e.g. age, education level on the connectivity features. This study identified abnormal significant connectivity changes of three patterns in TRS patients and their unaffected siblings: 1 69 patient-specific connectivity (PCN; 2 102 shared connectivity (SCN; and 3 457 unshared connectivity (UCN. While the first two patterns were widely reported by previous non-TRS specific studies, we were among the first to report widespread significant connectivity differences between TRS patient groups and their healthy sibling groups. Observations of this study may provide new insights for the understanding of the neurophysiological mechanisms of TRS.

  6. Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression

    Science.gov (United States)

    Widge, Alik S.; Malone, Donald A.; Dougherty, Darin D.

    2018-01-01

    Major depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS) in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial “failures” are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this “valley of disillusionment,” DBS may be nearing a “slope of enlightenment.” Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI), the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care. PMID:29618967

  7. Clozapine potentiation of GABA mediated cortical inhibition in treatment resistant schizophrenia.

    Science.gov (United States)

    Kaster, Tyler S; de Jesus, Danilo; Radhu, Natasha; Farzan, Faranak; Blumberger, Daniel M; Rajji, Tarek K; Fitzgerald, Paul B; Daskalakis, Zafiris J

    2015-07-01

    Cortical inhibition (CI) deficits have been demonstrated in schizophrenia using transcranial magnetic stimulation (TMS). These CI deficits may be related to decreased GABA activity which may be involved in schizophrenia pathophysiology. Previous cross-sectional studies have also demonstrated greater CI in patients treated with clozapine than other typical/atypical antipsychotics. However, it is not clear if these differences in CI are a result of treatment-resistant illness which necessitates clozapine or are related to clozapine treatment. TMS measures of CI (i.e., cortical silent period (CSP) and short-interval cortical inhibition (SICI)) were measured over the motor cortex in 16 patients with schizophrenia before starting clozapine, then 6 weeks and 6 months after starting clozapine. CSP was significantly longer after 6 weeks of treatment with clozapine (p=0.014). From 6 weeks to 6 months, there was no significant difference in CSP (p>0.05). Short-interval cortical inhibition (SICI) was not significantly different at any time after treatment with clozapine (p>0.05). This prospective-longitudinal study demonstrates that treatment with clozapine is associated with an increase in GABAB mediated inhibitory neurotransmission. Potentiation of GABAB may be a novel neurotransmitter mechanism that is involved in the pathophysiology and treatment of schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression.

    Science.gov (United States)

    Widge, Alik S; Malone, Donald A; Dougherty, Darin D

    2018-01-01

    Major depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS) in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial "failures" are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this "valley of disillusionment," DBS may be nearing a "slope of enlightenment." Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI), the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care.

  9. An Innovative Framework for Delivering Psychotherapy to Patients With Treatment-Resistant Posttraumatic Stress Disorder: Rationale for Interactive Motion-Assisted Therapy

    Directory of Open Access Journals (Sweden)

    Marieke J. van Gelderen

    2018-05-01

    Full Text Available Despite an array of evidence-based psychological treatments for patients with a posttraumatic stress disorder (PTSD, a majority of patients do not fully benefit from the potential of these therapies. In veterans with PTSD, up to two-thirds retain their diagnosis after psychotherapy and often their disorder is treatment-resistant, which calls for improvement of therapeutic approaches for this population. One of the factors hypothesized to underlie low response in PTSD treatment is high behavioral and cognitive avoidance to traumatic reminders. In the current paper we explore if a combination of personalized virtual reality, multi-sensory input, and walking during exposure can enhance treatment engagement, overcome avoidance, and thereby optimize treatment effectiveness. Virtual reality holds potential to increase presence and in-session attention and to facilitate memory retrieval. Multi-sensory input such as pictures and music can personalize this experience. Evidence for the positive effect of physical activity on fear extinction and associative thinking, as well as embodied cognition theories, provide a rationale for decreased avoidance by literally approaching cues of the traumatic memories. A dual-attention task further facilitates new learning and reconsolidation. These strategies have been combined in an innovative framework for trauma-focused psychotherapy, named Multi-modular Motion-assisted Memory Desensitization and Reconsolidation (3MDR. In this innovative treatment the therapeutic setting is changed from the face-to-face sedentary position to a side-by-side activating context in which patients walk toward trauma-related images in a virtual environment. The framework of 3MDR has been designed as a boost for patients with treatment-resistant PTSD, which is illustrated by three case examples. The intervention is discussed in context of other advancements in treatment for treatment-resistant PTSD. Novel elements of this approach are

  10. An Innovative Framework for Delivering Psychotherapy to Patients With Treatment-Resistant Posttraumatic Stress Disorder: Rationale for Interactive Motion-Assisted Therapy.

    Science.gov (United States)

    van Gelderen, Marieke J; Nijdam, Mirjam J; Vermetten, Eric

    2018-01-01

    Despite an array of evidence-based psychological treatments for patients with a posttraumatic stress disorder (PTSD), a majority of patients do not fully benefit from the potential of these therapies. In veterans with PTSD, up to two-thirds retain their diagnosis after psychotherapy and often their disorder is treatment-resistant, which calls for improvement of therapeutic approaches for this population. One of the factors hypothesized to underlie low response in PTSD treatment is high behavioral and cognitive avoidance to traumatic reminders. In the current paper we explore if a combination of personalized virtual reality, multi-sensory input, and walking during exposure can enhance treatment engagement, overcome avoidance, and thereby optimize treatment effectiveness. Virtual reality holds potential to increase presence and in-session attention and to facilitate memory retrieval. Multi-sensory input such as pictures and music can personalize this experience. Evidence for the positive effect of physical activity on fear extinction and associative thinking, as well as embodied cognition theories, provide a rationale for decreased avoidance by literally approaching cues of the traumatic memories. A dual-attention task further facilitates new learning and reconsolidation. These strategies have been combined in an innovative framework for trauma-focused psychotherapy, named Multi-modular Motion-assisted Memory Desensitization and Reconsolidation (3MDR). In this innovative treatment the therapeutic setting is changed from the face-to-face sedentary position to a side-by-side activating context in which patients walk toward trauma-related images in a virtual environment. The framework of 3MDR has been designed as a boost for patients with treatment-resistant PTSD, which is illustrated by three case examples. The intervention is discussed in context of other advancements in treatment for treatment-resistant PTSD. Novel elements of this approach are activation

  11. Low-dose ketamine for treatment resistant depression in an academic clinical practice setting.

    Science.gov (United States)

    Feifel, David; Malcolm, Benjamin; Boggie, Danielle; Lee, Kelly

    2017-10-15

    Recent studies demonstrating a rapid, robust improvement in treatment resistant depression (TRD) following a single sub-anesthetic infusion of ketamine have generated much excitement. However, these studies are limited in their generalizability to the broader TRD population due to their subject exclusion criteria which typically limit psychiatric comorbidity, concurrent medication, and level of suicide risk. This paper describes the safety and efficacy of sub-anesthetic ketamine infusions in a naturalistic TRD patient sample participating in a real-world TRD treatment program within a major university health system. The effects of a sub-anesthetic dose (0.5mg/kg) of ketamine infused IV over forty minutes on TRD patients participating in a treatment program at the University of California, San Diego was investigated by retrospectively analyzing the medical charts of 41 adult TRD patients with a diagnosis of Major Depressive Disorder (MDD) or Bipolar Disorder (BD). Subjects were aged 48.6, 78% white, 36.6% female, and 82.9% had MDD. Significant psychiatric comorbidity existed in 73%. Average pre-infusion BDI score was 32.6 ± 8.4 (S.D) and dropped to 16.8 ± 3.1 at 24-h post-infusion (p Ketamine infusions were well tolerated with occasional nausea or anxiety and mild hemodynamic effects during the infusion. Retrospective nature of this study, lack of control group and use of self-report depression ratings scales. This is the first published study of sub-anesthetic ketamine infusions in a real-world TRD population. The results suggest that this treatment is effective and well tolerated in this population. Copyright © 2017. Published by Elsevier B.V.

  12. Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Carola Rong

    2018-04-01

    Full Text Available Objectives: Extant evidence indicates that ketamine exerts rapid antidepressant effects in treatment-resistant depressive (TRD symptoms as a part of major depressive disorder (MDD and bipolar disorder (BD. The identification of depressed sub-populations that are more likely to benefit from ketamine treatment remains a priority. In keeping with this view, the present narrative review aims to identify the pretreatment predictors of response to ketamine in TRD as part of MDD and BD. Method: Electronic search engines PubMed/MEDLINE, ClinicalTrials.gov, and Scopus were searched for relevant articles from inception to January 2018. The search term ketamine was cross-referenced with the terms depression, major depressive disorder, bipolar disorder, predictors, and response and/or remission. Results: Multiple baseline pretreatment predictors of response were identified, including clinical (i.e., Body Mass Index (BMI, history of suicide, family history of alcohol use disorder, peripheral biochemistry (i.e., adiponectin levels, vitamin B12 levels, polysomnography (abnormalities in delta sleep ratio, neurochemistry (i.e., glutamine/glutamate ratio, neuroimaging (i.e., anterior cingulate cortex activity, genetic variation (i.e., Val66Met BDNF allele, and cognitive functioning (i.e., processing speed. High BMI and a positive family history of alcohol use disorder were the most replicated predictors. Conclusions: A pheno-biotype of depression more, or less likely, to benefit with ketamine treatment is far from complete. Notwithstanding, metabolic-inflammatory alterations are emerging as possible pretreatment response predictors of depressive symptom improvement, most notably being cognitive impairment. Sophisticated data-driven computational methods that are iterative and agnostic are more likely to provide actionable baseline pretreatment predictive information.

  13. Nitrous Oxide for Treatment-Resistant Major Depression: A Proof-of-Concept Trial.

    Science.gov (United States)

    Nagele, Peter; Duma, Andreas; Kopec, Michael; Gebara, Marie Anne; Parsoei, Alireza; Walker, Marie; Janski, Alvin; Panagopoulos, Vassilis N; Cristancho, Pilar; Miller, J Philip; Zorumski, Charles F; Conway, Charles R

    2015-07-01

    N-methyl-D-aspartate receptor antagonists, such as ketamine, have rapid antidepressant effects in patients with treatment-resistant depression (TRD). We hypothesized that nitrous oxide, an inhalational general anesthetic and N-methyl-D-aspartate receptor antagonist, may also be a rapidly acting treatment for TRD. In this blinded, placebo-controlled crossover trial, 20 patients with TRD were randomly assigned to 1-hour inhalation of 50% nitrous oxide/50% oxygen or 50% nitrogen/50% oxygen (placebo control). The primary endpoint was the change on the 21-item Hamilton Depression Rating Scale (HDRS-21) 24 hours after treatment. Mean duration of nitrous oxide treatment was 55.6 ± 2.5 (SD) min at a median inspiratory concentration of 44% (interquartile range, 37%-45%). In two patients, nitrous oxide treatment was briefly interrupted, and the treatment was discontinued in three patients. Depressive symptoms improved significantly at 2 hours and 24 hours after receiving nitrous oxide compared with placebo (mean HDRS-21 difference at 2 hours, -4.8 points, 95% confidence interval [CI], -1.8 to -7.8 points, p = .002; at 24 hours, -5.5 points, 95% CI, -2.5 to -8.5 points, p nitrous oxide and placebo, p nitrous oxide compared with one patient (5%) and none after placebo (odds ratio for response, 4.0, 95% CI, .45-35.79; OR for remission, 3.0, 95% CI, .31-28.8). No serious adverse events occurred; all adverse events were brief and of mild to moderate severity. This proof-of-concept trial demonstrated that nitrous oxide has rapid and marked antidepressant effects in patients with TRD. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Gamma synchrony: towards a translational biomarker for the treatment resistant symptoms of schizophrenia

    Science.gov (United States)

    Gandal, Michael J.; Edgar, J. Christopher; Klook, Kerstin; Siegel, Steven J.

    2011-01-01

    The lack of efficacy for antipsychotics with respect to negative symptoms and cognitive deficits is a significant obstacle for the treatment of schizophrenia. Developing new drugs to target these symptoms requires appropriate neural biomarkers that can be investigated in model organisms, be used to track treatment response, and provide insight into pathophysiological disease mechanisms. A growing body of evidence indicates that neural oscillations in the gamma frequency range (30–80 Hz) are disturbed in schizophrenia. Gamma synchrony has been shown to mediate a host of sensory and cognitive functions, including perceptual encoding, selective attention, salience, and working memory – neurocognitive processes that are dysfunctional in schizophrenia and largely refractory to treatment. This review summarizes the current state of clinical literature with respect to gamma band responses (GBRs) in schizophrenia, focusing on resting and auditory paradigms. Next, preclinical studies of schizophrenia that have investigated gamma band activity are reviewed to gain insight into neural mechanisms associated with these deficits. We conclude that abnormalities in gamma synchrony are ubiquitous in schizophrenia and likely reflect an elevation in baseline cortical gamma synchrony (‘noise’) coupled with reduced stimulus-evoked GBRs (‘signal’). Such a model likely reflects hippocampal and cortical dysfunction, as well as reduced glutamatergic signaling with downstream GABAergic deficits, but is probably less influenced by dopaminergic abnormalities implicated in schizophrenia. Finally, we propose that analogous signal-to-noise deficits in the flow of cortical information in preclinical models are useful targets for the development of new drugs that target the treatment-resistant symptoms of schizophrenia. PMID:21349276

  15. Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression.

    Science.gov (United States)

    Roseman, Leor; Demetriou, Lysia; Wall, Matthew B; Nutt, David J; Carhart-Harris, Robin L

    2017-12-27

    Recent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin. Psychological support was provided before, during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last. Neutral, fearful and happy faces were presented in the scanner and analyses focused on the amygdala. Group results revealed rapid and enduring improvements in depressive symptoms post psilocybin. Increased responses to fearful and happy faces were observed in the right amygdala post-treatment, and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1-week. Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments' therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions. ISRCTN, number ISRCTN14426797. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Increased nature relatedness and decreased authoritarian political views after psilocybin for treatment-resistant depression.

    Science.gov (United States)

    Lyons, Taylor; Carhart-Harris, Robin L

    2018-01-01

    Previous research suggests that classical psychedelic compounds can induce lasting changes in personality traits, attitudes and beliefs in both healthy subjects and patient populations. Here we sought to investigate the effects of psilocybin on nature relatedness and libertarian-authoritarian political perspective in patients with treatment-resistant depression (TRD). This open-label pilot study with a mixed-model design studied the effects of psilocybin on measures of nature relatedness and libertarian-authoritarian political perspective in patients with moderate to severe TRD ( n=7) versus age-matched non-treated healthy control subjects ( n=7). Psilocybin was administered in two oral dosing sessions (10 mg and 25 mg) 1 week apart. Main outcome measures were collected 1 week and 7-12 months after the second dosing session. Nature relatedness and libertarian-authoritarian political perspective were assessed using the Nature Relatedness Scale (NR-6) and Political Perspective Questionnaire (PPQ-5), respectively. Nature relatedness significantly increased ( t(6)=-4.242, p=0.003) and authoritarianism significantly decreased ( t(6)=2.120, p=0.039) for the patients 1 week after the dosing sessions. At 7-12 months post-dosing, nature relatedness remained significantly increased ( t(5)=-2.707, p=0.021) and authoritarianism remained decreased at trend level ( t(5)=-1.811, p=0.065). No differences were found on either measure for the non-treated healthy control subjects. This pilot study suggests that psilocybin with psychological support might produce lasting changes in attitudes and beliefs. Although it would be premature to infer causality from this small study, the possibility of drug-induced changes in belief systems seems sufficiently intriguing and timely to deserve further investigation.

  17. Dextromethorphan/quinidine pharmacotherapy in patients with treatment resistant depression: A proof of concept clinical trial.

    Science.gov (United States)

    Murrough, James W; Wade, Elizabeth; Sayed, Sehrish; Ahle, Gabriella; Kiraly, Drew D; Welch, Alison; Collins, Katherine A; Soleimani, Laili; Iosifescu, Dan V; Charney, Dennis S

    2017-08-15

    At least one-third of patients with major depressive disorder (MDD) have treatment-resistant depression (TRD), defined as lack of response to two or more adequate antidepressant trials. For these patients, novel antidepressant treatments are urgently needed. The current study is a phase IIa open label clinical trial examining the efficacy and tolerability of a combination of dextromethorphan (DM) and the CYP2D6 enzyme inhibitor quinidine (Q) in patients with TRD. Dextromethorphan acts as an antagonist at the glutamate N-methyl-d-aspartate (NMDA) receptor, in addition to other pharmacodynamics properties that include activity at sigma-1 receptors. Twenty patients with unipolar TRD who completed informed consent and met all eligibility criteria we enrolled in an open-label study of DM/Q up to 45/10mg by mouth administered every 12h over the course of a 10-week period, and constitute the intention to treat (ITT) sample. Six patients discontinued prior to study completion. There was no treatment-emergent suicidal ideation, psychotomimetic or dissociative symptoms. Montgomery-Asberg Depression Rating Scale (MADRS) score was reduced from baseline to the 10-week primary outcome (mean change: -13.0±11.5, t 19 =5.0, p<0.001), as was QIDS-SR score (mean change: -5.9±6.6, t 19 =4.0, p<0.001). The response and remission rates in the ITT sample were 45% and 35%, respectively. Open-label, proof-of-concept design. Herein we report acceptable tolerability and preliminary efficacy of DM/Q up to 45/10mg administered every 12h in patients with TRD. Future larger placebo controlled randomized trials in this population are warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Magnetic Seizure Therapy in Treatment-Resistant Schizophrenia: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Victor M. Tang

    2018-01-01

    Full Text Available ObjectiveElectroconvulsive therapy is effective in treatment-resistant schizophrenia (TRS but use is limited due to stigma and concerns around cognitive adverse effects. Magnetic seizure therapy (MST is a promising new neuromodulation technique that uses transcranial magnetic stimulation to induce therapeutic seizures. Studies of MST in depression have shown clinical improvement with a favorable adverse effect profile. No studies have examined the clinical utility of MST in schizophrenia.MethodsWe conducted an open-label pilot clinical trial of MST in eight TRS patients. Up to 24 MST treatments were delivered depending on treatment response. We assessed clinical outcome through the Brief Psychiatric Rating Scale (BPRS and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q. Cognitive testing included a neuropsychological test battery, the Autobiographical Memory Inventory (AMI, Montreal Cognitive Assessment (MoCA, and reorientation time.ResultsFour patients completed the trial as per protocol. For all patients and for trial completers alone, there was a significant clinical and quality of life improvement. Three met pre-determined criteria for remission (total score ≤25 on the BPRS and one met criteria for response (i.e., ≥25% BPRS improvement from baseline for two consecutive assessments. Pre and post neurocognitive data showed no significant cognitive adverse effects apart from a decrease in AMI scores.ConclusionIn this pilot study, MST demonstrated evidence for feasibility in patients with TRS, with promise for clinical efficacy and negligible cognitive side effects. Further study in larger clinical populations is needed.Clinical Trial Registrationwww.ClinicalTrials.gov, Identifier NCT01596608.

  19. Plasmin in urine from patients with type 2 diabetes and treatment-resistant hypertension activates ENaC in vitro

    DEFF Research Database (Denmark)

    Buhl, Kristian B; Stolzenburg Oxlund, Christina; Friis, Ulla G

    2014-01-01

    diabetes mellitus (T2DM) and treatment-resistant hypertension excrete plasmin(ogen) in urine in proportion to albumin and that plasmin confers to urine the ability to activate ENaC. METHOD:: Patients (n = 113) with T2DM and resistant hypertension, defined as systolic blood pressure (SBP) more than 130 mm...... of plasmin in preurine may inappropriately activate ENaC in patients with type 2 diabetes and microalbuminuria. This may contribute to treatment-resistant hypertension.......BACKGROUND:: Aberrant filtration of plasminogen from plasma and subsequent activation to plasmin in the urinary space may activate proteolytically the epithelial sodium channel, ENaC. In conditions with chronic albuminuria, this may cause hypertension. It was hypothesized that patients with type 2...

  20. Using imaging to target the prefrontal cortex for transcranial magnetic stimulation studies in treatment-resistant depression

    OpenAIRE

    Johnson, Kevin A.; Ramsey, Dave; Kozel, Frank A.; Bohning, Daryl E.; Anderson, Berry; Nahas, Ziad; Sacke?m, Harold A.; George, Mark S.

    2006-01-01

    Structural imaging studies of the brains of patients with treatment-resistant depression (TRD) have found several abnormalities, including smaller hippocampus, orbitofrontal cortex, or pre?frontal cortex. Transcranial magnetic stimulation (TMS) is a noninvasive means of modulating brain activity, and has shown antidepressant treatment efficacy. 1 The initial methods used for targeting the prefrontal cortex are most likely insufficient. Herwig et al found that a common rule-based approach (the...

  1. Beta-amyloid deposition in patients with major depressive disorder with differing levels of treatment resistance: a pilot study.

    Science.gov (United States)

    Li, Peng; Hsiao, Ing-Tsung; Liu, Chia-Yih; Chen, Chia-Hsiang; Huang, She-Yao; Yen, Tzu-Chen; Wu, Kuan-Yi; Lin, Kun-Ju

    2017-12-01

    Lack of treatment response in patients with late-life depression is common. The role of brain beta-amyloid (Aβ) deposition in treatment outcome in subjects with late-life depression remains unclear. The present study aimed to investigate brain Aβ deposition in patients with major depressive disorder (MDD) with differing treatment outcomes in vivo using 18 F-florbetapir imaging. This study included 62 MDD patients and 18 healthy control subjects (HCs).We first employed the Maudsley staging method (MSM) to categorize MDD patients into two groups according to treatment response: mild treatment resistance (n = 29) and moderate-to-severe treatment resistance (n = 33).The standard uptake value ratio (SUVR) of each volume of interest was analysed, and voxel-wise comparisons were made between the MDD patients and HCs. Vascular risk factors, serum homocysteine level, and apolipoprotein E (ApoE) genotype were also determined. The MDD patients with moderate-to-severe treatment resistance had higher 18 F-florbetapir SUVRs than the HCs in the parietal region (P depressive symptoms may represent prodromal manifestations of Alzheimer's disease (AD). Depressive symptomatology in old age, particularly in subjects with a poor treatment response, may underscore early changes of AD-related pathophysiology.

  2. Failure of hippocampal deactivation during loss events in treatment-resistant depression.

    Science.gov (United States)

    Johnston, Blair A; Tolomeo, Serenella; Gradin, Victoria; Christmas, David; Matthews, Keith; Steele, J Douglas

    2015-09-01

    Major depressive disorder is characterized by anhedonia, cognitive biases, ruminations, hopelessness and increased anxiety. Blunted responses to rewards have been reported in a number of recent neuroimaging and behavioural studies of major depressive disorder. In contrast, neural responses to aversive events remain an under-studied area. While selective serotonergic reuptake inhibitors are often effective in treating major depressive disorder, their mechanism of action remains unclear. Following a series of animal model investigations of depressive illness and serotonergic function, Deakin and Graeff predicted that brain activity in patients with major depressive disorder is associated with an overactive dorsal raphe nucleus with overactive projections to the amygdala, periaqueductal grey and striatum, and an underactive median raphe nucleus with underactive projections to the hippocampus. Here we describe an instrumental loss-avoidance and win-gain reinforcement learning functional magnetic resonance imaging study with 40 patients with highly treatment-resistant major depressive disorder and never-depressed controls. The dorsal raphe nucleus/ periaqueductal grey region of the midbrain and hippocampus were found to be overactive in major depressive disorder during unsuccessful loss-avoidance although the median raphe nucleus was not found to be underactive. Hippocampal overactivity was due to a failure to deactivate during loss events in comparison to controls, and hippocampal over-activity correlated with depression severity, self-report 'hopelessness' and anxiety. Deakin and Graeff argued that the median raphe nucleus normally acts to inhibit consolidation of aversive memories via the hippocampus and this system is underactive in major depressive disorder, facilitating the development of ruminations, while the dorsal raphe nucleus system is engaged by distal cues predictive of threats and is overactive in major depressive disorder. During win events the striatum

  3. Blockade of dopamine D1-family receptors attenuates the mania-like hyperactive, risk-preferring, and high motivation behavioral profile of mice with low dopamine transporter levels.

    Science.gov (United States)

    Milienne-Petiot, Morgane; Groenink, Lucianne; Minassian, Arpi; Young, Jared W

    2017-10-01

    Patients with bipolar disorder mania exhibit poor cognition, impulsivity, risk-taking, and goal-directed activity that negatively impact their quality of life. To date, existing treatments for bipolar disorder do not adequately remediate cognitive dysfunction. Reducing dopamine transporter expression recreates many bipolar disorder mania-relevant behaviors (i.e. hyperactivity and risk-taking). The current study investigated whether dopamine D 1 -family receptor blockade would attenuate the risk-taking, hypermotivation, and hyperactivity of dopamine transporter knockdown mice. Dopamine transporter knockdown and wild-type littermate mice were tested in mouse versions of the Iowa Gambling Task (risk-taking), Progressive Ratio Breakpoint Test (effortful motivation), and Behavioral Pattern Monitor (activity). Prior to testing, the mice were treated with the dopamine D 1 -family receptor antagonist SCH 23390 hydrochloride (0.03, 0.1, or 0.3 mg/kg), or vehicle. Dopamine transporter knockdown mice exhibited hyperactivity and hyperexploration, hypermotivation, and risk-taking preference compared with wild-type littermates. SCH 23390 hydrochloride treatment decreased premature responding in dopamine transporter knockdown mice and attenuated their hypermotivation. SCH 23390 hydrochloride flattened the safe/risk preference, while reducing activity and exploratory levels of both genotypes similarly. Dopamine transporter knockdown mice exhibited mania-relevant behavior compared to wild-type mice. Systemic dopamine D 1 -family receptor antagonism attenuated these behaviors in dopamine transporter knockdown, but not all effects were specific to only the knockdown mice. The normalization of behavior via blockade of dopamine D 1 -family receptors supports the hypothesis that D 1 and/or D 5 receptors could contribute to the mania-relevant behaviors of dopamine transporter knockdown mice.

  4. Effect of clinical response to active drugs and placebo on antipsychotics and mood stabilizers relative efficacy for bipolar depression and mania: A meta-regression analysis.

    Science.gov (United States)

    Bartoli, Francesco; Clerici, Massimo; Di Brita, Carmen; Riboldi, Ilaria; Crocamo, Cristina; Carrà, Giuseppe

    2018-04-01

    Randomised placebo-controlled trials investigating treatments for bipolar disorder have been hampered by wide variations of active drugs and placebo clinical response rates. It is important to estimate whether the active drug or placebo response has a greater influence in determining the relative efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood stabilisers) for bipolar depression and mania. We identified 53 randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser monotherapy ('active drugs') for bipolar depression or mania. We carried out random-effects meta-regressions, estimating the influence of active drugs and placebo response rates on treatment relative efficacy. Meta-regressions showed that treatment relative efficacy for bipolar mania was influenced by the magnitude of clinical response to active drugs ( p=0.002), but not to placebo ( p=0.60). On the other hand, treatment relative efficacy for bipolar depression was influenced by response to placebo ( p=0.047), but not to active drugs ( p=0.98). Despite several limitations, our unexpected findings showed that antipsychotics / mood stabilisers relative efficacy for bipolar depression seems unrelated to active drugs response rates, depending only on clinical response to placebo. Future research should explore strategies to reduce placebo-related issues in randomised, placebo-controlled trials for bipolar depression.

  5. Fenproporex increases locomotor activity and alters energy metabolism, and mood stabilizers reverse these changes: a proposal for a new animal model of mania.

    Science.gov (United States)

    Rezin, Gislaine T; Furlanetto, Camila B; Scaini, Giselli; Valvassori, Samira S; Gonçalves, Cinara L; Ferreira, Gabriela K; Jeremias, Isabela C; Resende, Wilson R; Cardoso, Mariane R; Varela, Roger B; Quevedo, João; Streck, Emilio L

    2014-04-01

    Fenproporex (Fen) is converted in vivo into amphetamine, which is used to induce mania-like behaviors in animals. In the present study, we intend to present a new animal model of mania. In order to prove through face, construct, and predictive validities, we evaluated behavioral parameters (locomotor activity, stereotypy activity, and fecal boli amount) and brain energy metabolism (enzymes citrate synthase; malate dehydrogenase; succinate dehydrogenase; complexes I, II, II-III, and IV of the mitochondrial respiratory chain; and creatine kinase) in rats submitted to acute and chronic administration of fenproporex, treated with lithium (Li) and valproate (VPA). The administration of Fen increased locomotor activity and decreased the activity of Krebs cycle enzymes, mitochondrial respiratory chain complexes, and creatine kinase, in most brain structures evaluated. In addition, treatment with mood stabilizers prevented and reversed this effect. Our results are consistent with the literature that demonstrates behavioral changes and mitochondrial dysfunction caused by psychostimulants. These findings suggest that chronic administration of Fen may be a potential animal model of mania.

  6. Augmentation of clozapine with amisulpride: an effective therapeutic strategy for violent treatment-resistant schizophrenia patients in a UK high-security hospital.

    Science.gov (United States)

    Hotham, James E; Simpson, Patrick J D; Brooman-White, Rosalie S; Basu, Amlan; Ross, Callum C; Humphreys, Sharon A; Larkin, Fintan; Gupta, Nitin; Das, Mrigendra

    2014-10-01

    Clozapine is used in the management of treatment-resistant schizophrenia and is effective in reducing aggression; however a subgroup of patients is poorly responsive. For violent patients in this group, there is limited literature on the use of strategies to augment clozapine with other agents. Here we present a case series of 6 schizophrenia patients, within a high-security hospital, who have a history of serious violence and who were treated with clozapine augmented with amisulpride. We reviewed case notes and health records for evidence of violence/aggression and positive factors such as engagement in activities, and Clinical Global Impression (CGI) scores were formulated. We also examined metabolic parameters before and after augmentation. All 6 of the patients showed clinical improvement in symptoms and a reduction in their risk of violence to others. Five patients had a reduction in number of violent/aggressive incidents, and all patients showed improvement in engagement in occupational, vocational, and/or psychological work. Metabolic parameters were largely unchanged except for 1 patient whose Body Mass Index (BMI) increased. Five patients reported side effects as unchanged or improved. These schizophrenia patients with a history of violence showed clinical improvement and reduced aggression and violence with amisulpride augmentation of clozapine. To our knowledge, this is the first report of an antiaggressive benefit of this combination in forensic psychiatric patients. Further studies are warranted to establish the efficacy and anti-aggressive effects of amisulpride augmentation of clozapine.

  7. Histone deacetylase activity and brain-derived neurotrophic factor (BDNF levels in a pharmacological model of mania

    Directory of Open Access Journals (Sweden)

    Laura Stertz

    2014-03-01

    Full Text Available Objective: In the present study, we aimed to examine the effects of repeated D-amphetamine (AMPH exposure, a well-accepted animal model of acute mania in bipolar disorder (BD, and histone deacetylase (HDAC inhibitors on locomotor behavior and HDAC activity in the prefrontal cortex (PFC and peripheral blood mononuclear cells (PBMCs of rats. Moreover, we aimed to assess brain-derived neurotrophic factor (BDNF protein and mRNA levels in these samples. Methods: We treated adult male Wistar rats with 2 mg/kg AMPH or saline intraperitoneally for 14 days. Between the 8th and 14th days, rats also received 47.5 mg/kg lithium (Li, 200 mg/kg sodium valproate (VPT, 2 mg/kg sodium butyrate (SB, or saline. We evaluated locomotor activity in the open-field task and assessed HDAC activity in the PFC and PBMCs, and BDNF levels in the PFC and plasma. Results: AMPH significantly increased locomotor activity, which was reversed by all drugs. This hyperactivity was associated with increased HDAC activity in the PFC, which was partially reversed by Li, VPT, and SB. No differences were found in BDNF levels. Conclusion: Repeated AMPH administration increases HDAC activity in the PFC without altering BDNF levels. The partial reversal of HDAC increase by Li, VPT, and SB may account for their ability to reverse AMPH-induced hyperactivity.

  8. Cell therapy in the treatment of bipolar mania in an animal model: a proof of concept study

    Directory of Open Access Journals (Sweden)

    Bruna M. Ascoli

    2017-05-01

    Full Text Available Abstract Introduction The rationale of mesenchymal stem cells (MSCs as a novel therapeutic approach in certain neurodegenerative diseases is based on their ability to promote neurogenesis. Hippocampal atrophy has been related to bipolar disorder (BD in preclinical, imaging and postmortem studies. Therefore, the development of new strategies to stimulate the neurogenesis process in BD is crucial. Objectives To investigate the behavioral and neurochemical changes induced by transplantation of MSCs in a model of mania-like behavior induced by lisdexamfetamine dimesylate (LDX. Methods Wistar rats (n=65 received one oral daily dose of LDX (10 mg/kg or saline for 14 days. On the 8th day of treatment, the animals additionally received intrahippocampal saline or MSC (1 µL containing 25,000 cells or lithium (47.5 mg/kg as an internal experimental control. Two hours after the last administration, behavioral and neurochemical analyses were performed. Results LDX-treated rats had increased locomotor activity compared to saline-saline rats (p=0.004, and lithium reversed LDX-related hyperactive behavior (p0.05 in the hippocampus of rats. Conclusion Even though these results suggest that a single intrahippocampal injection of MSCs was not helpful to treat hyperactivity induced by LDX and neither influenced BDNF secretion, we cannot rule out the possible therapeutic effects of MSCs. Further research is required to determine direct effects of LDX on brain structures as well as in other pathophysiological targets related to BD.

  9. Matching of treatment-resistant heroin-dependent patients to medical prescription of heroin or oral methadone treatment: results from two randomized controlled trials

    NARCIS (Netherlands)

    Blanken, Peter; Hendriks, Vincent M.; Koeter, Maarten W. J.; van Ree, Jan M.; van den Brink, Wim

    2005-01-01

    AIMS: To investigate which baseline patient characteristics of treatment-resistant heroin addicts differentially predicted treatment response to medical heroin prescription compared to standard methadone maintenance treatment. DESIGN: Two open-label randomized controlled trials; pooled data.

  10. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy.

    Science.gov (United States)

    Porter, Brenda E; Jacobson, Catherine

    2013-12-01

    Severe childhood epilepsies are characterized by frequent seizures, neurodevelopmental delays, and impaired quality of life. In these treatment-resistant epilepsies, families often seek alternative treatments. This survey explored the use of cannabidiol-enriched cannabis in children with treatment-resistant epilepsy. The survey was presented to parents belonging to a Facebook group dedicated to sharing information about the use of cannabidiol-enriched cannabis to treat their child's seizures. Nineteen responses met the following inclusion criteria for the study: a diagnosis of epilepsy and current use of cannabidiol-enriched cannabis. Thirteen children had Dravet syndrome, four had Doose syndrome, and one each had Lennox-Gastaut syndrome and idiopathic epilepsy. The average number of antiepileptic drugs (AEDs) tried before using cannabidiol-enriched cannabis was 12. Sixteen (84%) of the 19 parents reported a reduction in their child's seizure frequency while taking cannabidiol-enriched cannabis. Of these, two (11%) reported complete seizure freedom, eight (42%) reported a greater than 80% reduction in seizure frequency, and six (32%) reported a 25-60% seizure reduction. Other beneficial effects included increased alertness, better mood, and improved sleep. Side effects included drowsiness and fatigue. Our survey shows that parents are using cannabidiol-enriched cannabis as a treatment for their children with treatment-resistant epilepsy. Because of the increasing number of states that allow access to medical cannabis, its use will likely be a growing concern for the epilepsy community. Safety and tolerability data for cannabidiol-enriched cannabis use among children are not available. Objective measurements of a standardized preparation of pure cannabidiol are needed to determine whether it is safe, well tolerated, and efficacious at controlling seizures in this pediatric population with difficult-to-treat seizures. © 2013.

  11. Pindolol augmentation in patients with treatment-resistant panic disorder: A double-blind, placebo-controlled trial.

    Science.gov (United States)

    Hirschmann, S; Dannon, P N; Iancu, I; Dolberg, O T; Zohar, J; Grunhaus, L

    2000-10-01

    The objective of this study was to determine the efficacy of pindolol as an augmentor of fluoxetine in treatment-resistant panic disorder (PD). Twenty-five outpatients having PD with or without agoraphobia were included. These patients had not responded to two different trials with antidepressants and an 8-week trial of fluoxetine 20 mg/day. Treatment-resistant PD was defined as a less than 20% reduction in score on the Panic Self-Questionnaire (number of attacks per week) (PSQ) and the Clinical Anxiety Scale With Panic Attacks (CAS+PA). These patients continued to receive fluoxetine 20 mg/day and were randomly assigned to additionally receive either pindolol (2.5 mg three times daily) or placebo for the following 4 weeks. Evaluations were performed weekly using the Hamilton Rating Scale for Anxiety, the Hamilton Rating Scale for Depression (HAM-D), the CAS+PA, the NIMH Anxiety Scale, the PSQ, and the Clinical Global Impression Scale. The data were analyzed using a repeated-measures analysis of variance (ANOVA) and a t-test for independent samples. Patients treated with the combination of pindolol and fluoxetine (N = 13) demonstrated a significant improvement over the patients treated with fluoxetine and placebo on all rating scales, with the exception of HAM-D. The statistical differences were shown using the repeated-measures ANOVA (baseline, week 2, week 4) and also with t-tests from the second week of the trial. These preliminary results demonstrate that pindolol has an augmenting effect on fluoxetine in patients with treatment-resistant PD.

