Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized…

Add-on antipsychotics help more people reach remission but are harder to tolerate — how long a trial would we give aripiprazole before deciding whether to keep it?

strong evidence71/100

Well-supported by good-quality research. how we score evidence

Caveat on this rating: Funding and author industry relationships for this meta-analysis could not be read from open sources; several included trials were manufacturer-run.

FDA approvedaripiprazole (Abilify)abilify

Pooling 16 placebo-controlled trials with 3,480 patients, adding an atypical antipsychotic such as aripiprazole to an antidepressant roughly doubled the odds of depression remission (OR 2.00), but dropout because of side-effects was nearly four times more likely than with placebo (OR 3.91).

Worth asking

Add-on antipsychotics help more people reach remission but are harder to tolerate — how long a trial would we give aripiprazole before deciding whether to keep it?

What it is FDA approved for

Read off the label. Trial duration and approval year are shown only where they were recorded — never inferred.

  • Schizophrenia (adults and adolescents 13-17)
  • Bipolar I disorder, acute and maintenance treatment of manic and mixed episodes, monotherapy or adjunct to lithium/valproate (adults and ages 10-17)
  • Adjunctive treatment of major depressive disorder (adults)
  • Irritability associated with autistic disorder (ages 6-17)
  • Tourette's disorder (ages 6-18)
  • Agitation associated with schizophrenia or bipolar mania (injection, adults)

Source

Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials — Nelson JC, Papakostas GI (2009)

Top-tier peer-reviewed journal

Read the source: https://doi.org/10.1176/appi.ajp.2009.09030312

DOI: 10.1176/appi.ajp.2009.09030312

How this was scored

Study design
Meta-analysis of randomised trials
Funding
Funding not disclosed
Published in
Top-tier peer-reviewed journal
Sample size
3,480
Preregistered
No
Conflicts disclosed
No
Independent of proponent
not recorded
Retracted
No

Read the full scoring rubric, including what it can't tell you.

Published August 19, 2026.

Questions

How strong is the evidence behind this?

Resolv rates this source "strong evidence". Well-supported by good-quality research. It scores 71 out of 100 on our published rubric. One caveat travels with that badge: Funding and author industry relationships for this meta-analysis could not be read from open sources; several included trials were manufacturer-run. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.

What is the source for this?

Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials — Nelson JC, Papakostas GI (2009). Published in: Top-tier peer-reviewed journal. DOI: 10.1176/appi.ajp.2009.09030312. The full source is linked on this page so you can read it yourself.

Who paid for this research, and does that matter?

Study design: Meta-analysis of randomised trials. Funding: Funding not disclosed. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.

Is aripiprazole (Abilify), abilify FDA approved?

Yes — FDA approved for Schizophrenia (adults and adolescents 13-17), Bipolar I disorder, acute and maintenance treatment of manic and mixed episodes, monotherapy or adjunct to lithium/valproate (adults and ages 10-17), Adjunctive treatment of major depressive disorder (adults), Irritability associated with autistic disorder (ages 6-17), Tourette's disorder (ages 6-18), Agitation associated with schizophrenia or bipolar mania (injection, adults). Approval is for a specific indication, not for everything the drug is prescribed for.

Is this medical advice?

This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.

This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.