Distractibility, anxiety, irritability, and agitation symptoms are associated with the severity of depressive and manic symptoms in mixed depression.

OBJECTIVE: To explore whether there is an association between distractibility, anxiety, irritability, and agitation (DAIA) symptoms and the severity of depressive and manic symptoms. METHODS: Patients with unipolar and bipolar disorder (I and II) and mixed depression were evaluated. DAIA symptoms were assessed using previously described definitions. RESULTS: The full analysis set comprised 100 patients. The severity of depressive symptoms in mixed depression, assessed by Montgomery-Åsberg Depression Rating Scale (MADRS), was significantly associated with the presence of two or more DAIA symptoms in the bipolar sample, influenced mainly by anxiety. The severity of manic symptoms in mixed depression, assessed by Young Mania Rating Scale (YMRS), was significantly associated with the presence of two or more DAIA symptoms in the bipolar sample and three or four DAIA symptoms in the unipolar sample. CONCLUSION: DAIA symptoms were associated with greater severity of manic symptoms in mixed depression. DAIA symptoms must be evaluated in all patients with mixed features and are associated with the severity of depressive and manic symptoms in mixed depression.

Distractibility, anxiety, irritability, and agitation symptoms are associated with the severity of depressive and manic symptoms in mixed depression

Objective: To explore whether there is an association between distractibility, anxiety, irritability, and agitation (DAIA) symptoms and the severity of depressive and manic symptoms. Methods: Patients with unipolar and bipolar disorder (I and II) and mixed depression were evaluated. DAIA symptoms were assessed using previously described definitions. Results: The full analysis set comprised 100 patients. The severity of depressive symptoms in mixed depression, assessed by Montgomery-Åsberg Depression Rating Scale (MADRS), was significantly associated with the presence of two or more DAIA symptoms in the bipolar sample, influenced mainly by anxiety. The severity of manic symptoms in mixed depression, assessed by Young Mania Rating Scale (YMRS), was significantly associated with the presence of two or more DAIA symptoms in the bipolar sample and three or four DAIA symptoms in the unipolar sample. Conclusion: DAIA symptoms were associated with greater severity of manic symptoms in mixed depression. DAIA symptoms must be evaluated in all patients with mixed features and are associated with the severity of depressive and manic symptoms in mixed depression. Clinical trial registration: ClinicalTrials.gov (NCT04123301).

Treatment of mixed depression with theta-burst stimulation (TBS): results from a double-blind, randomized, sham-controlled clinical trial.

Mixed depression is probably different in terms of clinical course and response to treatment. Repetitive transcranial magnetic stimulation (rTMS) is well established in non-mixed depression, and theta-burst stimulation (TBS) protocol is replacing conventional protocols because of noninferiority and reduced delivery time. However, TBS has not been adequately studied in mixed states. This study was a double-blind, six-week, sham-controlled, and randomized clinical trial of bilateral TBS targeting the right and left dorsolateral prefrontal cortex, respectively. Adults with bipolar and major depressive disorder experiencing an acute mixed depression were eligible if they had not benefited from a first- or second-line treatment for acute unipolar or bipolar depression recommended by the Canadian Network for Mood and Anxiety Treatments. Out of 100 patients included, 90 composed modified intention-to-treat sample, which was patients that completed at least one week of the intervention. There were no significant differences in Montgomery-Asberg depression rating scale score changes (least squares mean difference between groups at week 3, -0.06 [95% CI, - 3.39 to 3.51; P = 0.97] in favor of sham TBS). Response and remission rates per MADRS were also not statistically different among active and sham groups (35.7% vs. 43.7%, and 28.5% vs. 37.5% respectively at week 6, ps > 0.51). No other analyses from baseline to weeks 3 or 6 revealed significant time x group interaction or mean differences among groups in the mITT sample. Bilateral TBS targeting the DLPFC is not efficacious as an add-on treatment of acute bipolar and unipolar mixed depression. ClinicalTrials.govIdentifier: NCT04123301.

A randomized controlled trial comparing lithium plus valproic acid versus lithium plus carbamazepine in young patients with type 1 bipolar disorder: the LICAVAL study.