  12. The study protocol of the Norwegian randomized controlled trial of electroconvulsive therapy in treatment resistant depression in bipolar disorder

    Directory of Open Access Journals (Sweden)

    Oedegaard Ketil J

    2010-02-01

    Full Text Available Abstract Background The treatment of depressive phases of bipolar disorder is challenging. The effects of the commonly used antidepressants in bipolar depression are questionable. Electroconvulsive therapy is generally considered to be the most effective treatment even if there are no randomized controlled trials of electroconvulsive therapy in bipolar depression. The safety of electroconvulsive therapy is well documented, but there are some controversies as to the cognitive side effects. The aim of this study is to compare the effects and side effects of electroconvulsive therapy to pharmacological treatment in treatment resistant bipolar depression. Cognitive changes and quality of life during the treatment will be assessed. Methods/Design A prospective, randomised controlled, multi-centre six- week acute treatment trial with seven clinical assessments. Follow up visit at 26 weeks or until remission (max 52 weeks. A neuropsychological test battery designed to be sensitive to changes in cognitive function will be used. Setting: Nine study centres across Norway, all acute psychiatric departments. Sample: n = 132 patients, aged 18 and over, who fulfil criteria for treatment resistant depression in bipolar disorder, Montgomery Åsberg Depression Rating Scale Score of at least 25 at baseline. Intervention: Intervention group: 3 sessions per week for up to 6 weeks, total up to 18 sessions. Control group: algorithm-based pharmacological treatment as usual. Discussion This study is the first randomized controlled trial that aims to investigate whether electroconvulsive therapy is better than pharmacological treatment as usual in treatment resistant bipolar depression. Possible long lasting cognitive side effects will be evaluated. The study is investigator initiated, without support from industry. Trial registration NCT00664976

  13. Adjunctive treatment with transcranial magnetic stimulation in treatment resistant depression: a randomized, double-blind, sham-controlled study

    Directory of Open Access Journals (Sweden)

    Qiang LIU

    2011-02-01

    Full Text Available Background: High-frequency repetitive transcranial magnetic stimulation (rTMS to the left prefrontal cortex is a promising antidepressant treatment but the appropriate duration of treatment andits effect on cognitive symptoms in treatment resistant patients is uncertain.Hypotheis: Patients with treatment resistant depression on standard antidepressant medication who receive four weeks of adjunctive treatment with high-frequency rTMS to the left prefrontal cortex will have better clinical outcomes and better cognitive functioning than those who receive sham rTMS treatments.Methods: Thirty patients with treatment resistant depression (defined as failure to respond to two or more antidepressants of different classes administered for at least 6 weeks at or above two-thirds of the recommended maximum dose receiving selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors wererandomly assigned to receive adjundive treatment with either real rTMS (n=15 or sham rTMS (n=15 5 times a week for 4 conseculive weeks. Blinded pre-post evaluations were conducted using the 17-item Hamilton Depression Rating Scale (HAMD, the Montgomery-Asberg Depression Rating Scale (MADRS, the severity of illness measure from the Clinical Global Impression Rating scale(CGI-S, the Wechsler Adult Intelligence ScaIe (WAIS, the Wechsler Memory Scale (WMS, and the Wisconsjn Card Sorting Test(WC5T.Results:14 subjects from each group completed the study. There was no significant difference in the HAMD total scores between the two groups after 2 weeks of treatment but after 4 weeks of treatment the mean percentage drop in the HAMD total score was significantly greater in the real rTMS group (49%, SD=19% than in the sham rTMS group(29%, SD=25%, with a mean difference of 20% [95%CI=3%-37%;t26=2.42; P=0.023]. At 4 weeks the mean (SD reduction in the MADRS total score was also greater in the real rTMS group [47%(23% vs 16%(40

  14. Deep brain stimulation for severe treatment-resistant obsessive-compulsive disorder: An open-label case series.

    Science.gov (United States)

    Farrand, Sarah; Evans, Andrew H; Mangelsdorf, Simone; Loi, Samantha M; Mocellin, Ramon; Borham, Adam; Bevilacqua, JoAnne; Blair-West, Scott; Walterfang, Mark A; Bittar, Richard G; Velakoulis, Dennis

    2017-09-01

    Deep brain stimulation can be of benefit in carefully selected patients with severe intractable obsessive-compulsive disorder. The aim of this paper is to describe the outcomes of the first seven deep brain stimulation procedures for obsessive-compulsive disorder undertaken at the Neuropsychiatry Unit, Royal Melbourne Hospital. The primary objective was to assess the response to deep brain stimulation treatment utilising the Yale-Brown Obsessive Compulsive Scale as a measure of symptom severity. Secondary objectives include assessment of depression and anxiety, as well as socio-occupational functioning. Patients with severe obsessive-compulsive disorder were referred by their treating psychiatrist for assessment of their suitability for deep brain stimulation. Following successful application to the Psychosurgery Review Board, patients proceeded to have deep brain stimulation electrodes implanted in either bilateral nucleus accumbens or bed nucleus of stria terminalis. Clinical assessment and symptom rating scales were undertaken pre- and post-operatively at 6- to 8-week intervals. Rating scales used included the Yale-Brown Obsessive Compulsive Scale, Obsessive Compulsive Inventory, Depression Anxiety Stress Scale and Social and Occupational Functioning Assessment Scale. Seven patients referred from four states across Australia underwent deep brain stimulation surgery and were followed for a mean of 31 months (range, 8-54 months). The sample included four females and three males, with a mean age of 46 years (range, 37-59 years) and mean duration of obsessive-compulsive disorder of 25 years (range, 15-38 years) at the time of surgery. The time from first assessment to surgery was on average 18 months. All patients showed improvement on symptom severity rating scales. Three patients showed a full response, defined as greater than 35% improvement in Yale-Brown Obsessive Compulsive Scale score, with the remaining showing responses between 7% and 20%. Deep brain stimulation was an effective treatment for obsessive-compulsive disorder in these highly selected patients. The extent of the response to deep brain stimulation varied between patients, as well as during the course of treatment for each patient. The results of this series are comparable with the literature, as well as having similar efficacy to ablative psychosurgery techniques such as capsulotomy and cingulotomy. Deep brain stimulation provides advantages over lesional psychosurgery but is more expensive and requires significant multidisciplinary input at all stages, pre- and post-operatively, ideally within a specialised tertiary clinical and/or academic centre. Ongoing research is required to better understand the neurobiological basis for obsessive-compulsive disorder and how this can be manipulated with deep brain stimulation to further improve the efficacy of this emerging treatment.

  15. Tavistock Adult Depression Study (TADS: a randomised controlled trial of psychoanalytic psychotherapy for treatment-resistant/treatment-refractory forms of depression

    Directory of Open Access Journals (Sweden)

    Taylor David

    2012-07-01

    Full Text Available Abstract Background Long-term forms of depression represent a significant mental health problem for which there is a lack of effective evidence-based treatment. This study aims to produce findings about the effectiveness of psychoanalytic psychotherapy in patients with treatment-resistant/treatment-refractory depression and to deepen the understanding of this complex form of depression. Methods/Design INDEX GROUP: Patients with treatment resistant/treatment refractory depression. DEFINITION & INCLUSION CRITERIA: Current major depressive disorder, 2 years history of depression, a minimum of two failed treatment attempts, ≥14 on the HRSD or ≥21 on the BDI-II, plus complex personality and/or psycho-social difficulties. EXCLUSION CRITERIA: Moderate or severe learning disability, psychotic illness, bipolar disorder, substance dependency or receipt of test intervention in the previous two years. DESIGN: Pragmatic, randomised controlled trial with qualitative and clinical components. TEST INTERVENTION: 18 months of weekly psychoanalytic psychotherapy, manualised and fidelity-assessed using the Psychotherapy Process Q-Sort. CONTROL CONDITION: Treatment as usual, managed by the referring practitioner. RECRUITMENT: GP referrals from primary care. RCT MAIN OUTCOME: HRSD (with ≤14 as remission. SECONDARY OUTCOMES: depression severity (BDI-II, degree of co-morbid disorders Axis-I and Axis-II (SCID-I and SCID-II-PQ, quality of life and functioning (GAF, CORE, Q-les-Q, object relations (PROQ2a, Cost-effectiveness analysis (CSRI and GP medical records. FOLLOW-UP: 2 years. Plus: a. Qualitative study of participants’ and therapists’ problem formulation, experience of treatment and of participation in trial. (b Narrative data from semi-structured pre/post psychodynamic interviews to produce prototypes of responders and non-responders. (c Clinical case-studies of sub-types of TRD and of change. Discussion TRD needs complex, long-term intervention and

  16. Choreatic Side Effects of Deep Brain Stimulation of the Anteromedial Subthalamic Nucleus for Treatment-Resistant Obsessive-Compulsive disorder.

    Science.gov (United States)

    Mulders, Anne E P; Leentjens, Albert F G; Schruers, Koen; Duits, Annelien; Ackermans, Linda; Temel, Yasin

    2017-08-01

    Patients with treatment-resistant obsessive-compulsive disorder (OCD) are potential candidates for deep brain stimulation (DBS). The anteromedial subthalamic nucleus (STN) is among the most commonly used targets for DBS in OCD. We present a patient with a 30-year history of treatment-resistant OCD who underwent anteromedial STN-DBS. Despite a clear mood-enhancing effect, stimulation caused motor side effects, including bilateral hyperkinesia, dyskinesias, and sudden large amplitude choreatic movements of arms and legs when stimulating at voltages greater than approximately 1.5 V. DBS at lower amplitudes and at other contact points failed to result in a significant reduction of obsessions and compulsions without inducing motor side effects. Because of this limitation in programming options, we decided to reoperate and target the ventral capsule/ventral striatum (VC/VS), which resulted in a substantial reduction in key obsessive and compulsive symptoms without serious side effects. Choreatic movements and hemiballismus have previously been linked to STN dysfunction and have been incidentally reported as side effects of DBS of the dorsolateral STN in Parkinson disease (PD). However, in PD, these side effects were usually transient, and they rarely interfered with DBS programming. In our patient, the motor side effects were persistent, and they made optimal DBS programming impossible. To our knowledge, such severe and persistent motor side effects have not been described previously for anteromedial STN-DBS. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Amisulpride as adjunct to clozapine in treatment-resistant schizophrenia and schizoaffective disoder: An open-label pilot study

    Directory of Open Access Journals (Sweden)

    Liezl Koen

    2006-03-01

    Full Text Available Background. Although clozapine is the treatment of choice for treatment-resistant schizophrenia, many patients remain symptomatic despite adequate treatment with this medication. One suggested strategy to improve efficacy has been the addition of a potent D2 blocker such as amisulpride to treatment with clozapine. Methods. In this study, 20 subjects who were treatment-resistant to conventional antipsychotics and who were still symptomatic despite adequate treatment with clozapine received amisulpride as adjunctive treatment. After baseline assessment all subjects were titrated to amisulpride 400 mg per day and then reassessed after 8 weeks by a blinded rater. Results. Analysis showed statistically significant improvements in PANSS (Positive and Negative Symptom Scale total score (t = 3.49, df = 18, p = 0.003, PANSS negative subscale score (t = 3.22, df = 18, p = 0.005, and PANSS depression factor score (t = 3.89, df = 19, p = 0.001. Discussion. This study suggests that addition of the second- generation antipsychotic amisulpride to a stable treatment regimen with clozapine may offer additional benefits in terms of negative and depressive symptoms.

  18. Sibutramine-induced mania as the first manifestation of bipolar disorder

    Directory of Open Access Journals (Sweden)

    Waszkiewicz Napoleon

    2012-05-01

    Full Text Available Abstract Background Sibutramine, used in obesity treatment, has been associated with many neuropsychiatric side effects including hypomanic and manic episodes. Hypomanic/manic episodes related to sibutramine treatment were earlier reported in patients who had previous history of bipolar disorder, after sibutramine overdose, after over-the-counter product illegally containing very high dose of sibutramine, together with psychotic symptoms, in organic patient, or after interaction of sibutramine with other drugs. Case presentation We report the first case of a patient with clear manic episode, after treatment with recommended dose of sibutramine, without previous history of mood disorders, organic changes or drug interactions, that was followed by episode of depression. Conclusion Minimal recommended dose of sibutramine induced manic episode that was the first manifestation of bipolar disorder. The manic episode, associated with sibutramine treatment, was induced in a person without previous history of mood disorders. Potential risks associated with the treatment of obesity using sibutramine warn physicians to be alert not only to common and cardiovascular but also to psychiatric adverse effects. A careful assessment of patient’s mental state and detailed psychiatric family history should be done before sibutramine treatment. In patients with a family history for bipolar disorder the use of even minimal dose of sibutramine should be contraindicated.

  19. An 8-Year-Old Boy With Treatment-Resistant Encopresis

    NARCIS (Netherlands)

    Stein, Martin T.; Benninga, Marc A.; Felt, Barbara T.

    2010-01-01

    CASE: Paul is an 8-year-old boy with a long-standing history of encopresis and enuresis. Potty training was initiated when he was 21/2 years old. At this time, his mother was absent from the home for 6 weeks when she cared for her ill father in a different city. The process of teaching Paul to use

  20. The effects of reduced dopamine transporter function and chronic lithium on motivation, probabilistic learning, and neurochemistry in mice: Modeling bipolar mania.

    Science.gov (United States)

    Milienne-Petiot, Morgane; Kesby, James P; Graves, Mary; van Enkhuizen, Jordy; Semenova, Svetlana; Minassian, Arpi; Markou, Athina; Geyer, Mark A; Young, Jared W

    2017-02-01

    Bipolar disorder (BD) mania patients exhibit poor cognition and reward-seeking/hypermotivation, negatively impacting a patient's quality of life. Current treatments (e.g., lithium), do not treat such deficits. Treatment development has been limited due to a poor understanding of the neural mechanisms underlying these behaviors. Here, we investigated putative mechanisms underlying cognition and reward-seeking/motivational changes relevant to BD mania patients using two validated mouse models and neurochemical analyses. The effects of reducing dopamine transporter (DAT) functioning via genetic (knockdown vs. wild-type littermates), or pharmacological (GBR12909- vs. vehicle-treated C57BL/6J mice) means were assessed in the probabilistic reversal learning task (PRLT), and progressive ratio breakpoint (PRB) test, during either water or chronic lithium treatment. These tasks quantify reward learning and effortful motivation, respectively. Neurochemistry was performed on brain samples of DAT mutants ± chronic lithium using high performance liquid chromatography. Reduced DAT functioning increased reversals in the PRLT, an effect partially attenuated by chronic lithium. Chronic lithium alone slowed PRLT acquisition. Reduced DAT functioning increased motivation (PRB), an effect attenuated by lithium in GBR12909-treated mice. Neurochemical analyses revealed that DAT knockdown mice exhibited elevated homovanillic acid levels, but that lithium had no effect on these elevated levels. Reducing DAT functioning recreates many aspects of BD mania including hypermotivation and improved reversal learning (switching), as well as elevated homovanillic acid levels. Chronic lithium only exerted main effects, impairing learning and elevating norepinephrine and serotonin levels of mice, not specifically treating the underlying mechanisms identified in these models. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Sibutramine-induced mania as the first manifestation of bipolar disorder.

    Science.gov (United States)

    Waszkiewicz, Napoleon; Zalewska-Szajda, Beata; Szajda, Sławomir Dariusz; Simonienko, Katarzyna; Zalewska, Anna; Szulc, Agata; Ładny, Jerzy Robert; Zwierz, Krzysztof

    2012-05-18

    Sibutramine, used in obesity treatment, has been associated with many neuropsychiatric side effects including hypomanic and manic episodes. Hypomanic/manic episodes related to sibutramine treatment were earlier reported in patients who had previous history of bipolar disorder, after sibutramine overdose, after over-the-counter product illegally containing very high dose of sibutramine, together with psychotic symptoms, in organic patient, or after interaction of sibutramine with other drugs. We report the first case of a patient with clear manic episode, after treatment with recommended dose of sibutramine, without previous history of mood disorders, organic changes or drug interactions, that was followed by episode of depression. Minimal recommended dose of sibutramine induced manic episode that was the first manifestation of bipolar disorder. The manic episode, associated with sibutramine treatment, was induced in a person without previous history of mood disorders. Potential risks associated with the treatment of obesity using sibutramine warn physicians to be alert not only to common and cardiovascular but also to psychiatric adverse effects. A careful assessment of patient's mental state and detailed psychiatric family history should be done before sibutramine treatment. In patients with a family history for bipolar disorder the use of even minimal dose of sibutramine should be contraindicated.

  2. Coxsackie-adenovirus receptor as a novel marker of stem cells in treatment-resistant non-small cell lung cancer

    International Nuclear Information System (INIS)

    Zhang, Xiaochun; Fang, Bingliang; Mohan, Radhe; Chang, Joe Y.

    2012-01-01

    Background: Treatment resistance resulting from the presence of cancer stem cells (CSCs) remains a challenge in cancer treatment. Little is known about possible markers of CSCs in treatment-resistant non-small cell lung cancer (NSCLC). We explored the coxsackie-adenovirus receptor (CAR) as one such marker of CSCs in models of treatment-resistant NSCLC. Materials and methods: Resistant H460 and A549 cell lines were established by repeated exposure to paclitaxel or fractionated radiation. CSC markers were measured by Western blotting and flow cytometry. We also established stable CAR-overexpressing and stable shRNA-CAR-knockdown cell lines and assessed their survival, invasiveness, and tumorigenic capabilities with clonogenic, telomerase, Matrigel, and tumor formation assays. Results: CAR expression was associated with CSC phenotype both in vitro and in vivo. CAR-overexpressing cells were more treatment-resistant, self-renewing, and tumorigenic than were parental cells, and shRNA-mediated knockdown of CAR expression was sufficient to inhibit these functions. CAR expression also correlated with the epithelial–mesenchymal transition. Conclusions: We showed for the first time that CAR is a marker of CSCs and may affect the activities of CSCs in treatment-resistant NSCLC. CAR may prove to be a target for CSC treatment and a predictor of treatment response in patients with NSCLC.

  3. Neurobiology of hedonic tone: the relationship between treatment-resistant depression, attention-deficit hyperactivity disorder, and substance abuse

    Directory of Open Access Journals (Sweden)

    Sternat T

    2016-08-01

    of MDD, such as treatment-resistant depression, as well as comorbidities of these disorders. Keywords: dopamine, catecholamines, noradrenaline, anhedonia, treatment-resistance, prefrontal cortex 

  4. A Network Meta-Analysis of Clinical Management Strategies for Treatment-Resistant Hypertension: Making Optimal Use of the Evidence.

    Science.gov (United States)

    Makai, Peter; IntHout, Joanna; Deinum, Jaap; Jenniskens, Kevin; Wilt, Gert Jan van der

    2017-08-01

    With the addition of surgical interventions to current medicinal treatments, it is increasingly challenging for clinicians to rationally choose among the various options for treating patients with apparent treatment-resistant hypertension (ATRHTN). This study aims to establish the comparative effectiveness of mineralocorticoid receptor antagonists (MRA), renal denervation (RDN), darusentan and central arteriovenous anastomosis (CAA) for patients with ATRHTN by performing a network meta-analysis. Data Sources: Studies from recent meta-analyses for RDN and placebo effect were supplemented with a systematic search for MRAs in ATRHTN in the Pubmed, EMBASE, CINAHL and Cochrane databases through November 2016. Randomized controlled trials comparing treatment options for patients with ATRHTN. Data were extracted using predefined data extraction forms, including the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. A Bayesian random effects model was used to conduct a network meta-analysis. Spironolactone was used as the main comparator. Main Outcomes and Measures: Reduction in 24-h ambulatory blood pressure measurement (ABPM). Twenty articles met our inclusion criteria, and seven treatment alternatives were compared. Compared to MRA, CAA had the highest probability of being more effective, further reducing 24-h SBP (-4.8 mmHg [-13.0, 3.7]) and 24-h DBP (-9.7 mmHg [-18, -0.63]). This difference is likely to be clinically meaningful, with a probability of 78 and 96% at a threshold of a 2-mmHg reduction in blood pressure. When compared to MRA as anchor, darusentan, CAA and RDN are not more effective in achieving a clinically significant reduction in ambulatory blood pressure in individuals with apparent treatment-resistant hypertension.

  5. Thioredoxin is not a marker for treatment-resistance depression but associated with cognitive function: An rTMS study.

    Science.gov (United States)

    Aydın, Efruz Pirdoğan; Genç, Abdullah; Dalkıran, Mihriban; Uyar, Ece Türkyilmaz; Deniz, İpek; Özer, Ömer Akil; Karamustafalıoğlu, Kayıhan Oğuz

    2018-01-03

    Elevated oxidative stress is known to play an important role in development of depression and cognitive dysfunction. To date, thioredoxin (TRX), an antioxidant protein, has been investigated as a marker for psychiatric disorders such as schizophrenia, bipolar disorder and autism but its relationship with depression is yet to be unknown. The aim of this study is to detect the TRX levels in patients with treatment-resistant depression (TRD), analyse the effect of rTMS (repetitive transcranial magnetic stimulation) application on TRX levels and display the relationship of TRX with cognitive areas. This study included 27 treatment-resistant unipolar depression patients and 29 healthy subjects. Patients were evaluated by Hamilton Depression Scale (HDRS), Hamilton Anxiety Scale (HARS) and Montreal Cognitive Assessment (MoCA) before and after rTMS application. 23 of TRD patients were applied high-frequency rTMS over left DLPFC for 2 to 4weeks and plasma TRX levels of patients and healthy subjects were measured. No significant difference was determined between the TRX levels of patients and healthy subjects (p>0.05). After rTMS application there were significant decrease in severity of depression (pTRX levels of the patients after rTMS application (p>0.005). High language scores of the patients were found to be associated with high TRX levels (pTRX levels cannot be used as a marker for TRD or rTMS treatment in TRD. In spite of this TRX levels have a positive correlation with language functions of the patients of TRD. More extensive studies are required to clarify the mechanism of action of TRX and the effect of TRX on cognitive functions. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Minocycline as an adjunct for treatment-resistant depressive symptoms: A pilot randomised placebo-controlled trial.

    Science.gov (United States)

    Husain, Muhammad I; Chaudhry, Imran B; Husain, Nusrat; Khoso, Ameer B; Rahman, Raza R; Hamirani, Munir M; Hodsoll, John; Qurashi, Inti; Deakin, John Fw; Young, Allan H

    2017-09-01

    Evidence suggests that anti-inflammatory medication may be effective in the treatment of depressive symptoms. In this study, we aimed to investigate whether minocycline added to treatment as usual (TAU) for 3 months in patients with treatment-resistant depression will lead to an improvement in depressive symptoms. Multi-site, 12-week, double-blind, placebo-controlled, pilot trial of minocycline added to TAU for patients suffering from DSM-5 major depressive disorder, whose current episode has failed to respond to at least two antidepressants. The primary outcome measure was mean change in Hamilton Depression Rating Scale (HAMD-17) scores from baseline to week 12. Secondary measures were the Clinical Global Impression scale (CGI), Patient Health Questionnaire-9 (PHQ-9), the Generalised Anxiety Disorder scale (GAD-7) and EuroQoL (EQ-5D) quality-of-life questionnaire. Side-effect checklists were also used. Minocycline was started at 100 mg once daily (OD) and increased to 200 mg after 2 weeks. A total of 41 participants were randomised, with 21 in the minocycline group and 20 in the placebo group. A large decrease in HAMD scores was observed in the minocycline group compared to the placebo group (standardised effect size (ES) -1.21, p minocycline group also showed a large improvement compared with placebo (odds ratio (OR): 17.6, p minocycline leads to improvement in symptoms of treatment-resistant depression. However, our findings require replication in a larger sample. ClinicalTrials.gov identifier: NCT02263872, registered October 2014.

  7. [Sequential prescriptions: Arguments for a change of therapeutic patterns in treatment resistant depressions].

    Science.gov (United States)

    Allouche, G

    2016-02-01

    Among the therapeutic strategies in treatment of resistant depression, the use of sequential prescriptions is discussed here. A number of observations, initially quite isolated and few controlled studies, some large-scale, have been reported, which showed a definite therapeutic effect of certain requirements in sequential treatment of depression. The Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D) is up to now the largest clinical trial exploring treatment strategies in non psychotic resistant depression in real-life conditions with an algorithm of sequential decision. The main conclusions of this study are the following: after two unsuccessful attempts, the chance of remission decreases considerably. A 12-months follow-up showed that the higher the use of the processing steps were high, the more common the relapses were during this period. The pharmacological differences between psychotropic did not cause clinically significant difference. The positive effect of lithium in combination with antidepressants has been known since the work of De Montigny. Antidepressants allow readjustment of physiological sequence involving different monoaminergic systems together. Studies with tricyclic antidepressant-thyroid hormone T3: in depression, decreased norepinephrine at the synaptic receptors believed to cause hypersensitivity of these receptors. Thyroid hormones modulate the activity of adrenergic receptors. There would be a balance of activity between alpha and beta-adrenergic receptors, depending on the bioavailability of thyroid hormones. ECT may in some cases promote pharmacological response in case of previous resistance, or be effective in preventing relapse. Cognitive therapy and antidepressant medications likely have an effect on different types of depression. We can consider the interest of cognitive therapy in a sequential pattern after effective treatment with an antidepressant effect for treatment of residual symptoms, preventing relapses

  8. Abnormal functional-structural cingulum connectivity in mania: combined functional magnetic resonance imaging-diffusion tensor imaging investigation in different phases of bipolar disorder.

    Science.gov (United States)

    Martino, M; Magioncalda, P; Saiote, C; Conio, B; Escelsior, A; Rocchi, G; Piaggio, N; Marozzi, V; Huang, Z; Ferri, F; Amore, M; Inglese, M; Northoff, G

    2016-10-01

    The objective of the study was to investigate the relationship between structural connectivity (SC) and functional connectivity (FC) in the cingulum in bipolar disorder (BD) and its various phases. We combined resting-state functional magnetic resonance imaging and probabilistic tractographic diffusion tensor imaging to investigate FC and SC of the cingulum and its portions, the SC-FC relationship, and their correlations with clinical and neurocognitive measures on sustained attention in manic (n = 21), depressed (n = 20), and euthymic (n = 20) bipolar patients and healthy controls (HC) (n = 42). First, we found decreased FC between the anterior and posterior parts of the cingulum in manic patients when compared to depressed patients and HC. Second, we observed decreased SC of the cingulum bundle, particularly in its anterior part, in manic patients when compared to HC. Finally, alterations in the cingulum FC (but not SC) correlated with clinical severity scores while changes in the cingulum SC (but not FC) were related with neurocognitive deficits in sustained attention in BD. We demonstrate for the first time a reduction in FC and concomitantly in SC of the cingulum in mania, which correlated with psychopathological and neurocognitive parameters, respectively, in BD. This supports the central role of cingulum connectivity specifically in mania. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Asenapine effects on individual Young Mania Rating Scale items in bipolar disorder patients with acute manic or mixed episodes: a pooled analysis

    Directory of Open Access Journals (Sweden)

    Cazorla P

    2013-03-01

    Full Text Available Pilar Cazorla, Jun Zhao, Mary Mackle, Armin Szegedi Merck, Rahway, NJ, USA Background: An exploratory post hoc analysis was conducted to evaluate the potential differential effects over time of asenapine and olanzapine compared with placebo on the eleven individual items comprising the Young Mania Rating Scale (YMRS in patients with manic or mixed episodes in bipolar I disorder. Methods: Data were pooled from two 3-week randomized, controlled trials in which the eleven individual items comprising the YMRS were measured over 21 days. An analysis of covariance model adjusted by baseline value was used to test for differences in changes from baseline in YMRS scores between groups. Results: Each of the eleven individual YMRS item scores was significantly reduced compared with placebo at day 21. After 2 days of treatment, asenapine and olanzapine were superior to placebo for six of the YMRS items: disruptive/aggressive behavior, content, irritability, elevated mood, sleep, and speech. Conclusion: Reduction in manic symptoms over 21 days was associated with a broad-based improvement across all symptom domains with no subset of symptoms predominating. Keywords: asenapine, Young Mania Rating Scale, bipolar disorder, YMRS, antipsychotic, olanzapine

  10. Hexanucleotide Repeat Expansion in C9ORF72 Is Not Detected in the Treatment-Resistant Schizophrenia Patients of Chinese Han.

    Directory of Open Access Journals (Sweden)

    Xijia Xu

    Full Text Available Hexanucleotide (GGGGCC repeat expansion in C9ORF72 (HRE causes frontotemporal lobar degeneration, frontotemporal dementia-amyotrophic lateral sclerosis, and amyotrophic lateral sclerosis. HRE was also seen in the genomes of patients suffering from several other degenerative diseases. However, whether it is present in the treatment-resistant schizophrenia patients remains unknown. Genotyping 386 patients suffering from treatment-resistant schizophrenia using the method of Repeat-Primed PCR, we reported here that no HRE was detected in the patients of Chinese Han.

  11. Dopamine hypothesis of mania

    OpenAIRE

    Cookson, John

    2014-01-01

    s­of­the­Speakers­/­Konuşmacı­leriThe discovery of dopamine and its pathwaysDopamine (DA) was first synthesized in 1910 from 3,4-dihydroxy phenyl alanine (DOPA) by Barger and Ewens at Wellcome Laboratories in London. It is a cathecholamine and in the 1940s Blaschko in Cambridge proposed that DA was a precursor in synthesis of the cat-echolamine neurotransmitters noradrenaline (norepinephrine) and adrenaline (epinephrine). In 1957 it was shown to be present in the brain with other catecholamin...

  12. Mania and depression explained

    African Journals Online (AJOL)

    are thought to play a role in neuro-developmental processes, lending further ... Because serotonin, noradrenaline and dopamine are strongly implicated in the .... Genome-wide association study reveals two new risk loci for bipolar disorder.

  13. Efficacy, acceptability, and safety of adjunctive aripiprazole in treatment-resistant depression: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Luan SX

    2018-02-01

    Full Text Available Shuxin Luan,1,2 Hongquan Wan,2 Lei Zhang,3 Hua Zhao1,4 1Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun, China; 2Department of Mental Health, The First Hospital of Jilin University, Changchun, China; 3Department of Radiology, The First Hospital of Jilin University, Changchun, China; 4Neuroscience Research Center, The First Hospital of Jilin University, Changchun, China Background: Treatment-resistant depression (TRD is common and potentially life-threatening in adults, and the benefits and risks of adjunctive aripiprazole in these patients remain controversial. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs to assess the efficacy, acceptability, safety, and quality of life of adjunctive aripiprazole in patients with TRD.Methods: RCTs published in PubMed, Web of Science, and Embase were systematically reviewed to evaluate the efficacy and safety profiles of TRD patients who were treated with adjunctive aripiprazole. The main outcome measures included response rate, remission rate, changes from baseline in Montgomery–Asberg Depression Rating Scale (MADRS, Clinical Global Impression-severity (CGI-S, Clinical Global Impression-improvement (CGI-I, 17-Item Hamilton Rating Scale for Depression (HAM-D17, Sheehan Disability scale (SDS, and Inventory of Depressive Symptomatology Self-Report Scale (IDS-SR, discontinuation due to adverse events, and adverse events. Risk ratio (RR or weight mean difference with 95% confidence intervals (CIs were pooled using a fixed-effects or random-effects model according to the heterogeneity among studies.Results: A total of 8 RCTs involving 2,260 patients were included in this meta-analysis. Adjunctive aripiprazole was associated with a significantly higher remission rate (RR =1.64, 95% CI: 1.42 to 1.89; P<0.001 and response rate (RR =1.45, 95% CI: 1.13 to 1.87; P=0.004 than other treatments. Moreover, adjunctive aripiprazole had greater changes in

  14. Predictive modeling of treatment resistant depression using data from STAR*D and an independent clinical study.

    Science.gov (United States)

    Nie, Zhi; Vairavan, Srinivasan; Narayan, Vaibhav A; Ye, Jieping; Li, Qingqin S

    2018-01-01

    Identification of risk factors of treatment resistance may be useful to guide treatment selection, avoid inefficient trial-and-error, and improve major depressive disorder (MDD) care. We extended the work in predictive modeling of treatment resistant depression (TRD) via partition of the data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) cohort into a training and a testing dataset. We also included data from a small yet completely independent cohort RIS-INT-93 as an external test dataset. We used features from enrollment and level 1 treatment (up to week 2 response only) of STAR*D to explore the feature space comprehensively and applied machine learning methods to model TRD outcome at level 2. For TRD defined using QIDS-C16 remission criteria, multiple machine learning models were internally cross-validated in the STAR*D training dataset and externally validated in both the STAR*D testing dataset and RIS-INT-93 independent dataset with an area under the receiver operating characteristic curve (AUC) of 0.70-0.78 and 0.72-0.77, respectively. The upper bound for the AUC achievable with the full set of features could be as high as 0.78 in the STAR*D testing dataset. Model developed using top 30 features identified using feature selection technique (k-means clustering followed by χ2 test) achieved an AUC of 0.77 in the STAR*D testing dataset. In addition, the model developed using overlapping features between STAR*D and RIS-INT-93, achieved an AUC of > 0.70 in both the STAR*D testing and RIS-INT-93 datasets. Among all the features explored in STAR*D and RIS-INT-93 datasets, the most important feature was early or initial treatment response or symptom severity at week 2. These results indicate that prediction of TRD prior to undergoing a second round of antidepressant treatment could be feasible even in the absence of biomarker data.

  15. Validity of the Maudsley Staging Method in Predicting Treatment-Resistant Depression Outcome Using the Netherlands Study of Depression and Anxiety

    NARCIS (Netherlands)

    van Belkum, Sjoerd M; Geugies, Hanneke H; Lysen, Thom S; Cleare, Anthony J; Peeters, Frenk P M L; Penninx, Brenda W J H; Schoevers, Robert A; Ruhe, Eric G

    2018-01-01

    OBJECTIVE: We investigated if the degree of treatment resistance of depression, as measured by the Maudsley Staging Method (MSM), is predictive of a worse depression outcome by using a large naturalistic cohort of depressed patients. METHODS: 643 subjects from the general population, primary care,

  16. Assignment refusal and its relation to outcome in a randomized controlled trial comparing Cognitive Therapy and Fluvoxamine in treatment-resistant patients with obsessive compulsive disorder

    NARCIS (Netherlands)

    Landsheer, Johannes A.; Smit, Johannes H.; van Oppen, Patricia; van Balkom, Anton J L M

    2015-01-01

    The effectiveness of Fluvoxamine was compared to that of Cognitive Therapy (CT) in a 12-week randomized controlled trial (RCT) in 48 patients with obsessive-compulsive disorder (OCD), who were treatment-resistant to a previous behavior therapy (BT). A considerable amount of patients did not comply

  17. Lithium ameliorates sleep deprivation-induced mania-like behavior, hypothalamic-pituitary-adrenal (HPA) axis alterations, oxidative stress and elevations of cytokine concentrations in the brain and serum of mice.

    Science.gov (United States)

    Valvassori, Samira S; Resende, Wilson R; Dal-Pont, Gustavo; Sangaletti-Pereira, Heron; Gava, Fernanda F; Peterle, Bruna R; Carvalho, André F; Varela, Roger B; Dal-Pizzol, Felipe; Quevedo, João

    2017-06-01

    The goal of the present study was to investigate the effects of lithium administration on behavior, oxidative stress parameters and cytokine levels in the periphery and brain of mice subjected to an animal model of mania induced by paradoxical sleep deprivation (PSD). Male C57 mice were treated with saline or lithium for 7 days. The sleep deprivation protocol started on the 5th day during for the last 36 hours of the treatment period. Immediately after the sleep deprivation protocol, animals locomotor activity was evaluated and serum and brain samples was extracted to evaluation of corticosterone and adrenocorticotropic hormone circulating levels, oxidative stress parameters and citokynes levels. The results showed that PSD induced hyperactivity in mice, which is considered a mania-like behavior. PSD increased lipid peroxidation and oxidative damage to DNA, as well as causing alterations to antioxidant enzymes in the frontal cortex, hippocampus and serum of mice. In addition, PSD increased the levels of cytokines in the brains of mice. Treatment with lithium prevented the mania-like behavior, oxidative damage and cytokine alterations induced by PSD. Improving our understanding of oxidative damage in biomolecules, antioxidant mechanisms and the inflammatory system - alterations presented in the animal models of mania - is important in helping us to improve our knowledge concerning the pathophysiology of BD, and the mechanisms of action employed by mood stabilizers. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. N-Acetyl Cysteine and Vitamin D Supplementation in Treatment Resistant Obsessive- compulsive Disorder Patients: a General Review.

