A randomized, double-blind, placebo-controlled, proof-of-concept trial of creatine monohydrate as adjunctive treatment for bipolar depression.

Depressive episodes are a major cause of morbidity and dysfunction in individuals suffering from bipolar disorder. Currently available treatments for this condition have limited efficacy and new therapeutic options are needed. Extensive research in the pathophysiology of bipolar disorder points to the existence of mitochondrial and bioenergetic dysfunction. We hypothesized that creatine monohydrate, a nutraceutical that works as a mitochondrial modulator, would be effective as an adjunctive therapy for bipolar depression. We conducted a double-blind trial in which 35 patients with bipolar disorder type I or II in a depressive episode by DSM-IV criteria and in use of regular medication for the treatment of this phase of the disease were randomly allocated into two adjunctive treatment groups for 6 weeks: creatine monohydrate 6 g daily (N = 17) or placebo (N = 18). Primary efficacy was assessed by the change in the Montgomery-Åsberg Depression Rating Scale (MADRS). We did not find a statistically significant difference in the comparison between groups for the change in score on the MADRS after 6 weeks in an intention-to-treat (ITT) analysis (p = 0.560; Cohen's d = 0.231). However, we found significant superiority of creatine add-on vs. placebo when we considered the remission criterion of a MADRS score ≤ 12 at week 6 analyzing the outcome of the 35 randomized patients on ITT (52.9% remission in the creatine group vs. 11.1% remission in the placebo group) and of the 23 completers (66.7% remission in the creatine group vs. 18.2% remission in the placebo group) (p = 0.012; OR = 9.0 and p = 0.036; OR = 9.0, respectively). Two patients who received creatine switched to hypomania/mania early in the trial. No clinically relevant physical side-effects were reported or observed. This proof-of-concept study, aiming to restore brain bioenergetics using an adjunctive mitochondrial modulator, is not conclusive on the efficacy of creatine add-on for bipolar depression, but suggests that this compound may have a role in the adjunctive treatment of this phase of the illness. Further investigation through randomized controlled trials with larger samples should be conducted to verify the efficacy of creatine supplementation for bipolar depression and also for subsyndromal depressive symptoms.

Bipolar disorder and comorbid obsessive-compulsive disorder is associated with higher rates of anxiety and impulse control disorders.

UNLABELLED: Issler CK, Monkul ES, Amaral JAMS, Tamada RS, Shavitt RG, Miguel EC, Lafer B. Bipolar disorder and comorbid obsessive-compulsive disorder is associated with higher rates of anxiety and impulse control disorders. OBJECTIVE: Although bipolar disorder (BD) with comorbid obsessive-compulsive disorder (OCD) is highly prevalent, few controlled studies have assessed this comorbidity. The objective of this study was to investigate the clinical characteristics and expression of comorbid disorders in female BD patients with OCD. METHOD: We assessed clinically stable female outpatients with BD: 15 with comorbid OCD (BD+OCD group) and 15 without (BD/no-OCD group). All were submitted to the Structured Clinical Interview for DSM-IV, with additional modules for the diagnosis of kleptomania, trichotillomania, pathological gambling, onychophagia and skin picking. RESULTS: The BD+OCD patients presented more chronic episodes, residual symptoms and previous depressive episodes than the BD/no-OCD patients. Of the BD+OCD patients, 86% had a history of treatment-emergent mania, compared with only 40% of the BD/no-OCD patients. The following were more prevalent in the BD+OCD patients than the BD/no-OCD patients: any anxiety disorder other than OCD; impulse control disorders; eating disorders; and tic disorders. CONCLUSION: Female BD patients with OCD may represent a more severe form of disorder than those without OCD, having more depressive episodes and residual symptoms, and being at a higher risk for treatment-emergent mania, as well as presenting a greater anxiety and impulse control disorder burden.

Clinical expression of obsessive-compulsive disorder in women with bipolar disorder.

