Schizophrenia symptom severity predicts atypical antipsychotic benefit

By Lynda Williams, Senior medwireNews Reporter

Atypical antipsychotic drugs benefit patients with acute schizophrenia across the full spectrum of symptom severity, as well as highly symptomatic patients with predominantly negative symptoms, suggests a meta-analysis published in JAMA Psychiatry.

However, there was a significant correlation between increasing baseline symptom severity and the level of benefit patients derived from treatment, report Toshi Furukawa, from Kyoto University in Japan, and co-authors.

Noting that all patients are at risk of experiencing a full range of side effects, they therefore recommend: “Toward the mildest end of the spectrum, judicious clinical consideration of trade-offs between benefits and risks of the antipsychotic treatment is required.”

Analysis of three pivotal clinical trials comparing two atypical antipsychotics against placebo indicated that patients with mild symptoms of acute schizophrenia on the Positive and Negative Syndrome Scale (PANSS; mean baseline score 58) achieved an average score change of 9.5 points after 6 weeks of treatment.

This compared with a score change of 13.7 points for moderately ill patients (baseline PANSS=75 points), 18.8 points for markedly ill patients (baseline PANSS=95 points) and 24.0 points for severely ill patients (baseline PANSS=116 points).

There was a similar relationship between symptom severity at baseline and change in the Scale for the Assessment of Negative Symptoms (SANS) for highly symptomatic patients with predominantly negative symptoms.

Specifically, moderately ill patients (baseline SANS=55) achieved a 1.7 score change after 6 weeks of treatment compared with a change of 5.7 for markedly ill patients (baseline SANS=70) and 9.7 for severely ill patients (baseline SANS=85).

The researchers suggest that a PANSS score of 55 for acute schizophrenia patients and a SANS score of 65 for predominantly negative symptoms could act as a threshold for the use of atypical antipsychotic agents.

Discussing the wider implications of their study, Furukawa et al agree that placebo-controlled trials of antipsychotics should focus on more severely ill patients to increase the likelihood of detecting a treatment response.

“The current practice of setting this threshold to a score of 75 on the PANSS may be justifiable to strike a balance between patient recruitment and signal detection; if there is less difficulty in patient recruitment, the threshold could be higher”, they conclude.

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