Cláudia Hara

Combination of antidepressants in the treatment of major depressive disorder: a systematic review and meta-analysis.

Abstract The objective was to perform a systematic review and meta-analysis of studies that assessed the effect of the combination of antidepressants from the beginning of the treatment of major depressive disorder. Studies were retrieved from PubMed (1966 to August 2010), Cochrane Library (August 2010), Embase (1980 to August 2010), PsycINFO (1980 to August 2010), Lilacs (1982 to August 2010), clinical trials registry, thesis database (www.capes.gov.br), and secondary references. All randomized controlled trials that compared a combination of antidepressants with a single antidepressant from the beginning of the treatment of major depressive disorder in adults were included. Data analysis was performed using the Review Manager 5.0. Of 3492 studies retrieved, five satisfied the inclusion criteria. In one study, only data about dropouts were included. Antidepressant combination was shown to be better than a single antidepressant considering remission (relative risk [RR], 2.71; 95% confidence interval [CI], 1.69–4.35) and response (RR, 1.55; 95% CI, 1.21–1.97). Mirtazapine plus selective serotonin reuptake inhibitor (SSRI) was superior to an isolated SSRI for remission (RR, 1.88; 95% CI, 1.06–3.33). Tricyclic antidepressant plus SSRI was superior to SSRI for remission and response (RR, 8.58; 95% CI, 1.70–43.32 and RR, 1.78; 95% CI, 1.07–2.93, respectively). There was no difference between combined and monotherapy groups in dropouts owing to adverse effects. The results suggest that antidepressant combination is more efficient than a single antidepressant without a significant decrease in tolerability. However, the small number of clinical trials and methodological problems precludes definitive conclusions.

Antidepressants for depression in Parkinson's disease: systematic review and meta-analysis.

Depression is common in Parkinson’s disease (PD) and is associated with several poor outcomes. However the literature regarding treatment with antidepressants in this population is controversial. The aim of this paper was to systematically review all randomized controlled trials that studied the efficacy of antidepressants for depression in PD (dPD). Studies were retrieved from PubMed (1966–July 2012), Cochrane Library (–July 2012, issue 7), Embase (1980–July 2012), PsycINFO (1980–July 2012), Lilacs (1982–July 2012), secondary references, clinical trials registries and a thesis database. Only double-blind, randomized controlled trials in which an antidepressant was given as the main treatment and compared with placebo and/or another antidepressant were included. Out of the 1438 studies retrieved, only six could be included. Taking into account the five placebo-controlled trials, the overall risk ratio (RR) for response was 1.36 (0.98, 1.87), indicating no statistically significant superiority of antidepressants over placebo. However, in the sensitivity analysis, the RR for response was 1.41 (1.01, 1.96) and 1.48 (1.05, 2.10) after exclusion of one study with questionable results, and when only studies with low risk of bias were considered, respectively. No specific antidepressant class was superior to placebo. In general antidepressant medications were well tolerated. The results suggest antidepressants may be efficacious in the treatment of dPD. However, the results were unstable. In fact, the small number of trials and methodological drawbacks preclude definitive conclusions about their efficacy and tolerability in dPD.

An Exploratory Open-Label Trial of Ziprasidone for the Treatment of Behavioral and Psychological Symptoms of Dementia

Objective: To evaluate the efficacy and tolerability of ziprasidone in behavioral and psychological symptoms of dementia. Method: A 7-week open-label trial of ziprasidone. Results: Of the 25 patients who participated, 15 completed the study. The main reason for discontinuation was adverse events. The mean total Neuropsychiatric Inventory (NPI) score fell significantly from 47.1 ± 17.1 (baseline) to 25.8 ± 17.9 (day 49) (p < 0.01). The NPI caregiver burden showed a significant improvement from 22.6 ± 8.3 at baseline to 11.8 ± 7.3. The most frequent adverse events were somnolence, gastrointestinal symptoms and parkinsonism. Conclusions: Ziprasidone was able to significantly improve distressing non-cognitive symptoms of dementia although adverse effects occurred. Additional large-scale, double-blind, well-controlled studies are necessary to evaluate the use of ziprasidone in this indication.

