Systematic evaluation of dose-escalation strategies after initial non-response to standard-dose pharmacotherapy in schizophrenia

Objectives This meta-analysis investigates if dose increase of an antipsychotic drug (high-dose treatment, dose escalation) is advantageous for schizophrenic patients who failed to respond adequately to standard-dose treatment with the same antipsychotic. Methods Within a systematic literature survey, we identified all randomized controlled trials (RCTs) comparing a dose increase directly to standard-dose continuation treatment in schizophrenic subjects with initial non-response to prospective standard-dose pharmacotherapy with the same antipsychotic. The primary outcome was mean change in the Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcomes were dichotomous response and attrition rates. Study selection and data extraction were conducted independently by two authors. We calculated effect sizes (Hedgesu0027s  g and risks ratios) using the Mante–Haenszel random-effects model. Meta-regression analyses were performed to explore the influence of the degree of the dose increase on effect sizes. Results Five trials ( n  = 348) examining quetiapine ( n  = 2, n  = 191), ziprasidone ( n  = 1, n  = 75), haloperidol ( n  = 1, n  = 48), and fluphenazine ( n  = 1, n  = 34) were included. We found no significant between-group differences for the mean PANSS/BPRS total score change, even not when itemized according to the individual antipsychotic agents. There were no between-group differences for response and dropout rates. The non-significant meta-regressions indicate no impact of the different amounts of dose increments on effect sizes. Conclusions We found no evidence for the efficacy of a dose escalation after initial non-response to standard-dose pharmacotherapy as general advisable treatment strategy. As the high-dose treatment was not accompanied by significant increased attrition rates, appropriate tolerability and acceptability of this pharmacological option can be assumed.