    Science.gov (United States)

    di Michele, Flavia; Siracusano, Alberto; Talamo, Alessandra; Niolu, Cinzia

    2018-04-17

    Obsessive-compulsive disorder (OCD) is a disabling mental illness for which pharmacological and psychosocial interventions are all too often inadequate. This demonstrates the need for more targeted therapeutics. Recent preclinical and clinical studies have implicated dysfunction of glutamatergic neurotransmission in the pathophysiology of OCD. Moreover there are studies suggesting that neuroimmune abnormalities may play an important role in the pathogenesis of OCD. N-acetyl cysteine (NAC) is a safe and readily available agent that would modify the synaptic release of glutamate in subcortical brain regions via modulation of the cysteine-glutamate antiporter. The modulation of inflammatory pathways may also play a role in the benefits seen following NAC treatment. Therefore NAC can be considered a neuroprotective agent. This paper explores the role of NAC in the treatment of OCD conditions refractory to first-line pharmacological interventions, reviewing the clinical studies published in the last decade. The possible benefit mechanisms of NAC for this disorder will be discussed, as well as the role of vitamin D supplementation, given its specific property of stimulating the formation of glutathione in the brain. Nutraceutical supplementation in treatment resistance OCD may be important not only for improving obsessive-compulsive symptomatology, but also from a psychological perspective, given its better acceptance by the patients compared to pharmacological treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Results of a randomized controlled pilot trial of intravascular renal denervation for management of treatment-resistant hypertension.

    Science.gov (United States)

    Jacobs, Lotte; Persu, Alexandre; Huang, Qi-Fang; Lengelé, Jean-Philippe; Thijs, Lutgarde; Hammer, Frank; Yang, Wen-Yi; Zhang, Zhen-Yu; Renkin, Jean; Sinnaeve, Peter; Wei, Fang-Fei; Pasquet, Agnès; Fadl Elmula, Fadl Elmula M; Carlier, Marc; Elvan, Arif; Wunder, Cora; Kjeldsen, Sverre E; Toennes, Stefan W; Janssens, Stefan; Verhamme, Peter; Staessen, Jan A

    2017-12-01

    Previous trials of catheter-based renal-artery denervation (RDN) as treatment modality in resistant hypertension (rHT) generated unconvincing results. In the Investigator-Steered Project on Intravascular Denervation for Management of Treatment-Resistant Hypertension (INSPiRED; NCT01505010), we optimized selection and management of rHT patients. With ethical clearance to randomize 18 patients, three Belgian hypertension centers screened 29 rHT patients on treatment with ≥3 drugs, of whom 17 after optimization of treatment (age efficacy endpoint, and 2.5 mL/min/1.73 m 2 (+1.5 vs. -1.1 mL/min/1.73 m 2 ; P = .86) for eGFR, the primary safety endpoint. At 6 month, ECG voltages and the number of prescribed drugs (P ≤ .036) were lower in RDN patients, but quality of life and adherence, captured by questionnaire and urine analysis were similar in both groups. Changes in BP and adherence were unrelated. No major complications occurred. The INSPiRED pilot suggests that RDN with the EnligHTN ™ system is effective and safe and generated insights useful for the design of future RDN trials.

  20. Drug adherence in treatment resistant and in controlled hypertension-Results from the Swedish Primary Care Cardiovascular Database (SPCCD).

    Science.gov (United States)

    Holmqvist, Lina; Boström, Kristina Bengtsson; Kahan, Thomas; Schiöler, Linus; Qvarnström, Miriam; Wettermark, Björn; Hjerpe, Per; Hasselström, Jan; Manhem, Karin

    2018-03-01

    To assess drug adherence in patients treated with ≥3 antihypertensive drug classes, with both controlled and uncontrolled blood pressure and describe associated factors for nonadherence. Patients with hypertension, without cardiovascular comorbidity, aged >30 years treated with ≥3 antihypertensive drug classes were followed for 2 years. Both patients with treatment resistant hypertension (TRH) and patients with controlled hypertension were included. Clinical data were derived from a primary care database. Pharmacy refill data from the Swedish Prescribed drug registry was used to calculate proportion of days covered (PDC). Patients with a PDC level ≥ 80% were included. We found 5846 patients treated ≥3 antihypertensive drug classes, 3508 with TRH (blood pressure ≥ 140/90), and 2338 with controlled blood pressure (drug therapy had similar decline in adherence over time regardless of initial blood pressure control. Diabetes was associated with better adherence, which may imply that the structured caregiving of these patients enhances antihypertensive drug treatment. Copyright © 2018 John Wiley & Sons, Ltd.

  1. Two Cases Of Multiple Sclerosis Accompanying Psychiatric Symptoms

    Directory of Open Access Journals (Sweden)

    Ayşegül Şengel

    2007-10-01

    Full Text Available Scientific bacground: It has been reported that; Multiple Sclerosis (MS may be presented with many psychiatric symptoms such as anxiety, depression, mania and psychosis. MS cases, presented with psychiatric symptoms were also reported. Cases: Two MS cases, diagnosed as psychotic and bipolar disorder respectively, were reported in this paper. Both of the cases were responded to the steroid treatment, and neurological and psychiatric examinations were found to be normal after one month. CONCLUSION: MS cases might be presented with psychiatric complaints and symptoms except neurological ones. We conclude that; psychiatric evaluation as well as the neurological evaluation is important in the MS cases presented with psychiatric symptoms

  2. Cross-generational trans fat intake modifies BDNF mRNA in the hippocampus: Impact on memory loss in a mania animal model.

    Science.gov (United States)

    Trevizol, Fabíola; Dias, Verônica T; Roversi, Katiane; Barcelos, Raquel C S; Kuhn, Fábio T; Roversi, Karine; Pase, Camila S; Golombieski, Ronaldo; Veit, Juliana C; Piccolo, Jaqueline; Emanuelli, Tatiana; Rocha, João B T; Bürger, Marilise E

    2015-05-01

    Recently, we have described the influence of dietary fatty acids (FA) on mania-like behavior of first generation animals. Here, two sequential generations of female rats were supplemented with soybean oil (SO, rich in n-6 FA, control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) from pregnancy and during lactation. In adulthood, half of each group was exposed to an amphetamine (AMPH)-induced mania animal model for behavioral, biochemical and molecular assessments. FO supplementation was associated with lower reactive species (RS) generation and protein carbonyl (PC) levels and increased dopamine transporter (DAT) levels, while HVF increased RS and PC levels, thus decreasing catalase (CAT) activity and DAT levels in hippocampus after AMPH treatment. AMPH impaired short- (1 h) and long- (24 h) term memory in the HVF group. AMPH exposure was able to reduce hippocampal BDNF- mRNA expression, which was increased in FO. While HVF was related to higher trans FA (TFA) incorporation in hippocampus, FO was associated with increased percentage of n-3 polyunsaturated FA (PUFA) together with lower n-6/n-3 PUFA ratio. Interestingly, our data showed a positive correlation between brain-derived neurotrophic factor (BDNF) mRNA and short- and long-term memory (r(2)  = 0.53; P = 0.000/r(2)  = 0.32; P = 0.011, respectively), as well as a negative correlation between PC and DAT levels (r(2)  = 0.23; P = 0.015). Our findings confirm that provision of n-3 or TFA during development over two generations is able to change the neuronal membrane lipid composition, protecting or impairing the hippocampus, respectively, thus affecting neurothrophic factor expression such as BDNF mRNA. In this context, chronic consumption of trans fats over two generations can facilitate the development of mania-like behavior, so leading to memory impairment and emotionality, which are related to neuropsychiatric conditions. © 2014 Wiley

  3. Treatment-Resistant Depression

    Science.gov (United States)

    ... on your own, talk to your doctor or mental health professional. Depression treatment may be unsuccessful until you address your substance use. Manage stress. Relationship issues, financial problems, an unhappy work life and many other issues can all contribute ...

  4. [French Society for Biological Psychiatry and Neuropsychopharmacology and Fondation FondaMental task force: Formal Consensus for the management of treatment-resistant depression].

    Science.gov (United States)

    Charpeaud, T; Genty, J-B; Destouches, S; Yrondi, A; Lancrenon, S; Alaïli, N; Bellivier, F; Bennabi, D; Bougerol, T; Camus, V; D'amato, T; Doumy, O; Haesebaert, F; Holtzmann, J; Lançon, C; Lefebvre, M; Moliere, F; Nieto, I; Richieri, R; Schmitt, L; Stephan, F; Vaiva, G; Walter, M; Leboyer, M; El-Hage, W; Haffen, E; Llorca, P-M; Courtet, P; Aouizerate, B

    2017-09-01

    situations (clinical features, specific populations, psychiatric comorbidities, etc.). Thus, the present approach will be especially helpful for the clinicians enabling to substantially facilitate and guide their clinical decision when confronted to difficult-to-treat forms of major depression in the daily clinical practice. This will be expected to significantly improve the poor prognosis of the treatment-resistant depression thereby lowering the clinical, functional and costly impact owing directly to the disease. © 2017 L’Encéphale, Paris.

  5. Rapid onset of treatment effects on psychosis, depression, and mania in patients with acute exacerbation of schizoaffective disorder following treatment with oral extended-release paliperidone.

    Science.gov (United States)

    Fu, Dong-Jing; Turkoz, Ibrahim; Bossie, Cynthia A; Patel, Hiren; Alphs, Larry

    2016-03-15

    Patients with schizoaffective disorder (SCA) experience complicated interplays of psychotic, depressive, and manic symptoms. Paliperidone extended-release (pali ER) tablets have been shown to be efficacious in these patients, but treatment response has not been studied relative to the onset of effects for these symptom domains. In a pooled analysis of data from two 6-week, randomized, placebo-controlled studies, the onset of treatment effects with oral pali ER was evaluated by symptom domain (psychosis, depression, mania) in patients with an acute SCA exacerbation. Subjects were categorized as having prominent psychotic (Positive and Negative Syndrome Scale score >70), depressive (Hamilton Rating Scale for Depression-21 score ≥16), or manic (Young Mania Rating Scale score ≥16) symptoms at baseline. Of the 614 patients in these analyses, 597 (97.2%), 411 (66.9%), and 488 (79.5%) had prominent psychotic, depressive, and manic symptoms at baseline, respectively. Pali ER treatment was associated with rapid and significant improvement of all three symptom domains versus placebo within 1 week of initiation, regardless of whether treatment was given as monotherapy or in combination with mood stabilizers and/or antidepressants. Adverse events were similar to those reported in the original published studies. This post hoc analysis of two phase 3 trials requires confirmation in prospective studies. This pooled analysis suggests that treatment with pali ER is associated with rapid control of psychotic, depressive, and manic symptoms in patients with SCA. Its findings support the benefit of pali ER as a primary treatment for the management of SCA. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Health-related quality of life in persons with apparent treatment-resistant hypertension on at least four antihypertensives.

    Science.gov (United States)

    Carris, N W; Ghushchyan, V; Libby, A M; Smith, S M

    2016-03-01

    Little is known about the impact of treatment-resistant hypertension (TRH) on health-related quality of life (HrQoL). We aimed to compare HrQoL measures in adults with apparent TRH (aTRH) and non-resistant hypertension among nationally representative US Medical Expenditure Panel Survey data pooled from 2000 to 2011. Cohorts compared were adults with aTRH (⩾2 unique fills from ⩾4 antihypertensive classes during a year) versus non-resistant hypertension (those with hypertension not meeting the aTRH definition). Key outcomes were cohort differences in SF-12v2 physical component summary (PCS) and mental component summary (MCS) scores and disease-state utility using the SF-6D. Of 57 150 adults with hypertension, 2501 (4.4%) met criteria for aTRH. Persons with aTRH, compared with non-resistant hypertension, were older (mean, 68 vs 61 years), had a higher BMI (30.9 vs 29.7 kg m(-)(2)) and were more likely to be Black (20% vs 14%), but less likely to be female (46% vs 54%). Persons with aTRH, compared with non-resistant hypertension, had lower mean PCS scores (35.8 vs 43.2; Phypertension. In conclusion, aTRH was associated with substantially lower HrQoL in physical functioning and health utility, but not in mental functioning, compared with non-resistant hypertension. The multivariable-adjusted reduction in physical functioning was similar in magnitude to previous observations comparing hypertension with no hypertension.

  7. Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes.

    Science.gov (United States)

    Russo, Ethan B

    2016-01-01

    Medicine continues to struggle in its approaches to numerous common subjective pain syndromes that lack objective signs and remain treatment resistant. Foremost among these are migraine, fibromyalgia, and irritable bowel syndrome, disorders that may overlap in their affected populations and whose sufferers have all endured the stigma of a psychosomatic label, as well as the failure of endless pharmacotherapeutic interventions with substandard benefit. The commonality in symptomatology in these conditions displaying hyperalgesia and central sensitization with possible common underlying pathophysiology suggests that a clinical endocannabinoid deficiency might characterize their origin. Its base hypothesis is that all humans have an underlying endocannabinoid tone that is a reflection of levels of the endocannabinoids, anandamide (arachidonylethanolamide), and 2-arachidonoylglycerol, their production, metabolism, and the relative abundance and state of cannabinoid receptors. Its theory is that in certain conditions, whether congenital or acquired, endocannabinoid tone becomes deficient and productive of pathophysiological syndromes. When first proposed in 2001 and subsequently, this theory was based on genetic overlap and comorbidity, patterns of symptomatology that could be mediated by the endocannabinoid system (ECS), and the fact that exogenous cannabinoid treatment frequently provided symptomatic benefit. However, objective proof and formal clinical trial data were lacking. Currently, however, statistically significant differences in cerebrospinal fluid anandamide levels have been documented in migraineurs, and advanced imaging studies have demonstrated ECS hypofunction in post-traumatic stress disorder. Additional studies have provided a firmer foundation for the theory, while clinical data have also produced evidence for decreased pain, improved sleep, and other benefits to cannabinoid treatment and adjunctive lifestyle approaches affecting the ECS.

  8. Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension.

    Science.gov (United States)

    Fadl Elmula, Fadl Elmula M; Hoffmann, Pavel; Larstorp, Anne C; Fossum, Eigil; Brekke, Magne; Kjeldsen, Sverre E; Gjønnæss, Eyvind; Hjørnholm, Ulla; Kjaer, Vibeke N; Rostrup, Morten; Os, Ingrid; Stenehjem, Aud; Høieggen, Aud

    2014-05-01

    We aimed to investigate for the first time the blood pressure (BP)-lowering effect of renal sympathetic denervation (RDN) versus clinically adjusted drug treatment in true treatment-resistant hypertension (TRH) after excluding patients with confounding poor drug adherence. Patients with apparent TRH (n=65) were referred for RDN, and those with secondary and spurious hypertension (n=26) were excluded. TRH was defined as office systolic BP (SBP) >140 mm Hg, despite maximally tolerated doses of ≥3 antihypertensive drugs including a diuretic. In addition, ambulatory daytime SBP >135 mm Hg after witnessed intake of antihypertensive drugs was required, after which 20 patients had normalized BP and were excluded. Patients with true TRH were randomized and underwent RDN (n=9) performed with Symplicity Catheter System versus clinically adjusted drug treatment (n=10). The study was stopped early for ethical reasons because RDN had uncertain BP-lowering effect. Office SBP and diastolic BP in the drug-adjusted group changed from 160±14/88±13 mm Hg (±SD) at baseline to 132±10/77±8 mm Hg at 6 months (P<0.0005 and P=0.02, SBP and diastolic BP, respectively) and in the RDN group from 156±13/91±15 to 148±7/89±8 mm Hg (P=0.42 and P=0.48, SBP and diastolic BP, respectively). SBP and diastolic BP were significantly lower in the drug-adjusted group at 6 months (P=0.002 and P=0.004, respectively), and absolute changes in SBP were larger in the drug-adjusted group (P=0.008). Ambulatory BPs changed in parallel to office BPs. Our data suggest that adjusted drug treatment has superior BP lowering effects compared with RDN in patients with true TRH. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01673516.

  9. Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

    Science.gov (United States)

    Sehatzadeh, Shayan; Tu, Hong Anh; Palimaka, Stefan; Yap, Belinda; O'Reilly, Daria; Bowen, Jim; Higgins, Caroline; Holubowich, Corinne

    2016-01-01

    Background To date, several randomized controlled trials (RCTs) have shown the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depression. Objective This analysis examined the antidepressant efficacy of rTMS in patients with treatment-resistant unipolar depression. Methods A literature search was performed for RCTs published from January 1, 1994, to November 20, 2014. The search was updated on March 1, 2015. Two independent reviewers evaluated the abstracts for inclusion, reviewed full texts of eligible studies, and abstracted data. Meta-analyses were conducted to obtain summary estimates. The primary outcome was changes in depression scores measured by the Hamilton Rating Scale for Depression (HRSD), and we considered, a priori, the mean difference of 3.5 points to be a clinically important treatment effect. Remission and response to the treatment were secondary outcomes, and we calculated number needed to treat on the basis of these outcomes. We examined the possibility of publication bias by constructing funnel plots and by Begg's and Egger's tests. A meta-regression was undertaken to examine the effect of specific rTMS technical parameters on the treatment effects. Results Twenty-three RCTs compared rTMS with sham, and six RCTs compared rTMS with electroconvulsive therapy (ECT). Trials of rTMS versus sham showed a statistically significant improvement in depression scores with rTMS (weighted mean difference [WMD] 2.31, 95% CI 1.19–3.43; P transcranial magnetic stimulation had a small short-term effect for improving depression in comparison with sham, but follow-up studies did not show that the small effect will continue for longer periods. PMID:27099642

  10. The bi-directional relationship between parent-child conflict and treatment outcome in treatment-resistant adolescent depression.

    Science.gov (United States)

    Rengasamy, Manivel; Mansoor, Brandon M; Hilton, Robert; Porta, Giovanna; He, Jiayan; Emslie, Graham J; Mayes, Taryn; Clarke, Gregory N; Wagner, Karen Dineen; Keller, Martin B; Ryan, Neal D; Birmaher, Boris; Shamseddeen, Wael; Asarnow, Joan Rosenbaum; Brent, David A

    2013-04-01

    To examine the bidirectional relationship between parent-child discord and treatment outcome for adolescent treatment-resistant depression. Depressed youth who had not responded to an adequate course of a selective serotonin reuptake inhibitor (SSRI) were randomized to either a switch to another SSRI or venlafaxine, with or without the addition of cognitive behavior therapy (CBT) in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study. The Conflict Behavior Questionnaire was used to assess adolescent (CBQ-A) and parent-reported (CBQ-P) parent-child discord. The impact of remission on parent-child conflict, and the differential impact of medication and CBT on the CBQ-A and CBQ-P, were assessed using generalized linear models. Although there were no differential treatment effects on parent or adolescent-report of conflict, remission was associated with improvement in the CBQ-P. In general, intake family conflict did not predict remission, except in the sub-group of participants whose parents reported clinically significant parent-child conflict at intake, for whom high levels of parent-reported conflict predicted a lower likelihood of remission. Conflict also did not moderate treatment response. Remission of depression may be sufficient to reduce parent-reported parent-child conflict. However, higher parent-reported conflict, in the clinically significant range, predicts a lower likelihood of remission from depression. Clinical trial registration information-Treatment of SSRI-Resistant Depression in Adolescents (TORDIA); http://clinicaltrials.gov/; NCT00018902. Copyright © 2013 American Academy of Child & Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. A longitudinal study on deep brain stimulation of the medial forebrain bundle for treatment-resistant depression.

    Science.gov (United States)

    Fenoy, Albert J; Schulz, Paul E; Selvaraj, Sudhakar; Burrows, Christina L; Zunta-Soares, Giovanna; Durkin, Kathryn; Zanotti-Fregonara, Paolo; Quevedo, Joao; Soares, Jair C

    2018-06-04

    Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB) has been reported to lead to rapid antidepressant effects. In this longitudinal study, we expand upon the initial results we reported at 26 weeks (Fenoy et al., 2016), showing sustained antidepressant effects of MFB DBS on six patients with treatment-resistant depression (TRD) over 1 year. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary assessment tool. Deterministic fiber tracking was used to individually map the target area; analysis was performed to compare modulated fiber tracts between patients. Intraoperatively, upon stimulation at target, responders reported immediate increases in energy and motivation. An insertional effect was seen during the 4-week sham stimulation phase from baseline (28% mean MADRS reduction, p = 0.02). However, after 1 week of initiating stimulation, three of six patients had a > 50% decrease in MADRS scores relative to baseline (43% mean MADRS reduction, p = 0.005). One patient withdrew from study participation. At 52 weeks, four of remaining five patients have > 70% decrease in MADRS scores relative to baseline (73% mean MADRS reduction, p = 0.007). Evaluation of modulated fiber tracts reveals significant common orbitofrontal connectivity to the target region in all responders. Neuropsychological testing and 18 F-fluoro-deoxyglucose-positron emission tomography cerebral metabolism evaluations performed at baseline and at 52 weeks showed minimal changes and verified safety. This longitudinal evaluation of MFB DBS demonstrated rapid antidepressant effects, as initially reported by Schlaepfer et al. (2013), and supports the use of DBS for TRD.

  12. A Randomized Double-Blind Sham-Controlled Study of Transcranial Direct Current Stimulation for Treatment-Resistant Major Depression

    Directory of Open Access Journals (Sweden)

    Daniel eBlumberger

    2012-08-01

    Full Text Available Objectives: Transcranial direct current stimulation (tDCS has demonstrated some efficacy in treatment-resistant major depression (TRD. The majority of previous controlled studies have used anodal stimulation to the left dorsolateral prefrontal cortex (DLPFC and a control location such as the supraorbital region on for the cathode. Several open label studies have suggested effectiveness from anodal stimulation to the left DLPFC combined with cathodal stimulation to the right DLPFC. Thus, this study evaluated the efficacy of tDCS using anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC compared to sham tDCS. Methods: Subjects between the ages of 18 and 65 were recruited from a tertiary care university hospital. Twenty-four subjects with TRD and a 17-item Hamilton Depression Rating Scale (HDRS greater than 21 were randomized to receive tDCS or sham tDCS. The rates of remission were compared between the two treatment groups.Results: The remission rates did not differ significantly between the two groups using an intention to treat analysis. More subjects in the active tDCS group had failed a course of electroconvulsive therapy in the current depressive episode. Side effects did not differ between the two groups and in general the treatment was very well tolerated. Conclusion: Anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC was not efficacious in TRD. However, a number of methodological limitations warrant caution in generalizing from this study. Ongoing, controlled studies should provide further clarification on the efficacy of this stimulation configuration in TRD.

  13. Refining Prediction in Treatment-Resistant Depression: Results of Machine Learning Analyses in the TRD III Sample.

    Science.gov (United States)

    Kautzky, Alexander; Dold, Markus; Bartova, Lucie; Spies, Marie; Vanicek, Thomas; Souery, Daniel; Montgomery, Stuart; Mendlewicz, Julien; Zohar, Joseph; Fabbri, Chiara; Serretti, Alessandro; Lanzenberger, Rupert; Kasper, Siegfried

    The study objective was to generate a prediction model for treatment-resistant depression (TRD) using machine learning featuring a large set of 47 clinical and sociodemographic predictors of treatment outcome. 552 Patients diagnosed with major depressive disorder (MDD) according to DSM-IV criteria were enrolled between 2011 and 2016. TRD was defined as failure to reach response to antidepressant treatment, characterized by a Montgomery-Asberg Depression Rating Scale (MADRS) score below 22 after at least 2 antidepressant trials of adequate length and dosage were administered. RandomForest (RF) was used for predicting treatment outcome phenotypes in a 10-fold cross-validation. The full model with 47 predictors yielded an accuracy of 75.0%. When the number of predictors was reduced to 15, accuracies between 67.6% and 71.0% were attained for different test sets. The most informative predictors of treatment outcome were baseline MADRS score for the current episode; impairment of family, social, and work life; the timespan between first and last depressive episode; severity; suicidal risk; age; body mass index; and the number of lifetime depressive episodes as well as lifetime duration of hospitalization. With the application of the machine learning algorithm RF, an efficient prediction model with an accuracy of 75.0% for forecasting treatment outcome could be generated, thus surpassing the predictive capabilities of clinical evaluation. We also supply a simplified algorithm of 15 easily collected clinical and sociodemographic predictors that can be obtained within approximately 10 minutes, which reached an accuracy of 70.6%. Thus, we are confident that our model will be validated within other samples to advance an accurate prediction model fit for clinical usage in TRD. © Copyright 2017 Physicians Postgraduate Press, Inc.

  14. A 2-year follow-up study of patients participating in our transcranial pulsating electromagnetic fields augmentation in treatment-resistant depression

    DEFF Research Database (Denmark)

    Bech, Per; Lindberg, Lone; Straasø, Birgit

    2015-01-01

    OBJECTIVE: We have made a 2-year follow-up study to evaluate the effect of repeated transcranial pulsating electromagnetic fields (T-PEMF) augmentation in patients who had achieved remission but later on relapsed, as well as to identify factors contributing to treatment-resistant depression......: In group A, comprising 27 patients, 13 had relapsed; they obtained a clear remission after a repeated course of T-PEMF augmentation. In group D, comprising 16 patients, we identified misdiagnostic factors both concerning the event of remission after the previous T-PEMF augmentation and concerning...... with the first series of T-PEMF. Treatment-resistant depression is a condition that has a high degree of multivariate problems. Misuse of alcohol or drugs, severe somatic disorders and other psychosocial problems may need other kinds of treatment before T-PEMF augmentation....

  15. Healthy lifestyle factors and risk of cardiovascular events and mortality in treatment-resistant hypertension: the Reasons for Geographic and Racial Differences in Stroke study.

    Science.gov (United States)

    Diaz, Keith M; Booth, John N; Calhoun, David A; Irvin, Marguerite R; Howard, George; Safford, Monika M; Muntner, Paul; Shimbo, Daichi

    2014-09-01

    Few data exist on whether healthy lifestyle factors are associated with better prognosis among individuals with apparent treatment-resistant hypertension, a high-risk phenotype of hypertension. The purpose of this study was to assess the association of healthy lifestyle factors with cardiovascular events, all-cause mortality, and cardiovascular mortality among individuals with apparent treatment-resistant hypertension. We studied participants (n=2043) from the population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) study with apparent treatment-resistant hypertension (blood pressure ≥140/90 mm Hg despite the use of 3 antihypertensive medication classes or the use of ≥4 classes of antihypertensive medication regardless of blood pressure control). Six healthy lifestyle factors adapted from guidelines for the management of hypertension (normal waist circumference, physical activity ≥4 times/week, nonsmoking, moderate alcohol consumption, high Dietary Approaches to Stop Hypertension diet score, and low sodium-to-potassium intake ratio) were examined. A greater number of healthy lifestyle factors were associated with lower risk for cardiovascular events (n=360) during a mean follow-up of 4.5 years. Multivariable-adjusted hazard ratios [HR (95% confidence interval)] for cardiovascular events comparing individuals with 2, 3, and 4 to 6 versus 0 to 1 healthy lifestyle factors were 0.91 (0.68-1.21), 0.80 (0.57-1.14), and 0.63 (0.41-0.95), respectively (P-trend=0.020). Physical activity and nonsmoking were individual healthy lifestyle factors significantly associated with lower risk for cardiovascular events. Similar associations were observed between healthy lifestyle factors and risk for all-cause and cardiovascular mortality. In conclusion, healthy lifestyle factors, particularly physical activity and nonsmoking, are associated with a lower risk for cardiovascular events and mortality among individuals with apparent treatment-resistant

  16. Double-blind, randomized crossover study of intravenous infusion of magnesium sulfate versus 5% dextrose on depressive symptoms in adults with treatment-resistant depression.

    Science.gov (United States)

    Mehdi, Syed M A; Atlas, Steven E; Qadir, Sidra; Musselman, Dominique; Goldberg, Sharon; Woolger, Judi M; Corredor, Raul; Abbas, Muhammad H; Arosemena, Leopoldo; Caccamo, Simone; Campbell, Carmen S G; Farooqi, Ashar; Gao, Jinrun; Konefal, Janet; Lages, Lucas C; Lantigua, Laura; Lopez, Johanna; Padilla, Vanessa; Rasul, Ammar; Ray, Anna M; Simões, Herbert G; Tiozzo, Eduard; Lewis, John E

    2017-03-01

    Treatment-resistant depression patients are more likely to suffer from comorbid physical and mental disorders, experience marked and protracted functional impairment, and incur higher health-care costs than non-affected individuals. Magnesium sulfate is a treatment option that may offer great potential for patients with treatment-resistant depression based on prior work in animals and humans. Twelve subjects with mild or moderate treatment-resistant depression were randomized into a double-blind crossover trial to receive an infusion of 4 g of magnesium sulfate in 5% dextrose or placebo infusion of 5% dextrose with a 5-day washout in between the 8-day intervention period. Subjects were assessed before and after the intervention for serum and urine magnesium, lipid panel, the Hamilton Rating Scale for Depression, and the Patient Health Questionnaire-9. We found a difference in serum magnesium from day 2 to 8 (pre-infusion) (P < 0.002) and from baseline to day 8 (P < 0.02). No changes were noted on the Hamilton Rating Scale for Depression or the Patient Health Questionnaire-9 24 h post-treatment, but as serum magnesium increased from baseline to day 7, the Patient Health Questionnaire-9 decreased from baseline to day 7 (P = 0.02). Magnesium sulfate did not significantly affect depression 24 h post-infusion, but other results were consistent with the literature. The association between changes in serum magnesium and the Patient Health Questionnaire-9 supports the idea that magnesium sulfate may be used to address treatment-resistant depression, an ongoing medical challenge. © 2016 The Authors Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

  17. Randomized, Double-Blind, Placebo-Controlled Trial of N-Acetylcysteine Augmentation for Treatment-Resistant Obsessive-Compulsive Disorder.

    Science.gov (United States)

    Costa, Daniel L C; Diniz, Juliana B; Requena, Guaraci; Joaquim, Marinês A; Pittenger, Christopher; Bloch, Michael H; Miguel, Euripedes C; Shavitt, Roseli G

    2017-07-01

    To evaluate the efficacy of serotonin reuptake inhibitor (SRI) augmentation with N-acetylcysteine (NAC), a glutamate modulator and antioxidant medication, for treatment-resistant obsessive-compulsive disorder (OCD). We conducted a randomized, double-blind, placebo-controlled, 16-week trial of NAC (3,000 mg daily) in adults (aged 18-65 years) with treatment-resistant OCD, established according to DSM-IV criteria. Forty subjects were recruited at an OCD-specialized outpatient clinic at a tertiary hospital (May 2012-October 2014). The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores. To evaluate the variables group, time, and interaction effects for Y-BOCS scores at all time points, we used nonparametric analysis of variance with repeated measures. Secondary outcomes were the severity scores for anxiety, depression, specific OCD symptom dimensions, and insight. Both groups showed a significant reduction of baseline Y-BOCS scores at week 16: the NAC group had a reduction of 4.3 points (25.6 to 21.3), compared with 3.0 points (24.8 to 21.8) for the placebo group. However, there were no significant differences between groups (P = .92). Adding NAC was superior to placebo in reducing anxiety symptoms (P = .02), but not depression severity or specific OCD symptom dimensions. In general, NAC was well tolerated, despite abdominal pain being more frequently reported in the NAC group (n [%]: NAC = 9 [60.0], placebo = 2 [13.3]; P < .01). Our trial did not demonstrate a significant benefit of NAC in reducing OCD severity in treatment-resistant OCD adults. Secondary analysis suggested that NAC might have some benefit in reducing anxiety symptoms in treatment-resistant OCD patients. ClinicalTrials.gov identifier: NCT01555970. © Copyright 2017 Physicians Postgraduate Press, Inc.

  18. Treatment of Adults With Treatment-Resistant Depression: Electroconvulsive Therapy Plus Antidepressant or Electroconvulsive Therapy Alone? Evidence From an Indirect Comparison Meta-Analysis

    OpenAIRE

    Song, Guo-Min; Tian, Xu; Shuai, Ting; Yi, Li-Juan; Zeng, Zi; Liu, Shuang; Zhou, Jian-Guo; Wang, Yan

    2015-01-01

    Abstract Electroconvulsive therapy (ECT) and antidepressant are the effective treatment alternatives for patients with treatment-resistant depression (TRD); however, the effects and safety of the ECT plus antidepressant relative to ECT alone remain controversial. We decide to assess the potential of ECT plus antidepressant compared with ECT alone by undertaking an indirect comparison meta-analysis. Databases from PubMed, ISI Web of Science, CENTRAL, Clinicaltrials.gov, EMBASE, CBM (China Biom...

  19. A retrospective study of predictive factors for effective aripiprazole augmentation of antidepressant therapy in treatment-resistant depression

    Directory of Open Access Journals (Sweden)

    Sugawara H

    2016-05-01

    Full Text Available Hiroko Sugawara,1,2 Kaoru Sakamoto,1 Tsuyoto Harada,3 Satoru Shimizu,4 Jun Ishigooka1 1Department of Psychiatry, Tokyo Women’s Medical University, 2Support Center for Women Health Care Professionals and Researchers, Tokyo Women’s Medical University, Shinjuku-ku, 3Department of Psychiatry, Tokyo Women’s Medical University Medical Center East, Arakawa-ku, 4Department of Research, Medical Research Institute, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan Background: Several studies have evaluated the efficacy and tolerability of aripiprazole for augmentation of antidepressant therapy for treatment-resistant depression (TRD. Here, we investigated the efficacy of aripiprazole augmentation for TRD including both major depressive disorder and bipolar disorder and the clinical predictors of treatment efficacy in a Japanese population.  Methods: Eighty-five depressed Japanese patients who underwent aripiprazole augmentation therapy after failing to respond satisfactorily to antidepressant monotherapy were included in the study. Treatment responses were evaluated based on Clinical Global Impression Improvement scores assessed 8 weeks after initiation of aripiprazole administration. We compared demographic and diagnostic variables, psychiatric medication variables, and clinical variables between remission and nonremission groups.  Results: The aripiprazole augmentation remission rate was 36.5%. Multiple logistic regression analysis indicated that aripiprazole augmentation was significantly more effective for bipolar depression than for major depressive disorder, and both absence of comorbid anxiety disorders and current episode duration >3 months were significantly associated with the efficacy of aripiprazole augmentation.  Conclusion: Polarity of depression, comorbidity of anxiety disorders, and current episode duration may predict the efficacy of aripiprazole augmentation for TRD including both major depressive disorder and

  20. Electroconvulsive Therapy Added to Non-Clozapine Antipsychotic Medication for Treatment Resistant Schizophrenia: Meta-Analysis of Randomized Controlled Trials.

    Directory of Open Access Journals (Sweden)

    Wei Zheng

    Full Text Available This meta-analysis of randomized controlled trials (RCTs examined the efficacy and safety of the combination of electroconvulsive therapy (ECT and antipsychotic medication (except for clozapine versus the same antipsychotic monotherapy for treatment-resistant schizophrenia (TRS. Two independent investigators extracted data for a random effects meta-analysis and pre-specified subgroup and meta-regression analyses. Weighted and standard mean difference (WMD/SMD, risk ratio (RR ±95% confidence intervals (CIs, number needed to treat (NNT, and number needed to harm (NNH were calculated. Eleven studies (n = 818, duration = 10.2±5.5 weeks were identified for meta-analysis. Adjunctive ECT was superior to antipsychotic monotherapy regarding (1 symptomatic improvement at last-observation endpoint with an SMD of -0.67 (p<0.00001; I2 = 62%, separating the two groups as early as weeks 1–2 with an SMD of -0.58 (p<0.00001; I2 = 0%; (2 study-defined response (RR = 1.48, p<0.0001 with an NNT of 6 (CI = 4–9 and remission rate (RR = 2.18, p = 0.0002 with an NNT of 8 (CI = 6–16; (3 PANSS positive and general symptom sub-scores at endpoint with a WMD between -3.48 to -1.32 (P = 0.01 to 0.009. Subgroup analyses were conducted comparing double blind/rater-masked vs. open RCTs, those with and without randomization details, and high quality (Jadad≥adadup analyses were Jadad<3 studies. The ECT-antipsychotic combination caused more headache (p = 0.02 with an NNH of 6 (CI = 4–11 and memory impairment (p = 0.001 with an NNH of 3 (CI = 2–5. The use of ECT to augment antipsychotic treatment (clozapine excepted can be an effective treatment option for TRS, with increased frequency of self-reported memory impairment and headache.CRD42014006689 (PROSPERO.

  1. Desenvolvimento da versão em português da Escala Administrada pelo Clínico para Avaliação de Mania (EACA-M: "Escala de Mania de Altman" Desarrollo de la versión para Portugués de la Escala Administrativa por el Clínico para Avaluación de Manía (EACA - M: "Escala de Manía de Altman" Development of the Portuguese-language versión of the Clinician-Administered Rating Scale for Mania (CARS-M: "Altman Scale for Mania"

    Directory of Open Access Journals (Sweden)

    Flávio Shansis

    2003-12-01

    Full Text Available OBJETIVOS: No presente artigo é apresentado o desenvolvimento da versão em português da "Clinician-Administered Rating Scale for Mania" (CARS-M de Altman e colaboradores intitulada: Escala Administrada pelo Clínico para Avaliação de Mania (EACA-M ou "Escala de Mania de Altman". Os objetivos desse artigo são: (1 descrever a metodologia de elaboração da versão em português da CARS-M, (2 transmitir as impressões dos profissionais que a utilizaram e (3 disponibilizar a escala na íntegra em língua portuguesa. MÉTODOS: Os métodos utilizados foram: a painel bilíngüe de tradução e discussão de todos os itens; b retrotradução por pessoa habilitada; c envio ao próprio autor da escala da nova versão em inglês originada a partir da sua tradução para o português; d discussão com o autor dos pontos pendentes, bem como nova discussão entre os participantes do grupo de pesquisadores brasileiros até se chegar a um consenso. CONCLUSÕES: A impressão dos autores é a de que a EACA-M permite não apenas a fácil pontuação de todos os escores, mas também cobre o largo espectro de apresentação de uma síndrome maníaca. Com este artigo, a comunidade científica de Língua Portuguesa passa a dispor de um importante instrumento para avaliação do estado maníaco.OBJETIVOS: En el siguiente artículo se presenta el desarrollo de la versión en portugués de la "Clinician-Administered Rating Scale for Mania" (CARS-M de Altman y sus colaboradores titulada: "Escala Administrada por el Clínico para la Evaluación de Manía" (EACA-M, o "Escala de Altman". Los objetivos de este artículo son: 1 describir la metodología de elaboración de la versión en portugués de la CARS-M. 2 transmitir las impresiones de los profesionales que la utilizaron. 3 disponibilizar la escala en su íntegra, en lengua portuguesa. MÉTODOS: los métodos utilizados son: a panel bilingüe de traducción y discusión de todos los ítems; b retro traducción por

  2. Early Nonresponse in the Antipsychotic Treatment of Acute Mania: A Criterion for Reconsidering Treatment? Results From an Individual Patient Data Meta-Analysis.