Antidepressant combination for major depression in incomplete responders—a systematic review

BACKGROUND Antidepressant combination has been suggested as a strategy to increase treatment efficacy. The objective of this study was to perform a systematic review and meta-analysis of studies that assessed the effect of antidepressant combination for major depression in patients with incomplete response to an initial antidepressant. METHODS Studies were retrieved from PubMed (1966-February, 2012), Cochrane Library (-February, 2012), Embase (1980-February, 2012), PsycINFO (1980-February, 2012), Lilacs (1982-February, 2012), clinical trials registry, thesis database (www.capes.gov.br), and secondary references. Included studies had an open label phase in which an initial antidepressant was used for the treatment of major depression and a double blind phase for the incomplete responders that compared monotherapy with the first antidepressant versus the association of a second antidepressant to the first one. RESULTS Out of the 4,884 studies retrieved, only five satisfied the inclusion criteria. The total number of patients included was 483. Only two small trials reported benefits of adding a second antidepressant to the initial antidepressant. Dropouts due to side effects were not reported in three studies. Meta-analysis was not performed due to the small number of studies, the inconsistency in the direction of effect and the possible instability of effect size. Only limited kinds of combination, involving mianserin, mirtazapine and desipramine were studied. Some properties of the first two drugs such as the anxiolytic, sedative, and orexigenic effects, can mimic depression improvement. LIMITATIONS Publication bias cannot be ruled out. Only one study included a monotherapy arm with the antidepressant used for augmentation of the first antidepressant. CONCLUSIONS The practice of using a combination of antidepressants for major depression in incomplete responders is not warranted by the literature.

Duloxetine treatment for women with premenstrual dysphoric disorder: a single-blind trial

Premenstrual dysphoric disorder (PMDD) affects 3-8% of women of reproductive age and is characterized by severe mood symptoms that cause important functional impairment. Serotonergic antidepressants appear to be an effective treatment for this disorder. The purpose of this study was to collect evidence on the efficacy and tolerability of duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine, in the treatment of PMDD. We conducted a pilot, single-blind, non-controlled, fixed-dose trial. After two cycles for diagnosis confirmation, including a single-blind placebo cycle, 20 women with PMDD were treated continuously for three menstrual cycles with 60 mg/d duloxetine. The primary measure of the efficacy of treatment with duloxetine was the significant reduction in premenstrual symptoms demonstrated by the comparison between the mean Daily Record of Severity of Problems (DRSP) scores at baseline to endpoint (p=0.0002). Statistically significant symptom reduction was observed in the first treatment cycle and throughout all the treatment phase. Clinical response, defined as a reduction 50% of baseline premenstrual symptoms, occurred in 65% of subjects (intention-to-treat population). Significant improvements were demonstrated by secondary measures, including reduction in self-rated functional impairment (p=0.01) and improvement in quality of life (p=0.04). The main side-effects associated with duloxetine were dry mouth, nausea, drowsiness, insomnia, decreased appetite, decreased libido, and sweating. Duloxetine was effective and generally well tolerated in the treatment of PMDD. Further large-scale, double-blind, placebo-controlled studies are needed to evaluate duloxetine as an additional treatment strategy for the management of PMDD.

Alterações cognitivas na esquizofrenia: atualização

Cognitive dysfunctions are among the core features of schizophrenia. They remain relatively stable throughout the course of the disease, and are secondary neither to other symptoms nor to side effects of psychotropic drugs. Cognitive deficits are directly associated with functional impairment and poor quality of life. Many studies have been conducted to describe the main cognitive abnormalities observed in schizophrenia, to identify their neurobiological bases, and to standardize research instruments, which are of paramount importance for the identification of new targets for pharmacological interventions in schizophrenia. The main objective of this paper was to provide an updated review of the subject.

Versão brasileira da Escala de Avaliação da Cognição em Esquizofrenia (SCoRS-Br): validação em contextos clínicos sem informantes

OBJECTIVE: The SCoRS is an interview-based co-primary measure of cognitive function in schizophrenia that is related to cognitive performance as well as to real-world functioning. Its original version involves interviews with patients and informants. The objective of this study was to seek evidence of convergent validity and reliability of the Brazilian version of SCoRS (SCoRS-Br) with patients in clinical settings without qualified informants. METHOD: Forty nine patients with schizophrenia (DSM-IV) were assessed with the SCoRS-Br two potential convergent validators: the R1 test and the Mini Mental State Evaluation (MMSE). Pearson correlations between the mean scores of the instruments were estimated. Internal consistence of the SCoRS-Br was also evaluated. RESULTS: Pearson correlation between the SCoRS-Br interviewer rating and the R1 test was low but significative. Cronbachs coefficients were 0.8829 for the interviewer rating and 0.8468 for the patient rating. Split-half were 0.811 and 0.806 respectively. CONCLUSIONS: The results showed the convergent validity and reliability of the SCoRS-Br even when used without informants. Other studies are required to investigate other validation criteria.

