There is insufficient high-quality data to suggest whether physicians should increase or maintain an antipsychotic dose in patients with schizophrenia who have not shown a response to their first medication, according to a study recently published in The Cochrane Database of Systematic Reviews.

The study researchers included 10 randomized controlled trials from the Cochrane Schizophrenia Group Trials Register, using relative risks (RR) to analyze dichotomous data and mean differences (MD) for continuous data.

The randomized controlled trials in this review included 675 subjects, none of whom responded to their first antipsychotic treatment during a run-in phase. The study researchers note that the majority of studies provided small sample sizes and poor reporting of allocation, blinding, and randomization methods.

Continue Reading

The number of subjects who responded in a clinically relevant way was not significantly different between groups (relative risk [RR], 1.09; 95% CI, 0.86 to 1.40), nor was the number who quit the study because of adverse side effects (RR 1.63; 95%, CI 0.52 to 5.07) or other reasons (RR, 1.30; 95%, CI 0.89 to 1.90). 

The mental state between groups, measured via the score change in the Positive and Negative Syndrome Scale (PANSS), also showed no observable difference (MD -1.44; 95% CI, -6.85 to 3.97). There was at least 1 ambiguous adverse effect present in both groups (RR, 0.91; 95% CI, 0.55 to 1.50). Sensitivity and subgroup analyses, although insufficiently powered, showed no effect on the outcome.

Because satisfactory clinical outcomes are often not achieved with standard doses of the patient’s first prescribed antipsychotic drug, clinicians are often faced with a predicament of either increasing or maintaining the dose. This study sought to investigate the efficacy of increasing vs maintaining dose in nonresponsive patients with schizophrenia, as well as any adverse effects that result.

Related Articles

The study researchers conclude that “[current] data do not show any clear differences between increasing or maintaining the antipsychotic dose for people with schizophrenia who do not respond to their initial antipsychotic treatment.”


Samara MT, Klupp E, Helfer B, Rothe PH, Schneider-Thoma J, Leucht S. Increasing antipsychotic dose for non response in schizophrenia [published online May 11, 2018]. Cochrane Database Syst Rev. doi: 10.1002/14651858.CD011883.pub2.