Safety and Tolerability of Adjunctive Aripiprazole in Major Depressive Disorder

Abstract

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 treatmentemergent 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 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.

Long-term safety and tolerability of open-label aripiprazole augmentation of antidepressant therapy in major depressive disorder

“…In this long-term study, the safety and tolerability of aripiprazole augmentation was demonstrated by relatively low discontinuation rates due to adverse events (23%) over a 52–58-week exposure. Furthermore, the adverse event profile was consistent with that reported in the short-term, double-blind, placebo-controlled trials 23. Most adverse events were mild or moderate in severity and the incidence of serious adverse events was low.…”

Dose Trends of Aripiprazole from 2004 to 2014 in Psychiatric Inpatients in Korea

“…Moreover, Basu and Brar18) suggested that starting aripiprazole at lower doses, either 5 or 10 mg/day, minimizes the risk of akathisia and that starting at doses greater than 30 mg/day increases the risk of schizoaffective disorder. In line with the suggestion by Nelson et al 19). that lowering the starting dose of aripiprazole represents one of the most widely used strategies to minimize the incidence or the severity of akathisia, the results from the present study may reflect clinical experience that a low initial dose could reduce the risk of akathisia.…”

Metabolic Assessment of Aripiprazole as Adjunctive Therapy in Major Depressive Disorder

“…Most patients had 1 historical treatment failure before entering the trial, and the median duration of the current episode was 21.0 months in the placebo group and 18.8 months in the aripiprazole group. There were no differences between the aripiprazole and placebo groups in the distribution and average dose of each standard antidepressant, 13 and there was no pattern suggesting differential subject disposition for any single standard antidepressant compared with the overall population.…”

“…This pooled safety analysis included 737 patients who received at least 1 dose of study medication (adjunctive aripiprazole, n = 371; adjunctive placebo, n = 366) during the 6-week doubleblind treatment phase. Details of patient disposition and demographic characteristics have been reported previously 13 ; there were no clinically relevant differences between the treatment groups across demographic characteristics. The clinical trial population was predominantly female (64%) and white (88%).…”