BACKGROUND: Treatment of bipolar disorder (BD) usually requires drug combinations. Combinations of lithium plus valproic acid (Li/VPA) and lithium plus carbamazepine (Li/CBZ) are used in clinical practice but were not previously compared in a head-to-head trial. OBJECTIVE: The objective of this trial was to compare the efficacy and tolerability of Li/VPA versus Li/CBZ in treating type 1 BD in any phase of illness in young individuals. METHODS: LICAVAL was a randomized, unicenter, open-label, parallel-group trial that was conducted from January 2009 to December 2012 in a tertiary hospital in São Paulo, Brazil. Participants were between 18 and 35 years old and were followed up for 2 years. Our primary outcome was the number of participants achieving/maintaining response and remission during the acute and maintenance phases of BD treatment, respectively. Other outcomes assessed were symptom severity and adverse events throughout the study. In the analysis of the primary outcome, we compared groups by using a two-way repeated measures analysis of variance and estimated effect sizes by using Cohen's d. RESULTS: Of our 64 participants, 36 were allocated to Li/VPA and 28 to Li/CBZ. Our sample was composed predominantly of females (66.6%) and the average age was 27.8 years. A total of 27 (45.0%) participants had depression, 17 (28.3%) had mania/hypomania, and 16 (26.7%) had a mixed state. We found no between-group differences in CGI-BP (Clinical Global Impression Scale modified for use in bipolar disorder) scores (P = 0.326) or in any other outcome. Side effects differed significantly between groups only in the first week of treatment (P = 0.021), and there were more side effects in the Li/VPA group. Also, the Li/VPA group gained weight (+2.1 kg) whereas the Li/CBZ group presented slight weight loss (-0.2 kg). CONCLUSION: Our study suggests that Li/VPA and Li/CBZ have similar efficacy and tolerability in BD but that Li/CBZ might have metabolic advantages in the long term. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00976794 . Registered on September 9, 2009.

The ARIQUELI study: potentiation of quetiapine in bipolar I nonresponders with lithium versus aripiprazole.

BACKGROUND: The treatment of bipolar disorder (BD) remains a challenge due to the complexity of the disease. Current guidelines represent an effort to assist clinicians in routine practice but have several limitations, particularly concerning long-term treatment. The ARIQUELI (efficacy and tolerability of the combination of lithium or aripiprazole in young bipolar non or partial responders to quetiapine monotherapy) study aims to evaluate two different augmentation strategies for quetiapine nonresponders or partial responders in acute and maintenance phases of BD treatment. METHODS/DESIGN: The ARIQUELI study is a single-site, parallel-group, randomized, outcome assessor-blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic/hypomanic or mixed episode, aged 18 to 40 years, are eligible. After diagnostic assessments, patients initiated treatment in phase I with quetiapine. Nonresponders or partial responders after 8 weeks are allocated into one of two groups, potentiated with either lithium (0.5 to 0.8 mEq/l) or aripiprazole (10 or 15 mg). Patients will be followed up for 8 weeks in phase I (acute treatment), 6 months in phase II (continuation treatment) and 12 months in phase III (maintenance treatment). Outcome assessors are blinded to the treatment. The primary outcome is the evaluation of changes in mean scores on the CGI-BP-M between baseline and the endpoint at the end of each study phase. DISCUSSION: The ARIQUELI study is currently in progress, with patients undergoing acute treatment (phase I), potentiation (phase II) and maintenance (phase III). The study will be extended until January 2015. Trials comparing lithium and aripiprazole with potentiate treatment in young BD I nonresponders to quetiapine in monotherapy can provide relevant information on the safety of these drugs in clinical practice. Long-term treatment is an issue of great importance and should be evaluated further through more in-depth studies given that BD is a chronic disease. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01710163.

Burden of maternal bipolar disorder on at-risk offspring: a controlled study on family planning and maternal care.

