| Methods |
Double‐blind randomised controlled trial. Duration ‐ 3 weeks. Multicentre trial.
Washout period ‐ up to 3 days. (Followed by 9 week trial of sustained efficacy). |
| Participants |
438 participants.
Age 18 and over. Mean age 41.3 (sd 13.1) in risperidone group, 38.3 (sd12.5) in haloperidol group and 39.4 (sd13.0) in placebo group.
Inclusion criteria: Physically healthy. DSM‐IV bipolar disorder and at least one prior documented manic or mixed episode. Currently voluntarily hospitalised for manic episode meeting DSM‐IV criteria and with YMRS of at least 20 at screening and baseline. MADRS 20 or less.
Exclusion: Comorbid depressive symptoms not meeting criteria for mixed episode. DSM‐IV criteria for schizo‐affective disorder or rapid cycling bipolar disorder; borderline or antisocial personality disorder; recent substance abuse or dependence; risk of suicidal or violent behaviour; history of poor antimanic response to antipsychotic monotherapy. Antidepressant treatment or ECT within 4 weeks of screening; antiparkinsonian drugs; beta‐adrenergic blockers at baseline; clozapine within 1 month of screening; depot antipsychotic medication wihtin one treatment cycle of screening. Patients taking psychotropic drugs including mood stabilisers and antipsychotics completed a 3 day washout before randomisation. |
| Interventions |
Risperidone versus haloperidol and versus placebo all as monotherapy.
Acute phase: Risperidone: 2mg on day 1 increased or decreased by investigator by 1mg on day 2 to a minimum of 1mg/day and maximum of 6mg/day on day 5.
Haloperidol: 4mg on day 1 increased or decreased by investigator by 2mg on day 2 to a minimum of 2mg/day and maximum of 12mg/day on day 5.
After day 5 flexible doses of 1‐6mg'day risperidone and 2‐12mg/day haloperidol were allowed.
Continuation phase: Doses ranges as for acute phase.
Rescue medication: lorazepam and chloral hydrate days 1 ‐ 10 to treat agitation, irritability, restlessness, insomnia and hostility. Neither was permitted within the 8 hours preceding behavioural assessment or after day 10. bet‐adrenergic blockers and anticholinergic drugs could be initiated after baseline for treatment of akathisia and EPS respectively.
insight oriented therapies and CBT were not permitted but limited supportive therapy or psychoeducation and self‐help group meetings were allowed. |
| Outcomes |
Primary efficacy measure ‐ Young Mania Rating Scale (YMRS) at baseline, weekly for 4 weeks and then fortnightly. Other measures ‐ Clinical Global Impression (CGI‐ severity of illness; Montgomery‐Asperg Depression Rating Scale (MADRS) and Brief Psychiatric Rating Scale (BPRS) at baseline, weekly for 4 weeks and then fortnightly. Global Assessment of Functioning (GAS) at baseline and after 3 weeks and at endpoint. CGI ‐ severity alos at hospital discharge. Safety measures: monitoring of adverse event, vital signs, laboratory values, ECGs and body weight. EPS were assessed using the Extrapyramidal Symptom Rating Scale (ESRS). |
| Notes |
|
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Allocation concealment? |
Unclear risk |
B ‐ Unclear |
