---
title: "Psych News Alert: Ziprasidone Augmentation for MDD Appears Safe, But Precautions Advised"
description: Although the atypical antipsychotic ziprasidone has shown promise as an add-on therapy for patients with major depressive disorder (MDD),...
image: https://alert.psychnews.org/hubfs/Imported_Blog_Media/scale_83395837-Jun-24-2025-04-31-43-8208-PM.jpg
---

 11/10/16 12:00 AM

# Ziprasidone Augmentation for MDD Appears Safe, But Precautions Advised

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Although the atypical antipsychotic ziprasidone has shown promise as an add-on therapy for patients with major depressive disorder (MDD), little is known of possible side effects from this intervention. A [study](http://www.psychiatrist.com/JCP/article/Pages/2016/aheadofprint/15m10426.aspx) in the *Journal of Clinical Psychiatry* now suggests that patients with MDD who take ziprasidone in combination with escitalopram may be at greater risk of weight gain, akathisia, and an increase in the QT interval compared with those taking escitalopram alone. 

The findings were based on a randomized, double-blind, placebo-controlled trial of 139 adults with MDD who were assigned to take ziprasidone (mean dose of 98 mg/d) or placebo in combination with escitalopram for eight weeks after failing to respond to escitalopram alone. As was [previously reported](http://ajp.psychiatryonline.org/doi/pdf/10.1176/appi.ajp.2015.14101251) in the *American Journal of Psychiatry*, ziprasidone used adjunctively with escitalopram demonstrated greater antidepressant efficacy in patients with MDD compared with adjunctive placebo. As part of this trial, the researchers regularly measured metabolic and cardiac effects, and the Barnes Akathisia Scale and Abnormal Involuntary Movement Scale were used to assess akathisia and extrapyramidal symptoms, respectively.

In a follow-up analysis, David Mischoulon, M.D., Ph.D., of Massachusetts General Hospital and colleagues reported that patients on ziprasidone treatment had a significant increase in weight compared with placebo—with the ziprasidone-treated patients averaging a weight gain of 7.7 pounds compared with 2.2 pounds in the placebo-escitalopram group. Patients taking ziprasidone experienced a greater corrected QT interval (QTc) increase (8.8 milliseconds), which the authors noted is “generally in line with the known risks of ziprasidone on the QTc.” Ziprasidone-treated patients also encountered a greater increase in global akathisia scores compared with placebo, and about one-third of the patients on the combination therapy experienced sedation.

“Our findings, in the context of the risk of QTc prolongation with ziprasidone and SSRIs, suggest that the combination of ziprasidone and SSRIs is very likely safe but should be undertaken with caution, and clinicians who administer such combinations should monitor ECGs regularly,” the authors wrote. They also advised regular monitoring of weight, extrapyramidal symptoms, and involuntary movements.

For related information, see the *Psychiatric News *article “[Ziprasidone May Be Effective as Adjunctive Therapy for Depression](http://psychnews.psychiatryonline.org/doi/full/10.1176/appi.pn.2015.7b2).”

(Image: forestpath/Shutterstock)

[MDD](https://alert.psychnews.org/tag/mdd), [depression](https://alert.psychnews.org/tag/depression), [Journal of Clinical Psychiatry](https://alert.psychnews.org/tag/journal-of-clinical-psychiatry), [AJP](https://alert.psychnews.org/tag/ajp), [escitalopram](https://alert.psychnews.org/tag/escitalopram), [antipsychotic-induced weight gain](https://alert.psychnews.org/tag/antipsychotic-induced-weight-gain), [QT prolongation](https://alert.psychnews.org/tag/qt-prolongation), [ziprasidone](https://alert.psychnews.org/tag/ziprasidone), [David Mischoulon](https://alert.psychnews.org/tag/david-mischoulon)

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## [Switching to Aripiprazole or Ziprasidone May Reduce Weight Gain in Patients Taking Antipsychotics](https://alert.psychnews.org/2021/02/switching-to-aripiprazole-or.html)

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