Prevalence of excessive daytime sleepiness in Brazilian community-dwelling older adults with very low levels of schooling, and its association with sociodemographic characteristics and lifestyle: the Bambuí Health and Ageing Study (BHAS)

OBJECTIVE: Population-based studies on excessive daytime sleepiness (EDS) in older adults living in less developed countries are scarce. The purpose of this paper was to estimate the prevalence of EDS and its association with sociodemographic characteristics and lifestyle factors in Brazilian community-dwelling older adults. METHODS: The study was carried out in Bambui, a city in the state of Minas Gerais, Brazil. EDS was defined as the presence of sleepiness in the last month occurring three or more times per week, with any interference in usual activities. The exploratory variables were: gender, age, skin color, marital status, schooling level, current employment status, religion, recent migration, smoking, binge drinking and physical activities during leisure time. RESULTS: Of 1,742 residents aged > 60 years, 1,514 (86.9%) participated. The prevalence of EDS was 13%. After adjustment for confounders, female gender and low schooling level remained positively and independently associated with EDS. CONCLUSIONS: The prevalence of EDS in the study population was within the range observed in studies carried out in developed countries. The most impressive finding was the association of EDS with schooling, indicating that even in a population with low levels of schooling, this was an important factor to explain the distribution of EDS.

Depressão resistente a tratamento: uma revisão das estratégias farmacológicas de potencialização de antidepressivos

OBJETIVO: Fazer uma revisao sobre oito estrategias farmacologicas de potencializacao de antidepressivos na DRT. METODOS: Fez-se um levantamento bibliografico de 1990 ate janeiro de 2006, nas bases eletronicas 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 referencia dos artigos para obtencao de ensaios realizados em data anterior a 1990 e artigos originais de valor historico. RESULTADOS: Foram encontrados 17 estudos duplo-cegos com o litio, seis com o hormonio tireoidiano, dois com a buspirona, seis com o pindolol, um com a carbamazepina, dois com a lamotrigina e quatro com a olanzapina. Foram favoraveis a potencializacao 41,2% dos ensaios com litio; 60% daqueles com hormonio tireoidiano e antidepressivos triciclicos e nenhum com hormonio tireoidiano e inibidores seletivos da recaptacao da serotonina (ISRS); 50% dos com pindolol; 100% dos ensaios com carbamazepina e 40% daqueles com olanzapina. Nenhum dos estudos com a buspirona foi favoravel. No unico estudo com lamotrigina nao houve eficacia de tratamento na avaliacao pelo criterio principal, mas superioridade ao placebo em criterios secundarios. CONCLUSAO: Na DRT ha evidencia de eficacia apenas em relacao ao litio na potencializacao de varias classes de antidepressivos e ao hormonio tireoidiano na potencializacao de triciclicos. A olanzapina foi razoavelmente estudada e sua eficacia nao foi estabelecida. Os poucos estudos realizados com a buspirona e o pindolol nao comprovaram sua eficacia. A carbamazepina foi muito pouco estudada, e a lamotrigina ainda nao foi adequadamente avaliada.

Insomnia subtypes and their relationship to excessive daytime sleepiness in Brazilian community-dwelling older adults.

STUDY OBJECTIVES To investigate the association between different types of insomnia as exposures and excessive daytime sleepiness (EDS) as a binary outcome in older Brazilian residents. DESIGN The baseline examination of the Bambuí Health and Ageing Study (BHAS), which is an ongoing population-based prospective cohort study of older adults. SETTING Bambuí (15,000 inhabitants), a city in the State of Minas Gerais, Southeast Brazil PARTICIPANTS All residents aged ≥ 60 years were eligible to take part in the BHAS baseline. Of 1742 residents identified who were ≥ 60 years, 1606 (92.2%) were interviewed and received comprehensive examinations of health status. INTERVENTIONS None. MEASUREMENTS AND RESULTS EDS was defined as the presence of sleepiness ≥ 3 times per week in the last month, causing any interference in usual activities. All insomnia subtypes were significantly associated with EDS in unadjusted analyses, and these associations were only modestly altered after adjusting incrementally for the other covariates. In a final model, the 3 insomnia subtypes were entered into a fully adjusted model simultaneously to investigate mutual independence, giving prevalence ratios of 1.63 (95% CI 1.14-2.31) for initial insomnia, 2.13 (95% CI 1.48-3.07) for middle insomnia, and 1.36 (95% CI 0.94-1.96) for terminal insomnia. The population attributable fractions for initial, middle, and terminal insomnia on prevalence of EDS were 17.6%, 32.9%, and 9.7%, respectively. CONCLUSIONS Middle insomnia emerged as the insomnia subtype most strongly associated with EDS. Further research is required to clarify causal pathways underlying this cross-sectional association.