Aripiprazole or CBT Not More Effective Than Placebo at Preventing Transition to Psychosis

A randomized controlled trial found that neither cognitive behavioral therapy (CBT) nor low-dose aripiprazole better-prevented the transition to psychosis at 12 months compared with placebo. These findings were published in the Schizophrenia Bulletin.

In most help-seeking young adults, a period of clinical high risk for psychosis (CHRp) precedes the first psychotic episode. This time may be an opportunity for preventative intervention.

The PREVENT study was a randomized, multicenter, parallel-arm, controlled trial conducted at 11 sites in Germany from 2008 to 2013. Patients (N=280) seeking CHRp services were randomly assigned to receive clinical management plus placebo (n=55), clinical management plus aripiprazole with a maximum dose of 15 mg (n=96), or CBT (n=129) for 12 months. Clinical management comprised a maximum of 21 sessions of supportive therapy with basic advice and symptom monitoring and CBT comprised a maximum of 30 individual sessions lasting up to 50 minutes. The primary outcome was a transition to psychosis at 12 months.

The patients’ mean age was 24.2 to 24.9 years, 60.0%-74.0% were men, 63.6%-78.3% had attenuated positive symptoms, and 43.6%-57.3% had basic symptoms of cognitive disturbances cluster.

The median number of attended sessions was 18 for CBT and 7 for clinical management. Based on overall pill count, the median aripiprazole dose was 3.8 mg/day for 164 days. Among the aripiprazole and CBT treatment arms, 13% had adherence less than 50%. Adherence rates did not differ between study arms (P =.983). However, more aripiprazole recipients (P =.002) and placebo recipients (P =.004) terminated the study prematurely compared with CBT.

At 12 months, 7 placebo recipients, 96 aripiprazole recipients, and 129 CBT recipients transitioned to psychosis (χ², 1.29; P =.524).

The cumulative transition rates were 16.1% for placebo, 31.3% for aripiprazole, and 20.1% for CBT, which did not differ significantly between groups overall (P =.342). These rates did not differ in pair-wise comparisons between aripiprazole and placebo (P =.264), CBT and placebo (P =.775), or CBT and aripiprazole (P =.185).

Despite no apparent effect on psychosis prevention, significant changes in psychosocial functioning were observed from baseline in all 3 study arms.

A total of 18 serious adverse events were reported during the study, all of which were rated as unlikely or not related with the interventions. Overall, aripiprazole recipients reported more extrapyramidal symptoms, parkinsonism, akathisia, and tardive dyskinesia events than the CBT group.

In the patient survey, most (57.2%) preferred to receive CBT whereas 16.7% preferred aripiprazole and 25.7% had no preference (P <.0001).

This study may have been limited as the appropriate aripiprazole dose and exposure to CBT for preventing transition to psychosis is not fully understood and these interventions may not have been sufficient.

The study authors concluded, “To understand whether people with CHRp benefit best from [clinical management] or if an integrated psychotherapeutic treatment is a superior option, we suggest that future trials adopt a component research design to detect active therapeutic components by comparing [clinical management] to CBT and integrated psychological interventions.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.