Clinical Predictors of Extrapyramidal Symptoms Associated With Aripiprazole Augmentation for the Treatment of Late-Life Depression in a Randomized Controlled Trial

Abstract

Objective: Augmentation with aripiprazole is an effective pharmacotherapy for treatment-resistant late-life depression (LLD). However, aripiprazole can cause extrapyramidal symptoms (EPS) such as akathisia and parkinsonism; these symptoms are distressing and can contribute to treatment discontinuation. We investigated the clinical trajectories and predictors of akathisia and parkinsonism in older patients receiving aripiprazole augmentation for treatment-resistant LLD.

Methods: Between 2009 and 2013, depressed older adults who did not remit with venlafaxine were randomized to aripiprazole or placebo in a 12-week trial. Participants were 60 years or older and met DSM-IV-TR criteria for major depressive episode with at least moderate symptoms. The presence of akathisia and parkinsonism was measured at each visit using the Barnes Akathisia Scale (BAS) and Simpson-Angus Scale (SAS), respectively. In an exploratory analysis, we examined a broad set of potential clinical predictors and correlates: age, sex, ethnicity, weight, medical comorbidity, baseline anxiety severity, depression severity, concomitant medications including rescue medications, and aripiprazole dosage.

Results: Twenty-four (26.7%) of 90 participants randomized to aripiprazole and who had akathisia scores available developed akathisia compared to 11 (12.2%) of 90 randomized to placebo. Greater depression severity was the main predictor of treatment-emergent akathisia. Most participants who developed akathisia improved over time, especially with reductions in dosage. Fifteen (16.5%) of 91 participants taking aripiprazole and who had parkinsonism scores available developed parkinsonism, but no clinical predictors or correlates were identified.

Conclusions: Akathisia is a common side effect of aripiprazole, but it is typically mild and responds to dose reduction. Patients with greater baseline depression may warrant closer monitoring for akathisia. More research is needed to understand the course and predictors of treatment-emergent EPS with antipsychotic augmentation for treatment-resistant LLD.

Trial registration: ClinicalTrials.gov identifier: NCT00892047.

Conflict of interest statement

Declaration of Interests:

JHH reports no conflicts of interest.

BHM currently receives research funding from Brain Canada, the CAMH Foundation, the Canadian Institutes of Health Research, Patient-Centered Outcomes Research Institute, and the US National Institute of Health (NIH). During the last five years, he also received research support from Bristol-Myers Squibb (medications for a NIH-funded clinical trial), Eli-Lilly (medications for a NIH-funded clinical trial), and Pfizer (medications for a NIH-funded clinical trial). He directly own stocks of General Electric (less than $5,000).

EJL reports research funding (current/past) from Janssen, Alkermes, Acadia, Takeda, Lundbeck,Barnes Jewish Foundation, Patient-Centered Outcomes Research Institute, and Taylor Family Institute for Innovative Psychiatric Research.

MS reports no biomedical conflicts of interest.

JFK has received research support from Patient-Centered Outcomes Research Institute and medication supplies from Indivior and Pfizer for investigator initiated studies.

CFR has received research support from the NIH, the Patient Centered Outcomes Research Institute, the Center for Medicare and Medicaid Services, the American Foundation for Suicide Prevention, the Brain and Behavior Research Foundation, and the Commonwealth of Pennsylvania. BristolMeyerSquib and Pfizer have provided pharmaceutical supplies for his NIH sponsored research.

DMB has received research support from the Canadian Institutes of Health Research (CIHR), National Institute of Health (NIH), Brain Canada and the Temerty Family through the Centre for Addiction and Mental Health (CAMH) Foundation and the Campbell Research Institute. He receives research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. and he is the site principal investigator for three sponsor-initiated studies for Brainsway Ltd. He also receives in-kind equipment support from Magventure for an investigator-initiated study. He receives medication supplies for an investigator-initiated trial from Invidior. He has participated in advisory board for Janssen.

© Copyright 2018 Physicians Postgraduate Press, Inc.

Figures

Figure 1:

Trajectory for the development of akathisia in participants randomized to aripiprazole