Initial severity of schizophrenia and efficacy of antipsychotics: participant-level meta-analysis of 6 placebo-controlled studies.
OBJECTIVE
Antipsychotic drugs constitute the mainstay in the treatment of schizophrenia, and their efficacy is well established in hundreds of randomized clinical trials. However, it is not known whether they are effective or how effective they are across the wide range of baseline symptom severity.


OBJECTIVE
To examine the influence of baseline severity of schizophrenia on the efficacy of antipsychotic drugs.


METHODS
Meta-analysis of participant-level data from 3 pivotal randomized trials of acute schizophrenia (n = 611) and 3 pivotal trials in patients with predominantly negative symptoms of schizophrenia (n = 475).


METHODS
Olanzapine or risperidone vs placebo, and amisulpride vs placebo.


METHODS
Change scores on the Positive and Negative Syndrome Scale (PANSS; score range, 30-210) and the Scale for the Assessment of Negative Symptoms (SANS; score range, 0-125) up to 6 weeks after baseline. The relationship between baseline and change scores for the drug and placebo groups was examined with 8 competing mixed-effects models for repeated measures.


RESULTS
The best-fitting models showed that, for both types of patients, the interactions between baseline symptom severity and treatment were statistically significant (P < .01). The greater the baseline severity was, the greater the magnitude of the differences was between active treatment and placebo. In acute treatment, the mean differences in PANSS change scores were 9.5 points for patients who were mildly ill at baseline (baseline PANSS score of 58), 13.7 for moderately ill patients (baseline PANSS score of 75), 18.8 for markedly ill patients (baseline PANSS score of 95), and 24.0 for severely ill patients (baseline PANSS score of 116). In treatment of predominantly negative symptoms, the mean differences in SANS change scores were 1.7 for those who were moderately ill (baseline SANS score of 55), 5.7 for markedly ill patients (baseline SANS score of 70), and 9.7 for severely ill patients (baseline SANS score of 85).


CONCLUSIONS
We can expect benefits of antipsychotic drugs for the full spectrum of patients likely to be treated for acute schizophrenia and for highly symptomatic patients with predominantly negative symptoms. Toward the mildest end of the spectrum, clinicians need to be aware that patients benefit less in terms of symptom improvement but may experience full adverse effects of antipsychotics. Clinicians also need to be aware that in addition to the treatment of active symptoms, which was the focus of this study, antipsychotics have another important action, namely to prevent relapses among patients in remission.
Department of Health Promotion and Human Behavior, School of Public Health, Kyoto University Graduate School of Medicine, Kyoto, Japan2Department of Clinical Epidemiology, School of Public Health, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Toshi A
TA
Furukawa
Department of Community Mental Health, University of Haifa, Haifa, Israel.
Stephen Z
SZ
Levine
Department of Pharmacoepidemiology, School of Public Health, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Shiro
S
Tanaka
Department of Statistics, University of Haifa, Haifa, Israel.
Yair
Y
Goldberg
Department of Psychiatry and Psychotherapy, Technische Universität München, München, Germany.
Myrto
M
Samara
Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, Chicago.
John M
JM
Davis
World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Public Health and Community Medicine, Section of Psychiatry, University of Verona, Verona, Italy9Department of Psychiatry, Univ.
Andrea
A
Cipriani
Department of Psychiatry and Psychotherapy, Technische Universität München, München, Germany9Department of Psychiatry, University of Oxford, Oxford, United Kingdom10Institute of Psychiatry, King's College London, London, United Kingdom.
Stefan
S
Leucht
D000328:Adult; D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D000077152:Olanzapine; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D013469:Sulpiride; D000077582:Amisulpride; D018967:Risperidone; D000077152:Olanzapine