    Science.gov (United States)

    Welten, Carlijn C M; Koeter, Maarten W J; Wohlfarth, Tamar D; Storosum, Jitschak G; van den Brink, Wim; Gispen-de Wied, Christine C; Leufkens, Hubert G M; Denys, Damiaan A J P

    2016-09-01

    To investigate whether early nonresponse to antipsychotic treatment of acute mania predicts treatment failure and, if so, to establish the best definition or criterion of an early nonresponse. Short-term efficacy studies assessing antipsychotics that were submitted to the Dutch Medicines Evaluation Board during an 11-year period as part of the marketing authorization application for the indication of acute manic episode of bipolar disorder. Pharmaceutical companies provided their raw patient data, which enabled us to perform an individual patient data meta-analysis. All double-blind, randomized, placebo-controlled trials assessing the efficacy of antipsychotics for acute manic episode of bipolar disorder were included (10 trials). All patients with data available for completer analysis (N = 1,243), symptom severity scores on the Young Mania Rating Scale (YMRS) at weeks 0, 1, and 2 and at study end point (week 3 or 4). The a priori chances of nonresponse and nonremission at study end point were 40.9% (95% CI, 38.2%-43.6%) and 65.3% (95% CI, 62.0%-68.6%), respectively. Early nonresponse in weeks 1 and 2, defined by cutoff scores ranging from a ≤ 10% to a ≤ 50% reduction in symptoms compared to baseline on the YMRS, significantly predicted nonresponse (≤ 0% symptom reduction) and nonremission (YMRS score higher than 8) in week 3. The predictive value of early nonresponse (PVnr_se) at week 1 for both nonresponse and nonremission at study end point declined linearly with increasing cutoff scores of early nonresponse; nonresponse: 76.0% (95% CI, 69.7%-82.3%) for a ≤ 10% response to 48.7% (95% CI, 45.5%-51.9%) for a ≤ 50% response; nonremission: 92.2% (95% CI, 88.3%-96.1%) for a ≤ 10% response to 76.8% (95% CI, 74.4%-79.5%) for a ≤ 50% response. A similar linear decline was observed for increasing cutoff scores of early nonresponse at week 2 for nonresponse, but not for nonremission at end point: nonresponse 90.3% (95% CI, 84.6%-96.0%) for a ≤ 10% response

  3. Sodium butyrate has an antimanic effect and protects the brain against oxidative stress in an animal model of mania induced by ouabain.

    Science.gov (United States)

    Valvassori, Samira S; Dal-Pont, Gustavo C; Steckert, Amanda V; Varela, Roger B; Lopes-Borges, Jéssica; Mariot, Edemilson; Resende, Wilson R; Arent, Camila O; Carvalho, André F; Quevedo, João

    2016-01-30

    Studies have consistently reported the participation of oxidative stress in bipolar disorder (BD). Evidence indicates that epigenetic regulations have been implicated in the pathophysiology of mood disorders. Considering these evidences, the present study aimed to investigate the effects of sodium butyrate (SB), a histone deacetylase (HDAC)inhibitor, on manic-like behavior and oxidative stress parameters (TBARS and protein carbonyl content and SOD and CAT activities) in frontal cortex and hippocampus of rats subjected to the animal model of mania induced by intracerebroventricular (ICV) ouabain administration.The results showed that SB reversed ouabain-induced hyperactivity, which represents a manic-like behavior in rats. In addition, the ouabain ICV administration induced oxidative damage to lipid and protein and alters antioxidant enzymes activity in all brain structures analyzed. The treatment with SB was able to reversesboth behavioral and oxidative stress parameters alteration induced by ouabain.In conclusion, we suggest that SB can be considered a potential new mood stabilizer by acts on manic-like behavior and regulatesthe antioxidant enzyme activities, protecting the brain against oxidative damage. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Exploring a post-traumatic stress disorder paradigm in Flinders sensitive line rats to model treatment-resistant depression I: bio-behavioural validation and response to imipramine.

    Science.gov (United States)

    Brand, Sarel Jacobus; Harvey, Brian Herbert

    2017-08-01

    Co-morbid depression with post-traumatic stress disorder (PTSD) is often treatment resistant. In developing a preclinical model of treatment-resistant depression (TRD), we combined animal models of depression and PTSD to produce an animal with more severe as well as treatment-resistant depressive-like behaviours. Male Flinders sensitive line (FSL) rats, a genetic animal model of depression, were exposed to a stress re-stress model of PTSD [time-dependent sensitisation (TDS)] and compared with stress-naive controls. Seven days after TDS stress, depressive-like and coping behaviours as well as hippocampal and cortical noradrenaline (NA) and 5-hydroxyindoleacetic acid (5HIAA) levels were analysed. Response to sub-chronic imipramine treatment (IMI; 10 mg/kg s.c.×7 days) was subsequently studied. FSL rats demonstrated bio-behavioural characteristics of depression. Exposure to TDS stress in FSL rats correlated negatively with weight gain, while demonstrating reduced swimming behaviour and increased immobility versus unstressed FSL rats. IMI significantly reversed depressive-like (immobility) behaviour and enhanced active coping behaviour (swimming and climbing) in FSL rats. The latter was significantly attenuated in FSL rats exposed to TDS versus unstressed FSL rats. IMI reversed reduced 5HIAA levels in unstressed FSL rats, whereas exposure to TDS negated this effect. Lowered NA levels in FSL rats were sustained after TDS with IMI significantly reversing this in the hippocampus. Combining a gene-X-environment model of depression with a PTSD paradigm produces exaggerated depressive-like symptoms that display an attenuated response to antidepressant treatment. This work confirms combining FSL rats with TDS exposure as a putative animal model of TRD.

  5. Culturally adapted CBT (CA-CBT) for Latino women with treatment-resistant PTSD: a pilot study comparing CA-CBT to applied muscle relaxation.

    Science.gov (United States)

    Hinton, Devon E; Hofmann, Stefan G; Rivera, Edwin; Otto, Michael W; Pollack, Mark H

    2011-04-01

    We examined the therapeutic efficacy of a culturally adapted form of CBT (CA-CBT) for PTSD as compared to applied muscle relaxation (AMR) for female Latino patients with treatment-resistant PTSD. Participants were randomized to receive either CA-CBT (n = 12) or AMR (n = 12), and were assessed before treatment, after treatment, and at a 12-week follow-up. The treatments were manualized and delivered in the form of group therapy across 14 weekly sessions. Assessments included a measure of PTSD, anxiety, culturally relevant idioms of distress (nervios and ataque de nervios), and emotion regulation ability. Patients receiving CA-CBT improved significantly more than in the AMR condition. Effect size estimates showed very large reductions in PTSD symptoms from pretreatment to posttreatment in the CA-CBT group (Cohen's d = 2.6) but only modest improvements in the AMR group (0.8). These results suggest that CA-CBT can be beneficial for previously treatment-resistant PTSD in Latino women. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. GLUT1 deficiency syndrome as a cause of encephalopathy that includes cognitive disability, treatment-resistant infantile epilepsy and a complex movement disorder.

    Science.gov (United States)

    Graham, John M

    2012-05-01

    Glucose transporter-1 (GLUT1) deficiency syndrome is caused by heterozygous mutations in the SLC2A1 gene, resulting in impaired glucose transport into the brain. It is characterized by a low glucose concentration in the cerebrospinal fluid (hypoglycorrhachia) in the absence of hypoglycemia, in combination with low to normal lactate in the cerebrospinal fluid (CSF). It often results in treatment-resistant infantile epilepsy with progressive developmental disabilities and a complex movement disorder. Recognizing GLUT1 deficiency syndrome is important, since initiation of a ketogenic diet can reduce the frequency of seizures and the severity of the movement disorder. There can be a considerable delay in diagnosing GLUT1 deficiency syndrome, and this point is illustrated by the natural history of this disorder in a 21-year-old woman with severe, progressive neurological disabilities. Her encephalopathy consisted of treatment-resistant seizures, a complex movement disorder, progressive intellectual disability, and deceleration of her head growth after late infancy. Focused evaluation at age 21 revealed GLUT1 deficiency caused by a novel heterozygous missence mutation in exon 7 (c.938C > A; p.Ser313Try) in SLC2A1 as the cause for her disabilities. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  7. Plasma levels of mature brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) in treatment-resistant schizophrenia treated with clozapine.

    Science.gov (United States)

    Yamamori, Hidenaga; Hashimoto, Ryota; Ishima, Tamaki; Kishi, Fukuko; Yasuda, Yuka; Ohi, Kazutaka; Fujimoto, Michiko; Umeda-Yano, Satomi; Ito, Akira; Hashimoto, Kenji; Takeda, Masatoshi

    2013-11-27

    Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. Peripheral BDNF levels in patients with schizophrenia have been widely reported in the literature. However, it is still controversial whether peripheral levels of BDNF are altered in patients with schizophrenia. The peripheral BDNF levels previously reported in patients with schizophrenia were total BDNF (proBDNF and mature BDNF) as it was unable to specifically measure mature BDNF due to limited BDNF antibody specificity. In this study, we examined whether peripheral levels of mature BDNF were altered in patients with treatment-resistant schizophrenia. Matrix metalloproteinase-9 (MMP-9) levels were also measured, as MMP-9 plays a role in the conversion of proBDNF to mature BDNF. Twenty-two patients with treatment-resistant schizophrenia treated with clozapine and 22 age- and sex-matched healthy controls were enrolled. The plasma levels of mature BDNF and MMP-9 were measured using ELISA kits. No significant difference was observed for mature BDNF however, MMP-9 was significantly increased in patients with schizophrenia. The significant correlation was observed between mature BDNF and MMP-9 plasma levels. Neither mature BDNF nor MMP-9 plasma levels were associated clinical variables. Our results do not support the view that peripheral BDNF levels are associated with schizophrenia. MMP-9 may play a role in the pathophysiology of schizophrenia and serve as a biomarker for schizophrenia. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  8. Repetitive transcranial magnetic stimulation of the supplementary motor area in treatment-resistant obsessive-compulsive disorder: An open-label pilot study.

    Science.gov (United States)

    Lee, Young-Ji; Koo, Bon-Hoon; Seo, Wan-Seok; Kim, Hye-Geum; Kim, Ji-Yean; Cheon, Eun-Jin

    2017-10-01

    Obsessive-compulsive disorder (OCD) is a severely distressing disorder represented by obsessions and compulsions. A significant proportion of OCD patients fail to improve with conventional treatment methods. Repetitive transcranial magnetic stimulation (rTMS) has been proposed as an alternative for OCD treatment. Functional neuroimaging studies indicate that OCD is associated with increased activity in the supplementary motor area (SMA), a region that plays an important role in the pathophysiology of this disorder. In this study, we assessed the efficacy of augmentation with 1Hz rTMS over the SMA in treatment-resistant OCD patients. The participants received 1Hz rTMS over the SMA in 20 daily sessions for 4weeks. We observed significant reduction in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score at the 4th week of the treatment. Reduction in compulsion contributed to the reduction of global Y-BOCS whereas there was no significant reduction in obsession. Clinical global impression-global improvement also showed significant change at the 2nd and 4th week of the treatment. No additional significant changes or significant adverse effects were seen. These findings suggest that 1Hz rTMS over the SMA can be an efficient and safe add-on therapeutic method in treatment-resistant patients with OCD. Further controlled studies in larger samples are required to confirm the effect of 1Hz rTMS over the SMA in OCD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Natural speech algorithm applied to baseline interview data can predict which patients will respond to psilocybin for treatment-resistant depression.

    Science.gov (United States)

    Carrillo, Facundo; Sigman, Mariano; Fernández Slezak, Diego; Ashton, Philip; Fitzgerald, Lily; Stroud, Jack; Nutt, David J; Carhart-Harris, Robin L

    2018-04-01

    Natural speech analytics has seen some improvements over recent years, and this has opened a window for objective and quantitative diagnosis in psychiatry. Here, we used a machine learning algorithm applied to natural speech to ask whether language properties measured before psilocybin for treatment-resistant can predict for which patients it will be effective and for which it will not. A baseline autobiographical memory interview was conducted and transcribed. Patients with treatment-resistant depression received 2 doses of psilocybin, 10 mg and 25 mg, 7 days apart. Psychological support was provided before, during and after all dosing sessions. Quantitative speech measures were applied to the interview data from 17 patients and 18 untreated age-matched healthy control subjects. A machine learning algorithm was used to classify between controls and patients and predict treatment response. Speech analytics and machine learning successfully differentiated depressed patients from healthy controls and identified treatment responders from non-responders with a significant level of 85% of accuracy (75% precision). Automatic natural language analysis was used to predict effective response to treatment with psilocybin, suggesting that these tools offer a highly cost-effective facility for screening individuals for treatment suitability and sensitivity. The sample size was small and replication is required to strengthen inferences on these results. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Predictive value of dorso-lateral prefrontal connectivity for rTMS response in treatment-resistant depression: A brain perfusion SPECT study.

    Science.gov (United States)

    Richieri, Raphaëlle; Verger, Antoine; Boyer, Laurent; Boucekine, Mohamed; David, Anthony; Lançon, Christophe; Cermolacce, Michel; Guedj, Eric

    2018-05-18

    Previous clinical trials have suggested that repetitive transcranial magnetic stimulation (rTMS) has a significant antidepressant effect in patients with treatment resistant depression (TRD). However, results remain heterogeneous with many patients without effective response. The aim of this SPECT study was to determine before treatment the predictive value of the connectivity of the stimulated area on further rTMS response in patients with TRD. Fifty-eight TRD patients performed a brain perfusion SPECT before high frequency rTMS of the left dorsolateral prefrontal cortex (DLPFC). A voxel based-analysis was achieved to compare connectivity of the left DLPFC in responders and non-responders using inter-regional correlations (p left DLPFC and the right cerebellum in comparison to non-responders, independently of age, gender, severity of depression, and severity of treatment resistance. The area under the curve for the combination of these two SPECT clusters to predict rTMS response was 0.756 (p left DLPFC predicts rTMS response before treatment. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

  11. Omega-3 Fatty Acids and Mood Stabilizers Alter Behavioural and Energy Metabolism Parameters in Animals Subjected to an Animal Model of Mania Induced by Fenproporex.

    Science.gov (United States)

    Cancelier, Kizzy; Gomes, Lara M; Carvalho-Silva, Milena; Teixeira, Letícia J; Rebelo, Joyce; Mota, Isabella T; Arent, Camila O; Mariot, Edemilson; Kist, Luiza W; Bogo, Maurício R; Quevedo, João; Scaini, Giselli; Streck, Emilio L

    2017-08-01

    Studies have shown that changes in energy metabolism are involved in the pathophysiology of bipolar disorder (BD). It was suggested that omega-3 (ω3) fatty acids have beneficial properties in the central nervous system and that this fatty acid plays an important role in energy metabolism. Therefore, the study aimed to evaluate the effect of ω3 fatty acids alone and in combination with lithium (Li) or valproate (VPA) on behaviour and parameters of energy metabolism in an animal model of mania induced by fenproporex. Our results showed that co-administration of ω3 fatty acids and Li was able to prevent and reverse the increase in locomotor and exploratory activity induced by fenproporex. The combination of ω3 fatty acids with VPA was only able to prevent the fenproporex-induced hyperactivity. For the energy metabolism parameters, our results showed that the administration of Fen for the reversal or prevention protocol inhibited the activities of succinate dehydrogenase, complex II and complex IV in the hippocampus. However, hippocampal creatine kinase (CK) activity was decreased only for the reversal protocol. The ω3 fatty acids, alone and in combination with VPA or Li, prevented and reversed the decrease in complex II, IV and succinate dehydrogenase activity, whereas the decrease in CK activity was only reversed after the co-administration of ω3 fatty acids and VPA. In conclusion, our results showed that the ω3 fatty acids combined with VPA or Li were able to prevent and reverse manic-like hyperactivity and the inhibition of energy metabolism in the hippocampus, suggesting that ω3 fatty acids may play an important role in the modulation of behavioural parameters and energy metabolism.

  12. Transdiagnostic assessment of repetitive negative thinking and responses to positive affect: Structure and predictive utility for depression, anxiety, and mania symptoms.

    Science.gov (United States)

    McEvoy, Peter M; Hyett, Matthew P; Ehring, Thomas; Johnson, Sheri L; Samtani, Suraj; Anderson, Rebecca; Moulds, Michelle L

    2018-05-01

    Repetitive negative thinking (RNT) is a cognitive process that is repetitive, passive, relatively uncontrollable, and focused on negative content, and is elevated in emotional disorders including depression and anxiety disorders. Repetitive positive thinking is associated with bipolar disorder symptoms. The unique contributions of positive versus negative repetitive thinking to emotional symptoms are unknown. The first aim of this study was to use confirmatory factor analyses to evaluate the psychometrics of two transdiagnostic measures of RNT, the Repetitive Thinking Questionnaire (RTQ-10) and Perseverative Thinking Questionnaire (PTQ), and a measure of repetitive positive thinking, the Responses to Positive Affect (RPA) Questionnaire. The second aim was to determine incremental predictive utility of these measures. All measures were administered to a sample of 2088 undergraduate students from the Netherlands (n = 992), Australia (n = 698), and America (n = 398). Unidimensional, bifactor, and three-factor models were supported for the RTQ-10, PTQ, and RPA, respectively. A common factor measured by all PTQ items explained most variance in PTQ scores suggesting that this measure is essentially unidimensional. The RNT factor of the RTQ-10 demonstrated the strongest predictive utility, although the PTQ was also uniquely although weakly associated with anxiety, depression, and mania symptoms. The RPA dampening factor uniquely predicted anxiety and depression symptoms, suggesting that this scale is a separable process to RNT as measured by the RTQ-10 and PTQ. Findings were cross-sectional and need to be replicated in clinical samples. Transdiagnostic measures of RNT are essentially unidimensional, whereas RPA is multidimensional. RNT and RPA have unique predictive utility. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Amisulpride plus valproate vs haloperidol plus valproate in the treatment of acute mania of bipolar I patients: a multicenter, open-label, randomized, comparative trial

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    Pierre Thomas

    2008-06-01

    Full Text Available Pierre Thomas1, Eduard Vieta2 for the SOLMANIA study group1Department of Psychiatry, Fontan Hospital CHRU Lille, University of Lille 2, France; 2Bipolar Disorders Program, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, SpainAbstract: The primary objective of this study was to compare the effectiveness of combination treatment of valproate and amisulpride with that of valproate and haloperidol in bipolar I disorder. Adult inpatients with a current manic episode fulfilling DSM-IV-TR diagnostic criteria for bipolar type I disorder were included. Patients were randomized to amisulpride (400–800 mg/day or haloperidol (5–15 mg/day for 3 months and all received valproate. The primary effectiveness criterion was the percentage of responders (defined by a decrease of ≥50% of the Y-MRS in patients completing the study. Safety was evaluated by adverse event reporting, determination of extrapyramidal function and clinical examination. Sixty-two patients were randomized to receive valproate-amisulpride, and 61 to receive valproate-haloperidol. At study end, responder rates were 72.6% in the amisulpride group and 65.5% in the haloperidol group. Remission rates were 83.9% and 89.7%, respectively. At study end, neither response rates nor remission rates differed significantly between groups. Treatment-emergent adverse events occurred significantly (p = 0.009 more frequently in the haloperidol group (86.4% than in the amisulpride group (66.1%. In conclusion, the valproate–amisulpride combination was as effective as the valproate – haloperidol combination in bipolar I patients, with a better safety profile.Keywords: amisulpride, valproate, haloperidol, clinical trial, mania, bipolar disorder

  14. Effectiveness of olanzapine monotherapy and olanzapine combination treatment in the long term following acute mania--results of a two year observational study in bipolar disorder (EMBLEM).

    Science.gov (United States)

    Gonzalez-Pinto, Ana; Vieta, Eduard; Reed, Catherine; Novick, Diego; Barraco, Alessandra; Aguado, Jaume; Haro, Josep Maria

    2011-06-01

    This study compared the 2-year outcomes of patients with a manic/mixed episode of bipolar disorder taking olanzapine monotherapy or olanzapine in combination with other agents. EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 2-year, prospective, observational study of clinical and functional outcomes of bipolar patients with an index manic/mixed episode. The study consisted of two phases: acute (12 weeks) and maintenance (follow-up over 2 years). The longitudinal outcome measure was the Clinical Global Impression-Bipolar Disorder scale. Cox regression models compared outcomes of both therapy groups using intention-to-treat and switching medication analysis. Treatment-emergent adverse events were also assessed. 1076 patients were included in this analysis. 29% took olanzapine as monotherapy (n = 313) and 71% as combination (n = 763) at 12-weeks post-baseline (end of study acute phase). After adjusting for patient characteristics using switching medication analysis, only relapse rates differed (p = 0.01) in favour of monotherapy-treated patients. There was no significant difference in rates of improvement, remission, and recovery. Patients treated with combination therapy reported more tremor (OR 2.37, 95%CI 1.44-3.89) and polyuria (OR 3.08, 95%CI 1.45-6.54) treatment-emergent events than monotherapy, although weight change was greater in the monotherapy group. Unknown confounding and potential selection bias may differentially impact treatment outcomes. EMBLEM patients benefitted from the selected therapy to a similar extent. Differences in patient characteristics between those prescribed monotherapy and combination therapy appear to be clinically relevant in the treatment decision. Physicians must balance the benefits and risks when determining appropriate treatment for individual patients. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. The effect of Group Cognitive-Behaviour Therapy in combination with Pharmacotherapy on Mania and Depression Symptoms and Awareness of warming signs of relapse in patients with Bipolar Disorder

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    Bahram Ali Ghanbari Hashemabadi

    2009-04-01

    Full Text Available "n Objective: This research has been done according to the cognitivebehavioral theories and biochemical model in order to evaluate the efficiency of Group Cognitive-Behavior Therapy in combination with Pharmacotherapy on Mania and Depression Symptoms and Awareness of warning signs of relapse in patients with Bipolar Disorder. "n "nMethods:In this study with the experimental pretest- posttest- follow up plan , 30 women suffering from bipolar disorder, randomly assigned to receive either the group cognitive-behavior therapy (experimental group, n=15 or usual treatment (control group, n=15;and were follow-up for a six months. patients in both groups were prescribed standard Pharmacotherapy. First all subjects were put to a pretest in equal conditions with measures of scale 2 and 9 of MMPI Test, and warning signs checklist. Then the experimental group received group cognitive-behavior therapy for 8 sessions in addition to their medication therapy. The control group only received medicine. At the end of the experiment, all subjects were tested under equal conditions. After completion of the treatment process, the subjects of both groups were supervised for 6 months. The findings of the study were analyzed by the statistical method of Multi-variable analysis of variance with repetitive measurements. "nResults:The findings showed that the group cognitive-behavior therapy had been significantly more efficient in reduction of mania symptoms {p=0/03} and increment of awareness of warning signs of relapse {p=0/00} in comparison with control group; but there is no significantly differences in depression symptoms between two groups. "nConclusion: The findings of this study suggest the beneficial effect of Group cognitive-behavior therapy in reducing of mania symptoms and increment of awareness of warning signs of relapse. Therefore, it can be used as a complementary treatment by clinicians

  16. Brain microstructural abnormalities revealed by diffusion tensor images in patients with treatment-resistant depression compared with major depressive disorder before treatment

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Yan, E-mail: clare1475@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China); Qin Lingdi, E-mail: flyfool318@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China); Chen Jun, E-mail: doctor_cj@msn.com [Shanghai Mental Health Center, Jiao Tong University Medical School, Shanghai, 200030 (China); Qian Lijun, E-mail: dearqlj@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China); Tao Jing, E-mail: jing318@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China); Fang Yiru, E-mail: fangyr@sina.com [Shanghai Mental Health Center, Jiao Tong University Medical School, Shanghai, 200030 (China); Xu Jianrong, E-mail: xujianr@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China)

    2011-11-15

    Treatment-resistant depression (TRD) is a therapeutic challenge for clinicians. Despite a growing interest in this area, an understanding of the pathophysiology of depression, particularly TRD, remains lacking. This study aims to detect the white matter abnormalities of whole brain fractional anisotropy (FA) in patients with TRD compared with major depressive disorder (MDD) before treatment by voxel-based analysis using diffusion tensor imaging. A total of 100 patients first diagnosed with untreated MDD underwent diffusion tensor imaging scans. 8 weeks after the first treatment, 54 patients showed response to the medication, whereas 46 did not. Finally, 20 patients were diagnosed with TRD after undergoing another treatment. A total of 20 patients with TRD and another 20 with MDD before treatment matched in gender, age, and education was enrolled in the research. For every subject, an FA map was generated and analyzed using SPM5. Subsequently, t-test was conducted to compare the FA values voxel to voxel between the two groups (p < 0.001 [FDR corrected], t > 7.57, voxel size > 30). Voxel-based morphometric (VBM) analysis was performed using T1W images. Significant reductions in FA were found in the white matter located in the bilateral of the hippocampus (left hippocampus: t = 7.63, voxel size = 50; right hippocampus: t = 7.82, voxel size = 48). VBM analysis revealed no morphological abnormalities between the two groups. Investigation of brain anisotropy revealed significantly decreased FA in both sides of the hippocampus. Although preliminary, our findings suggest that microstructural abnormalities in the hippocampus indicate vulnerability to treatment resistance.

  17. Brain microstructural abnormalities revealed by diffusion tensor images in patients with treatment-resistant depression compared with major depressive disorder before treatment

    International Nuclear Information System (INIS)

    Zhou Yan; Qin Lingdi; Chen Jun; Qian Lijun; Tao Jing; Fang Yiru; Xu Jianrong

    2011-01-01

    Treatment-resistant depression (TRD) is a therapeutic challenge for clinicians. Despite a growing interest in this area, an understanding of the pathophysiology of depression, particularly TRD, remains lacking. This study aims to detect the white matter abnormalities of whole brain fractional anisotropy (FA) in patients with TRD compared with major depressive disorder (MDD) before treatment by voxel-based analysis using diffusion tensor imaging. A total of 100 patients first diagnosed with untreated MDD underwent diffusion tensor imaging scans. 8 weeks after the first treatment, 54 patients showed response to the medication, whereas 46 did not. Finally, 20 patients were diagnosed with TRD after undergoing another treatment. A total of 20 patients with TRD and another 20 with MDD before treatment matched in gender, age, and education was enrolled in the research. For every subject, an FA map was generated and analyzed using SPM5. Subsequently, t-test was conducted to compare the FA values voxel to voxel between the two groups (p 7.57, voxel size > 30). Voxel-based morphometric (VBM) analysis was performed using T1W images. Significant reductions in FA were found in the white matter located in the bilateral of the hippocampus (left hippocampus: t = 7.63, voxel size = 50; right hippocampus: t = 7.82, voxel size = 48). VBM analysis revealed no morphological abnormalities between the two groups. Investigation of brain anisotropy revealed significantly decreased FA in both sides of the hippocampus. Although preliminary, our findings suggest that microstructural abnormalities in the hippocampus indicate vulnerability to treatment resistance.

  18. A view from Riggs: treatment resistance and patient authority-IX. Integrative psychodynamic treatment of psychotic disorders.

    Science.gov (United States)

    Tillman, Jane G

    2008-01-01

    Psychotic spectrum disorders present treatment challenges for patients, families, and clinicians. This article addresses the history of the dualism in the field between biological and psychological approaches to mental disorders, and surveys the contemporary literature about the etiology and treatment of psychotic spectrum disorders. An integrative approach to treatment derived from work at Austen Riggs with previously treatment refractory patients with psychotic spectrum disorders is described that combines individual psycho- dynamic psychotherapy, psychopharmacology, family systems approaches, and intensive psychosocial engagement. Helping patients develop their own authority to join the treatment, use relationships for learning, and understand the meaning of their symptoms is central to the treatment at Austen Riggs. An extended case vignette of a patient diagnosed with a schizoaffective disorder is presented illustrating this integrative psychodynamic treatment approach.

  19. Desenvolvimento da versão em português da Escala de Avaliação de Mania de Bech-Rafaelsen (EAM-BR Desarrollo de la versión en portugués de la Escala de Evaluación de la Manía de Bech-Rafaelsen (EAM-BR Development of the Portuguese version of the Bech-Rafaelsen Mania Rating Scale (BRMaS

    Directory of Open Access Journals (Sweden)

    Flávio Shansis

    2004-04-01

    Full Text Available No presente artigo, é apresentado o desenvolvimento da versão em português da Bech-Rafaelsen Mania Rating Scale (BRMaS de Bech e colaboradores intitulada: Escala de Avaliação de Mania de Bech-Rafaelsen (EAM-BR. A EAM-BR foi desenvolvida para ser aplicada na forma de uma entrevista semi-estruturada breve conduzida pelo clínico. Ela investiga a presença versus a ausência de sintomas maníacos, sua severidade e sua mudança em resposta ao tratamento. São descritas as qualidades psicométricas da escala original. Com este artigo, a comunidade científica passa a dispor em português de mais um importante instrumento para avaliação do estado maníaco.En este artículo se presenta el desarrollo de la versión en portugués de la Bech-Rafaelsen Mania Rating Scale (BRMaS de Bech y colaboradores titulada: Escala de la Evaluación de Manía de Bech-Rafaelsen (EAM-BR. La EAM-BR fue desarrollada para ser aplicada en la forma de entrevista semi-estructurada breve conduzida por el clínico. Ella investiga la presencia versus la ausencia de síntomas maníacos, su severidad y su mudanza en respuesta al tratamiento. Son descriptas las cualidades psicométricas de la escala original. Con este artículo la comunidad científica dispone, en portugués, de un importante instrumento a más para la evaluación del estado maníaco.In this article the authors present the development of the Portuguese-language version of a scale intended to evaluate the manic state: Bech-Rafaelsen Mania Rating Scale (BRMaS. The BRMaS was created in order to assist the clinician to evaluate a manic patient in a semi-structured interview. This article provides the scientific community with an important instrument to rate manic presentations in native speakers of Portuguese.

  20. The impact of childhood trauma on cognitive functioning in patients recently recovered from a first manic episode: data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM).

    Science.gov (United States)

    Bücker, J; Kozicky, J; Torres, I J; Kauer-Sant'anna, M; Silveira, L E; Bond, D J; Lam, R W; Yatham, L N

    2013-06-01

    Both bipolar disorder (BD) and childhood trauma are associated with cognitive impairment. People with BD have high rates of childhood trauma, which confer greater overall disease severity, but, it is unknown if childhood trauma is associated with greater neurocognitive impairment in BD patients early in the course of their illnesses. In this study, we investigated the impact of childhood trauma on specific cognitive dysfunction in patients who recently recovered from their first episode of mania. Data were available for 64 patients and 28 healthy subjects matched by age, gender and pre-morbid IQ, recruited from a large university medical center. History of childhood trauma was measured using the Childhood Trauma Questionnaire. Cognitive function was assessed through a comprehensive neuropsychological test battery. Trauma was associated with poorer cognitive performance in patients on cognitive measures of IQ, auditory attention and verbal and working memory, and a different pattern was observed in healthy subjects. We had a modest sample size, particularly in the group of healthy subjects with trauma. Childhood trauma was associated with poorer cognition in BD patients who recently recovered from a first episode of mania compared to healthy subjects. The results require replication, but suggest that the co-occurrence of trauma and bipolar disorder can affect those cognitive areas that are already more susceptible in patients with BD. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Obsessive-Compulsive-Bipolar Disorder Comorbidity: A Case Report

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    João Pedro Ribeiro

    2013-12-01

    Full Text Available Anxiety disorders have been described as features of Bipolar Disorder (BD, and Obsessive-compulsive-bipolar disorder (OCBD may occur in as many as 56% of obsessive-compulsive patients. Mania in Obsessive-Compulsive Disorder (OCD can occur either as an independent comorbidity or as a result of an antidepressant-induced switch. We report the case of a 38-year-old male with a 3 year diagnosis of OCD treated with antidepressants, admitted due to a manic episode, and describe diagnostic and treatment challenges of this comorbidity.

  2. Incorporating Cancer Stem Cells in Radiation Therapy Treatment Response Modeling and the Implication in Glioblastoma Multiforme Treatment Resistance

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    Yu, Victoria Y.; Nguyen, Dan; Pajonk, Frank; Kupelian, Patrick; Kaprealian, Tania; Selch, Michael; Low, Daniel A.; Sheng, Ke, E-mail: ksheng@mednet.ucla.edu

    2015-03-15

    Purpose: To perform a preliminary exploration with a simplistic mathematical cancer stem cell (CSC) interaction model to determine whether the tumor-intrinsic heterogeneity and dynamic equilibrium between CSCs and differentiated cancer cells (DCCs) can better explain radiation therapy treatment response with a dual-compartment linear-quadratic (DLQ) model. Methods and Materials: The radiosensitivity parameters of CSCs and DCCs for cancer cell lines including glioblastoma multiforme (GBM), non–small cell lung cancer, melanoma, osteosarcoma, and prostate, cervical, and breast cancer were determined by performing robust least-square fitting using the DLQ model on published clonogenic survival data. Fitting performance was compared with the single-compartment LQ (SLQ) and universal survival curve models. The fitting results were then used in an ordinary differential equation describing the kinetics of DCCs and CSCs in response to 2- to 14.3-Gy fractionated treatments. The total dose to achieve tumor control and the fraction size that achieved the least normal biological equivalent dose were calculated. Results: Smaller cell survival fitting errors were observed using DLQ, with the exception of melanoma, which had a low α/β = 0.16 in SLQ. Ordinary differential equation simulation indicated lower normal tissue biological equivalent dose to achieve the same tumor control with a hypofractionated approach for 4 cell lines for the DLQ model, in contrast to SLQ, which favored 2 Gy per fraction for all cells except melanoma. The DLQ model indicated greater tumor radioresistance than SLQ, but the radioresistance was overcome by hypofractionation, other than the GBM cells, which responded poorly to all fractionations. Conclusion: The distinct radiosensitivity and dynamics between CSCs and DCCs in radiation therapy response could perhaps be one possible explanation for the heterogeneous intertumor response to hypofractionation and in some cases superior outcome from

  3. Incorporating Cancer Stem Cells in Radiation Therapy Treatment Response Modeling and the Implication in Glioblastoma Multiforme Treatment Resistance

    International Nuclear Information System (INIS)

    Yu, Victoria Y.; Nguyen, Dan; Pajonk, Frank; Kupelian, Patrick; Kaprealian, Tania; Selch, Michael; Low, Daniel A.; Sheng, Ke

    2015-01-01

    Purpose: To perform a preliminary exploration with a simplistic mathematical cancer stem cell (CSC) interaction model to determine whether the tumor-intrinsic heterogeneity and dynamic equilibrium between CSCs and differentiated cancer cells (DCCs) can better explain radiation therapy treatment response with a dual-compartment linear-quadratic (DLQ) model. Methods and Materials: The radiosensitivity parameters of CSCs and DCCs for cancer cell lines including glioblastoma multiforme (GBM), non–small cell lung cancer, melanoma, osteosarcoma, and prostate, cervical, and breast cancer were determined by performing robust least-square fitting using the DLQ model on published clonogenic survival data. Fitting performance was compared with the single-compartment LQ (SLQ) and universal survival curve models. The fitting results were then used in an ordinary differential equation describing the kinetics of DCCs and CSCs in response to 2- to 14.3-Gy fractionated treatments. The total dose to achieve tumor control and the fraction size that achieved the least normal biological equivalent dose were calculated. Results: Smaller cell survival fitting errors were observed using DLQ, with the exception of melanoma, which had a low α/β = 0.16 in SLQ. Ordinary differential equation simulation indicated lower normal tissue biological equivalent dose to achieve the same tumor control with a hypofractionated approach for 4 cell lines for the DLQ model, in contrast to SLQ, which favored 2 Gy per fraction for all cells except melanoma. The DLQ model indicated greater tumor radioresistance than SLQ, but the radioresistance was overcome by hypofractionation, other than the GBM cells, which responded poorly to all fractionations. Conclusion: The distinct radiosensitivity and dynamics between CSCs and DCCs in radiation therapy response could perhaps be one possible explanation for the heterogeneous intertumor response to hypofractionation and in some cases superior outcome from

  4. Combined use of electroconvulsive therapy and antipsychotics (both clozapine and non-clozapine in treatment resistant schizophrenia: A comparative meta-analysis

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    Saeed Ahmed

    2017-11-01

    Full Text Available Aim: To assess the relative efficacies of clozapine plus Electroconvulsive Therapy (ECT compared against non-clozapine typical and atypical antipsychotics plus ECT for the treatment of “Treatment Resistant Schizophrenia” (TRS. Primarily to assess if clozapine delivers a significant improvement over other antipsychotics when combined with ECT. Design: Major electronic databases were searched between 1990 and March 2017 for trials measuring the effects of either clozapine augmented ECT, other antipsychotic-augmented ECT, or both. After the systematic review of the data, a random-effects meta-analysis was conducted measuring the relative effect sizes of the different treatment regimens. Subjects: 1179 patients in 23 studies reporting the usage of ECT augmentation with antipsychotics. A total of 95 patients were tested with clozapine, and ECT (9 studies and 1084 patients were tested with non-clozapine antipsychotics (14 studies such as flupenthixol, chlorpromazine, risperidone, sulpiride, olanzapine, and loxapine with concurrent ECT treatment considered for systematic review. Of these, 13 studies reported pre and post-treatment scores were included in the meta-analysis. Main outcome measures: The main outcome measure was the presence and degree of both positive and negative psychotic symptoms, as measured by either of two standardized clinician administered tests, the Brief Psychiatric Rating Scale (BPRS, and the Positive and Negative Symptom Scale (PANSS. Results: The comparison of the different antipsychotics established the supremacy of ECT-augmented clozapine treatment against other typical and atypical antipsychotics. The Forest Plot revealed that the overall standard mean difference was 0.891 for non-clozapine studies and 1.504 for clozapine studies, at a 95% interval. Furthermore, the heterogeneity plots showed that while clozapine studies showed no significant heterogeneity, non-clozapine studies showed an I2 statistic value at 42

  5. A case report of isotretinoin-induced manic psychosis

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    Jisha M Lucca

    2016-01-01

    Full Text Available Isotretinoin, an oral vitamin A derivative, used to treat severe treatment-resistant acne. Psychiatric side effects of isotretinoin particularly depression and suicidal thoughts have been well documented. We report a case of isotretinoin-induced manic psychosis in a young female without a family history and history of mental illness.

