The aim of this study was to assess the efficacy and safety of sertraline compared with placebo in a good clinical practice trial conducted with major depressive disorder patients naive to selective serotonin reuptake inhibitors.
This was a 10-week randomized, multicenter, placebo-controlled, double blind, superiority trial. Adult patients diagnosed with major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria), total score of 19 to 36 in the 17-item Hamilton Depression Rating Scale (HAMD-17), were randomly allocated to sertraline (n = 39) or placebo (n = 38). Each patient received a fixed dose of sertraline 50 mg/d or placebo for 4 weeks. Afterward a flexible dose up to 200 mg/d was allowed if needed. The primary efficacy end point was clinical response defined as 50% score reduction in HAMD-17 at 10 weeks relative to baseline. Supplementary analysis was performed on HAMD-17 score change from baseline.
The clinical response favored sertraline (72% vs 32%; relative risk, 2.27; 95% confidence interval, 1.37–3.78; P = 0.0006). A linear mixed model showed arm × time interaction was significant (likelihood ratio test χ2 on 7 df = 48.42, P < 0.0001). The HAMD-17 change score favored sertraline from week 8 onwards. The most frequent adverse events in the sertraline arm were headache, diarrheas, and weight loss.
In this trial, the benefit of sertraline compared with placebo appeared later than usual. The therapeutic process with a close doctor-patient relationship throughout the trial and the effect expectancy due to a new treatment might explain the response delay.
Trial registration: RPCEC, ID no. 00000128.
From the *Centro Nacional Coordinador de Ensayos Clínicos (CENCEC), Havana, Cuba;
†University of the Basque Country UPV/EHU, Leioa, Spain;
‡CIBERSAM, Spain; and
§Hospital Clínico Quirúrgico Gustavo Aldereguía Lima, Cienfuegos;
∥Centro Comunitario de Salud Mental, Guanabacoa; and
¶Hospital Clínico Quirúrgico de 10 de Octubre, Havana, Cuba; and
#Dalhousie University, Halifax, Nova Scotia, Canada.
Received May 17, 2017; accepted after revision June 20, 2018.
Reprints: Javier Ballesteros, PhD, Department of Neuroscience, Medical School, University of the Basque Country UPV/EHU, Barrio Sarriena S/N. E-48940 Leioa, Spain (e-mail: firstname.lastname@example.org); or Maytee Robaina-García, MD, Centro Nacional Coordinador de Ensayos Clínicos (CENCEC), Calle 5ta A e/60 y 62, Miramar, Playa, Havana, Cuba (e-mail: email@example.com).
GESEDEC Researchers: Guillermo Barrientos de Llano (Hospital Clínico Quirúrgico de 10 de Octubre, La Habana); Odalis Isabel Fernández-López, Regla Beatriz Alfonso-Almirall, Lilia Saborido-Martín, Leslie Pérez-Ruiz, Iván Domínguez-Casillas, Marina Caridad Guerrero-Nicado, Orieta Mediaceja-Vicente (Hospital CQ Gustavo Aldereguía Lima, Cienfuegos); Magaly Leyva-Concepción, Paula Lomba-Acevedo, Olivia Prado-Sosa, Ana Isabel Gesty-Vancol, Nilo V. Noroño-Morales, Aracelis Morales-García, Lourdes Bello-Gárciga, María Elena Pérez Martín (Centro Comunitario de Salud Mental de Guanabacoa); Ana Ramos-Cedeño (Coordinadora Provincial Ensayos Clínicos, Cienfuegos); Yamilé Cachimaille-Benavides, Clara Ballagas-Flores, Gladys Jiménez-Rivero, María Amparo Pascual, Martha Fors-López, Grisel Soto-Argüelles, Maylín González-Massens, Yanet Álvarez-González, Daniel Peña-Amador, Alberto Hernández-Rodríguez (CENCEC); Alejandro Valdevila-Figueira (Hospital Psiquiátrico de Holguín); Stan P. Kutcher, Bianca Lauria-Horner (Department of Psychiary, Dalhousie University), Marina Sokolenko, Janet Gallant (Dalhousie University).
R.V.-C. and Y.M.-R. shared equal responsibility on this work.
This trial was funded by the Canadian International Development Agency, Canada; Centro Nacional Coordinador de Ensayos Clínicos, Cuba; and Ministerio de Salud Pública, Cuba. This trial was part of a cooperation framework between Cuba (Dr Maria Amparo Pascual, Dr Martha Maria Fors López) and Canada (Dr Stanley Kutcher) International Health Office (IHO), Dalhousie University, Nova Scotia, Canada. J.B. is supported by UPV/EHU (GIU14/27, UFI11/35) and CIBERSAM.