Chouinard 1983.
| Methods | Study design: randomised, double‐blind cross‐over study | |
| Participants |
Diagnosis: mania Method of diagnosis: confirmed by the research psychiatrist on the basis of the Research Diagnostic Criteria Age: 25 – 63 years old, median 43 years Sex: 4 women; 9 men Location: Hopital Louis‐H Lafontaine Co‐morbidities: not described Adjunctive therapy: none Adjunctive medication: "For ethical reasons haloperidol was administered in cases of agitation that could not be controlled by the study medications. Thus, PRN medication presented an indirect measure of efficacy, and reflected the judgement of the nurses in direct contact with the participants. A standard procedure was used and nurses needed to obtain the approval of the investigating psychiatrist before giving the PRN medication. The need for haloperidol PRN was assessed on each occasion and it was never prescribed on a regular basis. Procyclidine HCL was administered with the haloperidol for control of parkinsonian symptoms." |
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| Interventions | Participants were randomly assigned to either: Experimental arm ‐lithium N = 6 Duration: 10 days + 10 days Treatment protocol: "Patients were treated with clonazepam or lithium carbonate in a double blind crossover design: six participants chosen randomly received 10 days of treatment with clonazepam followed immediately by 10 days of treatment with lithium, while the others received the same treatments in reverse order. Patients were started on the experimental treatment as soon as the evaluations and laboratory tests were completed (1 or 2 days after admission. Before the study started, participants were given haloperidol on a PRN basis whenever their behaviour was uncontrolled. After treatment with the research drug had begun, no other medications (including hypnotics) were administered, expect for haloperidol in cases of severe agitation. Clonazepam and lithium carbonate were administered under double‐blind conditions. While participants were treated with lithium, they received clonazepam placebos and vice versa. Both medications were given in an equally divided four time daily regimen. Clonazepam was administered in 2 mg tablets and lithium carbonate in 300 mg tablets. To ensure compliance the tablets were taken with water in the presence of a nurse the initial doses were chosen on the basis of an equivalency of 2mg of clonazepam for 300mg lithium carbonate. Dosages were subsequently adjusted according to therapeutic effect and side effects. lithium plasma levels were sent to an internist who could request substitution of lithium by placebo if abnormally high lithium concentrations occurred. However, this never happened. The daily dosages of clonazepam given on day 1 varied from x to 8mg (mean 4.2 mg) and on day 10 from 4 to 16 mg (mean 10.4 mg), the daily doses of lithium given on day 1 varied from 900 to 1500 mg (mean 1118 mg) and on day 10 from 900 to 2100 mg (mean 1691 mg)." Therapist/face‐to‐face contact: not described Comparator arm ‐ clonazepam N = 6 Duration: 10 days + 10 days Treatment protocol: "Patients were treated with clonazepam or lithium carbonate in a double blind crossover design: six participants chosen randomly received 10 days of treatment with clonazepam followed immediately by 10 days of treatment with lithium, while the others received the same treatments in reverse order. Patients were started on the experimental treatment as soon as the evaluations and laboratory tests were completed (1 or 2 days after admission. Before the study started, participants were given haloperidol on a PRN basis whenever their behaviour was uncontrolled. After treatment with the research drug had begun, no other medications (including hypnotics) were administered, expect for haloperidol in cases of severe agitation. Clonazepam and lithium carbonate were administered under double‐blind conditions. While participants were treated with lithium, they received clonazepam placebos and vice versa. Both medications were given in an equally divided four times daily regimen. Clonazepam was administered in 2 mg tablets and lithium carbonate in 300 mg tablets. To ensure compliance the tablets were taken with water in the presence of a nurse the initial doses were chosen on the basis of an equivalency of 2 mg of clonazepam for 300 mg lithium carbonate. Dosages were subsequently adjusted according to therapeutic effect and side effects. lithium plasma levels were sent to an internist who could request substitution of lithium by placebo if abnormally high lithium concentrations occurred. However, this never happened. The daily dosages of clonazepam given on day 1 varied from x to 8 mg (mean 4.2 mg) and on day 10 from 4 to 16 mg (mean 10.4 mg), the daily doses of lithium given on day 1 varied from 900 to 1500 mg (mean 1118 mg) and on day 10 from 900 to 2100 mg (mean 1691 mg)". Therapist/face‐to‐face contact: not described |
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| Outcomes |
Timepoints for assessment: 0, 10, (+20) days Primary outcome:
Secondary outcome:
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| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "Randomly" ‐ no further description |
| Allocation concealment (selection bias) | Unclear risk | Not described |
| Blinding (performance bias and detection bias) All outcomes | Low risk | Clonazepam and lithium carbonate were administered under double‐blind conditions, Assessment of symptoms was based on clinical interviews conducted by the psychiatrist. Performance = low Detection = unclear |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Good completion rate (11/12) |
| Selective reporting (reporting bias) | Low risk | Comprehensive reporting |
| Other bias | Low risk | None identified |