REVIEW OF: Wang D et al, J Clin Psychopharmacol 2022;42(4):383–390

STUDY TYPE: Randomized, double-blind, controlled trial

Olanzapine ranks among the most effective antipsychotics in meta-analyses, and this new study compared paliperidone extended release (ER) to olanzapine in treatment-resistant schizophrenia.

This multisite, 12-week trial randomized 86 adults with treatment-resistant schizophrenia (ages 18–45; 77.9% male) to paliperidone ER (n=45; mean dose of 10.73±2.260 mg/day) or olanzapine (n=41; mean dose of 20.49±4.001 mg/day). Researchers defined treatment resistance as failure of at least two antipsychotic trials due to inadequate response, intolerance, or both. Over four weeks, paliperidone ER and olanzapine were titrated in a fixed manner from 3–12 and 5–20 mg/day, respectively. After week four, doses were adjusted based on clinical response.

The primary outcome was baseline-to-endpoint change in psychotic symptom severity measured with the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions–Severity of Illness Scale. Secondary outcomes included changes in cognitive functioning on the MATRICS Consensus Cognitive Battery and changes in metabolic parameters. Follow-up visits were conducted on weeks one, two, four, eight, and 12. Researchers performed an intention-to-treat analysis and implemented a last-observation-carried-forward imputation strategy for missing data.

On the primary outcome measures, there were no between-group differences in symptom severity improvement. Within-group improvements in PANSS total scores from baseline were observed for both groups by week two of treatment and at all subsequent follow-up visits (p<0.001).

Compared to baseline, there were no differences in cognitive functioning within or between the groups. While weight, waist circumference, and BMI increased within both groups (p<0.001), baseline-to-endpoint waist circumference increase was greater for olanzapine than paliperidone ER (p=0.030).

Eight patients discontinued treatment in each group. The most reported treatment-related adverse events were somnolence and extrapyramidal symptoms in the olanzapine and paliperidone groups.

CARLAT TAKE

This study implies that paliperidone ER may be as effective as olanzapine for treatment-resistant schizophrenia. Paliperidone’s advantages include a favorable side effect profile and availability as a long-acting injection. However, the study’s sample size casts doubt on its ability to detect a true difference between the antipsychotics.