Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis.
OBJECTIVE
To develop an evidence base for recommendations on the use of atypical antipsychotics for patients with schizophrenia.


METHODS
Systematic overview and meta-regression analyses of randomised controlled trials, as a basis for formal development of guidelines.


METHODS
12 649 patients in 52 randomised trials comparing atypical antipsychotics (amisulpride, clozapine, olanzapine, quetiapine, risperidone, and sertindole) with conventional antipsychotics (usually haloperidol or chlorpromazine) or alternative atypical antipsychotics.


METHODS
Overall symptom scores. Rate of drop out (as a proxy for tolerability) and of side effects, notably extrapyramidal side effects.


RESULTS
For both symptom reduction and drop out, there was substantial heterogeneity between the results of trials, including those evaluating the same atypical antipsychotic and comparator drugs. Meta-regression suggested that dose of conventional antipsychotic explained the heterogeneity. When the dose was </=12 mg/day of haloperidol (or equivalent), atypical antipsychotics had no benefits in terms of efficacy or overall tolerability, but they still caused fewer extrapyramidal side effects.


CONCLUSIONS
There is no clear evidence that atypical antipsychotics are more effective or are better tolerated than conventional antipsychotics. Conventional antipsychotics should usually be used in the initial treatment of an episode of schizophrenia unless the patient has previously not responded to these drugs or has unacceptable extrapyramidal side effects.
Geddes
J
J
Department of Psychiatry University of Oxford, Warneford Hospital, Oxford OX3 7JX. john.geddes@psych.ox.ac.uk
Freemantle
N
N
Harrison
P
P
Bebbington
P
P
D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines; D003024:Clozapine / Q000627:therapeutic use; D003987:Dibenzothiazepines / Q000627:therapeutic use; D016527:Drug Costs; D006801:Humans; D007093:Imidazoles; D007211:Indoles; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069348:Quetiapine Fumarate; D012044:Regression Analysis; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000627:therapeutic use
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D007093:Imidazoles; D007211:Indoles; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D010890:Pirenzepine; D013469:Sulpiride; D000077582:Amisulpride; C066304:sertindole; D003024:Clozapine; D018967:Risperidone; D000077152:Olanzapine