  6. A pilot randomized controlled trial of the Occupational Goal Intervention method for the improvement of executive functioning in patients with treatment-resistant schizophrenia.

    Science.gov (United States)

    Vizzotto, Adriana D B; Celestino, Diego L; Buchain, Patricia C; Oliveira, Alexandra M; Oliveira, Graça M R; Di Sarno, Elaine S; Napolitano, Isabel C; Elkis, Helio

    2016-11-30

    Schizophrenia is a chronic disabling mental disorder that involves impairments in several cognitive domains, especially in executive functions (EF), as well as impairments in functional performance. This is particularly true in patients with Treatment-Resistant Schizophrenia (TRS). The aim of this study was to test the efficacy of the Occupational Goal Intervention (OGI) method for the improvement of EF in patients with TRS. In this randomized, controlled, single-blind pilot study, 25 TRS patients were randomly assigned to attend 30 sessions of either OGI or craft activities (control) over a 15-week period and evaluated by the Behavioural Assessment of the Dysexecutive Syndrome (BADS) as the primary outcome and the Direct Assessment of Functional Status (DAFS-BR) as well as the Independent Living Skills Survey (ILSS-BR) as secondary outcomes, all adapted for the Brazilian population. The Positive and Negative Syndrome Scale (PANSS) was used for monitoring symptom severity. Results showed significant statistical differences, favoring the OGI group in terms of improvement on the BADS, both in subtests (Action Program and Key Search) and the total score. Improvements in EFs were observed by families in various dimensions as measured by different subtests of the ILSS-BR inventory. The OGI group showed no significant results in secondary outcomes (DAFS-BR) except in terms of improvement of communication skills. Although preliminary, our results indicate that the OGI method is efficacious and effective for patients with TRS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Patterns of clozapine and other antipsychotics prescriptions in patients with treatment-resistant schizophrenia in community mental health centers in São Paulo, Brazil

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    Ana Stella de Azevedo Silveira

    2015-12-01

    Full Text Available Abstract Background Despite of its global underuse, clozapine is still the golden standard antipsychotic for patients with treatment-resistant schizophrenia (TRS. Objective To evaluate the patterns of clozapine and other antipsychotic drugs prescription in TRS in community mental health centers in São Paulo, Brazil. Methods A multiple-choice questionnaire was applied to fifteen psychiatrists at five centers inquiring about patients’ clinical condition, adherence to oral treatment and current antipsychotic treatment. History of previous and current antipsychotic treatment was collected through medical chart review. Results Out of 442 schizophrenia patients, 103 (23.3% fulfilled the criteria for TRS. Fifty-eight patients (56.3% were receiving polypharmacy; 30 (29.1% were on atypical antipsychotic monotherapy, 14 (13.6% were on typical antipsychotic monotherapy, 25 (24.3% were taking depot antipsychotic medication and only 22 (21.4% were receiving clozapine. Discussion As well as in other parts of the world, many TRS patients (78.6% receive other drugs instead of clozapine in São Paulo, the best evidence-based medication for patients with TRS. The government should make every effort to provide medical training and the equipment and logistic support to adequately serve those who could benefit from clozapine treatment at the community health centers.

  8. Patients with poor response to antipsychotics have a more severe pattern of frontal atrophy: a voxel-based morphometry study of treatment resistance in schizophrenia.

    Science.gov (United States)

    Quarantelli, Mario; Palladino, Olga; Prinster, Anna; Schiavone, Vittorio; Carotenuto, Barbara; Brunetti, Arturo; Marsili, Angela; Casiello, Margherita; Muscettola, Giovanni; Salvatore, Marco; de Bartolomeis, Andrea

    2014-01-01

    Approximately 30% of schizophrenia patients do not respond adequately to the therapy. Previous MRI studies have suggested that drug treatment resistance is associated with brain morphological abnormalities, although region-of-interest analysis of MR studies from nonresponder and responder patients failed to demonstrate a statistically significant difference between these two schizophrenia subgroups. We have used a voxel-based analysis of segmented MR studies to assess structural cerebral differences in 20 nonresponder and 15 responder patients and 16 age-matched normal volunteers. Differences between the three groups emerged bilaterally mainly at the level of the superior and middle frontal gyri, primarily due to reduced grey matter volumes in nonresponders, as compared to both normal volunteers and responder patients. Post hoc direct comparison between the two schizophrenia subgroups demonstrated significantly reduced grey matter volumes in middle frontal gyrus bilaterally, in the dorsolateral aspects of left superior frontal gyrus extending into postcentral gyrus and in the right medial temporal cortex. Our results extend and integrate previous findings suggesting a more severe atrophy in nonresponder schizophrenia patients, compared to responder patients, mainly at the level of the superior and middle frontal gyri. Longitudinal studies in drug-naïve patients are needed to assess the role of these associations.

  9. Management of treatment resistant schizophrenia

    African Journals Online (AJOL)

    Adele

    Whilst gains have been made in recent years in the pharmacological treatment of schizophrenia, a number of ... pharmacotherapy to include psychological and occupational ... outcome studies suggesting that only 20-30% of people with.

  10. Creatine kinase levels in patients with bipolar disorder: depressive, manic, and euthymic phases Comparação das fases de depressão, mania e eutimia sobre os níveis de creatina quinase em pacientes bipolares

    Directory of Open Access Journals (Sweden)

    Gustavo Feier

    2011-01-01

    Full Text Available OBJECTIVE: Bipolar disorder is a severe, recurrent, and often chronic psychiatric illness associated with significant functional impairment, morbidity, and mortality. Creatine kinase is an important enzyme, particularly for cells with high and fluctuating energy requirements, such as neurons, and is a potential marker of brain injury. The aim of the present study was to compare serum creatine kinase levels between bipolar disorder patients, in the various phases (depressive, manic, and euthymic, and healthy volunteers. METHOD: Forty-eight bipolar patients were recruited: 18 in the euthymic phase; 17 in the manic phase; and 13 in the depressive phase. The control group comprised 41 healthy volunteers. The phases of bipolar disorder were defined as follows: euthymic-not meeting the DSM-IV criteria for a mood episode and scoring 7 on the YMRS; depressive-scoring > 7 on the HDRS and OBJETIVO: O transtorno do humor bipolar é uma doença psiquiátrica grave, recorrente e crônica associada a significativo prejuízo funcional, morbidade e mortalidade. A creatina quinase tem sido proposta como um marcador de dano cerebral. A creatina quinase é uma enzima importante principalmente para células que necessitam de uma grande quantidade de energia, como os neurônios. O objetivo do presente estudo foi comparar os níveis de creatina quinase entre as fases depressiva, maníaca e eutímica de pacientes com transtorno do humor bipolar. MÉTODO: Para avaliação dos níveis de creatina quinase no soro, 48 pacientes bipolares foram recrutados; 18 estavam eutímicos, 17 estavam em mania e 13 em episódio depressivo. Foi feita também uma comparação com um grupo controle que incluiu 41 voluntários saudáveis. Grupo eutimia: foram incluídos os pacientes que não cumpriam os critérios do DSM-IV para episódios de humor e deveriam ter a pontuação inferior a oito nas escalas de avaliação de mania (YMRS e depressão (HDRS; grupo mania: foram incluídos os

  11. Creatine kinase levels in patients with bipolar disorder: depressive, manic, and euthymic phases Comparação das fases de depressão, mania e eutimia sobre os níveis de creatina quinase em pacientes bipolares

    Directory of Open Access Journals (Sweden)

    Gustavo Feier

    2011-06-01

    Full Text Available OBJECTIVE: Bipolar disorder is a severe, recurrent, and often chronic psychiatric illness associated with significant functional impairment, morbidity, and mortality. Creatine kinase is an important enzyme, particularly for cells with high and fluctuating energy requirements, such as neurons, and is a potential marker of brain injury. The aim of the present study was to compare serum creatine kinase levels between bipolar disorder patients, in the various phases (depressive, manic, and euthymic, and healthy volunteers. METHOD: Forty-eight bipolar patients were recruited: 18 in the euthymic phase; 17 in the manic phase; and 13 in the depressive phase. The control group comprised 41 healthy volunteers. The phases of bipolar disorder were defined as follows: euthymic-not meeting the DSM-IV criteria for a mood episode and scoring 7 on the YMRS; depressive-scoring > 7 on the HDRS and OBJETIVO: O transtorno do humor bipolar é uma doença psiquiátrica grave, recorrente e crônica associada a significativo prejuízo funcional, morbidade e mortalidade. A creatina quinase tem sido proposta como um marcador de dano cerebral. A creatina quinase é uma enzima importante principalmente para células que necessitam de uma grande quantidade de energia, como os neurônios. O objetivo do presente estudo foi comparar os níveis de creatina quinase entre as fases depressiva, maníaca e eutímica de pacientes com transtorno do humor bipolar. MÉTODO: Para avaliação dos níveis de creatina quinase no soro, 48 pacientes bipolares foram recrutados; 18 estavam eutímicos, 17 estavam em mania e 13 em episódio depressivo. Foi feita também uma comparação com um grupo controle que incluiu 41 voluntários saudáveis. Grupo eutimia: foram incluídos os pacientes que não cumpriam os critérios do DSM-IV para episódios de humor e deveriam ter a pontuação inferior a oito nas escalas de avaliação de mania (YMRS e depressão (HDRS; grupo mania: foram incluídos os

  12. Delayed sleep phase cases and controls

    Directory of Open Access Journals (Sweden)

    Nievergelt Caroline M

    2008-04-01

    Full Text Available Abstract Background Delayed sleep phase disorder (DSPD is a condition in which patients have difficulty falling asleep before the early morning hours and commonly have trouble awakening before late morning or even early afternoon. Several studies have suggested that variations in habitual bedtime are 40–50% heritable. Methods We recruited a case series of 205 participants, along with 221 controls (DSPD-C with normal sleep, roughly matched for age, gender, and ancestry. A representative sample of San Diego adults recruited some years before was already available to confirm the control group. Both DSPD and DSPD-C provided blood or saliva samples for DNA and completed extensive questionnaires about sleep habits, sleep history, family history, sleep quality, morningness-eveningness traits, depression, mania, and seasonality of symptoms. The DSPD group wore wrist actigraphs for a median of 13.2 days. The representative sample collected previously had undergone actigraphic recordings, from which 48 hours of data were generally available. Results The DSPD and DSPD-C samples showed almost no overlap on morningness-eveningness scores. DSPD cases went to bed and arose about 3 hours later than the DSPD-C and the representative sample. DSPD cases reported more difficulties with sleep, poorer sleep quality, and more depression, but there was no significant difference in a history of mania. DSPD cases reported more family history of late bedtimes, but female DSPD reported that their fathers' bedtimes were later than the fathers of male DSPD. Conclusion These results indicate a DSPD phenotype is familial and associated with unipolar depression.

  13. Effectiveness of cognitive behaviour therapy for treatment-resistant depression with psychiatric comorbidity: comparison of individual versus group CBT in an interdisciplinary rehabilitation setting.

    Science.gov (United States)

    Hauksson, Pétur; Ingibergsdóttir, Sylvía; Gunnarsdóttir, Thórunn; Jónsdóttir, Inga Hrefna

    2017-08-01

    Cognitive behaviour therapy (CBT) has been shown to be effective, yet there is a paucity of research on the differential effectiveness of individual and group CBT for adults with treatment-resistant depression with psychiatric comorbidity. To investigate the effectiveness of individual and group CBT for inpatients, in an interdisciplinary rehabilitation setting; the extent of psychiatric comorbidity; and who benefits the most from group CBT. All patients (n = 181) received 6 weeks of rehabilitation (treatment as usual, TAU). In addition, they were randomly allocated to group CBT (n = 86) or individual CBT (n = 59) combined with TAU, or TAU only (n = 36). All CBT therapists were part of an interdisciplinary team, had at least 1-year CBT training, and attended weekly supervision. The same CBT manual was used for individual and group therapy, providing 12 sessions, two per week. Groups had 12-15 participants and two therapists in each session. Individual CBT was superior in efficacy to group CBT and TAU, with a large within-subject effect size (ES = 2.10). Group CBT was not superior to TAU. The benefits of treatment decreased over time, but remained large at 18-month follow-up for individual CBT (ES = 1.02), and medium for group CBT (ES = 0.46) and TAU (ES = 0.60). Individual CBT was an effective addition to TAU and showed significant improvements in symptom severity post-treatment and at 18-month follow-up. Disorder severity and comorbidity may have decreased effectiveness of group therapy primarily aimed at depression.

  14. The HDAC inhibitor SAHA improves depressive-like behavior of CRTC1-deficient mice: possible relevance for treatment-resistant depression

    KAUST Repository

    Meylan, Elsa M.; Halfon, Olivier; Magistretti, Pierre J.; Cardinaux, Jean-René

    2016-01-01

    Major depression is a highly complex disabling psychiatric disorder affecting millions of people worldwide. Despite the availability of several classes of antidepressants, a substantial percentage of patients are unresponsive to these medications. A better understanding of the neurobiology of depression and the mechanisms underlying antidepressant response is thus critically needed. We previously reported that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) exhibit a depressive-like phenotype and a blunted antidepressant response to the selective serotonin reuptake inhibitor fluoxetine. In this study, we similarly show that Crtc1‒/‒ mice are resistant to the antidepressant effect of chronic desipramine in a behavioral despair paradigm. Supporting the blunted response to this tricyclic antidepressant, we found that desipramine does not significantly increase the expression of Bdnf and Nr4a1-3 in the hippocampus and prefrontal cortex of Crtc1‒/‒ mice. Epigenetic regulation of neuroplasticity gene expression has been associated with depression and antidepressant response, and histone deacetylase (HDAC) inhibitors have been shown to have antidepressant-like properties. Here, we show that unlike conventional antidepressants, chronic systemic administration of the HDAC inhibitor SAHA partially rescues the depressive-like behavior of Crtc1‒/‒ mice. This behavioral effect is accompanied by an increased expression of Bdnf, but not Nr4a1-3, in the prefrontal cortex of these mice, suggesting that this epigenetic intervention restores the expression of a subset of genes by acting downstream of CRTC1. These findings suggest that CRTC1 alterations may be associated with treatment-resistant depression, and support the interesting possibility that targeting HDACs may be a useful therapeutic strategy in antidepressant development.

  15. The HDAC inhibitor SAHA improves depressive-like behavior of CRTC1-deficient mice: possible relevance for treatment-resistant depression

    KAUST Repository

    Meylan, Elsa M.

    2016-03-09

    Major depression is a highly complex disabling psychiatric disorder affecting millions of people worldwide. Despite the availability of several classes of antidepressants, a substantial percentage of patients are unresponsive to these medications. A better understanding of the neurobiology of depression and the mechanisms underlying antidepressant response is thus critically needed. We previously reported that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) exhibit a depressive-like phenotype and a blunted antidepressant response to the selective serotonin reuptake inhibitor fluoxetine. In this study, we similarly show that Crtc1‒/‒ mice are resistant to the antidepressant effect of chronic desipramine in a behavioral despair paradigm. Supporting the blunted response to this tricyclic antidepressant, we found that desipramine does not significantly increase the expression of Bdnf and Nr4a1-3 in the hippocampus and prefrontal cortex of Crtc1‒/‒ mice. Epigenetic regulation of neuroplasticity gene expression has been associated with depression and antidepressant response, and histone deacetylase (HDAC) inhibitors have been shown to have antidepressant-like properties. Here, we show that unlike conventional antidepressants, chronic systemic administration of the HDAC inhibitor SAHA partially rescues the depressive-like behavior of Crtc1‒/‒ mice. This behavioral effect is accompanied by an increased expression of Bdnf, but not Nr4a1-3, in the prefrontal cortex of these mice, suggesting that this epigenetic intervention restores the expression of a subset of genes by acting downstream of CRTC1. These findings suggest that CRTC1 alterations may be associated with treatment-resistant depression, and support the interesting possibility that targeting HDACs may be a useful therapeutic strategy in antidepressant development.

  16. Nicotine and caffeine modulate haloperidol-induced changes in postsynaptic density transcripts expression: Translational insights in psychosis therapy and treatment resistance.

    Science.gov (United States)

    de Bartolomeis, Andrea; Iasevoli, Felice; Marmo, Federica; Buonaguro, Elisabetta Filomena; Avvisati, Livia; Latte, Gianmarco; Tomasetti, Carmine

    2018-04-01

    Caffeine and nicotine are widely used by schizophrenia patients and may worsen psychosis and affect antipsychotic therapies. However, they have also been accounted as augmentation strategies in treatment-resistant schizophrenia. Despite both substances are known to modulate dopamine and glutamate transmission, little is known about the molecular changes induced by these compounds in association to antipsychotics, mostly at the level of the postsynaptic density (PSD), a site of dopamine-glutamate interplay. Here we investigated whether caffeine and nicotine, alone or combined with haloperidol, elicited significant changes in the levels of both transcripts and proteins of the PSD members Homer1 and Arc, which have been implicated in synaptic plasticity, schizophrenia pathophysiology, and antipsychotics molecular action. Homer1a mRNA expression was significantly reduced by caffeine and nicotine, alone or combined with haloperidol, compared to haloperidol. Haloperidol induced significantly higher Arc mRNA levels than both caffeine and caffeine plus haloperidol in the striatum. Arc mRNA expression was significantly higher by nicotine plus haloperidol vs. haloperidol in the cortex, while in striatum gene expression by nicotine was significantly lower than that by both haloperidol and nicotine plus haloperidol. Both Homer1a and Arc protein levels were significantly increased by caffeine, nicotine, and nicotine plus haloperidol. Homer1b mRNA expression was significantly increased by nicotine and nicotine plus haloperidol, while protein levels were unaffected. Locomotor activity was not significantly affected by caffeine, while it was reduced by nicotine. These data indicate that both caffeine and nicotine trigger relevant molecular changes in PSD sites when given in association with haloperidol. Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

  17. Randomised Controlled Trial (RCT) of cannabinoid replacement therapy (Nabiximols) for the management of treatment-resistant cannabis dependent patients: a study protocol.

    Science.gov (United States)

    Bhardwaj, Anjali K; Allsop, David J; Copeland, Jan; McGregor, Iain S; Dunlop, Adrian; Shanahan, Marian; Bruno, Raimondo; Phung, Nghi; Montebello, Mark; Sadler, Craig; Gugusheff, Jessica; Jackson, Melissa; Luksza, Jennifer; Lintzeris, Nicholas

    2018-05-18

    The cannabis extract nabiximols (Sativex®) effectively supresses withdrawal symptoms and cravings in treatment resistant cannabis dependent individuals, who have high relapse rates following conventional withdrawal treatments. This study examines the efficacy, safety and cost-effectiveness of longer-term nabiximols treatment for outpatient cannabis dependent patients who have not responded to previous conventional treatment approaches. A phase III multi-site outpatient, randomised, double-blinded, placebo controlled parallel design, comparing a 12-week course of nabiximols to placebo, with follow up at 24 weeks after enrolment. Four specialist drug and alcohol outpatient clinics in New South Wales, Australia. One hundred forty-two treatment seeking cannabis dependent adults, with no significant medical, psychiatric or other substance use disorders. Nabiximols is an oromucosal spray prescribed on a flexible dose regimen to a maximum daily dose of 32 sprays; 8 sprays (total 21.6 mg tetrahydrocannabinol (THC) and 20 mg cannabidiol (CBD)) four times a day, or matching placebo, dispensed weekly. All participants will receive six-sessions of individual cognitive behavioural therapy (CBT) and weekly clinical reviews. Primary endpoints are use of non-prescribed cannabis (self-reported cannabis use days, urine toxicology), safety measures (adverse events and abuse liability), and cost effectiveness (incremental cost effectiveness in achieving additional Quality Adjusted Life Years). Secondary outcomes include, improvement in physical and mental health parameters, substance use other than cannabis, cognitive functioning and patient satisfaction measures. This is the first outpatient community-based randomised controlled study of nabiximols as an agonist replacement medication for treating cannabis dependence, targeting individuals who have not previously responded to conventional treatment approaches. The study and treatment design is modelled upon an earlier study with

  18. TIGA-CUB - manualised psychoanalytic child psychotherapy versus treatment as usual for children aged 5-11 years with treatment-resistant conduct disorders and their primary carers: study protocol for a randomised controlled feasibility trial.

    Science.gov (United States)

    Edginton, Elizabeth; Walwyn, Rebecca; Burton, Kayleigh; Cicero, Robert; Graham, Liz; Reed, Sadie; Tubeuf, Sandy; Twiddy, Maureen; Wright-Hughes, Alex; Ellis, Lynda; Evans, Dot; Hughes, Tom; Midgley, Nick; Wallis, Paul; Cottrell, David

    2017-09-15

    The National Institute for Health and Care Excellence (NICE) recommends evidence-based parenting programmes as a first-line intervention for conduct disorders (CD) in children aged 5-11 years. As these are not effective in 25-33% of cases, NICE has requested research into second-line interventions. Child and Adolescent Psychotherapists (CAPTs) address highly complex problems where first-line treatments have failed and there have been small-scale studies of Psychoanalytic Child Psychotherapy (PCP) for CD. A feasibility trial is needed to determine whether a confirmatory trial of manualised PCP (mPCP) versus Treatment as Usual (TaU) for CD is practicable or needs refinement. The aim of this paper is to publish the abridged protocol of this feasibility trial. TIGA-CUB (Trial on improving Inter-Generational Attachment for Children Undergoing Behaviour problems) is a two-arm, pragmatic, parallel-group, multicentre, individually randomised (1:1) controlled feasibility trial (target n = 60) with blinded outcome assessment (at 4 and 8 months), which aims to develop an optimum practicable protocol for a confirmatory, pragmatic, randomised controlled trial (RCT) (primary outcome: child's behaviour; secondary outcomes: parental reflective functioning and mental health, child and parent quality of life), comparing mPCP and TaU as second-line treatments for children aged 5-11 years with treatment-resistant CD and inter-generational attachment difficulties, and for their primary carers. Child-primary carer dyads will be recruited following a referral to, or re-referral within, National Health Service (NHS) Child and Adolescent Mental Health Services (CAMHS) after an unsuccessful first-line parenting intervention. PCP will be delivered by qualified CAPTs working in routine NHS clinical practice, using a trial-specific PCP manual (a brief version of established PCP clinical practice). Outcomes are: (1) feasibility of recruitment methods, (2) uptake and follow-up rates, (3

  19. Persistent antidepressant effect of low-dose ketamine and activation in the supplementary motor area and anterior cingulate cortex in treatment-resistant depression: A randomized control study.

    Science.gov (United States)

    Chen, Mu-Hong; Li, Cheng-Ta; Lin, Wei-Chen; Hong, Chen-Jee; Tu, Pei-Chi; Bai, Ya-Mei; Cheng, Chih-Ming; Su, Tung-Ping

    2018-01-01

    A single low-dose ketamine infusion exhibited a rapid antidepressant effect within 1h. Despite its short biological half-life (approximately 3h), the antidepressant effect of ketamine has been demonstrated to persist for several days. However, changes in brain function responsible for the persistent antidepressant effect of a single low-dose ketamine infusion remain unclear METHODS: Twenty-four patients with treatment-resistant depression (TRD) were randomized into three groups according to the treatment received: 0.5mg/kg ketamine, 0.2mg/kg ketamine, and normal saline infusion. Standardized uptake values (SUVs) of glucose metabolism measured through 18 F-FDG positron-emission-tomography before infusion and 1day after a 40-min ketamine or normal saline infusion were used for subsequent whole-brain voxel-wise analysis and were correlated with depressive symptoms, as defined using the Hamilton Depression Rating Scale-17 (HDRS-17) score RESULTS: The voxel-wise analysis revealed that patients with TRD receiving the 0.5mg/kg ketamine infusion had significantly higher SUVs (corrected for family-wise errors, P = 0.014) in the supplementary motor area (SMA) and dorsal anterior cingulate cortex (dACC) than did those receiving the 0.2mg/kg ketamine infusion. The increase in the SUV in the dACC was negatively correlated with depressive symptoms at 1day after ketamine infusion DISCUSSION: The persistent antidepressant effect of a 0.5mg/kg ketamine infusion may be mediated by increased activation in the SMA and dACC. The higher increase in dACC activation was related to the reduction in depressive symptoms after ketamine infusion. A 0.5mg/kg ketamine infusion facilitated the glutamatergic neurotransmission in the SMA and dACC, which may be responsible for the persistent antidepressant effect of ketamine much beyond its half-life. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression in Adult and Youth Populations: A Systematic Literature Review and Meta-Analysis

    Science.gov (United States)

    Leggett, Laura E.; Soril, Lesley J. J.; Coward, Stephanie; Lorenzetti, Diane L.; MacKean, Gail; Clement, Fiona M.

    2015-01-01

    Background: Between 30% and 60% of individuals with major depressive disorder will have treatment-resistant depression (TRD): depression that does not subside with pharmaceutical treatment. Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for TRD. Objective: To establish the efficacy and optimal protocol for rTMS among adults and youth with TRD. Data Sources: Two systematic reviews were conducted: one to determine the efficacy of rTMS for adults with TRD and another to determine the effectiveness of rTMS for youth with TRD. For adults, MEDLINE, Cochrane Central Register of Controlled Trials, PubMed, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews, and Health Technology Assessment Database were searched from inception until January 10, 2014 with no language restrictions. Terms aimed at capturing the target diagnosis, such as depression and depressive disorder, were combined with terms describing the technology, such as transcranial magnetic stimulation and rTMS. Results were limited to studies involving human participants and designed as a randomized controlled trial. For youth, the search was altered to include youth only (aged 13–25 years) and all study designs. When possible, meta-analysis of response and remission rates was conducted. Study Selection: Seventy-three articles were included in this review: 70 on adult and 3 on youth populations. Results: Meta-analysis comparing rTMS and sham in adults found statistically significant results favoring rTMS for response (RR: 2.35 [95% CI, 1.70–3.25]) and remission (RR: 2.24 [95% CI, 1.53–3.27]). No statistically significant differences were found when comparing high- and low-frequency, unilateral and bilateral, low- and high-intensity rTMS or rTMS and electroconvulsive therapy (ECT). While meta-analysis of results from the youth literature was not possible, the limited evidence base suggests that rTMS may be effective for treating TRD in youth. Conclusions: The evidence

  1. Renal denervation in treatment-resistant essential hypertension. A randomized, SHAM-controlled, double-blinded 24-h blood pressure-based trial.

    Science.gov (United States)

    Mathiassen, Ole N; Vase, Henrik; Bech, Jesper N; Christensen, Kent L; Buus, Niels H; Schroeder, Anne P; Lederballe, Ole; Rickers, Hans; Kampmann, Ulla; Poulsen, Per L; Hansen, Klavs W; Btker, Hans E; Peters, Christian D; Engholm, Morten; Bertelsen, Jannik B; Lassen, Jens F; Langfeldt, Sten; Andersen, Gratien; Pedersen, Erling B; Kaltoft, Anne

    2016-08-01

    Renal denervation (RDN), treating resistant hypertension, has, in open trial design, been shown to lower blood pressure (BP) dramatically, but this was primarily with respect to office BP. We conducted a SHAM-controlled, double-blind, randomized, single-center trial to establish efficacy data based on 24-h ambulatory BP measurements (ABPM). Inclusion criteria were daytime systolic ABPM at least 145 mmHg following 1 month of stable medication and 2 weeks of compliance registration. All RDN procedures were carried out by an experienced operator using the unipolar Medtronic Flex catheter (Medtronic, Santa Rosa, California, USA). We randomized 69 patients with treatment-resistant hypertension to RDN (n = 36) or SHAM (n = 33). Groups were well balanced at baseline. Mean baseline daytime systolic ABPM was 159 ± 12 mmHg (RDN) and 159 ± 14 mmHg (SHAM). Groups had similar reductions in daytime systolic ABPM compared with baseline at 3 months [-6.2 ± 18.8 mmHg (RDN) vs. -6.0 ± 13.5 mmHg (SHAM)] and at 6 months [-6.1 ± 18.9 mmHg (RDN) vs. -4.3 ± 15.1 mmHg (SHAM)]. Mean usage of antihypertensive medication (daily defined doses) at 3 months was equal [6.8 ± 2.7 (RDN) vs. 7.0 ± 2.5 (SHAM)].RDN performed at a single center and by a high-volume operator reduced ABPM to the same level as SHAM treatment and thus confirms the result of the HTN3 trial. Further, clinical use of RDN for treatment of resistant hypertension should await positive results from double-blinded, SHAM-controlled trials with multipolar ablation catheters or novel denervation techniques.

  2. D-serine plasma concentration is a potential biomarker of (R,S)-ketamine antidepressant response in subjects with treatment-resistant depression.

    Science.gov (United States)

    Moaddel, Ruin; Luckenbaugh, David A; Xie, Ying; Villaseñor, Alma; Brutsche, Nancy E; Machado-Vieira, Rodrigo; Ramamoorthy, Anuradha; Lorenzo, Maria Paz; Garcia, Antonia; Bernier, Michel; Torjman, Marc C; Barbas, Coral; Zarate, Carlos A; Wainer, Irving W

    2015-01-01

    (R,S)-ketamine is a rapid and effective antidepressant drug that produces a response in two thirds of patients with treatment-resistant depression (TRD). The underlying biochemical differences between a (R,S)-ketamine responder (KET-R) and non-responder (KET-NR) have not been definitively identified but may involve serine metabolism. The aim of the study was to examine the relationship between baseline plasma concentrations of D-serine and its precursor L-serine and antidepressant response to (R,S)-ketamine in TRD patients. Plasma samples were obtained from 21 TRD patients at baseline, 60 min before initiation of the (R,S)-ketamine infusion. Patients were classified as KET-Rs (n = 8) or KET-NRs (n = 13) based upon the difference in Montgomery-Åsberg Depression Rating Scale (MADRS) scores at baseline and 230 min after infusion, with response defined as a ≥50 % decrease in MADRS score. The plasma concentrations of D-serine and L-serine were determined using liquid chromatography-mass spectrometry. Baseline D-serine plasma concentrations were significantly lower in KET-Rs (3.02 ± 0.21 μM) than in KET-NRs (4.68 ± 0.81 μM), p < 0.001. A significant relationship between baseline D-serine plasma concentrations and percent change in MADRS at 230 min was determined using a Pearson correlation, r = 0.77, p < 0.001, with baseline D-serine explaining 60 % of the variance in (R,S)-ketamine response. The baseline concentrations of L-serine (L-Ser) in KET-Rs were also significantly lower than those measured in KET-NRs (66.2 ± 9.6 μM vs 242.9 ± 5.6 μM, respectively; p < 0.0001). The results demonstrate that the baseline D-serine plasma concentrations were significantly lower in KET-Rs than in KET-NRs and suggest that this variable can be used to predict an antidepressant response following (R,S)-ketamine administration.

  3. Intramuscular Olanzapine – a UK case series of early cases

    Directory of Open Access Journals (Sweden)

    Taylor Mark

    2007-04-01

    Full Text Available Abstract Background Clinical trials assessing efficacy and safety of Intramuscular (IM Olanzapine in acute schizophrenia and acute mania have previously been undertaken in studies required for drug registration in patients who were required to give informed consent. These patients may have less severe forms of psychosis than patients treated in routine practice. Data derived from naturalistic practice following the launch of IM olanzapine may be helpful for clinicians in assessing efficacy and safety of IM olanzapine. The PANSS-EC scale used in the clinical studies may represent a tool that could be used in routine clinical practice. Case presentation We report on an early unselected case series of 7 patients who received IM olanzapine in routine clinical practice settings in the UK. In this case series, olanzapine IM was generally effective, and no adverse events were reported. Adjunctive benzodiazepines were given concomitantly in 1 of the 7 subjects. This is relevant as concomitant benzodiazepines are not recommended for a minimum of 1 hour post IM olanzapine administration. PANSS-EC data was collected in 2 of the 7 subjects. Conclusion Although patients had greater severity of psychosis than clinical trial patients there were no unexpected findings. In addition the PANSS-EC scale is a scale that may be useful in assessing the efficacy of IM antipsychotics in routine clinical practice.

  4. Mycophenolate mofetil in erosive genital lichen planus: a case and review of the literature.

    Science.gov (United States)

    Deen, Kristyn; McMeniman, Erin

    2015-03-01

    Erosive genital lichen planus is a disabling, inflammatory mucocutaneous condition that can cause significant patient morbidity and loss of function. Treatment initially involves topical corticosteroids but some patients can have severe treatment-resistant courses requiring systemic immunosuppression. With potentially unfavorable adverse effect profiles and subsequent intolerance of these agents by patients, erosive lichen planus can ultimately be a challenging condition to treat effectively. We present a case of a 66-year-old woman with treatment-resistant erosive genital lichen planus who was successfully managed with mycophenolate mofetil. Although there is only weak evidence for this agent in this condition, its role in dermatology is growing due to its efficacy and advantageous adverse effect profile and should therefore be considered in patients with treatment-resistant erosive genital lichen planus. © 2015 Japanese Dermatological Association.

  5. La locura en la obra de Lacan: articulaciones con las nociones de cuerpo, manía y sexuación Madness in the Lacan work's: joints with the body, mania and sexuation

    Directory of Open Access Journals (Sweden)

    Pablo D. Muñoz

    2009-12-01

    Full Text Available En este artículo se presentan algunos avances del proyecto de investigación P601 (2008-2010: "Variaciones del concepto de locura en la obra de J. Lacan. Su incidencia en el diagnóstico diferencial neurosis-psicosis". Con el objetivo de avanzar en la precisión de la formalización del concepto de locura en la enseñanza de Lacan, su traducción en términos clínicos, y ponderar el modo en que dicha formalización reordena las concepciones de la locura desplegadas anteriormente en la psiquiatría y el psicoanálisis, indagamos aquí la relación de la locura con los conceptos de cuerpo, manía y sexuación.We present in this work the state and forward of the project UBACyT 2008-2010 (P601: "Variations of the concept of madness in the work of J. Lacan. Its incidence in the diagnosis differential neurosis-psychosis". With the goal of specify the formalization of the madness concept in Lacan's work, its translation in clinical terms, and analyse the way in which this formalization reorganizes the previous conceptions of madness developed in psychiatry and psychoanalysis, we investigate here the relation of madness with the concepts of body, mania and sexuation.

  6. An item response theory evaluation of the young mania rating scale and the montgomery-asberg depression rating scale in the systematic treatment enhancement program for bipolar disorder (STEP-BD).