INTRODUCTION: Bipolar disorder (BD) is a highly incapacitating disease typically associated with high rates of familial dysfunction. Despite recent literature suggesting that maternal care is an important environmental factor in the development of behavioral disorders, it is unclear how much maternal care is dysfunctional in BD subjects. OBJECTIVE: The objective of this study was to characterize maternal care in DSM-IV/SCID diagnosed BD type I subjects compared to healthy controls with (PD) and without (NPD) other psychiatric diagnoses. MATERIALS AND METHODS: Thirty-four BD mothers and 106 controls underwent an interview about family planning and maternal care, obstetrical complications, and mother-child interactions. K-SADS-PL questions about violence exposure were used to ascertain domestic violence and physical/sexual abuse. RESULTS: BD mothers were less likely to have stable unions (45.5%; p<0.01) or to live with the biological father of their children (33.3%; p<0.01), but had higher educational level and higher rates of social security use/retirement. They also had fewer children and used less contraceptive methods than controls. Children of BD women had higher rates of neonatal anoxia, and reported more physical abuse (16.1%; p=0.02) than offspring of NPD mothers. Due to BD mothers' symptoms, 33.3% of offspring suffered physical and/or psychological abuse. LIMITATIONS: Post hoc analysis, and the use of questions as a surrogate of symptoms as opposed to validated instruments. CONCLUSION: This is one of few reports confirming that maternal care given by BD women is dysfunctional. BD psychopathology can lead to poor maternal care and both should be considered important environmental risk factors in BD, suggesting that BD psychoeducation should include maternal care orientation.

Validity and reliability of the Structured Clinical Interview for Mood Spectrum: Brazilian version (SCIMOODS-VB).

OBJECTIVE: The aim of this study was to translate the Structured Clinical Interview for Mood Spectrum into Brazilian Portuguese, measuring its reliability, validity, and defining scores for bipolar disorders. METHOD: Questionnaire was translated (into Brazilian Portuguese) and back-translated into English. Sample consisted of 47 subjects with bipolar disorder, 47 with major depressive disorder, 18 with schizophrenia and 22 controls. Inter-rater reliability was tested in 20 subjects with bipolar disorder and MDD. Internal consistency was measured using the Kuder Richardson formula. Forward stepwise discriminant analysis was performed. Scores were compared between groups; manic (M), depressive (D) and total (T) threshold scores were calculated through receiver operating characteristic (ROC) curves. RESULTS: Kuder Richardson coefficients were between 0.86 and 0.94. Intraclass correlation coefficient was 0.96 (CI 95 % 0.93-0.97). Subjects with bipolar disorder had higher M and T, and similar D scores, when compared to major depressive disorder (ANOVA, p < 0.001). The sub-domains that best discriminated unipolar and bipolar subjects were manic energy and manic mood. M had the best area under the curve (0.909), and values of M equal to or greater than 30 yielded 91.5% sensitivity and 74.5% specificity. CONCLUSION: Structured Clinical Interview for Mood Spectrum has good reliability and validity. Cut-off of 30 best differentiates subjects with bipolar disorder vs. unipolar depression. A cutoff score of 30 or higher in the mania sub-domain is appropriate to help make a distinction between subjects with bipolar disorder and those with unipolar depression.

Validity and reliability of the Structured Clinical Interview for Mood Spectrum: Brazilian version (SCIMOODS-VB) / Validade e confiabilidade da versão brasileira da Entrevista Clínica Estruturada para o Espectro do Humor (SCIMOODS-VB)

OBJECTIVE: The aim of this study was to translate the Structured Clinical Interview for Mood Spectrum into Brazilian Portuguese, measuring its reliability, validity, and defining scores for bipolar disorders. METHOD: Questionnaire was translated (into Brazilian Portuguese) and back-translated into English. Sample consisted of 47 subjects with bipolar disorder, 47 with major depressive disorder, 18 with schizophrenia and 22 controls. Inter-rater reliability was tested in 20 subjects with bipolar disorder and MDD. Internal consistency was measured using the Kuder Richardson formula. Forward stepwise discriminant analysis was performed. Scores were compared between groups; manic (M), depressive (D) and total (T) threshold scores were calculated through receiver operating characteristic (ROC) curves. RESULTS: Kuder Richardson coefficients were between 0.86 and 0.94. Intraclass correlation coefficient was 0.96 (CI 95 percent 0.93-0.97). Subjects with bipolar disorder had higher M and T, and similar D scores, when compared to major depressive disorder (ANOVA, p < 0.001). The sub-domains that best discriminated unipolar and bipolar subjects were manic energy and manic mood. M had the best area under the curve (0.909), and values of M equal to or greater than 30 yielded 91.5 percent sensitivity and 74.5 percent specificity. CONCLUSION: Structured Clinical Interview for Mood Spectrum has good reliability and validity. Cut-off of 30 best differentiates subjects with bipolar disorder vs. unipolar depression. A cutoff score of 30 or higher in the mania sub-domain is appropriate to help make a distinction between subjects with bipolar disorder and those with unipolar depression.

