Augmentation of Antidepressants with Antipsychotics

Research Updates in PsychiatryAugmentation of antidepressants with antipsychotics has become a common practice, and aripiprazole (Abilify) has been FDA approved at doses from 2 mg/day to 15 mg/day for this purpose.

In a recent report, 225 patients with major depressive disorder (MDD) who had failed one to four antidepressant trials were studied to determine whether low dose Abilify really works.

Using the Sequential Parallel Combined Design (SPCD), a strategy designed to minimize placebo response, patients were randomized to receive adjunctive treatment with Abilify or placebo across two 30-day phases. Some patients received 2 mg/day in phase one with an increase to 5 mg/day in phase two. Others received a placebo in both phases, while still others received a placebo in phase one and 2 mg/day of Abilify in phase two. All patients continued to receive their original antidepressant throughout the trial, and no patients had a history of bipolar disorder or psychosis.

After 30 days, patients taking 2 mg/ day of Abilify had only a slightly higher response rate (defined as a 50% decrease in MADRS score) relative to those taking placebo, 18.5% vs 17.4%, respectively — a difference of only 1.1%.

When the dose was increased to 5 mg/day for another 30 days — while the placebo subjects continued taking placebo — response rates were also similar between groups, differing by only 4.3% (not statistically significant). Even when earlystage placebo responders were taken out of the analysis — to increase likelihood of finding a response in the Abilify group — the response rate to 2 mg/d Abilify was still only 18%, indistinguishable from placebo.

Dropout rates were low, reflecting generally good tolerability of low-dose Abilify when added to antidepressants. In fact, only constipation and dry mouth were significantly more common with Abilify. This was an investigator-initiated study supported by Bristol-Myers Squibb, which also provided blinded study medication (Fava M et al, Psychother Psychosom 2012;81:87–97).

TCPR’s Take: The authors’ primary conclusion is that Abilify is well tolerated at low doses. This is not surprising, since the average doses in the two trials to obtain FDA approval as an adjunctive antidepressant were above 10 mg/ day, where akathisia and fatigue were common.

However, lower doses — which are recommended by the manufacturer and frequently used by clinicians — were ineffective for depression. Based on these results, the authors suggest that Abilify’s antidepressant effect may be restricted to doses over 10 mg, where, they point out, it acts more like a dopamine antagonist. This raises the question of whether a different antipsychotic might perform just as well.

Augmentation of Antidepressants with Antipsychotics

This article originally appeared in:

The Carlat Psychiatry Report
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This article was published in print 7 & 8/2012 in Volume:Issue 10: 7 & 8.