    Science.gov (United States)

    Prisciandaro, James J; Tolliver, Bryan K

    2016-11-15

    The Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS) are among the most widely used outcome measures for clinical trials of medications for Bipolar Disorder (BD). Nonetheless, very few studies have examined the measurement characteristics of the YMRS and MADRS in individuals with BD using modern psychometric methods. The present study evaluated the YMRS and MADRS in the Systematic Treatment Enhancement Program for BD (STEP-BD) study using Item Response Theory (IRT). Baseline data from 3716 STEP-BD participants were available for the present analysis. The Graded Response Model (GRM) was fit separately to YMRS and MADRS item responses. Differential item functioning (DIF) was examined by regressing a variety of clinically relevant covariates (e.g., sex, substance dependence) on all test items and on the latent symptom severity dimension, within each scale. Both scales: 1) contained several items that provided little or no psychometric information, 2) were inefficient, in that the majority of item response categories did not provide incremental psychometric information, 3) poorly measured participants outside of a narrow band of severity, 4) evidenced DIF for nearly all items, suggesting that item responses were, in part, determined by factors other than symptom severity. Limited to outpatients; DIF analysis only sensitive to certain forms of DIF. The present study provides evidence for significant measurement problems involving the YMRS and MADRS. More work is needed to refine these measures and/or develop suitable alternative measures of BD symptomatology for clinical trials research. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Resistência ao tratamento nos transtornos de ansiedade: fobia social, transtorno de ansiedade generalizada e transtorno do pânico Treatment-resistant anxiety disorders: social phobia, generalized anxiety disorder and panic disorder

    Directory of Open Access Journals (Sweden)

    Gabriela Bezerra de Menezes

    2007-10-01

    Full Text Available OBJETIVOS: Os transtornos de ansiedade são condições psiquiátricas prevalentes que determinam importante prejuízo funcional, piora na qualidade de vida do indivíduo e um enorme custo social. Embora diversas medicações eficazes para os transtornos de ansiedade encontrem-se disponíveis, um número significativo de pacientes não responde adequadamente ao tratamento e muitos permanecem com sintomas residuais clinicamente significativos. O objetivo deste estudo é rever aspectos relacionados à resistência ao tratamento e estratégias farmacológicas no manejo dos transtornos de ansiedade resistentes ao tratamento. MÉTODO: Revisão narrativa. RESULTADOS: São discutidos os diversos aspectos conceituais relacionados à resistência ao tratamento, os possíveis preditores de resistência e, finalmente, algumas estratégias a serem utilizadas no manejo dos transtornos de ansiedade (incluindo transtorno de ansiedade social, transtorno de ansiedade generalizada e transtorno do pânico que não respondem às abordagens terapêuticas convencionais. CONCLUSÃO: A resistência ao tratamento ainda é um desafio para a prática clínica que começa em conceitos não operacionalizados de resposta e resistência e termina na escassez de estudos controlados sobre estratégias de tratamento nesse último cenário clínico.OBJECTIVES: Anxiety disorders are common psychiatric conditions that cause significant disability, poor quality of life and enormous social cost. Although treatments with demonstrable efficacy are available a great number of patients fail to respond or remains with clinically significant residual symptoms after treatment. The objective of this study is to review aspects related to treatment resistance and pharmacological strategies to deal with anxiety disorders resistant to treatment. METHOD: Narrative review. RESULTS: We discuss conceptual aspects related to treatment resistance or refractoriness, predictors of poor treatment outcome

  8. A Combination of Targeted Therapy with Chemotherapy Backbone Induces Response in a Treatment-Resistant Triple-Negative MCL1-Amplified Metastatic Breast Cancer Patient

    Directory of Open Access Journals (Sweden)

    Siraj M. Ali

    2016-02-01

    Full Text Available After failure of anthracycline- and platinum-based therapy, no effective therapies exist for management of metastatic triple-negative breast cancer (TNBC. We report a case of metastatic TNBC harboring MCL1 amplification, as identified by comprehensive genomic profiling in the course of clinical care. MCL1 is an antiapoptotic gene in the BCL2 family, and MCL1 amplification is common in TNBC (at least 20%. A personalized dose-reduced regimen centered on a combination of sorafenib and vorinostat was implemented, based on preclinical evidence demonstrating treatment synergy in the setting of MCL1 amplification. Although hospice care was being considered before treatment initiation, the personalized regimen yielded 6 additional months of life for this patient. Further rigorous studies are needed to confirm that this regimen or derivatives thereof can benefit the MCL1-amplified subset of TNBC patients.

  9. The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study.

    Science.gov (United States)

    Mithoefer, Michael C; Wagner, Mark T; Mithoefer, Ann T; Jerome, Lisa; Doblin, Rick

    2011-04-01

    Case reports indicate that psychiatrists administered ±3,4-methylenedioxymethamphetamine (MDMA) as a catalyst to psychotherapy before recreational use of MDMA as 'Ecstasy' resulted in its criminalization in 1985. Over two decades later, this study is the first completed clinical trial evaluating MDMA as a therapeutic adjunct. Twenty patients with chronic posttraumatic stress disorder, refractory to both psychotherapy and psychopharmacology, were randomly assigned to psychotherapy with concomitant active drug (n = 12) or inactive placebo (n = 8) administered during two 8-h experimental psychotherapy sessions. Both groups received preparatory and follow-up non-drug psychotherapy. The primary outcome measure was the Clinician-Administered PTSD Scale, administered at baseline, 4 days after each experimental session, and 2 months after the second session. Neurocognitive testing, blood pressure, and temperature monitoring were performed. After 2-month follow-up, placebo subjects were offered the option to re-enroll in the experimental procedure with open-label MDMA. Decrease in Clinician-Administered PTSD Scale scores from baseline was significantly greater for the group that received MDMA than for the placebo group at all three time points after baseline. The rate of clinical response was 10/12 (83%) in the active treatment group versus 2/8 (25%) in the placebo group. There were no drug-related serious adverse events, adverse neurocognitive effects or clinically significant blood pressure increases. MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory to other treatments.

  10. The Prevalence of Japanese Outpatients with Hypertension Who Meet the Definition of Treatment Resistant Hypertension and Are Eligible for Enrolment in Clinical Trials of Endovascular Ultrasound Renal Denervation.

    Science.gov (United States)

    Okamura, Keisuke; Shirai, Kazuyuki; Okuda, Tetsu; Urata, Hidenori

    2018-01-01

    Objective A clinical trial (REQUIRE) was started to investigate the use of an ultrasound renal denervation system in the treatment of resistant hypertension (RHT). We analyzed the prevalence of patients who were eligible for inclusion in this cross-sectional study at the time of screening. Methods Nine-hundred ninety-nine consecutive hypertension (HT) patients who were treated in our hospital as outpatients were classified into the following categories: patients treated with at least 3 types of antihypertensive drugs including diuretic agents who were eligible for enrolment in SYMPLICITY HTN-Japan (SH-J) with an office systolic blood pressure (SBP) of ≥160 mmHg, who were ≤80 years of age, and an estimated glomerular filtration rate (eGFR) of ≥45 mL/min/1.73 m 2 (RHT-S); and patients who were treated similar medications and who were eligible for enrolment in REQUIRE, with an SBP of ≥150 mmHg, ≤75 years of age, and an eGFR of ≥40 mL/min/1.73 m 2 (RHT-R). We investigated the proportion of patients in each category. We also investigated HT patients (1,423 cases) who were enrolled in the Chikushi Anti-Hypertension Trial (CHAT), a research network that includes general practitioners. Results Eleven patients (1.1%) with RHT-S and 18 patients (1.8%) with RHT-R were identified. After the exclusion of patients with secondary HT and a diastolic blood pressure (DBP) of <90 mmHg (applied in REQUIRE), 5 patients (0.5%) with RHT-S and 4 patients (0.4%) with RHT-R remained. In the analysis of the CHAT study, only 2 (0.1%) patients with RHT-R remained. Conclusion The number of eligible patients in the REQUIRE trial was decreased, largely due to the strict age restriction and the new DBP limitation. The prevalence of eligible patients in REQUIRE was estimated to be approximately 0.5 to 0.8 times that in SH-J. Since patient enrollment will be difficult, drastic measures may be required to recruit eligible patients.

  11. Managing Multimedia Mania: Taming the Technology Beast

    Science.gov (United States)

    Shepherd, Carol; Mullane, Ann Mary

    2010-01-01

    Harnessing student energy for the positive use of technology in the classroom requires significant change for many educators. Students today exhibit a one-click mentality when using computers in the classroom, and are frustrated when they are not provided with instant gratification. Gone are the reading and higher level thinking skills of the pen…

  12. The disastrous boomerang effects of "citation mania".

    Science.gov (United States)

    Perbal, Annick

    2017-09-01

    The recent publication of a commentary article by Dadkhah et al. (J Cell Commun Signal 11:181-185, 2017) which addressed issues raised by the citation of questionable scientific papers in current databases and the recent retraction of manuscripts dealing with the biological properties of the CCN1 protein by Lin et al. (J Biol Chem 291(53):27433, 2016) prompted us to examine how this situation reflects an evolution of the original citation system, endangering scientific communication. We argue that the increasing number of publication retractions that have been witnessed over several years is a direct consequence of the bias created by the inconsistency of citation metrics.

  13. Seasonal variations in hospital admissions for mania

    DEFF Research Database (Denmark)

    Medici, Clara Reece; Vestergaard, Claus Høstrup; Hadzi-Pavlovic, Dusan

    2016-01-01

    in summer. Higher admission rates were associated with more sunshine, more ultraviolet radiation, higher temperature and less snow but were unassociated with rainfall. We did not find a secular trend in the seasonal pattern. Finally, neither gender nor admission status impacted on the overall seasonal...

  14. [Mania associated with Usher syndrome type II].

    Science.gov (United States)

    Praharaj, Samir Kumar; Acharya, Mahima; Sarvanan, Arul; Kongasseri, Sreejayan; Behere, Rishikesh V; Sharma, P S V N

    2012-01-01

    Usher syndrome (or Hallgren syndrome) is an autosomal recessive genetic disorder characterized by sensorineural deafness, retinitis pigmentosa, and variable vestibular deficit; Usher syndrome type II is the most common form. Various neuropsychiatric disorders have been reported to occur in those with Usher syndrome, including schizophrenia-like disorder, atypical psychosis, recurrent depressive illness, neurotic disorder, and mental retardation; however, bipolar disorder is not common in those with Usher syndrome. Herein we describe a 30-year-old male with Usher syndrome type II that developed features indicative of a probable manic episode. The patient had complete remission of symptoms in response to treatment with olanzapine 20 mg d-1. In persons with dual sensory impairment there are inherent problems with assessment and diagnosis is difficult due to their limited communication abilities. The diagnosis of Usher syndrome depends heavily on behavioral observation and disturbances in vegetative functions.

  15. Female monozygotic twins with selective mutism--a case report.

    Science.gov (United States)

    Sharkey, L; Mc Nicholas, F

    2006-04-01

    Selective mutism is a rare social anxiety disorder characterized by a total lack of speech in certain specific situations despite the ability to speak in others. Both genetic and psychosocial factors are thought to be involved in its presentation, persistence, and response to treatment. This case report describes a case of young female monozygotic twins who presented with selective mutism and their treatment spanning a 2-year period. It highlights the strong genetic association along with environmental factors such as social isolation and consequences of maternal social phobia, all contributing to treatment resistance, despite an intensive multimodal biopsychosocial approach. General issues related to the difficulties in treating monozygotic twins are also addressed.

  16. Case study of first episode schizophrenia in pregnancy and postpartum.

    Science.gov (United States)

    Kast, Kristopher A; Agarkar, Smita

    2017-08-01

    Patients with first-episode psychosis of peripartum onset commonly prove to have a mood-disorder diathesis; however, a proportion of cases represent first-episode schizophrenia. We present such a case and discuss the clinical relevance of recognizing this small but important population of new mothers. These patients are at considerable risk of misdiagnosis, resulting in ineffective maintenance therapy, poorer recovery of function, and development of treatment resistance. Accurate diagnosis in the peripartum period will impact treatment decisions and long-term therapy. Clinicians need to be vigilant, especially during maintenance therapy, to identify these patients and ensure appropriate antipsychotic therapy is provided.

  17. First clinical results of a personalized immunotherapeutic vaccine against recurrent, incompletely resected, treatment-resistant glioblastoma multiforme (GBM) tumors, based on combined allo- and auto-immune tumor reactivity.

    Science.gov (United States)

    Schijns, Virgil E J C; Pretto, Chrystel; Devillers, Laurent; Pierre, Denis; Hofman, Florence M; Chen, Thomas C; Mespouille, Pascal; Hantos, Peter; Glorieux, Philippe; Bota, Daniela A; Stathopoulos, Apostolos

    2015-05-28

    Glioblastoma multiforme (GBM) patients have a poor prognosis. After tumor recurrence statistics suggest an imminent death within 1-4.5 months. Supportive preclinical data, from a rat model, provided the rational for a prototype clinical vaccine preparation, named Gliovac (or ERC 1671) composed of autologous antigens, derived from the patient's surgically removed tumor tissue, which is administered together with allogeneic antigens from glioma tissue resected from other GBM patients. We now report the first results of the Gliovac treatment for treatment-resistant GBM patients. Nine (9) recurrent GBM patients, after standard of care treatment, including surgery radio- and chemotherapy temozolomide, and for US patients, also bevacizumab (Avastin™), were treated under a compassionate use/hospital exemption protocol. Gliovac was given intradermally, together with human GM-CSF (Leukine(®)), and preceded by a regimen of regulatory T cell-depleting, low-dose cyclophosphamide. Gliovac administration in patients that have failed standard of care therapies showed minimal toxicity and enhanced overall survival (OS). Six-month (26 weeks) survival for the nine Gliovac patients was 100% versus 33% in control group. At week 40, the published overall survival was 10% if recurrent, reoperated patients were not treated. In the Gliovac treated group, the survival at 40 weeks was 77%. Our data suggest that Gliovac has low toxicity and a promising efficacy. A phase II trial has recently been initiated in recurrent, bevacizumab naïve GBM patients (NCT01903330). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Management of treatment resistant schizophrenia | Jones | African ...

    African Journals Online (AJOL)

    African Journal of Psychiatry. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 9, No 1 (2006) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register · Download this PDF file. The PDF file you selected should load ...

  19. Pharmacological strategies in treatment-resistant depression

    African Journals Online (AJOL)

    clinicians should re-evaluate the diagnosis, ongoing life stressors, screen for substance abuse, ensure adequate .... thyroxine concentration and a decrease in cortisol level suggesting. WAJM VOL. 32 NO 3, SEPTF.Ml1ER_ 2()l)¥ .... Some improvement in sexual dysfunc- tion was also noted. This is discussed in more detail ...

  20. Management of treatment-resistant depression.

    Science.gov (United States)

    Keitner, Gabor I; Mansfield, Abigail K

    2012-03-01

    Given the limitations of evidence for treatment options that are consistently effective for TRD and the possibility that TRD is in fact a form of depression that has a low probability of resolving, how can clinicians help patients with TRD? Perhaps the most important conceptual shift that needs to take place before treatment can be helpful is to accept TRD as a chronic illness, an illness similar to many others, one that can be effectively managed but that is not, at our present level of knowledge, likely to be cured. An undue focus on remission or even a 50% diminution of symptoms sets unrealistic goals for both patients and therapists and may lead to overtreatment and demoralization. The focus should be less on eliminating depressive symptoms and more on making sense of and learning to function better in spite of them. It is important to acknowledge the difficult nature of the depressive illness, to remove blame from the patient and clinician for not achieving remission, to set realistic expectations, and to help promote better psychosocial functioning even in the face of persisting symptoms. The critical element when implementing such an approach is a judicious balance between maintaining hope for improvement without setting unrealistic expectations. It is important to reemphasize that following a disease management model with acceptance of the reality of a chronic illness is not nihilistic and does not mean the abandonment of hope for improvement. The first step in treating a patient with TRD is to perform a comprehensive assessment of the patient’s past and current treatment history to ensure that evidence-based treatment trials have in fact been undertaken, and if not, such treatment trials should be implemented. If the patient continues to have significant residual symptoms, it is important to determine the impact is of these symptoms on the patient’s quality of life and ability to function. It is also important to evaluate the factors that may be contributing to the persistence of depressive symptoms such as comorbid personality disorders, somatic disorders, substance abuse, and work and interpersonal conflicts. The treatment of patients with TRD needs to move beyond attempts to modify symptoms without taking into consideration and attempting to modify the patient’s personality, coping skills, and social system. Further somatic treatment trials can be undertaken, if desired by the patient and therapist, as a small (5%–15%) percentage of patients may respond and further treatment trials, and this may engender hope. The risk with this approach is that patients and therapists may not work at disease management skills if they believe there may be a resolution of the depression if they could just find the right medication or intervention. Therapists may also feel pressured by patients, families, insurance companies, as well as their own sense of helplessness to escalate treatment in a more and more aggressive manner in an attempt to achieve an elusive remission. A disease management program can provide the therapist and patient with sufficient structure, skills, and goals to encourage ongoing treatment without resorting to unproven measures that may create more side effects and problems. It is particularly important to include the patient’s significant others in the reformulation of the patient’s problem and thereby learn how to manage the illness more effectively. Significant others and family members can be invaluable in providing support for dealing with the difficult process of acquiring a new skill set. Indeed, they spend significantly more time with the patient than does any therapist. Family members are likely to provide this kind of support only if they have been part of the assessment and treatment process. Patients with a wide range of chronic medical illnesses can and do learn to function effectively and to achieve a satisfying quality of life in spite of their illness. There is no reason to think that patients with TRD should not be able to achieve a similar level of illness management, functioning, and quality of life.

  1. Depressão resistente a tratamento: uma revisão das estratégias farmacológicas de potencialização de antidepressivos Treatment-resistant depression: review of pharmacologic antidepressant strategies

    Directory of Open Access Journals (Sweden)

    Milena Antunes Santos

    2006-01-01

    Full Text Available OBJETIVO: Fazer uma revisão sobre oito estratégias farmacológicas de potencialização de antidepressivos na DRT. MÉTODOS: Fez-se um levantamento bibliográfico de 1990 até janeiro de 2006, nas bases eletrônicas de busca Medline, LILACS e da Biblioteca Cochrane, utilizando-se os termos de busca treatment, resistant, refractory e depression e os descritores depression, drug resistance e augmentation, incluindo apenas ensaios controlados duplo-cegos. Foi consultada a referência dos artigos para obtenção de ensaios realizados em data anterior a 1990 e artigos originais de valor histórico. RESULTADOS: Foram encontrados 17 estudos duplo-cegos com o lítio, seis com o hormônio tireoidiano, dois com a buspirona, seis com o pindolol, um com a carbamazepina, dois com a lamotrigina e quatro com a olanzapina. Foram favoráveis à potencialização 41,2% dos ensaios com lítio; 60% daqueles com hormônio tireoidiano e antidepressivos tricíclicos e nenhum com hormônio tireoidiano e inibidores seletivos da recaptação da serotonina (ISRS; 50% dos com pindolol; 100% dos ensaios com carbamazepina e 40% daqueles com olanzapina. Nenhum dos estudos com a buspirona foi favorável. No único estudo com lamotrigina não houve eficácia de tratamento na avaliação pelo critério principal, mas superioridade ao placebo em critérios secundários. CONCLUSÃO: Na DRT há evidência de eficácia apenas em relação ao lítio na potencialização de várias classes de antidepressivos e ao hormônio tireoidiano na potencialização de tricíclicos. A olanzapina foi razoavelmente estudada e sua eficácia não foi estabelecida. Os poucos estudos realizados com a buspirona e o pindolol não comprovaram sua eficácia. A carbamazepina foi muito pouco estudada, e a lamotrigina ainda não foi adequadamente avaliada.OBJECTIVE: The aim of this study is to review eight pharmacologic antidepressant augmentation strategies in TRD. METHODS: Database search on Medline

  2. Clinical effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: the CoBalT randomised controlled trial.

    Science.gov (United States)

    Wiles, Nicola; Thomas, Laura; Abel, Anna; Barnes, Maria; Carroll, Fran; Ridgway, Nicola; Sherlock, Sofie; Turner, Nicholas; Button, Katherine; Odondi, Lang'o; Metcalfe, Chris; Owen-Smith, Amanda; Campbell, John; Garland, Anne; Hollinghurst, Sandra; Jerrom, Bill; Kessler, David; Kuyken, Willem; Morrison, Jill; Turner, Katrina; Williams, Chris; Peters, Tim; Lewis, Glyn

    2014-05-01

    Only one-third of patients with depression respond fully to treatment with antidepressant medication. However, there is little robust evidence to guide the management of those whose symptoms are 'treatment resistant'. The CoBalT trial examined the clinical effectiveness and cost-effectiveness of cognitive behavioural therapy (CBT) as an adjunct to usual care (including pharmacotherapy) for primary care patients with treatment-resistant depression (TRD) compared with usual care alone. Pragmatic, multicentre individually randomised controlled trial with follow-up at 3, 6, 9 and 12 months. A subset took part in a qualitative study investigating views and experiences of CBT, reasons for completing/not completing therapy, and usual care for TRD. General practices in Bristol, Exeter and Glasgow, and surrounding areas. Patients aged 18-75 years who had TRD [on antidepressants for ≥ 6 weeks, had adhered to medication, Beck Depression Inventory, 2nd version (BDI-II) score of ≥ 14 and fulfilled the International Classification of Diseases and Related Health Problems, Tenth edition criteria for depression]. Individuals were excluded who (1) had bipolar disorder/psychosis or major alcohol/substance abuse problems; (2) were unable to complete the questionnaires; or (3) were pregnant, as were those currently receiving CBT/other psychotherapy/secondary care for depression, or who had received CBT in the past 3 years. Participants were randomised, using a computer-generated code, to usual care or CBT (12-18 sessions) in addition to usual care. The primary outcome was 'response', defined as ≥ 50% reduction in depressive symptoms (BDI-II score) at 6 months compared with baseline. Secondary outcomes included BDI-II score as a continuous variable, remission of symptoms (BDI-II score of social care use, personal costs, and time off work were collected at 6 and 12 months. Costs from these three perspectives were reported using a cost-consequence analysis. A cost-utility analysis

  3. Improved health-related quality of life, participation, and autonomy in patients with treatment-resistant chronic pain after an intensive social cognitive intervention with the participation of support partners

    Directory of Open Access Journals (Sweden)

    Jongen PJ

    2017-12-01

    Full Text Available Peter Joseph Jongen,1,2 Rob P Ruimschotel,3 YM Museler-Kreijns,4 TMC Dragstra,4 L Duyverman,3 J Valkenburg-Vissers,5 J Cornelissen,6 R Lagrand,7 Rogier Donders,8 A Hartog1Department of Community and Occupational Medicine, University Medical Centre Groningen, Groningen, 2MS4 Research Institute, Nijmegen, 3Medical Psychiatric Centre PsyToBe, 4DC Klinieken Rotterdam, Rotterdam, 5Fysiotherapie Maaspoort, ‘s Hertogenbosch, 6Dansjobs, Landsmeer, 7Fysio- en Manuele Therapie R. & Y.M. Lagrand, Rotterdam, 8Department for Health Evidence, Radboud University Medical Centre, Nijmegen, The NetherlandsAbstract: Despite the availability of various specific treatments, most patients with chronic pain (CP consider their pain problem as undertreated. Recently, multiple sclerosis (MS patients who were given an intensive 3-day social cognitive treatment with the participation of support partners experienced lasting improvements in health-related quality of life (HRQoL and self-efficacy. In this study, a similar intervention was given to treatment-resistant CP patients with stressors, relational problems with support partner, and distress, anxiety or depression. Before and 1, 3, and 6 months after the intervention, patients completed the Euro-Qol 5 Dimensions 5 Levels (EQ-5D-5L and Impact on Participation and Autonomy (IPA questionnaires (primary outcomes, and the Survey Of Pain Attitudes (SOPA, the Four-Dimensional Symptom Questionnaire (4DSQ (distress, depression, anxiety, and somatization, and Visual Analog Scale for pain intensity, whereas the support partners completed the Caregiver Strain Index (CSI questionnaire. Differences between baseline and post-treatment were tested via paired t-tests (significance level 0.05. Of the 39 patients who were included, 34 (87.2% completed the 3-day treatment. At 1, 3, and 6 months, improvements were seen in EQ-5D-5L-Index (+40.6%; +22.4%; +31.7%, Health Today (+61.8%; +36.3%; +46.8%, Control attitude (+45.8%; not

  4. Right unilateral electroconvulsive therapy does not cause more cognitive impairment than pharmacologic treatment in treatment-resistant bipolar depression: A 6-month randomized controlled trial follow-up study.

    Science.gov (United States)

    Bjoerke-Bertheussen, Jeanette; Schoeyen, Helle; Andreassen, Ole A; Malt, Ulrik F; Oedegaard, Ketil J; Morken, Gunnar; Sundet, Kjetil; Vaaler, Arne E; Auestad, Bjoern; Kessler, Ute

    2017-12-21

    Electroconvulsive therapy is an effective treatment for bipolar depression, but there are concerns about whether it causes long-term neurocognitive impairment. In this multicenter randomized controlled trial, in-patients with treatment-resistant bipolar depression were randomized to either algorithm-based pharmacologic treatment or right unilateral electroconvulsive therapy. After the 6-week treatment period, all of the patients received maintenance pharmacotherapy as recommended by their clinician guided by a relevant treatment algorithm. Patients were assessed at baseline and at 6 months. Neurocognitive functions were assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, and autobiographical memory consistency was assessed using the Autobiographical Memory Interview-Short Form. Seventy-three patients entered the trial, of whom 51 and 26 completed neurocognitive assessments at baseline and 6 months, respectively. The MATRICS Consensus Cognitive Battery composite score improved by 4.1 points in both groups (P = .042) from baseline to 6 months (from 40.8 to 44.9 and from 41.9 to 46.0 in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively). The Autobiographical Memory Interview-Short Form consistency scores were reduced in both groups (72.3% vs 64.3% in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively; P = .085). This study did not find that right unilateral electroconvulsive therapy caused long-term impairment in neurocognitive functions compared to algorithm-based pharmacologic treatment in bipolar depression as measured using standard neuropsychological tests, but due to the low number of patients in the study the results should be interpreted with caution. ClinicalTrials.gov: NCT00664976. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Two-year functional and anatomical results after converting treatment resistant eyes with exudative age-related macular degeneration to aflibercept in accordance with a treat and extend protocol.

    Science.gov (United States)

    Jørstad, Øystein Kalsnes; Faber, Rowan Thomas; Moe, Morten Carstens

    2017-08-01

    To study the effects of converting to aflibercept in accordance with a treat and extend (T&E) strategy in eyes with treatment resistant exudative age-related macular degeneration (AMD). Two-year prospective study of eyes with exudative AMD and persistent macular fluid despite monthly treatment with ranibizumab or bevacizumab. Eyes were converted to 2.0 mg aflibercept in accordance with a T&E protocol. Fifty eyes from 47 patients were included. At baseline, the mean central retinal thickness (CRT) was 273 μm and mean best-corrected visual acuity (BCVA) 0.25 logarithm of the minimal angle of resolution (logMAR). The mean number of aflibercept injections the first year was 9.2. After 1 year, there was a reduction in mean CRT to 228 μm (p < 0.001); 22 eyes (44%) had a dry macula; and the mean BCVA was 0.24 logMAR (p = 0.531). The mean number of aflibercept injections the second year was 8.0 (p = 0.013 compared to first year). After 2 years, 24 eyes (48%) received treatment more frequently than every eighth week. The mean CRT was 225 μm (p < 0.001 compared to baseline); 31 eyes (62%) had a dry macula; and mean BCVA was 0.32 logMAR (p = 0.005 compared to baseline). Five eyes did not complete 2 years of aflibercept treatment after failing to improve. A majority of eyes showed improved anatomic outcomes. There was a small decrease in mean BCVA after the second year of treatment. About half of the eyes required treatment more frequently than the recommended aflibercept label of an 8-week interval. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  6. Mental illness in Sweden (1896-1905) reflected through case records from a local general hospital.

    Science.gov (United States)

    Appelquist, Malin; Brådvik, Louise; Åsberg, Marie

    2018-02-01

    Mental illness in a hospital in a medium-sized town in Sweden was studied. Consecutive case records from 1896 to 1905, and also from 2011, were selected. In the historical sample, neurasthenia was the most common diagnosis, followed by affective disorders and alcohol abuse. ICD-10 diagnoses corresponded well with the historical diagnoses. Melancholia resembled modern criteria for depression. Mania, insania simplex and paranoia indicated more severe illness. Abuse was more common among men and hysteria among women. Those with a medical certificate for mental hospital care were very ill and showed no gender difference. There were no diagnoses for abuse, but 17% had a high level of alcohol consumption. The pattern of signs and symptoms displayed by patients does not appear to change with time.

  7. Treatment-resistant hypertension and the incidence of cardiovascular disease and end-stage renal disease: results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

    Science.gov (United States)

    Muntner, Paul; Davis, Barry R; Cushman, William C; Bangalore, Sripal; Calhoun, David A; Pressel, Sara L; Black, Henry R; Kostis, John B; Probstfield, Jeffrey L; Whelton, Paul K; Rahman, Mahboob

    2014-11-01

    Apparent treatment-resistant hypertension (aTRH) is defined as uncontrolled hypertension despite the use of ≥3 antihypertensive medication classes or controlled hypertension while treated with ≥4 antihypertensive medication classes. Although a high prevalence of aTRH has been reported, few data are available on its association with cardiovascular and renal outcomes. We analyzed data on 14 684 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants to determine the association between aTRH (n=1870) with coronary heart disease, stroke, all-cause mortality, heart failure, peripheral artery disease, and end-stage renal disease. We defined aTRH as blood pressure not at goal (systolic/diastolic blood pressure ≥140/90 mm Hg) while taking ≥3 classes of antihypertensive medication or taking ≥4 classes of antihypertensive medication with blood pressure at goal during the year 2 ALLHAT study visit (1996-2000). Use of a diuretic was not required to meet the definition of aTRH. Follow-up occurred through 2002. The multivariable adjusted hazard ratios (95% confidence intervals) comparing participants with versus without aTRH were as follows: coronary heart disease (1.44 [1.18-1.76]), stroke (1.57 [1.18-2.08]), all-cause mortality (1.30 [1.11-1.52]), heart failure (1.88 [1.52-2.34]), peripheral artery disease (1.23 [0.85-1.79]), and end-stage renal disease (1.95 [1.11-3.41]). aTRH was also associated with the pooled outcomes of combined coronary heart disease (hazard ratio, 1.47; 95% confidence interval, 1.26-1.71) and combined cardiovascular disease (hazard ratio, 1.46; 95% confidence interval, 1.29-1.64). These results demonstrate that aTRH increases the risk for cardiovascular disease and end-stage renal disease. Studies are needed to identify approaches to prevent aTRH and reduce risk for adverse outcomes among individuals with aTRH. © 2014 American Heart Association, Inc.

  8. Magnetic seizure therapy in an adolescent with refractory bipolar depression: a case report

    Directory of Open Access Journals (Sweden)

    Noda Y

    2014-10-01

    Full Text Available Yoshihiro Noda,1,2 Zafiris J Daskalakis,1–3 Jonathan Downar,4 Paul E Croarkin,5 Paul B Fitzgerald,6 Daniel M Blumberger1–3 1Department of Psychiatry, Faculty of Medicine, University of Toronto, 2Temerty Centre for Therapeutic Brain Intervention, 3Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 4MRI-Guided rTMS Clinic, University Health Network, Toronto, ON, Canada; 5Division of Child and Adolescent Psychiatry, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA; 6Monash Alfred Psychiatry Research Centre, The Alfred and Monash University Central Clinical School, Melbourne, Australia Abstract: Magnetic seizure therapy (MST has shown efficacy in adult patients with treatment-resistant depression with limited impairment in memory. To date, the use of MST in adolescent depression has not been reported. Here we describe the first successful use of MST in the treatment of an adolescent patient with refractory bipolar depression. This patient received MST in an ongoing open-label study for treatment-resistant major depression. Treatments employed a twin-coil MST apparatus, with the center of each coil placed over the frontal cortex (ie, each coil centered over F3 and F4. MST was applied at 100 Hz and 100% machine output at progressively increasing train durations. Depressive symptoms were assessed using the 24-item Hamilton Depression Rating Scale and cognitive function was assessed with a comprehensive neuropsychological battery. This adolescent patient achieved full remission of clinical symptoms after an acute course of 18 MST treatments and had no apparent cognitive decline, other than some autobiographical memory impairment that may or may not be related to the MST treatment. This case report suggests that MST may be a safe and well tolerated intervention for adolescents with treatment-resistant bipolar depression. Pilot studies to further evaluate the effectiveness and safety of

  9. Cranial dural arteriovenous fistula as a rare cause of tinnitus – case report

    International Nuclear Information System (INIS)

    Kuśmierska, Małgorzata; Gać, Paweł; Nahorecki, Artur; Szuba, Andrzej; JaŸwiec, Przemysław

    2013-01-01

    Tinnitus, occurring at least once in a lifetime in about 10–20% of the population, is an important clinical problem with complex etiology. Rare causes of tinnitus include cranial dural arteriovenous fistulas (DAVFs), which are usually small lesions consisting of abnormal connections between branches of dural arteries and venous sinuses or veins. Authors present a case of a 44-year-old woman with persistent, unilateral, treatment-resistant pulsatile tinnitus caused by a small dural arteriovenous fistula revealed in computed tomography angiography. Computed tomography angiography is a useful diagnostic method that in some cases allows for establishing the cause of unilateral, pulsatile tinnitus

  10. Cranial dural arteriovenous fistula as a rare cause of tinnitus – case report

    Energy Technology Data Exchange (ETDEWEB)

    Kuśmierska, Małgorzata; Gać, Paweł [Department of Medical Radiology and Imaging Diagnostics, 4th Military Clinical Hospital, Wrocław (Poland); Nahorecki, Artur [Department of Internal Diseases, 4th Military Clinical Hospital, Wrocław (Poland); Szuba, Andrzej [Department of Internal Diseases, 4th Military Clinical Hospital, Wrocław (Poland); Medical University, Wrocław (Poland); JaŸwiec, Przemysław [Department of Medical Radiology and Imaging Diagnostics, 4th Military Clinical Hospital, Wrocław (Poland)

    2013-07-01

    Tinnitus, occurring at least once in a lifetime in about 10–20% of the population, is an important clinical problem with complex etiology. Rare causes of tinnitus include cranial dural arteriovenous fistulas (DAVFs), which are usually small lesions consisting of abnormal connections between branches of dural arteries and venous sinuses or veins. Authors present a case of a 44-year-old woman with persistent, unilateral, treatment-resistant pulsatile tinnitus caused by a small dural arteriovenous fistula revealed in computed tomography angiography. Computed tomography angiography is a useful diagnostic method that in some cases allows for establishing the cause of unilateral, pulsatile tinnitus.

  11. A False Case of Clozapine-Resistant Schizophrenia

    Directory of Open Access Journals (Sweden)

    J. P. Maia-de-Oliveira

    2010-01-01

    Full Text Available One of the subjects that most concerns physicians is treatment-resistance. About 30%–60% of schizophrenia patients do not respond adequately to antipsychotic treatment and are known as refractory schizophrenia patients. Clozapine has been the drug of choice in such cases. However, approximately 30% of them do not respond to clozapine either. Here, we describe a patient with an initial diagnosis of refractory schizophrenia who had a history of dramatic aggressiveness. However, in this case, “refractoriness” was a wrong diagnosis. A case of psychosis secondary to epilepsy had been treated as schizophrenia for almost 20 years. Reports like this one are important because they remind us of how a thorough investigation can lead to the correct diagnosis and improve the patient's prognosis.

  12. Electroconvulsive therapy for manic state with mixed and psychotic features in a teenager with bipolar disorder and comorbid episodic obsessive-compulsive disorder: a case report.

    Science.gov (United States)

    Rask, Olof; Suneson, Klara; Holmström, Eva; Bäckström, Beata; Johansson, Björn Axel

    2017-12-12

    Comorbidity of bipolar disorder and obsessive-compulsive disorder is common in adolescence. Obsessive-compulsive disorder symptoms may be episodic and secondary to alterations in mood, and display specific features. Management of pediatric bipolar disorder-obsessive-compulsive disorder is challenging, as pharmacotherapy of obsessive-compulsive disorder may induce or exacerbate manic episodes and there is limited evidence of treatment efficacy. Electroconvulsive therapy is sparsely used in children and adolescents, but is documented to be a safe and efficacious intervention in adults with bipolar disorder. In view of the severity of symptoms in juvenile mania, studies on treatment strategies are warranted. We report a case of an adolescent with bipolar disorder-obsessive-compulsive disorder who was successfully treated with electroconvulsive therapy during an episode of severe mania. A 16-year-old girl of Middle East origin first presented to us with depressed mood, irritability, and increased obsessive-compulsive disorder symptoms, which were initially interpreted in the context of acute stress secondary to migration. She had been diagnosed with bipolar disorder and obsessive-compulsive disorder in her previous home country, but had difficulties in accounting for earlier psychiatric history. During hospitalization her mood switched to a manic state with mixed and psychotic features, at times showing aggression toward others. Interruption in her lithium treatment for a short period and possibly the introduction of an atypical antipsychotic could in part have been triggering factors. After 8 weeks of in-patient care and psychotropic drug trials, electroconvulsive therapy was initiated and administered every second or third day for 4 weeks, with marked positive response. No apparent side effects were reported. This case demonstrates the need for a detailed medical history, taking special note of periodicity and character of obsessive-compulsive disorder symptoms, in

  13. Hospital chain's LBO reads like textbook case.

    Science.gov (United States)

    Lutz, S

    1991-02-18

    Health Management Associates' leveraged buyout was done during the swirling and headlong LBO mania of the 1980s, but this one was structured to keep the company from being crushed under the weight of its debt. That cool calculation is paying off in cool millions for management and institutional investors as a return to public ownership reaps stock-price dividends.