OBJETIVO: Traduzir e validar para o português a Entrevista Clínica Estruturada para Distúrbios do Humor, mensurando sua validade, confiabilidade, bem como definindo os escores para transtornos bipolares. MÉTODO: A entrevista foi traduzida (para o português) e novamente traduzida para o inglês. A amostra incluiu 47 indivíduos com transtornos bipolares, 47 com transtorno depressivo maior, 18 com esquizofrenia e 22 controles. A confiabilidade entre avaliadores foi testada em 20 indivíduos com transtornos bipolares e transtorno depressivo maior. A consistência interna foi mensurada por meio da fórmula de Kuder Richardson. Análise discriminante foi realizada. Escores dos diversos grupos foram comparados; limiares para mania (M), depressão (D) e valores totais foram calculados usando curvas de "receiver operating characteristic" (ROC). RESULTADOS: Coeficientes de Kuder Richardson ficaram entre 0,86 e 0,94. O coeficiente de correlação intraclasse foi de 0,96 (IC 95 por cento 0,93-0,97). Participantes com transtornos bipolares apresentaram escores M e T aumentados, e escores D semelhantes aos do grupo transtorno depressivo maior (ANOVA, p < 0,001). Os subdomínios que melhor discriminaram indivíduos com doença uni ou bipolar foram energia maníaca e humor maníaco. M apresentou a melhor área sob a curva (0,909); valores de M igual ou superiores a 30 associaram-se a sensibilidade de 91,5 por cento e especificidade de 74,5 por cento. CONCLUSÃO: Entrevista Clínica Estruturada para Distúrbios do Humor apresenta boa validade e reliabilidade. Escore de mania igual ou superior a 30 adequadamente diferencia transtornos bipolares de depressão unipolar.

Reliability and validity of a Brazilian version of the Hypomania Checklist (HCL-32) compared to the Mood Disorder Questionnaire (MDQ) / Confiabilidade e validação da versão brasileira do Questionário de Hipomania (HCL-32 VB) comparado ao Questionário de Transtornos de Humor (MDQ)

OBJECTIVE: Bipolar disorders are often not recognized and undertreated. The diagnosis of current or past episodes of hypomania is of importance in order to increase diagnostic certainty. The Hypomania Checklist-32 is a self-applied questionnaire aimed at recognizing these episodes. As part of the international collaborative effort to develop multi-lingual versions of the Hypomania Checklist-32, we aimed to validate the Brazilian version and to compare its psychometric properties with those of the Mood Disorder Questionnaire. METHOD: Adult outpatients with bipolar disorder I (n = 37), bipolar disorder II (n = 44) and major depressive disorder (n = 42) of a specialized mood disorder unit were diagnosed according to DSM-IV-TR using a modified version of the SCID. We analyzed the internal consistency and discriminative ability of the Hypomania Checklist-32 Brazilian version in relation to the Mood Disorder Questionnaire. RESULTS: The internal consistency of the Brazilian Hypomania Checklist-32, analyzed using Cronbach's alpha coefficient, was 0.86. A score of 18 or higher in the Hypomania Checklist-32 Brazilian version distinguished between bipolar disorder and major depressive disorder, with a sensitivity of 0.75 and a specificity of 0.58, compared to 0.70 and 0.58, respectively, for the Mood Disorder Questionnaire (score > 7). The Hypomania Checklist-32 Brazilian version showed a dual factor structure characterized by "active/elated" and "risk-taking/irritable" items. Hence, the Hypomania Checklist-32 Brazilian version was found to have a higher sensitivity but the same specificity as the Mood Disorder Questionnaire. CONCLUSION: The Brazilian version of the Hypomania Checklist-32 has adequate psychometric properties and helps discriminating bipolar disorder from major depressive disorder (but not bipolar disorder I from bipolar disorder II) with good sensitivity and specificity indices, similar to those of the Mood Disorder Questionnaire.