OBJECTIVE: To study clinical and psychopathological features of obsessive-compulsive disorder (OCD) in women with bipolar disorder (BD). METHODS: Fifteen outpatients with concurrent bipolar disorder I (80.0%) or II (20.0%) and obsessive-compulsive disorder were studied. Most of them (80.0%) sought treatment for bipolar disorder. They were ascertained by means of the Structured Clinical Interview for DSM-IV (SCID/P), semi-structured interviews to investigate obsessions, compulsions and sensory phenomena that may precede compulsions and an additional module for the diagnosis of chronic motor and vocal tics. Severity of symptoms was assessed by the Yale-Brown Obsessive-Compulsive Rating Scale, Hamilton Depression Rating Scale and Young Mania Rating Scale. RESULTS: Obsessive-compulsive disorder presented early onset (before the age of 10) in 9 (60%) cases, preceded bipolar disorder in 10 (66.7%) and displayed chronic waxing and waning course in 13 (86.7%) of them. There was wide overlap between types of obsessive-compulsive symptoms and all patients experienced sensory phenomena preceding the compulsions. There was no clear-cut impact of depressive and manic episodes on the intensity of obsessive-compulsive symptoms, which increased in depression and decreased in mania in 40.0% of the cases, had the opposite pattern in 26.7% of the patients and fluctuated inconsistently in the rest of them. Tics disorders were diagnosed in 5 (33.3%) patients. CONCLUSIONS: Our results suggest that in women with comorbid bipolar disorder and obsessive-compulsive disorder the latter presents features that may be typical of the association of the two disorders, such as early onset and sensory phenomena preceding compulsions. A prospective controlled study is necessary to confirm these observations, due to some limitations of our study: small exclusively female sample, heterogeneity concerning the type of bipolar disorder and the disorder that determined sought of treatment and retrospective non-controlled design.

Clinical expression of obsessive-compulsive disorder in women with bipolar disorder

OBJETIVO: Estudar características clínicas e psicopatológicas do transtorno obsessivo-compulsivo (TOC) em mulheres com transtorno de humor bipolar (THB). MÉTODOS: Foram estudadas, retrospectivamente, 15 pacientes ambulatoriais com diagnósticos simultâneos de transtorno de humor bipolar I (80,0%) ou II (20,0%) e transtorno obsessivo-compulsivo. A maioria havia buscado tratamento para transtorno de humor bipolar (80,0%). A avaliação constou da Entrevista Clínica Estruturada para o DSM-IV (SCID/P), de entrevistas semi-estruturadas para pesquisa de obsessões, compulsões e fenômenos sensoriais que podem preceder as compulsões e de módulo adicional para diagnóstico de tiques motores e vocais crônicos. A gravidade dos sintomas foi investigada através das seguintes escalas: Escala Yale-Brown para Sintomas Obsessivo-Compulsivos, Escala de Avaliação para Depressão de Hamilton e Escala de Avaliação de Mania de Young. RESULTADOS: O transtorno obsessivo-compulsivo teve início precoce em nove (60%) casos, instalou-se antes do transtorno de humor bipolar em 10 (66,7%) e teve curso crônico flutuante em 13 (86,7%). Houve ampla superposição de tipos de sintomas obsessivo-compulsivos e todas as pacientes apresentaram fenômenos sensoriais precedendo as compulsões. Não houve padrão definido no impacto dos episódios depressivos e maníacos na intensidade dos sintomas obsessivo-compulsivos. Estes aumentaram na depressão e diminuíram na mania em 40,0% dos casos; tiveram o comportamento inverso em 26,7% das pacientes e oscilaram de forma inconsistente nas demais. Diagnosticou-se comorbidade com transtorno de tiques em cinco (33,3%) casos. CONCLUSÕES: Nossos resultados sugerem que, em mulheres com comorbidade de transtorno de humor bipolar e transtorno obsessivo-compulsivo, este último apresente características que talvez sejam específicas da associação dos dois transtornos, tais como instalação precoce e presença de fenômenos sensoriais antecedendo as compulsões. A confirmação destas observações em pesquisa prospectiva controlada é necessária, em função de algumas limitações do estudo: casuística reduzida e restrita ao sexo feminino, alguma heterogeneidade da amostra quanto ao tipo de transtorno de humor bipolar e com relação ao transtorno que determinou procura de tratamento, ausência de grupo controle e coleta de dados retrospectiva.

Espectroscopia de proton por ressonancia magnetica: aplicacoes em psiquiatria / Proton magnetic resonance spectroscopy: use in psychiatry

Os autores descrevem os principios fisicos da espectroscopia de proton por ressonancia magnetica (1H-MRS), assim como os aspectos fisiologicos relacionados as moleculas que podem ser detectadas pela tecnica. Os resultados dos estudos utilizando 1H-MRS em esquizofrenia, transtornos do humor, doenca de Alzheimer, abuso de alcool e drogas, transtornos ansiosos, anorexia nervosa e autismo sao apresentados, e suas implicacoes na compreensao da...