  14. Anti-N-methyl-D-aspartate receptor encephalitis: analysis of three cases

    Directory of Open Access Journals (Sweden)

    Hui SU

    2015-07-01

    Full Text Available Objective To study clinical features, diagnosis, therapy response and prognosis of anti-N-methyl-D-aspartate receptor (anti-NMDAR encephalitis.  Methods Three cases with anti-NMDAR encephalitis were reported. The clinical features, laboratory examinations, imaging, EEG and therapy response of 3 cases were retrospectively analyzed, and also related literatures were reviewed.  Results Two patients were young male and one patient was old female. Main symptoms included psychiatric symptoms in 3 cases (mania in 2 male patients and stupor in the female patient, epilepsy in 2 cases and respiratory failure in one case. The results of MRI examination revealed normal, while EEG examination showed abnormal in all cases. No tumor was detected in any of these patients. Lumbar puncture revealed normal cerebrospinal fluid (CSF pressure (3 cases, elevated white blood cell (WBC, 3 cases and protein quantification (one case. All cases were confirmed to have the disease by detection of anti-NMDAR antibodies in serum and CSF. One male patient got better after receiving immunotherapy with methylprednisolone and intravenous immunoglobulin (IVIg, but psychiatric symptoms were left over. Another male patient had no response to the above treatment. But the female patient was improved without immunotherapy. All 3 cases were followed up for one year after being discharged. One male patient died by accident because of mental disorders. Another male patient showed no sign of relief. The female patient got mild personality and memory change.  Conclusions Anti-NMDAR encephalitis is a new type of autoimmune encephalitis. It is characterized by fever, memory deficits, seizures, disturbance of consciousness, and autonomic dysfunction in males and females of all ages. This type of encephalitis is often associated with teratoma, and has a good response to immunotherapy. There is a certain correlation between progression and prognosis. DOI: 10.3969/j.issn.1672-6731.2015.07.013

  15. The safety and efficacy of ±3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study

    OpenAIRE

    Mithoefer, Michael C; Wagner, Mark T; Mithoefer, Ann T; Jerome, Lisa; Doblin, Rick

    2011-01-01

    Case reports indicate that psychiatrists administered ±3,4-methylenedioxymethamphetamine (MDMA) as a catalyst to psychotherapy before recreational use of MDMA as ‘Ecstasy’ resulted in its criminalization in 1985. Over two decades later, this study is the first completed clinical trial evaluating MDMA as a therapeutic adjunct. Twenty patients with chronic posttraumatic stress disorder, refractory to both psychotherapy and psychopharmacology, were randomly assigned to psychotherapy with concomi...

  16. Case Report Case Report

    African Journals Online (AJOL)

    User

    2013-03-26

    Mar 26, 2013 ... c Medicine and Palliative Cancer Care: A Case Report. Sanjoy Kumar Pal ... us complementary and alternative therapies for treatment about the .... controlled trials that homeopathy may be effective for the treatment of ...

  17. The safety and efficacy of ±3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study

    Science.gov (United States)

    Mithoefer, Michael C; Wagner, Mark T; Mithoefer, Ann T; Jerome, Lisa; Doblin, Rick

    2011-01-01

    Case reports indicate that psychiatrists administered ±3,4-methylenedioxymethamphetamine (MDMA) as a catalyst to psychotherapy before recreational use of MDMA as ‘Ecstasy’ resulted in its criminalization in 1985. Over two decades later, this study is the first completed clinical trial evaluating MDMA as a therapeutic adjunct. Twenty patients with chronic posttraumatic stress disorder, refractory to both psychotherapy and psychopharmacology, were randomly assigned to psychotherapy with concomitant active drug (n = 12) or inactive placebo (n = 8) administered during two 8-h experimental psychotherapy sessions. Both groups received preparatory and follow-up non-drug psychotherapy. The primary outcome measure was the Clinician-Administered PTSD Scale, administered at baseline, 4 days after each experimental session, and 2 months after the second session. Neurocognitive testing, blood pressure, and temperature monitoring were performed. After 2-month follow-up, placebo subjects were offered the option to re-enroll in the experimental procedure with open-label MDMA. Decrease in Clinician-Administered PTSD Scale scores from baseline was significantly greater for the group that received MDMA than for the placebo group at all three time points after baseline. The rate of clinical response was 10/12 (83%) in the active treatment group versus 2/8 (25%) in the placebo group. There were no drug-related serious adverse events, adverse neurocognitive effects or clinically significant blood pressure increases. MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory to other treatments. PMID:20643699

  18. Clozapine-induced interstitial nephritis - a rare but important complication: a case report

    Directory of Open Access Journals (Sweden)

    Hunter Robert

    2009-08-01

    Full Text Available Abstract Introduction Given the limited range of effective drug treatments for patients with schizophrenia, increasing numbers of patients, often termed 'treatment-resistant' are prescribed clozapine. While the induction of neutropenia or agranulocytosis by clozapine is well appreciated, other rare potentially fatal adverse reactions may also occur including acute interstitial nephritis as reported in this case. Case presentation A 57-year-old Caucasian woman with treatment-resistant chronic schizophrenia developed acute renal failure following initiation of treatment with clozapine. The adverse reaction occurred after only four doses of the drug had been administered (titrated from 12.5 to 25 mg per day. After clozapine had been withdrawn, the patient's renal function returned to normal with no other changes to medication. The patient had been exposed to clozapine about 4 years previously when she had developed a similar reaction. Conclusion Renal reactions to clozapine are extremely rare but, if not recognized promptly, may prove fatal. Psychiatrists need to be aware of this possible complication when clozapine is initiated.

  19. Clozapine for the treatment of agitated-depressed patients with cognitive impairment: a report of three cases.

    Science.gov (United States)

    Nacasch, N; Dolberg, O T; Hirschmann, S; Dannon, P; Grunhaus, L J

    1998-01-01

    Clozapine, an atypical antipsychotic, is mainly approved for the treatment of resistant schizophrenia. However, a substantial body of evidence suggests that it might be useful in other psychiatric indications, such as treatment-resistant depression, Parkinson's disease, and dementia. In this report we present the cases of three patients hospitalized at the psychiatric division of the Sheba Medical Center, diagnosed with major depressive disorder with cognitive impairment, whose presenting symptom was agitation. These patients were nonresponders to various treatment modalities. However, treatment with clozapine brought about a favorable response.

  20. Efficacy of intermittent Theta Burst Stimulation (iTBS) and 10-Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant unipolar depression: study protocol for a randomised controlled trial.

    Science.gov (United States)

    Bulteau, Samuel; Sébille, Veronique; Fayet, Guillemette; Thomas-Ollivier, Veronique; Deschamps, Thibault; Bonnin-Rivalland, Annabelle; Laforgue, Edouard; Pichot, Anne; Valrivière, Pierre; Auffray-Calvier, Elisabeth; Fortin, June; Péréon, Yann; Vanelle, Jean-Marie; Sauvaget, Anne

    2017-01-13

    The treatment of depression remains a challenge since at least 40% of patients do not respond to initial antidepressant therapy and 20% present chronic symptoms (more than 2 years despite standard treatment administered correctly). Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant therapy but still not ideal. Intermittent Theta Burst Stimulation (iTBS), which has only been used recently in clinical practice, could have a faster and more intense effect compared to conventional protocols, including 10-Hz high-frequency rTMS (HF-rTMS). However, no controlled study has so far highlighted the superiority of iTBS in resistant unipolar depression. This paper focuses on the design of a randomised, controlled, double-blind, single-centre study with two parallel arms, carried out in France, in an attempt to assess the efficacy of an iTBS protocol versus a standard HF- rTMS protocol. Sixty patients aged between 18 and 75 years of age will be enrolled. They must be diagnosed with major depressive disorder persisting despite treatment with two antidepressants at an effective dose over a period of 6 weeks during the current episode. The study will consist of two phases: a treatment phase comprising 20 sessions of rTMS to the left dorsolateral prefrontal cortex, localised via a neuronavigation system and a 6-month longitudinal follow-up. The primary endpoint will be the number of responders per group, defined by a decrease of at least 50% in the initial score on the Montgomery and Asberg Rating Scale (MADRS) at the end of rTMS sessions. The secondary endpoints will be: response rate 1 month after rTMS sessions; number of remissions defined by a MADRS score of iTBS superiority in the management of unipolar depression and we will discuss its effect over time. In case of a significant increase in the number of therapeutic responses with a prolonged effect, the iTBS protocol could be considered a first-line protocol in resistant unipolar depression

  1. Antidepressant treatment-emergent affective switch in bipolar disorder: a prospective case-control study of outcome Ciclagem afetiva associada a tratamento com antidepressivo no transtorno bipolar: estudo caso-controle prospectivo

    Directory of Open Access Journals (Sweden)

    Renata Sayuri Tamada

    2006-12-01

    Full Text Available OBJECTIVE: Treatment-emergent affective switch has been associated to cycle acceleration and poorer outcome, but there are few studies addressing this issue. The aim of this study was to prospectively compare the outcome of patients presenting treatment-emergent affective switch with patients with spontaneous mania, regarding presence and polarity of a new episode and time to relapse. METHOD: Twenty-four patients with bipolar disorder according to the DSM-IV were followed for 12 months. Twelve patients had treatment-emergent affective switch and twelve had spontaneous mania. Patients were evaluated weekly with the Young Mania Rating Scale and the Hamilton Depression Scale until remission of the index episode, and monthly until completion of the 12-month follow-up. RESULTS: Eleven patients with treatment-emergent affective switch had a recurrence on follow-up, all of them with major depressive episodes. In the group with spontaneous mania, six patients had a recurrence: two had a depressive episode, and four had a manic episode (p = 0.069 for new episode, p = 0.006 for polarity of the episode. Patients with treatment-emergent affective switch relapsed in a shorter period than patients with spontaneous mania (p = 0.016. CONCLUSIONS: In this first prospective study, treatment-emergent affective switch patients were at greater risk of relapses, especially depressive episodes, and presented a shorter duration of remission when compared with patients with spontaneous mania.OBJETIVO: A ciclagem para mania associada ao antidepressivo tem sido relacionada à aceleração do ciclo e pior evolução, mas há poucos estudos na literatura sobre este assunto. O objetivo deste estudo foi comparar prospectivamente a evolução de pacientes com mania associada a antidepressivo com pacientes com mania espontânea, em relação a tempo para recaída e polaridade do novo episódio. MÉTODO: Vinte e quatro pacientes com transtorno bipolar, de acordo com os crit

  2. Tiagabine in treatment refractory bipolar disorder : a clinical case series

    NARCIS (Netherlands)

    Suppes, T; Chisholm, KA; Dhavale, D; Frye, MA; Atshuler, LL; McElroy, SL; Keck, PE; Nolen, WA; Kupka, R; Denicoff, KD; Leverich, GS; Rush, AJ; Post, RM

    2002-01-01

    Objectives: Anticonvulsants have provided major treatment advances for patients with bipolar disorder. Many of these drugs, including several with proven efficacy in bipolar mania or depression, enhance the activity of the gamma-amino butyric acid (GABA) neurotransmitter system. A new

  3. [Homicide is strongly correlated to depression and not to mania].

    Science.gov (United States)

    Bénézech, M; Bourgeois, M

    1992-01-01

    Typical manic episodes could be the cause of penal infractions, usually benign. In contrast, forensic studies show a close relationship between depression, suicide and homicide. Killers (16-28%) are often depressed when they commit a crime. In the UK and USA, 4-35% of killers commit suicide immediately after their crime. Assessment of a depressed patient must include an evaluation of the risk of homicide as well as the risk of suicide. The past history of depression and suicidal attempts, the presence of depressive symptoms and suicidal ideas, are good predictors of impending danger of aggression and sometimes of homicide.

  4. Dynamic strategy for sustainable business development: mania or hazard?

    Directory of Open Access Journals (Sweden)

    Jarmila Šebestová

    2013-06-01

    Full Text Available The main goal of this paper is to present a practical model of sustainability ratio. In this context, the study provides an analysis of theoretical literature sources in area of strategy evaluation and possible measurement of success. The purpose of presented research was to discover the impact of external business environment factors (based on previous PESTLE analysis on current strategic behavior in small and medium sized business area. The survey was conducted on SMEs in the Czech Republic in 2011 within own research project. The proposed model of sustainability ratio incorporates dynamic behavior and shows how manipulating certain items can alter outcomes in the strategic system in a predicable way. As a contribution to the literature, the paper highlights on the flexibility of business strategy types and which items are the most important for strategy making in an uncertain and turbulent environment.

  5. GADGET-MANIA AND PROBLEMS OF PERSONALITY DEVELOPMENT

    OpenAIRE

    Anzhela Kh. Kurashinova

    2016-01-01

    Modern technological progress can’t be stopped. Today information technology and electronic gadgets have become part of our life and have caused changes in all spheres of human activity. Due to their main features, namely, portability, electronic gadgets are indispensable parts of the working process, they simplify daily life of people, they let you instantly connect to people in different parts of the world, etc. Along with adults they are actively used by children. And apparently, that's wr...

  6. Management of Patients Who Make Threats Against Elected Officials: A Case Report

    Directory of Open Access Journals (Sweden)

    Paulina Riess

    2018-05-01

    Full Text Available Federal law makes it a crime to threaten the President of the United States. The Secret Service conducts thousands of violence risk assessments each year. Literature suggests that 75% of individuals who make threats have been diagnosed with a mental illness (1. Studies show that prominent symptoms in presidential assassins include persecutory and grandiose delusions, hence falling into the category of psychotic disorders. We present a case of a patient diagnosed with Schizoaffective Disorder brought to CPEP (Comprehensive Psychiatric Emergency Program by the Secret Service for repeatedly dialing 911 and making threats to the President. In the past year the patient had been hospitalized three times for similar behavior. Initial presentation included acute symptoms of psychosis and mania including persecutory delusions, command auditory hallucinations, grandiosity, and thought disorder. Clinicians were faced with unique challenges and consulted the forensic service to navigate the role of the Secret Service and develop a plan to prevent future episodes. The patient was discharged with a court order for treatment, long acting medication, as well as an outpatient appointment. The treatment plan has been effective and the Secret Service has ceased their investigation. We aim to explore issues in patient confidentiality, duty to both report and protect. We will also provide strategies and recommendations for such patients on the inpatient unit.

  7. Case management.

    Science.gov (United States)

    Woodward, Judy; Rice, Eve

    2015-03-01

    Health care in the United States is changing rapidly under pressure from both political and professional stakeholders, and one area on the front line of required change is the discipline of case management. Historically, case management has worked to defragment the health care delivery system for clients and increase access to health care. Case management will have an expanded role resulting from Affordable Care Act initiatives to improve health care. This article includes definitions of case management, current issues related to case management, case management standards of practice, and a case study of the management of pediatric chronic disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Significant weight loss following clozapine use, how is it possible? A case report and review of published cases and literature relevant to the subject.

    Science.gov (United States)

    Tungaraza, Tongeji E

    2016-10-01

    It has been repeatedly shown that clozapine is more efficacious than other antipsychotics in the management of treatment-resistant schizophrenia. However, clozapine is associated with a number of side effects including weight gain. Antipsychotic-induced weight gain has been linked with a number of untoward events including psychological factors such as stigma and low self-esteem, and physical factors such as metabolic syndromes and untimely death. The mechanism underlying antipsychotic (including clozapine)-induced weight gain is not clearly understood, although it is said to involve several brain areas, several neurotransmitters, neuropeptides and genetic factors. To some individuals however, clozapine use is associated with significant weight loss (13.5-50% of body weight). The observed weight loss in these groups of patients has not been attributed to any underlying diagnosable physical disorders. There have been a handful cases published with this phenomenon, which seems to be contrary to what is expected when clozapine is prescribed. From the currently published cases three groups emerge - those who lost weight simply by taking clozapine, those who lost weight due to improved mental state, engaging in diet and increased exercise, and those for whom weight loss was a sign of a poor response to clozapine. A case of JX who has a diagnosis of schizoaffective disorder is presented. JX lost over 26% of her body weight when she was prescribed clozapine. A detailed review of other published cases is undertaken. The underlying mechanisms involving weight loss are discussed and the implications to clinicians are highlighted. Coordinated studies to examine these groups of patients may provide some insight, not only in the mechanism of clozapine-induced weight loss, but also in the better management of patients with treatment-resistant schizophrenia involving clozapine use.

  9. Pharmacotherapy for acute mania and disconcordance with treatment guidelines: bipolar mania pathway survey (BIPAS) in mainland China.

    Science.gov (United States)

    Wang, Zuowei; Gao, Keming; Hong, Wu; Xing, Mengjuan; Wu, Zhiguo; Chen, Jun; Zhang, Chen; Yuan, Chengmei; Huang, Jia; Peng, Daihui; Wang, Yong; Lu, Weihong; Yi, Zhenghui; Yu, Xin; Zhao, Jingping; Fang, Yiru

    2014-06-05

    With the recent attention to evidence-based medicine in psychiatry, a number of treatment guidelines for bipolar disorders have been published. This survey investigated prescribing patterns and predictors for guideline disconcordance in the acute treatment of a manic and mixed episode across mainland China. The pharmacological treatments of 2828 patients with a recent hypomanic/manic episode or mixed state were examined. Guidelines disconcordance was determined by comparing the medication(s) patients were prescribed with the recommendation(s) in the guidelines of the Canadian Network for Mood and Anxiety Treatments. The most common pattern of pharmacological treatments for an acute manic or mixed episode was a mood stabilizer plus an atypical antipsychotic (n = 1345, 47.6%), and the rate of guideline-disconcordant treatments was 11.1%. The patients who were treated in general hospitals were more likely to receive guideline-disconcordant treatments than those who were treated in psychiatric hospitals, with an OR of 1.84 (95% CI 1.44-2.36). Similarly, the patients with a mixed episode at study entry were more likely to receive guideline-disconcordant treatments than those with a manic episode, with an OR of 1.69 (95% CI 1.22-2.35). In contrast, the patients with a longer duration of disease (>5 years) were less likely to receive guideline-disconcordant treatments than those with a short duration, with an OR of 0.47 (95% CI 0.36-0.60). In mainland China, the disconcordance with treatment guidelines for a most recent acute manic or mixed episode was modest under naturalistic conditions. The higher risk for disconcordance in general hospitals than in psychiatric hospitals suggests that special education based on treatment guidelines to practitioners in general hospitals is necessary in order to reduce the risk for disconcordant treatments.

  10. Resistant and Refractory Hypertension: Antihypertensive Treatment Resistance vs Treatment Failure

    Science.gov (United States)

    Siddiqui, Mohammed; Dudenbostel, Tanja; Calhoun, David A.

    2017-01-01

    Resistant or difficult to treat hypertension is defined as high blood pressure that remains uncontrolled with 3 or more different antihypertensive medications, including a diuretic. Recent definitions also include controlled blood pressure with use of 4 or more medications as also being resistant to treatment. Recently, refractory hypertension, an extreme phenotype of antihypertensive treatment failure has been defined as hypertension uncontrolled with use of 5 or more antihypertensive agents, including a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Patients with resistant vs refractory hypertension share similar characteristics and comorbidities, including obesity, African American race, female sex, diabetes, coronary heart disease, chronic kidney disease, and obstructive sleep apnea. Patients with refractory vs resistant hypertension tend to be younger and are more likely to have been diagnosed with congestive heart failure. Refractory hypertension might also differ from resistant hypertension in terms of underlying cause. Preliminary evidence suggests that refractory hypertension is more likely to be neurogenic in etiology (ie, heightened sympathetic tone), vs a volume-dependent hypertension that is more characteristic of resistant hypertension in general. PMID:26514749

  11. Inverse association between urbanicity and treatment resistance in schizophrenia

    DEFF Research Database (Denmark)

    Wimberley, Theresa; Pedersen, Carsten B; MacCabe, James H

    2016-01-01

    duration. RESULTS: Among the 13,349 schizophrenia patients, 17.3% experienced TRS during follow-up (median follow-up: 7years, inter-quartile range: 3-12years). The 5-year risk of TRS ranged from 10.5% in the capital area to 17.6% in the rural areas. Compared with individuals with schizophrenia residing...

  12. Mismatch repair and treatment resistance in ovarian cancer

    International Nuclear Information System (INIS)

    Helleman, Jozien; Staveren, Iris L van; Dinjens, Winand NM; Kuijk, Patricia F van; Ritstier, Kirsten; Ewing, Patricia C; Burg, Maria EL van der; Stoter, Gerrit; Berns, Els MJJ

    2006-01-01

    The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR) inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. We determined, microsatellite instability (MSI) as a marker for MMR inactivation (analysis of BAT25 and BAT26), MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA) and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR) in 75 ovarian carcinomas and eight ovarian cancer cell lines MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation), SKOV3 (no MLH1 mRNA expression) and 2774 (no altered expression of MMR genes). Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response). The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation

  13. Mismatch repair and treatment resistance in ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Helleman, Jozien; Staveren, Iris L van [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Dinjens, Winand NM [Department of Pathology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Kuijk, Patricia F van; Ritstier, Kirsten [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Ewing, Patricia C [Department of Pathology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Burg, Maria EL van der; Stoter, Gerrit [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Berns, Els MJJ [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Erasmus MC, Department of Medical Oncology, Josephine Nefkens Institute, Room Be424, P.O. Box 1738, 3000 DR (Netherlands)

    2006-07-31

    The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR) inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. We determined, microsatellite instability (MSI) as a marker for MMR inactivation (analysis of BAT25 and BAT26), MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA) and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR) in 75 ovarian carcinomas and eight ovarian cancer cell lines MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation), SKOV3 (no MLH1 mRNA expression) and 2774 (no altered expression of MMR genes). Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response). The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation.

  14. Mismatch repair and treatment resistance in ovarian cancer

    Directory of Open Access Journals (Sweden)

    van der Burg Maria EL

    2006-07-01

    Full Text Available Abstract Background The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. Methods We determined, microsatellite instability (MSI as a marker for MMR inactivation (analysis of BAT25 and BAT26, MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR in 75 ovarian carcinomas and eight ovarian cancer cell lines Results MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation, SKOV3 (no MLH1 mRNA expression and 2774 (no altered expression of MMR genes. Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response. The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. Conclusion No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation.

  15. Treatment Resistance Mechanisms of Malignant Glioma Tumor Stem Cells

    International Nuclear Information System (INIS)

    Schmalz, Philip G.R.; Shen, Michael J.; Park, John K.

    2011-01-01

    Malignant gliomas are highly lethal because of their resistance to conventional treatments. Recent evidence suggests that a minor subpopulation of cells with stem cell properties reside within these tumors. These tumor stem cells are more resistant to radiation and chemotherapies than their counterpart differentiated tumor cells and may underlie the persistence and recurrence of tumors following treatment. The various mechanisms by which tumor stem cells avoid or repair the damaging effects of cancer therapies are discussed

  16. Renal sympathetic nerve ablation for treatment-resistant hypertension

    Science.gov (United States)

    Krum, Henry; Schlaich, Markus; Sobotka, Paul

    2013-01-01

    Hypertension is a major risk factor for increased cardiovascular events with accelerated sympathetic nerve activity implicated in the pathogenesis and progression of disease. Blood pressure is not adequately controlled in many patients, despite the availability of effective pharmacotherapy. Novel procedure- as well as device-based strategies, such as percutaneous renal sympathetic nerve denervation, have been developed to improve blood pressure in these refractory patients. Renal sympathetic denervation not only reduces blood pressure but also renal as well as systemic sympathetic nerve activity in such patients. The reduction in blood pressure appears to be sustained over 3 years after the procedure, which suggests absence of re-innervation of renal sympathetic nerves. Safety appears to be adequate. This approach may also have potential in other disorders associated with enhanced sympathetic nerve activity such as congestive heart failure, chronic kidney disease and metabolic syndrome. This review will focus on the current status of percutaneous renal sympathetic nerve denervation, clinical efficacy and safety outcomes and prospects beyond refractory hypertension. PMID:23819768

  17. White matter tract integrity in treatment-resistant gambling disorder

    DEFF Research Database (Denmark)

    Chamberlain, Samuel R.; Derbyshire, Katherine; Daws, Richard E.

    2016-01-01

    Background: Gambling disorder is a relatively common psychiatric disorder recently re-classified within the DSM-5 under the category of ‘substance-related and addictive disorders’. Aims: To compare white matter integrity in patients with gambling disorder with healthy controls; to explore...

  18. Enhancing motivation for change in treatment-resistant eating disorders.

    Science.gov (United States)

    Vitousek, K; Watson, S; Wilson, G T

    1998-06-01

    Denial and resistance to change are prominent features in most patients with anorexia nervosa. The egosyntonic quality of symptoms can contribute to inaccuracy in self-report, avoidance of treatment, difficulties in establishing a therapeutic relationship, and high rates of attrition and relapse. Individuals with bulimia nervosa are typically more motivated to recover, but often ambivalent about forfeiting the ideal of slenderness and the protective functions of binge-purge behavior. Few attempts have been made to assess denial and resistance in the eating disorders, or to examine alternative strategies for enhancing motivation to change. Review of the clinical literature indicates a striking convergence of recommendations across conceptually distinct treatment approaches. Clinicians are encouraged to acquire a frame of reference that can help them understand the private experience of individuals with eating disorders, empathize with their distress at the prospect of weight gain, and acknowledge the difficulty of change. The Socratic method seems particularly well-suited to work with this population because of its emphasis on collaboration, openness, curiosity, patience, focused and systematic inquiry, and individual discovery. Four themes are crucial in engaging reluctant eating-disordered clients in therapy: the provision of psychoeducational material, an examination of the advantages and disadvantages of symptoms, the explicit use of experimental strategies, and an exploration of personal values.

  19. Casing study

    Energy Technology Data Exchange (ETDEWEB)

    Roche, P.

    2000-12-01

    An unorthodox method of casing drilling used by Tesco Corporation at a gas well in Wyoming to drill deeper using casings as drillpipe is discussed. The process involves either rotating the casing as drill string or using a downhole mud motor to rotate the bit. In this instance, the surface hole and the production hole were casing-drilled to a record 8,312 feet by rotating the casing. The 8 1/2-inch surface hole was drilled with 7-inch casing to 1,200 feet using a Tesco underreamer and a polycrystalline pilot bit; drilling and cementing was completed in 12 1/2 hours. The 6 1/4-inch production hole was drilled with 4 1/2-inch casing and the bottomhole assembly was retrieved after 191 hours rotating. This case was the first in which the entire well was casing-drilled from surface to TD. Penetration rate compared favorably with conventional methods: 12 1/2 hours for casing-drilling to 18.9 hours for conventional drilling, despite the fact that the casing-drilling technology is still in its infancy. It is suggested that casing-drilling has the potential to eliminate the need for the drillpipe entirely. If these expectations were to be realised, casing-drilling could be one of the most radical drilling changes in the history of the oil and gas industry. 1 photo.

  20. Case series

    African Journals Online (AJOL)

    abp

    2013-06-20

    Jun 20, 2013 ... ... by a persistent neurological deficit in 2 cases, and infection in 2 cases controlled ... Upper cervical spine injuries are frequent due to increasing number .... the patient; it also takes more time for fracture healing and expose.

  1. Case series

    African Journals Online (AJOL)

    ebutamanya

    2015-01-29

    Jan 29, 2015 ... for tinnitus (Table 1). The otomicroscopic examination shows: central non marginal perforation in 29 patients, posterior perforation in 17 patients and anterior perforation in 14 patients. The tympanic cavity was dry in 27 cases, wet in 18 cases and inflammatory in the. 15 remaining cases. The conralateral ear ...

  2. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-02-12

    Feb 12, 2015 ... Abstract. Vaginal metastasis from pancreatic cancer is an extreme case and often indicates a poor prognosis. We present a case of pancreatic carcinoma with metastasis to the vagina that was discovered by vaginal bleeding. To our knowledge, this is the third case in the world of a primary pancreatic.

  3. Efficacy and safety of electroconvulsive therapy in the first trimester of pregnancy: a case of severe manic catatonia.

    Science.gov (United States)

    Pinna, Martina; Manchia, Mirko; Pillai, Gianluca; Salis, Piergiorgio; Minnai, Gian Paolo

    2015-08-01

    Electroconvulsive therapy (ECT) is an appropriate, albeit often neglected, option for managing severe or life-threatening psychiatric symptoms during pregnancy. We report on the rapid effectiveness and safety of ECT during the first trimester of pregnancy in a 28-year-old woman with severe catatonia. Catatonic symptoms were assessed using the Catatonia Rating Scale (CRS). The patient was treated with unilateral ECT using left anterior right temporal (LART) placement. Seizure quality and duration were monitored by a two-lead electroencephalograph (EEG) and by one-lead electromyography (EMG). During each ECT session, the fetal heart rate was monitored with electrocardiogram (ECG). After the second ECT treatment (day 13 of hospitalization), we observed remission of the catatonic symptoms, as shown by the drop in the CRS score from 22 to 0. No cognitive abnormalities were reported and no gynecological complications were detected (e.g. vaginal bleeding, abdominal pain, or uterine contraction). The patient delivered at term a healthy male neonate who presented normal growth as well as normal psychomotor development. This case highlights the effectiveness of ECT in treating severe catatonic mania during the first 3 months of pregnancy. In addition, ECT proved to be a safe therapeutic option, since neither mother nor infant experienced any adverse event. We suggest that ECT might be considered as a valid and safe option in the therapeutic decision-making process when catatonic symptoms manifest during pregnancy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Case report

    African Journals Online (AJOL)

    abp

    8 mai 2013 ... subsequent conception and placenta accreta: a case report. American Journal of Obstetrics and Gynecology. September. 2012; 207(3 ) : e7-e8. PubMed | Google Scholar. 5. Umashankar T, Patted S, Handigund R. Endometrial osseous metaplasia: Clinicopathological study of a case and literature review.

  5. Case report

    African Journals Online (AJOL)

    abp

    2015-08-31

    Aug 31, 2015 ... Dual intersection syndrome of the forearm: a case report. Bouchra Zhari1,& ... We reported a case of a 60-year-old man presented to our formation with painful swelling on .... With a fiddling clinical observation and diagnosis.

  6. Case law

    International Nuclear Information System (INIS)

    2016-01-01

    This section treats of the following case laws: 1 - Case Law France: Conseil d'etat decision, 22 February 2016, EDF v. Republic and Canton of Geneva relative to the Bugey nuclear power plant (No. 373516); United States: Brodsky v. US Nuclear Regulatory Commission, 650 Fed. Appx. 804 (2. Cir. 2016)

  7. Case law

    International Nuclear Information System (INIS)

    2015-01-01

    This section treats of the two following case laws: Slovak Republic: Further developments in cases related to the challenge by Greenpeace Slovakia to the Mochovce nuclear power plant; United States: Judgment of the Nuclear Regulatory Commission denying requests from petitioners to suspend final reactor licensing decisions pending the issuance of a final determination of reasonable assurance of permanent disposal of spent fuel

  8. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-10-09

    Oct 9, 2015 ... Aguas SC, Quarracino MC, Lence AN, Lanfranchi-Tizeira HE. Primary melanoma of the oral cavity: ten cases and review of. 177 cases from literature. Medicina oral, patologia oral y cirugia bucal. 2009;14(6):E265-71. PubMed | Google. Scholar. 6. Rapidis AD, Apostolidis C, Vilos G, Valsamis S. Primary.

  9. Case series

    African Journals Online (AJOL)

    ebutamanya

    2016-04-27

    Apr 27, 2016 ... Laparoscopic surgery for groin hernia in a third world country: a report of 9 cases of ... Concerning mesh repair, the (open) LICHENSTEIN and laparoscopic inguinal hernia techniques are ... Two cases were bilateral, 5 unilateral and all of them primary. ... In Africa, This approach is still marginal; few studies.

  10. Case report

    African Journals Online (AJOL)

    ebutamanya

    28 août 2015 ... (intra-osseous synovial cyst) Clinical and therapeutic aspect: case report. Chir Main. 2009 Feb; 28(1):37-41. PubMed |. Google Scholar. 10. Chantelot C, Laffargue P, Masmejean E, Peltier B, Barouk P,. Fontaine C. Fracture of the scaphoid carpal bone secondary to an intraosseous cyst: apropos of a case.

  11. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-01-21

    Jan 21, 2015 ... Published in partnership with the African Field Epidemiology Network (AFENET). (www.afenet.net). Case report. Open Access ... La quantité de tissu neural immature permet d'établir une classification .... Wu X, Han LY, Xu X, Li Z. Recurrent immature teratoma of the ovary: a case report of radical secondary ...

  12. Case Report

    African Journals Online (AJOL)

    the kidney could still be transplanted successfully. We describe a case of high ureteric injury during multi-organ recovery and successful implantation using a Boari flap ureterocystostomy. Case Report. The donor kidney was procured from a 55-year-old male brain stem deceased donor following intra-cerebral hemorrhage.

  13. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-12-04

    Dec 4, 2015 ... was made, while maintaining of valproic acid and clonazepam.This combination allowed a partial remission, allowing a best level of adaptation, it has been maintained. The clozapine has not been tried in this case. Discussion. This case illustrates the presentation of Schizophrenia characterized.

  14. Case series

    African Journals Online (AJOL)

    abp

    2017-07-13

    Jul 13, 2017 ... Its purpose is to assess the clinical and ... Other circumstances of discovery were atrial fibrillation, ... ventricular pacing (9.1%) and blood pressure intolerance to stress ... The mitral flow was a ... anterior mitral valve's pillar was found in one case with a left ... with a stop at the first level in another case.

  15. Case report

    African Journals Online (AJOL)

    raoul

    2011-10-20

    Oct 20, 2011 ... Abstract. A 22-year old man was bitten by a snake on his scrotum. This interesting and unusual case occurred in the rural area of District Aligarh, India. The uniqueness of the case lies in the fact that scrotum is an extremely rare and unusual site for snake bite. Further, with negligible local signs of.

  16. case series

    African Journals Online (AJOL)

    Administrator

    Key words: Case report, case series, concept analysis, research design. African Health Sciences 2012; (4): 557 - 562 http://dx.doi.org/10.4314/ahs.v12i4.25. PO Box 17666 .... According to the latest version of the Dictionary of. Epidemiology ...

  17. CASE STUDY

    African Journals Online (AJOL)

    HIV infection has several oral manifestations, including oral candidiasis and oral hairy leucoplakia. Occasionally unusual presentations requiring rigorous investigations are seen, and in these cases the diagnosis sometimes remains a dilemma owing to limited investigation facilities.1-3 We present the case of a patient who.

  18. Case Report

    African Journals Online (AJOL)

    Sarra

    failure and/or per vaginum (PV) leaN of dialysate. Case report: A ... had PV leaN of the dialysate that was misinterpreted by the .... as part of the management of this infection. On the .... case, we believe that laparoscopy represents a good tool.

  19. Case series

    African Journals Online (AJOL)

    abp

    30 mai 2017 ... All patients underwent systematic plaster immobilization for a period of ... On average, nails were removed after about 6 ... cases), osteitis associated with material (2 cases), refracture (3 ... Although intramedullary nailing ideally is an osteosynthesis ..... intramedullary fixation of pediatric forearm fractures.

  20. Clinical cases

    International Nuclear Information System (INIS)

    Servente, L.

    2012-01-01

    This presentation is about clinical cases and the contribution of the PET - CT Fag application in the diagnosis and treatment of different types of cancer. The cases presented were: neck diseases, epidermoid carcinoma, liver damage and metastasize, lymphoma, thrombosis, colonic cancer and lung disease

  1. Case report

    African Journals Online (AJOL)

    abp

    2015-08-13

    Aug 13, 2015 ... Middle East, Mediterranean region, Central Europe, Australia and. South America) [1, 2]. The incidence of musculoskeletal echinococcosis including involvement of subcutaneous tissue is 1%-. 5.4% among all cases of hydatid disease [2]. In this report, we present a case of recurrent hydatid cysts involving ...

  2. Case report

    African Journals Online (AJOL)

    abp

    2016-02-08

    Feb 8, 2016 ... pituitary metastases can be characteristic and evocative but in no case pathognomic. The diabetes insipidus is the most common clinical manifestation of the disease [2, 3]. We report herein a case of an acute adrenal insufficiency revealing pituitary metastases of lung cancer. Patient and observation.

  3. Clinical case

    International Nuclear Information System (INIS)

    Garcia Fontes, M

    2012-01-01

    This presentation is about a case of a patient with liver tumor. The ultrasound scan and Tc technique were used for the diagnosis and treatment. The application of PET - CT FDG contributed to detect peripheral cholangiocarcinoma, the lymph node distance to guide the therapeutic and the recurrence in case of a negative morphological methods.

