title: Early predictors of two month response with mianserin and selective serotonin reuptake inhibitors and influence of definition of outcome on prediction.
abstract: In order to identify clinical and demographic variables that predict response to antidepressants and to analyse prediction of outcome as a function of definition of outcome we analysed pooled data of two independent, multicentre, double blind parallel group studies. Study I compared the efficacy of mianserin with that of fluoxetine in 65, and study II compared mianserin with fluvoxamine in 60 patients with depression. Improvement was defined as at least 20% decrease in MADRS by day 14. Patients were considered as responders if they had greater than 50% decrease and non-responders if they had </= 50% decrease from baseline in the MADRS at day 56. Complete remission was defined as MADRS score </= 6 at day 56. Patients' characteristics did not differ between mianserin and SSRI groups. Early improvement predicted response in 92% and complete remission in 55% of the patients improved at day 14. Multivariate forward stepwise logistic regression analysis showed that response to treatments at day 56 was significantly (P = 0.0003) associated with early improvement, age (responders had higher age than non-responders) and weight (responders weighted more than non-responders). Complete remission was only predicted by early improvement. Treatments could not be differentiated when data were analysed according to responder/nonresponder status or complete remission/no complete remission. However, when the same data were analysed by analysis of variance a significant treatment effect (P = 0.02, mianserin > SSRIs) and a quadratic type treatment by time interaction (P = 0.023) were found. The robustness of the analysis was further improved by inclusion of covariates (age, weight). Early clinical improvement seems to be the best predictor of 2 month response to antidepressants (mianserin, SSRIs). Younger age and lower weight may predict non-response. Quantitative analysis differentiates treatments better than analysis of responder status. As obtenation of complete remission is a realistic objective with current antidepressants, studies longer than 2 months are needed to assess effectiveness of these drugs in the obtenation of complete remission.
authors.affiliation: Department of Pharmacology, Hôpital Pitié-Salpêtrière, 47 Bd de l'Hôpital, 75013 Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Berlin
authors.forename: F
authors.initials: F
authors.lastname: Lavergne