OBJETIVO: O transtorno bipolar muitas vezes não é reconhecido e deixa de ser tratado adequadamente. O diagnóstico de episódios atuais ou passados é importante, a fim de aumentar a certeza diagnóstica. O Questionário de Autoavaliação de Hipomania-32 é um questionário autoaplicável para o rastreamento desses episódios. Como parte do desenvolvimento em vários idiomas do Questionário de Autoavaliação de Hipomania-32, nós objetivamos validar a versão brasileira e comparar suas propriedades psicométricas com o Questionário de Transtornos do Humor. MÉTODO: Em uma unidade especializada em transtornos do humor foram selecionados pacientes ambulatoriais adultos com transtorno bipolar I (n = 37), transtorno bipolar II (N = 44) e transtorno depressivo maior (N = 42) de acordo com a DSM-IV-TR, utilizando uma versão modificada do SCID. Analisou-se a consistência interna e capacidade discriminativa do Questionário de Autoavaliação de Hipomania-32 versão brasileira comparada ao Questionário de Transtornos do Humor. RESULTADOS: A consistência interna do Questionário de Autoavaliação de Hipomania-32 versão brasileira é boa, com alfa de Cronbach 0,86. Um escore de 18 ou mais no Questionário de Autoavaliação de Hipomania-32 versão brasileira distingue entre o transtorno bipolar e o transtorno depressivo maior com uma sensibilidade de 0,75 e especificidade de 0,58, e para o Questionário de Transtornos do Humor, para um escore de 7 ou mais, de 0,70 e 0,58, respectivamente. O Questionário de Autoavaliação de Hipomania-32 mostrou uma estrutura caracterizada pela predominância de dois fatores (ativação/elação e irritabilidade/correr riscos). Assim, o Questionário de Autoavaliação de Hipomania-32 versão brasileira tem maior sensibilidade, mas a mesma especificidade que o Questionário de Transtornos do Humor. CONCLUSÃO: A versão brasileira do Questionário de Autoavaliação de Hipomania-32 possui propriedades psicométricas adequadas e ajuda a discriminar o transtorno bipolar do transtorno depressivo maior (mas não transtorno bipolar I de transtorno bipolar II), com boa sensibilidade e especificidade, semelhante ao Questionário de Transtornos do Humor.

SHORT COMMUNICATION: Apolipoprotein E genotype and cognition in bipolar disorder.

Apolipoprotein E (APOE) has been extensively studied as a risk factor for sporadic and late onset Alzheimer's Disease (AD). APOE allele (∗)3, the most frequent variant, is not associated to cognitive dysfunction (CD) or to increased AD risk. Differently, the (∗)4 allele is a well-established risk factor for CD, while the (∗)2 allele is associated with survival and longevity. CD is an important feature of Bipolar Disorder (BD) and recent data suggest that CD may be one of its endophenotypes, although controversial results exist. The aim of this research is to study the association of APOE genotype (APOE) and neurocognitive function in a sample of drug free young BD-type I patients. Sample consisted of 25 symptomatic BD (type I) patients (age 18-35 years old). They were submitted to an extensive neuropsychological evaluation and genotyped for APOE. Subjects with allele (∗)2 presented better cognitive performance. The presence of allele (∗)4 was associated with worse performance in a few executive tasks. APOE (∗)3(∗)3 was associated with overall severe dysfunction on cognitive performance. In young individuals with nontreated BD-type I, APOE may predict cognitive performance. Further and larger studies on APOE and cognition in BD are required to clarify whether APOE is a BD cognitive endophenotype.

Reliability and validity of a Brazilian version of the Hypomania Checklist (HCL-32) compared to the Mood Disorder Questionnaire (MDQ).