  4. Clinical experience using intranasal ketamine in the treatment of pediatric bipolar disorder/fear of harm phenotype.

    Science.gov (United States)

    Papolos, Demitri F; Teicher, Martin H; Faedda, Gianni L; Murphy, Patricia; Mattis, Steven

    2013-05-01

    Intravenous ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, has been shown to exert a rapid antidepressant effect in adults with treatment resistant depression. Children with bipolar disorder (BD) often respond poorly to pharmacotherapy, including polypharmacy. A pediatric-onset Fear of Harm (FOH) phenotype has been described, and is characterized by severe clinical features and resistance to accepted treatments for BD. The potential efficacy and safety of intranasal ketamine in children with BD with FOH-phenotype were assessed by a systematic retrospective chart review of a case series from the private practice of one of the authors, including cases with clear refractoriness to mood stabilizers, antipsychotics and benzodiazepines. A comparison was made between routinely collected symptom measures 1-2 weeks prior to and after the administration of ketamine, in 12 treatment-refractory youth, 10 males 2 females ages 6-19years. Ketamine administration was associated with a substantial reduction in measures of mania, fear of harm and aggression. Significant improvement was observed in mood, anxiety and behavioral symptoms, attention/executive functions, insomnia, parasomnias and sleep inertia. Treatment was generally well-tolerated. Intranasal ketamine administration in treatment-resistant youth with BD-FOH produced marked improvement in all symptomatic dimensions. A rapid, substantial therapeutic response, with only minimal side effects was observed. Formal clinical trials to assess safety and efficacy are warranted. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Case - Case-Law - Law

    DEFF Research Database (Denmark)

    Sadl, Urska

    2013-01-01

    Reasoning of the Court of Justice of the European Union – Constr uction of arguments in the case-law of the Court – Citation technique – The use of formulas to transform case-law into ‘law’ – ‘Formulaic style’ – European citizenship as a fundamental status – Ruiz Zambrano – Reasoning from...

  6. Dermatology case

    Directory of Open Access Journals (Sweden)

    Catarina Lacerda

    2017-11-01

    Full Text Available Aims: To report a case of uncharacteristic presentation of Parvovirus B19. This virus causes some atypical cutaneous rash such as papular-purpuric “gloves and socks” syndrome which is a rare entity, self-limited and resolves spontaneously to cure. Case Report: Authors describe a case of a six-year-old boy who went to the Emergency Department with a cutaneous rash initially on a finger and then mouth, hands and feet followed by fever. He fully recovered without sequelae. Conclusions: It is important to consider this agent as a possible responsible for atypical purpuric rash.

  7. Enhancing generalisation in biofeedback intervention using the challenge point framework: A case study

    Science.gov (United States)

    HITCHCOCK, ELAINE R.; BYUN, TARA McALLISTER

    2014-01-01

    Biofeedback intervention can help children achieve correct production of a treatment-resistant error sound, but generalisation is often limited. This case study suggests that generalisation can be enhanced when biofeedback intervention is structured in accordance with a “challenge point” framework for speech-motor learning. The participant was an 11-year-old with residual /r/ misarticulation who had previously attained correct /r/ production through a structured course of ultrasound biofeedback treatment but did not generalise these gains beyond the word level. Treatment difficulty was adjusted in an adaptive manner following predetermined criteria for advancing, maintaining, or moving back a level in a multidimensional hierarchy of functional task complexity. The participant achieved and maintained virtually 100% accuracy in producing /r/ at both word and sentence levels. These preliminary results support the efficacy of a semi-structured implementation of the challenge point framework as a means of achieving generalisation and maintenance of treatment gains. PMID:25216375

  8. Dermatology case

    Directory of Open Access Journals (Sweden)

    Fernando Mota

    2017-07-01

    In the present case, the patient was referred to the dermatology department due to an atypical lesion with an uncommon location, revealing the importance of a whole body examination in patients with this disease.

  9. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-10-14

    Oct 14, 2015 ... &Corresponding author: Hanane Massit, Department of Gastroenterology II, Mohamed V ... Crohn's disease, accounting for around 30-50 % of cases, its ... manuscript and have equally contributed to its content and to the.

  10. Case report

    African Journals Online (AJOL)

    abp

    2013-01-09

    . The electrolytes analysis revealed an acute hyponatremia. (sodium concentration 125 mmol/L). Medical treatment consisted of hypertonic saline solution 3%, volume expansion, intubation and ventilation. The presented case ...

  11. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-01-06

    Jan 6, 2015 ... optic disc edema and subsequent formation of a macular star [1]. (Figure 1). ... case of bilateral stellate neuroretinitis due to pheochromocytoma. ... clinical examination are irreplaceable, powerful diagnostic tools that.

  12. Case series

    African Journals Online (AJOL)

    abp

    2017-05-16

    May 16, 2017 ... Hepatocellular carcinoma: a clinicopathological study of 64 cases ... The presenting clinical symptoms were dominated by abdominal pain (n=34), followed by .... malaise, anorexia or weight loss and nausea or vomiting [4].

  13. Case report

    African Journals Online (AJOL)

    abp

    2017-10-10

    Oct 10, 2017 ... A rare case of important and recurrent abnormal uterine bleeding ... 1Department of Obstetrics and Gynecology, University Hospital of Yopougon, Abidjan, Ivory Coast, .... imaging (MRI) could guide us to the diagnosis.

  14. Case Report

    African Journals Online (AJOL)

    Administratör

    Uterus at 17 Weeks of Amenorrhea: Case Report and Literature. Review ... no bleeding but the patient was noted to have ... urinary tract abnormalities are frequent in ... of MRI [6]. Laparoscopy allows formal confirmation of this type of uterine.

  15. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-01-07

    Jan 7, 2015 ... Synchronous malignant renal mass in patient with a Lung cancer: case report and literature ... management and prognosis [4]. Patient and ... classed stage I. The patient got chemo radiotherapy for the lung cancer using ...

  16. Case series

    African Journals Online (AJOL)

    ebutamanya

    2016-06-02

    Jun 2, 2016 ... Epidemiological aspects of suicide attempts among Moroccan children .... Poorly drug intoxication was found in 25% of cases and included over 10 tablets in ... factors have been identified such as maltreatment, sexual abuse.

  17. Case report

    African Journals Online (AJOL)

    abp

    2017-12-13

    Dec 13, 2017 ... nodules measuring 10-6cm, erythematous, purple color, painful at mobilization ... After multi-disciplinary concertation a ... of view than positivity of AR. In contrast ... Katagiri Y, Ansai S. Two cases of cutaneous apocrine ductal.

  18. Case Report

    African Journals Online (AJOL)

    Hamid

    Key words: Case report, composite resin, fiber-reinforced composite. ABSTRACT. A variety of ... investigation will be required to provide additional information on the survival of directly-bonded anterior fixed prosthesis made with FRC systems.

  19. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-11-27

    Nov 27, 2015 ... systemic lupus erythematosus nor other connective tissue disease. Pregnancy was ... day of life, platelet level dropped to 20 x 109/L. The newborn has received platelet ... cases of aplastic anemia or hemolytic anemia [6,7].

  20. Case Report

    African Journals Online (AJOL)

    of permanent hemodialysis (HD) vascular access ... This catheter was removed and a translumbar dialysis ... In this case report, we describe a patient with the ... Rheumatology, the isolated detection of antiphospholipid .... Arthritis Rheum.

  1. Case report

    African Journals Online (AJOL)

    abp

    2016-07-20

    Jul 20, 2016 ... Brain abscess caused by streptococcus constellatus are very rarely ... We present a rare case of a left-sided thalamic abscess caused by streptococcus ... examination showed that the patient was lethargic and had right-.

  2. Case report

    African Journals Online (AJOL)

    abp

    2013-10-17

    Oct 17, 2013 ... We are reporting a case of hemoperitoneum followed by early post partum collapse due to bleeding ... diagnosis of postpartum hemoperitoneum after a vaginal delivery ... The patient was reviewed two weeks after discharge.

  3. Case report

    African Journals Online (AJOL)

    abp

    2012-05-13

    May 13, 2012 ... Missed opportunity for tuberculosis case detection in household contacts in a high ... Maywood, IL, USA, 4College of Public Health, University of Georgia, ... This is an Open Access article distributed under the terms of the ...

  4. Case report

    African Journals Online (AJOL)

    abp

    2017-11-07

    Nov 7, 2017 ... However, auricular disorders are rare and exceptionally inaugural. We describe the case of ... hypothalamic-pituitary axis dysfonction. There was ... tomography, and the salivary gland biopsy confirmed the diagnosis by finding ...

  5. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-03-03

    translucent, hyper-or hypopigmented or erythematous-to- violaceous in color. In addition, epidermal changes may be absent or include atrophy, hyperkeratosis, or telangiectasia [2]. In our case the diagnosis of cutaneous sarcoidosis is ...

  6. Case report

    African Journals Online (AJOL)

    raoul

    2012-02-22

    Feb 22, 2012 ... cancer. Case report. Written informed consent was obtained from the patient for ... colon and rectum (12 patients), uterus (8 patients), ovary (5 patients), head and neck (tongue, pharynx, larynx, nasal cavity, and mandible) (5 ...

  7. Case series

    African Journals Online (AJOL)

    abp

    7 avr. 2016 ... HTA were complicated by heart disease in 24% of cases and by renal disease in 20% of cases ... of clinical specificity. It is not unusual for HTA to be the only manifestation of the disease. In our study we .... Le syndrome de Cushing reste une cause rare d'HTA, sa prévalence dans des centres spécialisés en ...

  8. Casing drilling

    Energy Technology Data Exchange (ETDEWEB)

    Heenan, D. [Tesco Corp., Calgary, AB (Canada)

    2003-07-01

    This paper reviewed the experience that Tesco has gained by drilling several wells using only casings as the drill stem. Tesco has manufactured a mobile and compact hydraulic drilling rig called the Casing Drilling {sup TM} system. The system could be very effective and efficient for exploration and development of coalbed methane (CBM) reserves which typically require extensive coring. Continuous coring while drilling ahead, along wire line retrieval, can offer time savings and quick core recovery of large diameter core which is typically required for exploration core desorption tests. The proposed system may also have the potential to core or drill typically tight gas sands or underbalanced wells with air or foam. This would reduce drilling fluid damage while simultaneously finding gas. Compared to conventional drill pipes, Casing Drilling {sup TM} could also be effective with water production from shallow sands because of the smaller annual clearance which requires less air volumes to lift any produced water. 9 figs.

  9. Case Report

    DEFF Research Database (Denmark)

    Bilgin-Freiert, Arzu; Fugleholm, Kåre; Poulsgaard, Lars

    2015-01-01

    We report a case of an intraneural ganglion cyst of the hypoglossal canal. The patient presented with unilateral hypoglossal nerve palsy, and magnetic resonance imaging showed a small lesion in the hypoglossal canal with no contrast enhancement and high signal on T2-weighted imaging. The lesion...... irradiation as an option. This case illustrates a very rare location of an intraneural ganglion cyst in the hypoglossal nerve. To our knowledge there are no previous reports of an intraneural ganglion cyst confined to the hypoglossal canal....

  10. Case law

    International Nuclear Information System (INIS)

    2012-01-01

    This section gathers the following case laws: 1 - Canada: Judicial review of Darlington new nuclear power plant project; Appeal decision upholding criminal convictions related to attempt to export nuclear-related dual-use items to Iran: Her Majesty the Queen V. Yadegari; 2 - European Commission: Greenland cases; 3 - France: Chernobyl accident - decision of dismissal of the Court of Appeal of Paris; 4 - Slovak Republic: Aarhus Convention compliance update; 5 - United States: Judgement of a US court of appeals upholding the NRC's dismissal of challenges to the renewal of the operating licence for Oyster Creek Nuclear Generating Station; reexamination of the project of high-level waste disposal site at Yucca Mountain

  11. Case report

    African Journals Online (AJOL)

    abp

    2015-11-23

    Nov 23, 2015 ... found the presence of deletion of ELN locus, compatible with. Williams-Beuren syndrome. The diagnosis of Williams-Beuren syndrome was made, and the patient is under observation, with a decline of eight months. Discussion. This paper is about an original case of Williams-Beuren syndrome associated ...

  12. Case series

    African Journals Online (AJOL)

    ebutamanya

    10 déc. 2015 ... 5. Chandler JR, Langenbrunner DJ, Stevens ER. The Pathogenesis. Of Orbital complications in acute sinusitis. Laryngoscope. 1970. Sep; 80(9): 1414-28. PubMed | Google Scholar. 6. Hodges E, Tabbara KF. Orbital cellulitis: review of 23 cases from Saudi Arabia. Br J Ophthalmol. 1989 Mar; 73(3): 205-8.

  13. Case report

    African Journals Online (AJOL)

    abp

    2012-06-11

    Jun 11, 2012 ... Abstract. Churg Strauss syndrome is a rare systemic and pulmonary vasculitis exceptionally associated with AA amyloidosis. We report the case of a 65-year old woman with past medical history of asthma. She developed polyarthralgia, headache and purpura. A laboratory workout found hypereosinophilia ...

  14. Case report

    African Journals Online (AJOL)

    ebutamanya

    2016-04-14

    Apr 14, 2016 ... Abstract. Laparoscopic management of acute adhesive small bowel obstruction has been shown to be feasible and advantageous. However, widespread acceptance and application is still not observed. We describe the case report of a 58-year-old male who presented with signs and symptoms of.

  15. Case report

    African Journals Online (AJOL)

    abp

    and imperforate anus. Figure 3: The examination of the spinal column revealed a spina bifida occulta. References. 1. Varygin V, Bernotas S, Gurskas P, Karmanovas V, et al. Cloacal exstrophy: a case report and literature review. Medicina. 1978;. 47(12): 682-5. PubMed| Google Scholar. 2. Carey JC, Greenbaum B, Hall BD.

  16. Case report

    African Journals Online (AJOL)

    raoul

    12 août 2010 ... Estermann F, B Denis, P Gaucher, D Regent, and D Sondag. Pneumatosis cystoides of the colon: knowing how to recognize it - Apropos of 8 cases. Ann Gastroenterol Hepatol (Paris). 1994; 30(4): 151-155. This article on PubMed. 12. Pun YL, DM Russell, GJ Taggart, and DR Barraclough. Pneumatosis ...

  17. Case report

    African Journals Online (AJOL)

    abp

    un cas. Rev Chir Orthop Reparatrice. Appar Mot. 2000;86(1):98-103. PubMed | Google Scholar. 7. Nagamine N, Nohara Y, Ito E. Elastofibroma in Okinawa. A clinicopathologic study of 170 cases. Cancer. 1982;50(9):1794-.

  18. Case series

    African Journals Online (AJOL)

    abp

    14 oct. 2013 ... Nagamine N, Nohara Y, Ito E. Elastofibroma in Okinawa - A clinicopathologic study of 170 cases. Cancer. 1982;50(9):1794-. 805. PubMed | Google Scholar. 12. Schafmayer C, Kahlke V, Leuschner I, Pai M, Tepel J. Elastofibroma dorsi as differential diagnosis in tumors of the thoracic wall. Ann Thorac Surg.

  19. Case report

    African Journals Online (AJOL)

    abp

    2015-05-18

    May 18, 2015 ... Abstract. Vasa previa is a rare but clinically important obstetrical complication that can be associated with a low-lying placenta or placenta previa. We aim to present one case of vasa previa diagnosed during the placenta examination after the caesarean indicated for triple uterus scar. A 26-year-old.

  20. Case report

    DEFF Research Database (Denmark)

    Füchtbauer, Laila; Brusgaard, Klaus; Ledaal, Pål

    2015-01-01

    ey Clinical Message Vitamin D-dependent rickets type 1 VDDR-1 is a recessive inherited disorder with impaired activation of vitamin D, caused by mutations in CYP27B1. We present long-time follow-up of a case with a novel mutation including high-resolution peripheral quantitative computed tomography...

  1. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-01-14

    Jan 14, 2015 ... In addition, rare but life-threatening complications such as foreign body aspiration in the air passages may also be seen. Aspirated foreign bodies include teeth, implants, mechanical supports or materials used during procedures. We report two separate cases of aspiration risk developing during the course.

  2. Case report

    African Journals Online (AJOL)

    abp

    2013-02-19

    Feb 19, 2013 ... main disease and 70-80% stenosis of the proximal Left Anterior Descending Artery (LAD). ... He had a successful PTCA + DES stent to the LAD (Figure 3). ... In the case being presented, despite the benign appearance of the.

  3. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-02-27

    Feb 27, 2015 ... custody is an additional risk factor in the development of this complication. [4] After a dural tear, the majority of anesthesiologists, as was the case in our observation, search the epidural space in an intervertebral spacing or sus- underlying for epidural analgesia [5, 6]. However, it should be emphasized that.

  4. Case report

    African Journals Online (AJOL)

    abp

    2013-10-23

    Oct 23, 2013 ... Pyomyositis in Nodding Syndrome (NS) patient - a case report ... B0X 7072, Kampala, Uganda, 3Gulu University, Faculty of Medicine, P.O. B0X 166, Gulu, Uganda .... to pay particular attention to such children who may have.

  5. Case series

    African Journals Online (AJOL)

    abp

    2014-01-20

    Jan 20, 2014 ... Page number not for citation purposes. 1. Stroke in young adults: about 128 cases ... hypercholesterolemia, history of cigarette smoking, contraceptive intake treatment, alcohol intake, sexual ..... Carolei A, Marini C, Ferranti E, Frontoni M, Prencipe M, Fieschi. C. A prospective study of cerebral ischemia in ...

  6. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-09-10

    Sep 10, 2015 ... Abstract. To describe a case of breast cancer manifested by cerebellar syndrome and to establish a relationship between breast cancer and Paraneoplastic syndromes through the presence of anti- yo antibodies in serum and cerebrospinal fluid of a patient. Our patient was 52 years old, Multipara with 5.

  7. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-11-20

    Nov 20, 2015 ... We report a case of a farmer who has sustained of a severe hand wound due to ... open distal interphalangeal joint dislocation of the 5th finger; flexor tendons were .... biomechanical analysis and clinical application. J Orthop ...

  8. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-12-03

    Dec 3, 2015 ... surgical correction by high way by the Huntington technique or. Haultain or vaginally with the technique of Spinelli [1] - hysterectomy hemostasis remains the gold standard in case of persistent bleeding but is exceptionnel [6]. More recently the use of balloons such as Rusch or Bakri have been described in ...

  9. Case report

    African Journals Online (AJOL)

    abp

    26 avr. 2016 ... cases relating idiopathic gastric necrosis in a young patient who presented no heart failure, or particular psychological profiles (bulimia, anorexia) no venous or arterial thrombosis were found during surgical exploration during the pathological study, no toxic or bacteriological founded. Gastric necrosis is ...

  10. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-11-24

    Nov 24, 2015 ... High drug level and the absence of toxic effect (or the absence of toxic .... from the first order,"in which the extent of metabolism is directly correlated with the ... hepatocyte, the pancreatic ductuli, the glandular epithelial cells of ... cytochrome P-450 genes in diseases requiring chronic drug use. In our case ...

  11. Case report

    African Journals Online (AJOL)

    raoul

    25 sept. 2011 ... Robin A, Méry G, George JL, Maalouf T, Angioi K. Facial necrotizing fasciitis after mild trauma of the eyelid: role of nonsteroidal anti- inflammatory treatment. J Fr Ophtalmol. 2010 Oct;33(8):568-72. This article on PubMed. 6. Cornelia Poitelea, Michael J. Wearne. Periocular necrotising fasciitis--a case report.

  12. Case Report

    African Journals Online (AJOL)

    Arthritis: a Case Report. Intissar Haddiya*, Hakima Rhou, Loubna Benamar, Fatima Ezzaitouni, Rabia Bayahia, Naima. Ouzeddoun. Unit of Nephrology, Ibn Sina University Hospital, Rabat, Morocco. * Corresponding author; Unit of Nephrology, Ibn Sina University. Hospital, Rabat, Morocco; E. mail: intissarhaddiya@hotmail.

  13. Case series

    African Journals Online (AJOL)

    abp

    2017-07-14

    Jul 14, 2017 ... complications. Various methods have been used to treat these injuries, with variable results. The aim ... Soft tissue healing occurred without need for plastic surgery in all cases. ... Under general anesthesia, patients were placed in the supine .... of the ankle joint is another advantage of the ILIZAROV device.

  14. Case report

    African Journals Online (AJOL)

    abp

    2014-03-28

    Mar 28, 2014 ... Abstract. Cushing syndrome is a hormonal disorder caused by prolonged exposure of body tissue to cortisol. We report two cases of iatrogenic Cushing's syndrome in two Nigerian children following intranasal administration of aristobed-N (Betamethasone+Neomycin) given at a private hospital where.

  15. Case law

    International Nuclear Information System (INIS)

    Anon.

    1999-01-01

    This paper gives and analyses three examples of case law: decision rejecting application to close down Tomari nuclear power plant (Japan); judgement by the Supreme Administrative Court on the closing of Barsebaeck (Sweden); litigation relating to the Department of Energy's obligations under the Nuclear Waste Policy Act to accept spent nuclear fuel and high-level radioactive waste (United States). (A.L.B.)

  16. Case series

    African Journals Online (AJOL)

    abp

    4 déc. 2017 ... modify initial tumor stage in 60% of cases: upstaging in 23 patients (46%) and downstaging in ... (FDG) est injecté chez nos patients à la dose de 4 à 5 MBq/kg par ..... positron emission tomography in patients with lung cancer.

  17. Case Report

    African Journals Online (AJOL)

    through a small clinically-undetectable inguinal hernia, and may require ... conservative approach may be adopted. Case report: An 80 ... gross bilateral scrotal swelling (without cough impulse) ... Tenckhoff catheter was inserted using the open surgical technique ... role of surgery in treating dialysate leaks presenting as.

  18. case study

    African Journals Online (AJOL)

    Elton

    particularly in patients who commence ART with low CD4 counts and established opportunistic infections. IRIS results from a pathological inflammatory response to pre-existing infective, host or other antigens, alive or dead, causing clinical deterioration in HIV-infected patients after initiating ART.1 A case definition for IRIS ...

  19. Case series

    African Journals Online (AJOL)

    abp

    19 oct. 2017 ... Traitement des amyloses AL systémiques: à propos de 25 cas. Treatment of systemic AL amyloidosis: about 25 cases. Hicham Eddou1,&, Ali Zinebi1, Hicham El Maaroufi2, Mohammed Karim Moudden1, Kamal Doghmi2, Mohammed Mikdame2,. Mohammed El Baaj1. 1Service de Médecine Interne, Hôpital ...

  20. Case report

    African Journals Online (AJOL)

    ebutamanya

    15 janv. 2015 ... Les biopsies faites étaient revenues négatives. L'échographie abdominale a montré une masse au .... PubMed | Google. Scholar. 8. Nassiopoulos K, Stockhammer A, Hahnloser P, et al. Gastric leiomyoblastoma: literature review and report of a case. Rev. Med Suisse Romande .1997; 117 (2):147-150.

  1. Case report

    African Journals Online (AJOL)

    abp

    21 mai 2013 ... biopsie vaginale est revenue en faveur d'un ADK colloïde muqueux, franchement marqué par l'anti-corps anti-CK 20 .... Google Scholar. 7. Mudhar HS, Smith JH, Tidy J. Primary vaginal adenocarcinoma of intestinal type arising from an adenoma: case report and review of the literature. Int J Gynecol Pathol.

  2. CASE STUDY

    African Journals Online (AJOL)

    2011-06-02

    Jun 2, 2011 ... immunosuppression associated with HIV/AIDS puts them at a higher risk of developing oesophageal cancer. 47. CASE STUDY. A 49-year-old man was diagnosed as HIV infected, with a CD4 count of 60 cells/µl. He was started on an antiretroviral treatment regimen comprising zidovudine, lamivudine and ...

  3. Case report

    African Journals Online (AJOL)

    abp

    27 oct. 2017 ... We report the case of a menopausal woman with breast tuberculosis in order to raise concern for diagnosis. Key words: Tuberculosis, breast, diagnosis. Introduction. La tuberculose mammaire est une forme rare de la tuberculose extra-pulmonaire même dans les pays endémiques. Elle représente. 0,06 à 0 ...

  4. Case report

    African Journals Online (AJOL)

    abp

    2017-10-17

    Oct 17, 2017 ... Scholar. 2. Riccardo Campi, Sergio Serni, Maria Rosaria Raspollini,. Agostino Tuccio, Giampaolo Siena, Marco Carini et al. Robot-. Assisted Laparoscopic Vesiculectomy for Large Seminal Vesicle. Cystadenoma: a case report and review of the literature. Clinical Genitourinary Cancer. 2015; 13(5): e369-.

  5. Case series

    African Journals Online (AJOL)

    abp

    2017-09-15

    15 Ebola Virus Disease (EVD) outbreak in West Africa infected more than 28,000 persons out of which 11,000 died [20]. At the height of this outbreak, the huge load of cases and their contacts overwhelmed the response ...

  6. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-01-07

    Jan 7, 2015 ... Preeclampsia is an entity that may present from 20th week of gestation up to 48 hours postpartum and is associated with hypertension and ... The awareness of atypical cases of preeclampsia enhances early diagnosis and management which are critical to ... hypertensive disorder in previous pregnancy.

  7. Case report

    African Journals Online (AJOL)

    raoul

    28 avr. 2011 ... Spermatic cord sarcoma in adults. J Urol. 1978; 120: 301-305. This article on PubMed. 11. Romero Tenorio M, Farinas Varo JM, Baez Perez JM, Almaised J, Ramirez Chamorro R, and Beltran Ruiz-Hinestrosa M. Liposarcoma en la infancia: Aportacion de un case exceptional - Revision de la literatura.

  8. Case report

    African Journals Online (AJOL)

    abp

    2017-09-04

    Sep 4, 2017 ... Published in partnership with the African Field Epidemiology Network (AFENET). (www.afenet.net). Case report ... occurrence during infancy; and development from neural crest cells. [1, 5]. In a histological review, .... with adjuvant treatment is suggested for recurrent lesions [3, 17]. All of these have been ...

  9. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-11-17

    Nov 17, 2015 ... Abstract. Here we report a case of central retinal artery occlusionrevealing an ischemic cardiomyopathy. A 54-year old smoker man presented at the hospital because of sudden visual loss in his left eye. There was cherry-red spot in the macula in his left eye. We performed a fluorescein angiogram and.

  10. Case report

    African Journals Online (AJOL)

    abp

    2016-05-13

    May 13, 2016 ... Abstract. We report a rare case of an elderly woman presented with right renal mass with invasion of renal vein and several small lymphadenopathy in the hilar area .the diagnosis of kidney cancer is suspected and the patient underwent open radical nephrectomy, surrenalectomy and lymphadenectomy ...

  11. CASE REPORT

    African Journals Online (AJOL)

    NJSR

    cardiac failure, as in our patient, digitalis and radiography are considered before surgical excision. Occasional cases have involuted spontaneously, though a few have metastasized. 5 Other forms of treatment include corticosteroids, and hepatic artery ligation. 7 Malignant transformation has been reported after successful ...

  12. Case report

    African Journals Online (AJOL)

    abp

    2017-05-05

    May 5, 2017 ... Chondroblastic osteosarcoma of the distal tibia: a rare case report. Aymen Ben Fredj1,&, Lassaad Hassini1, Aymen Fekih1, Mohamed Allagui1, Issam Aloui1, Abderrazek Abid1. 1Department of Orthopaedic Surgery, University Hospital, Monastir, Tunisia. &Corresponding author: Aymen Ben Fredj, ...

  13. Case series

    African Journals Online (AJOL)

    ebutamanya

    2015-01-20

    Jan 20, 2015 ... The brainstem, cerebral white matter, basal ganglia, internal capsule, thalamus and spinal cord were involved in forty four, thirty one, thirty, twenty nine, seventeen and four patients, respectively. The cerebral peduncle was the brainstem structure mainly involved with thirty cases followed by the pons with, ...

  14. Case report

    African Journals Online (AJOL)

    abp

    Abstract. Primary omental torsion is a rare cause of acute abdominal pain, we report a case of 10-year-old boy admitted with crampy abdominal pain, routine laboratory tests and plain abdominal radiography was normal, the patient underwent surgical exploration with the initial diagnosis of appendicitis, primary omental ...

  15. Case report

    African Journals Online (AJOL)

    Raoul

    2009-10-15

    Oct 15, 2009 ... Meckel's diverticulum: a case report from the University Hospital Center ... The Pan African Medical Journal - ISSN 1937-8688. ... Usually discovered incidentally; it is often the cause of acute abdominal emergencies. It may present as intestinal obstruction with volvulus, intussusceptions or peritonitis due to ...

  16. Case report

    African Journals Online (AJOL)

    abp

    16 janv. 2017 ... We report the case of a 70-year-old man with no past medical history presenting with laryngeal dyspnea associated with low abundant paroxysmal hemoptysis. The patient underwent nasofibroscopy showing the presence of a living and mobile organism at the subglottic level evoking a leech. Extraction ...

  17. Case report

    African Journals Online (AJOL)

    abp

    2016-02-29

    Feb 29, 2016 ... Classification of subtrochanteric femoral fractures. Injury. 2010. Jul;41(7):739-45. PubMed | Google Scholar. 3. Kennedy MT, Mitra A, Hierlihy TG, Harty JA, Reidy D, Dolan M. Subtrochanteric hip fractures treated with cerclage cables and long cephalomedullary nails: a review of 17 consecutive cases over. 2.

  18. Case report

    African Journals Online (AJOL)

    abp

    2016-07-14

    Jul 14, 2016 ... sarcoma mimicking abscess: review of the MRI appearances. Skeletal Radiol. 2001; 30:173 -7. PubMed | Google Scholar. 6. Adrian HO, Louis SL, Howard AO, Kenneth WA, John RG. Epithelioid sarcoma of the penis: Report of an unusual case and review of the literature. Ann Diagn Patho. 2000; 14(2):88-.

  19. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-02-13

    Feb 13, 2015 ... mucoid, T.inkin, T. cutaneum) a rate of 11.15%. This rate confirms the one recorded by Pini G & al ... The authors declare no competing interest. Authors' ... due to Trichosporonasahii,first two cases in Chile. Rev. IberoamMicol.

  20. Case Report

    DEFF Research Database (Denmark)

    Klubien, Jeanett; Borgersen, Dorte Winther; Rosenberg, Jacob

    2016-01-01

    Introduction Perforation of the gallbladder is a benign and common complication during laparoscopic cholecystectomy. However, it may result in stone spilling, which potentially can lead to serious postoperative complications.  Case report A 70-year-old male underwent laparoscopic cholecystectomy...

  1. Case Report

    DEFF Research Database (Denmark)

    Sylvester-Hvid, Amalie; Avnstorp, Magnus B; Wagenblast, Lene

    2017-01-01

    Introduction Breast seroma may be caused by a variety of factors including lymphatic disruption, continuous inflammation and foreign bodies such as breast implants. In cases of breast implants associated seroma the diagnosis of Anaplastic Large Cell Lymphoma (ALCL) should be investigated. Present...

  2. Case report

    African Journals Online (AJOL)

    abp

    2015-07-10

    Jul 10, 2015 ... We herein describe a case of a 22-year-old man with a long history of cocaine abuse. ... African Medical Journal - ISSN 1937-8688. This is an Open Access article distributed under the terms of the Creative Commons Attribution ... a long history of cocaine, cannabis, and tobacco abuse. He presented to our.

  3. Case report

    African Journals Online (AJOL)

    ebutamanya

    19 févr. 2016 ... Enteropathy associated T-cell lymphoma (EATL) is a rare complication of celiac disease (CD). We report a case of EATL associated with CD revealed by acute intestinal obstruction. A North African woman of 38 years old with a history of infertility and chronic abdominal pain was admitted in emergency with ...

  4. Case report

    African Journals Online (AJOL)

    abp

    27 avr. 2016 ... Dysphagia revealing aberrant right subclavian artery: about a case. Abdelilah Mouhsine1,&, Oualid Bakzaza2, El Mehdi Atmane1, Ahmed Belkouch3, Redouane Rokhssi1, Youssef Berrada1, Mostapha. Alaoui2, M'barek Mahfoudi1, Abdelghani El Fikri1. 1Service de Radiologie, HMA, Marrakech, Maroc, ...

  5. Case report

    African Journals Online (AJOL)

    abp

    2014-05-30

    May 30, 2014 ... tumor size, pleural effusion, response to chemotherapy, and optimal radiotherapy [10]. Several authors assert that Surgical therapy has the most important implication and complete surgical resection is associated with a survival advantage [5]. In the index case, despite no distant metastasis were found at.

  6. Case report

    African Journals Online (AJOL)

    abp

    2013-08-29

    Aug 29, 2013 ... inflammatory bowel disease, in particular ulcerative colitis (UC), are often treated with immunosuppressive therapy and can develop colorectal KS [3]. We report the case of a human immunodeficiency negative-virus (HIV) man, with a severe refractory UC, who was treated with steroids, azathioprine and ...

  7. Case report

    African Journals Online (AJOL)

    abp

    5 mai 2016 ... Garcia JA, Garcia-Fernandez M, Romance A, Sanchez JC. Wandering spleen and gastric volvulus. Pediatr Radiol. 1994;. 24(7): 535-6. PubMed | Google Scholar. 3. Melikoglu M, Colak T, Kasasoglu. Two unusual cases of wandering spleen requiring splenectomy. Eur J Pediatr Surg. 1995; 5(1): 48-9.

  8. Case report

    African Journals Online (AJOL)

    ebutamanya

    French). 1984;30(3):177-81. PubMed |. Google Scholar. 12. Isla A, Paz JM, Sansivirini F, Zamora P, Garcia Grande A,. Fernandez A. Intramedullary spinal cord metastasis: a case report. J Neurosurg Sci. 2000 Jun; 44(2):99-101.

  9. Case report

    African Journals Online (AJOL)

    abp

    2013-05-21

    May 21, 2013 ... Imperforate Hymen - a rare cause of acute abdominal pain and tenesmus: case report and review of .... did a ten year retrospective analysis of the data of 15 patients treated for ... Low back pain (38-40%) [4, 13, 14]. Occurs as ...

  10. Case report

    African Journals Online (AJOL)

    abp

    2017-06-13

    Jun 13, 2017 ... Oxyuriasis's symptoms are extremely diverse in children, ranging from nausea, diarrhea, insomnia, irritability, recurrent cellulitis, loss of appetite, nightmares and endometritis. Here we report a curious case of oxyuriasis in the settings of a refugee camp in Greece. The patient was a. 10-year old Syrian ...

  11. Case report

    African Journals Online (AJOL)

    abp

    15 juin 2016 ... We report the case of a 17-year old admitted with diffuse bone pain, hypercalcemia and thrombopenia. Bone scan showed .... plus rares et ont été rapportée dans des observations isolées [13]. ... hypercalcemia in nude mice.

  12. Case series

    African Journals Online (AJOL)

    abp

    1 juin 2012 ... ... Ren- Xuan Guo, and Ke-Jian Guo. Adult intussusception: A retrospective review of 41 cases. World J Gastroenterol. 2009 Jul 14;15(26):3303-8. This article on PubMed. 14. Abou-Nukta F, Gutweiler J, Khaw J, Yavorek G. Giant lipoma causing a colo-colonic intussusception. Am Surg. 2007;73(4):417. This.

  13. Case report

    African Journals Online (AJOL)

    abp

    2013-02-14

    Feb 14, 2013 ... Abstract. Vaginal metastases of renal cell carcinoma have been rarely described. We report a case of a 75-year old woman, who underwent radical right nephrectomy for a renal cell carcinoma. Tumour was classified pT3bN0M0 and grade III of Furhmann grading. One year later, scanner discovered.

  14. Case report

    African Journals Online (AJOL)

    abp

    2013-11-04

    Nov 4, 2013 ... especially in developing countries. HBV can be complicated by acute glomerulonephritis , this association remains controversial. The optimal therapy is undefined, although in several studies, the antiviral drugs and the immunosuppressive therapy have been tried for those patients [1]. We report the case of ...

  15. Case report

    African Journals Online (AJOL)

    ebutamanya

    17 janv. 2016 ... Budd-Chiari syndrome: a rare complication of hepatic sarcoidosis (about one case). Ismael Ait Sghier1,&, Nabil Moatassim Billah1. 1Service de Radiologie Centrale, Hôpital Avicenne, Rabat, Maroc. &Corresponding author: Ismael Ait Sghier, Service de Radiologie Centrale, Hôpital Avicenne, Rabat, Maroc.

  16. Case competitions

    DEFF Research Database (Denmark)

    Schjoldager, Anne Gram

    2009-01-01

    The paper presents and discusses a teaching project with case competitions for MA students of specialised translation at the Aarhus School of Business, Aarhus University. Drawing on a series of online questionnaires, the paper ascertains how the project was evaluated by the participating students...

  17. Case report

    African Journals Online (AJOL)

    abp

    Cerebral venous sinus thrombosis in HIV-infected patients: report of 2 cases ... often affects young adults and children [1]. ... local trauma and infection, prothrombotic states like nephrotic ... head trauma. ... She denied any history of alcohol intake, cigarette smoking .... against protein S among HIV infected patients, leading to.

  18. Case report

    African Journals Online (AJOL)

    abp

    9 août 2017 ... We report a case of hemorrhagic stroke of the brainstem in a nonmonitored ... haemorrhagic stroke of the brainstem on the second post-operative day after cesarean section performed due to suspicion of retroplacental haematoma arisen .... syndrome hémorragique ont évolué favorablement et une patiente.

  19. Case series

    African Journals Online (AJOL)

    abp

    2015-01-19

    Jan 19, 2015 ... Child sexual abuse: report of 311 cases with review of literature. Laila Essabar1, Abdenbi Khalqallah2, Badr Sououd Benjelloun Dakhama1,&. 1Department of Paediatric Medical Emergencies of Rabat children's Hospital, Morocco, 2Laboratory of Clinical and Pathological Psychology,. Mohammed V ...

  20. CASE REPORT

    African Journals Online (AJOL)

    2011-12-02

    Dec 2, 2011 ... brain illustrated enhancement of the optic nerves post-. CASE REPORT ... improved bilaterally to 6/18 on the right and 6/12 on the left. There was .... the possible risks versus benefits of steroid therapy and invite them to ...