Antipsicóticos de segunda geração para a perturbação depressiva major e a distímia.
Abstract
Background
Major depressive disorder (MDD) is a common condition with a lifetime prevalence of 15% to 18%, which leads to considerable suffering and disability. Some antipsychotics have been reported to induce remission in major depression, when added to an antidepressant.
Objectives
To evaluate the effects of second‐generation antipsychotic (SGA) drugs (alone or augmentation) compared with placebo or antidepressants for people with MDD or dysthymia.
Search methods
The Cochrane Depression, Anxiety and Neurosis Group's controlled trial registers (CCDANCTR‐Studies and CCDANCTR‐References) were searched up to 21 July 2010. The author team ran complementary searches on clinicaltrials.gov and contacted key authors and drug companies.
Selection criteria
We included all randomised, double‐blind trials comparing oral SGA treatment (alone or augmentation) with other forms of pharmaceutical treatment or placebo in people with MDD or dysthymia.
Data collection and analysis
We extracted data independently. For dichotomous data we calculated the odds ratio (OR) and 95% confidence interval (CI) on an intention‐to‐treat basis, and for continuous data the mean difference (MD), based on a random‐effects model. We presented each comparison separately; we did not perform a pooled data analysis.
Main results
We included 28 trials with 8487 participants on five SGAs: amisulpride, aripiprazole, olanzapine, quetiapine and risperidone.
Three studies (1092 participants) provided data on aripiprazole augmentation in MDD. All efficacy data (response n = 1092, three RCTs, OR 0.48; 95% CI 0.37 to 0.63), (MADRS n = 1077, three RCTs, MD ‐3.04; 95% CI ‐4.09 to ‐2) indicated a benefit for aripiprazole but more side effects (weight gain, EPS) .
Seven trials (1754 participants) reported data on olanzapine. Compared to placebo fewer people discontinued treatment due to inefficacy; compared to antidepressants there were no efficacy differences, olanzapine augmentation showed symptom reduction (MADRS n = 808, five RCTs, MD ‐2.84; 95% CI ‐5.48 to ‐0.20), but also more weight or prolactin increase.
Quetiapine data are based on seven trials (3414 participants). Compared to placebo, quetiapine monotherapy (response n = 1342, three RCTs, OR 0.52; 95% CI 0.41 to 0.66) and quetiapine augmentation (response n = 937, two RCTs, OR 0.68; 95% CI 0.52 to 0.90) showed symptom reduction, but quetiapine induced more sedation.
Four trials (637 participants) presented data on risperidone augmentation, response data were better for risperidone (n = 371, two RCTs, OR 0.57; 95% CI 0.36 to 0.89) but augmentation showed more prolactin increase and weight gain.
Five studies (1313 participants) presented data on amisulpride treatment for dysthymia. There were some beneficial effects compared to placebo or antidepressants but tolerability was worse.
Authors' conclusions
Quetiapine was more effective than placebo treatment. Aripiprazole and quetiapine and partly also olanzapine and risperidone augmentation showed beneficial effects compared to placebo. Some evidence indicated beneficial effects of low‐dose amisulpride for dysthymic people. Most SGAs showed worse tolerability.
PICO
Plain language summary
Antipsicóticos de segunda geração para a perturbação depressiva major e a distímia.
Esta revisão encontrou 28 estudos sobre cinco fármacos antipsicóticos de segunda geração (amissulprida, aripiprazole, olanzapina, quetiapina e risperidona) comparando os efeitos dos fármacos per se ou ora adicionando‐os, ora adicionado ou placebo, aos antidepressivos para a perturbação depressiva major e distímia. Existe evidência de que a amissulprida possa conduzir à redução dos sintomas na distímia, enquanto nenhumas diferenças importantes tenham sido vistas para a depressão major. Existe evidência limitada de que o aripiprazole conduz à redução de sintomas quando adicionado a antidepressivos. A olanzapina não teve efeitos benéficos no tratamento da depressão quando comparada com antidepressivos ou com placebo, mas houve evidência limitada para os benefícios da olanzapina enquanto tratamento adicional. Dados acerca da quetiapina indicaram efeitos benéficos para a quetiapina per se ou como tratamento adjuvante quando comparada com o placebo; dados acerca da quetiapina versus duloxetina não demonstraram efeitos benéficos em termos redução de sintomas para qualquer dos grupos, mas o tratamento com quetiapina foi menos bem tolerado. Os dados, todavia, foram muito limitados. Benefícios discretos da risperidona como tratamento adicional, em termos de redução de sintomas, também foram baseados num número bastante pequeno de participantes aleatorizados. Globalmente, o tratamento com fármacos antipsicóticos de segunda geração foi associado a pior tolerabilidade, principalmente devido a sedação, ganho ponderal ou valores laboratoriais tais como um incremento na prolactina.
