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.

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.

Eficácia e segurança dos antipsicóticos atípicos nas demências: uma revisão sistemática / Efficacy and safety of atypical antipsychotics in dementia: a sistematic review

OBJETIVO: O emprego de antipsicóticos atípicos (AA) no tratamento de sintomas psicológicos e comportamentais das demências (SPCD) tem sido alvo de discussão em relação à eficácia e à segurança. O objetivo deste artigo é propiciar atualização sobre o tema. MÉTODOS: Revisão da literatura publicada nos últimos dez anos com ênfase em metanálises e ensaios clínicos randomizados (ECR) controlados com placebo. RESULTADOS: Três metanálises e nove ensaios clínicos foram analisados. Há evidências de eficácia clínica para risperidona (1mg/dia), olanzapina (5 a 10mg/dia) e aripiprazol (2 a 15mg/dia) no tratamento de agressividade e/ou SPCD em geral, e para risperidona (1mg/dia) no tratamento de sintomas psicóticos associados à demência. Os eventos adversos comuns com o uso de AA foram sonolência, sintomas extrapiramidais (SEP), incontinência ou infecção do trato urinário e alterações de marcha. O tratamento com AA associou-se a maior risco de eventos cerebrovasculares e de mortalidade em idosos com demência. CONCLUSÃO: Baixas dosagens de risperidona, olanzapina e aripiprazol são eficazes na redução de agressividade e/ou SPCD globais; risperidona é eficaz na redução de sintomas psicóticos associados à demência. Em virtude de esses tratamentos associarem-se a pequeno aumento no risco de eventos cerebrovasculares e mortalidade, seu uso deve ser reservado para sintomatologia moderada/grave.

OBJECTIVE: Concerns have been raised about efficacy and adverse events of atypical antipsychotics in the treatment of behavioural and psychological symptoms of dementia (BPSD). This paper is an update on current evidence of this theme. METHODS: Review of published meta-analysis and randomized placebo-controlled trials (RCTs) in the last ten years. RESULTS: Three meta-analysis and nine RCTs were evaluated. Evidence suggests that risperidone (1mg/day), olanzapine (5 to 10mg/day), and aripiprazole (2 to 15mg/day) are effective in treating aggression and/or BPSD overall; risperidone (1mg/day) reduces psychosis. Adverse events were mainly somnolence, extrapyramidal symptoms, urinary tract infection or incontinence, and abnormal gait with drug treatment. Atypical antipsychotics were associated with increased risk for cerebrovascular adverse events and mortality in elderly patients with dementia. CONCLUSION: Low doses of risperidone, olanzapine, and aripiprazole are effective in treating aggression and/or BPSD overall, and risperidone reduces psychosis associated with dementia. In view of the increased risk of cerebrovascular adverse events and mortality, the use of atypical antipsychotics in individuals with dementia should be reserved for patients with moderate/severe behavioural symptoms.