OBJECTIVE: Bipolar disorders are often not recognized and undertreated. The diagnosis of current or past episodes of hypomania is of importance in order to increase diagnostic certainty. The Hypomania Checklist-32 is a self-applied questionnaire aimed at recognizing these episodes. As part of the international collaborative effort to develop multi-lingual versions of the Hypomania Checklist-32, we aimed to validate the Brazilian version and to compare its psychometric properties with those of the Mood Disorder Questionnaire. METHOD: Adult outpatients with bipolar disorder I (n=37), bipolar disorder II (n=44) and major depressive disorder (n=42) of a specialized mood disorder unit were diagnosed according to DSM-IV-TR using a modified version of the SCID. We analyzed the internal consistency and discriminative ability of the Hypomania Checklist-32 Brazilian version in relation to the Mood Disorder Questionnaire. RESULTS: The internal consistency of the Brazilian Hypomania Checklist-32, analyzed using Cronbach's alpha coefficient, was 0.86. A score of 18 or higher in the Hypomania Checklist-32 Brazilian version distinguished between bipolar disorder and major depressive disorder, with a sensitivity of 0.75 and a specificity of 0.58, compared to 0.70 and 0.58, respectively, for the Mood Disorder Questionnaire (score>7). The Hypomania Checklist-32 Brazilian version showed a dual factor structure characterized by "active/elated" and "risk-taking/irritable" items. Hence, the Hypomania Checklist-32 Brazilian version was found to have a higher sensitivity but the same specificity as the Mood Disorder Questionnaire. CONCLUSION: The Brazilian version of the Hypomania Checklist-32 has adequate psychometric properties and helps discriminating bipolar disorder from major depressive disorder (but not bipolar disorder I from bipolar disorder II) with good sensitivity and specificity indices, similar to those of the Mood Disorder Questionnaire.

Latent class analysis of manic and depressive symptoms in a population-based sample in São Paulo, Brazil.

BACKGROUND: Current diagnostic criteria cannot capture the full range of bipolar spectrum. This study aims to clarify the natural co-segregation of manic-depressive symptoms occurring in the general population. METHODS: Using data from the Sao Paulo Catchment Area Study, latent class analysis (LCA) was applied to eleven manic and fourteen depressive symptoms assessed through CIDI 1.1 in 1464 subjects from a community-based study in Sao Paulo, Brazil. All manic symptoms were assessed, regardless of presence of euphoria or irritability, and demographics, services used, suicidality and CIDI/DSM-IIIR mood disorders used to external validate the classes. RESULTS: The four obtained classes were labeled Euthymics (EU; 49.1%), Mild Affectives (MA; 31.1%), Bipolars (BIP; 10.7%), and Depressives (DEP; 9%). BIP and DEP classes represented bipolar and depressive spectra, respectively. Compared to DEP class, BIP exhibited more atypical depressive characteristics (hypersomnia and increase in appetite and/or weight gain), risk of suicide, and use of services. Depressives had rates of atypical symptoms and suicidality comparable to oligosymptomatic MA class subjects. LIMITATIONS: The use of lay interviewers and DSM-IIIR diagnostic criteria, which are more restrictive than the currently used DSM-IV TR. CONCLUSIONS: Findings of high prevalence of bipolar spectrum and of atypical symptoms and suicidality as indicators of bipolarity are of great clinical importance, due to different treatment needs, and higher severity. Lifetime sub-affective and syndromic manic symptoms are clinically significant, arguing for the need of revising DSM bipolar spectrum categories.

The lifetime prevalence, health services utilization and risk of suicide of bipolar spectrum subjects, including subthreshold categories in the São Paulo ECA study.

BACKGROUND: Identifying the bipolar (BP) spectrum, including the classic Bipolar I subtype (BP-I), Bipolar II (BP-II) and subthreshold bipolar disorders not meeting DSM-IV diagnostic criteria has raised growing interest, as these softer expressions of bipolar spectrum have been underdiagnosed in spite of clinical consequences. METHODS: Data are from the Sao Paulo Epidemiological Catchment Area Study (N=1464). Non-affective controls were compared to BP spectrum groups, based on DSM-IIIR and on the "clinical significance" criteria: Subsyndromal Hypomania (SSH) and Manic Symptoms (MS). RESULTS: The lifetime prevalence of BP subgroups was 8.3% (N=122). All BP-I and -II and around 75% of SSH and MS subjects had a lifetime depressive syndrome. Compared to controls and MS subjects, BP-I, BP-II and SSH groups searched more medical help and mental health services. SSH group displayed higher rates of clinical significance than BP-I subjects, and suicidality was higher in BP groups compared to controls. Even the softer MS group had higher rate of suicide attempts than SSH subjects. LIMITATIONS: This is a cross-sectional study and interviews were conducted by lay personnel. Replication in bigger community samples using a mood spectrum approach is necessary to confirm these findings. However, our findings were very similar to those obtained by other authors. CONCLUSION: Softer expressions of BP disorders appear in 6.6% of this community sample and have serious clinical consequences, which supports the importance of including these categories in the BP spectrum.

