OBJECTIVE: To evaluate the safety and tolerability of aripiprazole adjunctive to standard antidepressant therapy (ADT) for patients with major depressive disorder (DSM-IV-TR criteria). METHOD: Data from 2 identical studies of aripiprazole augmentation (8 weeks of prospective ADT treatment followed by 6 weeks of randomized double-blind adjunctive treatment) were pooled. The incidence of treatment-emergent adverse events (TEAEs) and weight, electrocardiogram (ECG), and laboratory measurements were assessed during the 6-week phase, including time course, severity, resolution, and predictors. The studies were conducted from June 2004 to April 2006 and September 2004 to December 2006. RESULTS: The safety analysis included 737 outpatients (aripiprazole, n = 371; placebo, n = 366). The majority of patients completed the trials (aripiprazole, 86%; placebo, 88%). Common TEAEs (≥ 5% and twice the placebo rate) with aripiprazole were akathisia (25%), restlessness (12%), insomnia (8%), fatigue (8%), blurred vision (6%), and constipation (5%). Most TEAEs were of mild to moderate severity (aripiprazole, 89%; placebo, 95%). TEAE rates in the aripiprazole and placebo groups were not affected by ADT, age, or gender. Discontinuation due to TEAEs was low (aripiprazole, 3%; placebo, 1%). Mean weight change was higher with aripiprazole versus placebo (1.73 kg vs 0.38 kg, P < .001). At endpoint, clinical laboratory parameters, vital signs, and ECG indices (including QT(c) interval) were similar between groups. Akathisia with aripiprazole generally occurred in the first 3 weeks (76%), was of mild to moderate severity (92%), and led to discontinuation in 3 patients (0.8%). Within the aripiprazole group, age (18-40 years) was the only positive predictor for akathisia. CONCLUSIONS: In this short-term post hoc analysis, aripiprazole as augmentation to ADT demonstrated a safety and tolerability profile similar to that in monotherapy studies in other psychiatric populations. Controlled long-term safety and efficacy data of aripiprazole as adjunctive to ADT are warranted. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT00095823 (CN138-139) and NCT00095758 (CN138-163).
RCT Entities:
OBJECTIVE: To evaluate the safety and tolerability of aripiprazole adjunctive to standard antidepressant therapy (ADT) for patients with major depressive disorder (DSM-IV-TR criteria). METHOD: Data from 2 identical studies of aripiprazole augmentation (8 weeks of prospective ADT treatment followed by 6 weeks of randomized double-blind adjunctive treatment) were pooled. The incidence of treatment-emergent adverse events (TEAEs) and weight, electrocardiogram (ECG), and laboratory measurements were assessed during the 6-week phase, including time course, severity, resolution, and predictors. The studies were conducted from June 2004 to April 2006 and September 2004 to December 2006. RESULTS: The safety analysis included 737 outpatients (aripiprazole, n = 371; placebo, n = 366). The majority of patients completed the trials (aripiprazole, 86%; placebo, 88%). Common TEAEs (≥ 5% and twice the placebo rate) with aripiprazole were akathisia (25%), restlessness (12%), insomnia (8%), fatigue (8%), blurred vision (6%), and constipation (5%). Most TEAEs were of mild to moderate severity (aripiprazole, 89%; placebo, 95%). TEAE rates in the aripiprazole and placebo groups were not affected by ADT, age, or gender. Discontinuation due to TEAEs was low (aripiprazole, 3%; placebo, 1%). Mean weight change was higher with aripiprazole versus placebo (1.73 kg vs 0.38 kg, P < .001). At endpoint, clinical laboratory parameters, vital signs, and ECG indices (including QT(c) interval) were similar between groups. Akathisia with aripiprazole generally occurred in the first 3 weeks (76%), was of mild to moderate severity (92%), and led to discontinuation in 3 patients (0.8%). Within the aripiprazole group, age (18-40 years) was the only positive predictor for akathisia. CONCLUSIONS: In this short-term post hoc analysis, aripiprazole as augmentation to ADT demonstrated a safety and tolerability profile similar to that in monotherapy studies in other psychiatric populations. Controlled long-term safety and efficacy data of aripiprazole as adjunctive to ADT are warranted. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT00095823 (CN138-139) and NCT00095758 (CN138-163).
Authors: Richard C Shelton; Douglas J Williamson; Sara A Corya; Todd M Sanger; Luann E Van Campen; Michael Case; Susan D Briggs; Gary D Tollefson Journal: J Clin Psychiatry Date: 2005-10 Impact factor: 4.384
Authors: Gary Sachs; Raymond Sanchez; Ronald Marcus; Elyse Stock; Robert McQuade; William Carson; Neveen Abou-Gharbia; Cheryl Impellizzeri; Stephen Kaplita; Linda Rollin; Taro Iwamoto Journal: J Psychopharmacol Date: 2006-01-09 Impact factor: 4.153
Authors: Michael E Thase; Sara A Corya; Olawale Osuntokun; Michael Case; David B Henley; Todd M Sanger; Susan B Watson; Sanjay Dubé Journal: J Clin Psychiatry Date: 2007-02 Impact factor: 4.384
Authors: Keming Gao; David E Kemp; Stephen J Ganocy; Prashant Gajwani; Guohua Xia; Joseph R Calabrese Journal: J Clin Psychopharmacol Date: 2008-04 Impact factor: 3.153
Authors: Stephen R Marder; Robert D McQuade; Elyse Stock; Stephen Kaplita; Ronald Marcus; Allan Z Safferman; Anutosh Saha; Mirza Ali; Taro Iwamoto Journal: Schizophr Res Date: 2003-06-01 Impact factor: 4.939
Authors: David A Shapiro; Sean Renock; Elaine Arrington; Louis A Chiodo; Li-Xin Liu; David R Sibley; Bryan L Roth; Richard Mailman Journal: Neuropsychopharmacology Date: 2003-05-21 Impact factor: 7.853
Authors: Robert M Berman; Ronald N Marcus; René Swanink; Robert D McQuade; William H Carson; Patricia K Corey-Lisle; Arif Khan Journal: J Clin Psychiatry Date: 2007-06 Impact factor: 4.384
Authors: Teresa A Pigott; William H Carson; Anutosh R Saha; Anne F Torbeyns; Elyse G Stock; Gary G Ingenito Journal: J Clin Psychiatry Date: 2003-09 Impact factor: 4.384
Authors: David C Steffens; J Craig Nelson; James M Eudicone; Candace Andersson; Huyuan Yang; Quynh-Van Tran; Robert A Forbes; Berit X Carlson; Robert M Berman Journal: Int J Geriatr Psychiatry Date: 2010-09-09 Impact factor: 3.485
Authors: Michael E Thase; Madhukar H Trivedi; J Craig Nelson; Maurizio Fava; Rene Swanink; Quynh-Van Tran; Andrei Pikalov; Huyuan Yang; Berit X Carlson; Ronald N Marcus; Robert M Berman Journal: Prim Care Companion J Clin Psychiatry Date: 2008
Authors: Daniel E Casey; Kimberly K Laubmeier; Sabrina Vogel Marler; Robert A Forbes; Ross A Baker Journal: Prim Care Companion CNS Disord Date: 2012-05-31
Authors: Robert M Berman; Michael E Thase; Madhukar H Trivedi; James A Hazel; Sabrina Vogel Marler; Robert D McQuade; William Carson; Ross A Baker; Ronald N Marcus Journal: Neuropsychiatr Dis Treat Date: 2011-05-24 Impact factor: 2.570