Aripiprazole’s Effects on Worsening Psychosis in Schizophrenia Inconclusive

Investigators examined the risk for worsening psychosis when adding or switching to aripiprazole in patients with schizophrenia.

There is no direct evidence that switching individuals with schizophrenia to aripiprazole is responsible for psychotic worsening when compared with other antipsychotics, according to a study recently published in The Journal of Clinical Psychiatry.

There is a significant amount of literature linking aripiprazole to worsening psychosis in individuals with schizophrenia spectrum disorders. The medication’s unique affinity for dopamine D2 receptors has caused it to be a suspect. However, meta-analyses have found it to be an effective antipsychotic drug. To better understand its potential role in psychotic worsening, researchers conducted a meta-analysis with the hypothesis that switching to aripiprazole or adding it to a medication regimen increases likelihood of psychotic worsening compared with other antipsychotics.

Researchers examined 22 studies in this meta-analysis, 13 of which included a switch to aripiprazole (switching studies) and 9 in which aripiprazole was added to another antipsychotic (adding studies). The studies included a total of 3258 patients treated with aripiprazole and 2511 treated with other antipsychotics. All studies defined psychotic worsening as an adverse event.

In terms of psychotic worsening, there was no significant difference between the aripiprazole and other antipsychotic groups in the switching studies. There was also no significant difference between the 2 groups in the adding studies, though the quality of evidence was quite low. Switching to an antipsychotic other than aripiprazole significantly improved the rate of study discontinuation due to lack of efficacy (=.009), though the adding studies showed no significant difference in study discontinuation rate between the 2 groups. Due to the degree of study discontinuation and lack of robust evidence, it is unclear what degree of clinical risk aripiprazole poses when added to another antipsychotic.

Related Articles

The study researchers conclude that “there is no direct evidence that a switch to aripiprazole is related to risk of psychotic worsening in participants in clinical trials, although a switch to aripiprazole may be associated with a higher risk of study discontinuation due to lack of efficacy.”


Takeuchi H, Fathi A, Thiyanavadivel S, Agid O, Remington G. Can aripiprazole worsen psychosis in schizophrenia? A meta-analysis of double-blind, randomized, controlled trials.  J Clin Psychiatry. 2018; 79(2)