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

Pelo menos 5 por cento (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. As 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.

Estados mistos e quadros de ciclagem rápida no transtorno bipolar / Mixed states and rapid cycling in bipolar disorder

Estados mistos foram esquecidos por quase um século e os modernos critérios diagnósticos operacionais do DSM-IV e da CID-10 os caracterizam como episódios simultâneos de síndromes depressiva e maníaca, denominados mania mista, mania disfórica ou depressão durante a mania. Estudos de validação têm investigado várias linhas de corte dos estados mistos maníacos, dependendo do número de sintomas depressivos presentes no episódio maníaco. Paralelamente, crescem evidências acerca da existência de estados mistos depressivos, anteriormente descritos por Kraepelin, caracterizados por episódios depressivos com pelo menos três sintomas maníacos. O conhecimento sobre a terapêutica é limitado, pois deriva de ensaios clínicos de pacientes em mania que incluíram sujeitos em estados mistos. A ciclagem rápida é um tipo de curso do transtorno bipolar, definida pela presença de pelo menos quatro episódios distintos de mania, hipomania, depressão ou misto durante um ano. O tratamento é difícil e inclui a identificação de fatores de risco, como hipotireoidismo e transtornos relacionados ao uso de substâncias. Tanto nos estados mistos como na ciclagem rápida, preconiza-se evitar antidepressivos, quando possível. Neste trabalho são apresentadas formas clínicas dos estados mistos e algoritmos para o tratamento seqüencial de estados mistos maníacos e da ciclagem rápida baseadas nas evidências disponíveis na literatura.

[Anticonvulsants and antipsychotics in the treatment of bipolar disorder]. / Anticonvulsivantes e antipsicóticos no tratamento do transtorno bipolar.

Bipolar disorder is a complex medical condition, and up to the date there is no single treatment with proven efficacy in the control of all aspects of the illness. The available literature on the use of anticonvulsants (valproate, carbamazepine, oxcarbazepine, lamotrigine, gabapentin, topiramate, clonazepam) and atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole) for acute and prophylactic treatment of bipolar disorder was reviewed. There is a large amount of evidence that lithium is efficacious in the prophylaxis of episodes and better for acute mania than for depressive episodes. Other data show that carbamazepine and valproate are effective in acute manic episodes. Lamotrigine has been shown to reduce cycling and effective in depressive episodes. Based on the available data, olanzapine was found to be the most appropriate atypical antipsychotic agent for the treatment of manic bipolar patients, although there are also studies suggesting the efficacy of risperidone, aripiprazole and clozapine. The preliminary data evaluating the efficacy of quetiapine and ziprasidone in bipolar disorder are still very limited. There is no consistent information supporting the prophylactic use of newer antipsychotics.

Anticonvulsivantes e antipsicóticos no tratamento do transtorno bipolar / Anticonvulsants and antipsychotics in the treatment of Bipolar Disorder

O transtorno bipolar é uma condição médica complexa e até o momento não há um tratamento único comprovadamente eficaz no controle de todos aspectos da doença. Foram revisadas a literatura disponível sobre o uso de anticonvulsivantes (valproato, carbamazepina, oxcarbazepina, lamotrigina, gabapentina, topiramato, clonazepam) e antipsicóticos atípicos (clozapina, risperidona, olanzapina, quetiapina, ziprasidona e aripiprazole) no tratamento agudo e profilático do transtorno bipolar. Existe um acúmulo de evidências acerca da eficácia do lítio na profilaxia e de ser melhor no tratamento da mania aguda do que nos episódios depressivos. Outros dados indicam que a carbamazepina e o valproato são eficazes na mania aguda. A lamotrigina parece reduzir ciclagem e ser eficaz em episódios depressivos. Baseado nas informações disponíveis, as evidências apontam a olanzapina como o antipsicótico atípico mais apropriado no tratamento de pacientes bipolares em mania, embora existam estudos sugerindo a eficácia da risperidona, aripiprazol e da clozapina. Resultados preliminares avaliando a eficácia de ziprasidona e quetiapina no transtorno bipolar ainda são bastante limitadas. Não há dados consistentes apoiando o uso profilático dos novos antipsicóticos.