Hirschfeld 1999.
| Methods | Randomised double‐blind trial | |
| Participants |
Number of total participants/type of patients: 59 participants randomised. Inpatient study Inclusion criteria: Sex: male and female Age: 18 ‐ 60 years Diagnosis: DSM‐IV criteria for bipolar disorder currently manic or mixed episode and a score of ≥ 14 on the YMRS Exclusion criteria: Intolerance to valproate or lithium Concurrent medical disorders Substance dependence Serious risk of suicide Pregnancy Screened positive for amphetamines or phencyclidine Depot antipsychotic drugs Investigational drug within previous 4 weeks Any drug that may interfere with safety or efficacy of trial medications |
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| Interventions |
Location: USA, hospital site(s) (cities not stated) Date of study: Not stated Treatment groups: 1. Valproate ‐ non‐loading: 750 mg 3 times a day (days 1 and 2) with gradual dose titration (days 3 ‐ 10) Valproate ‐ loading: 30 mg/kg a day (days 1 and 2) then 20 mg/kg per day (days 3 ‐ 10) 2. Lithium: 300 mg 3 times a day (days 1 and 2); gradual dose titration (days 3 ‐ 10) Concomitant medications: Lorazepam was allowed to manage agitation, insomnia, restlessness, irritation, and hostility (4 mg/day on days 1 ‐ 4 and 2 mg/day on days 5 ‐ 7) Length of study: 10 days Randomisation: 20 patients randomised to valproate non‐loading 20 patients randomised to valproate loading 19 randomised to lithium |
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| Outcomes |
Outcomes: 1. Changes on the YMRS scores as assessed by the Schedule for Affective Disorders and Schizophrenia Change Version (SADS‐C) 2. GAS Adverse events were reported Study withdrawal was reported |
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| Funding | "Sponsored by Abbott Laboratories (M95‐305)." | |
| Conflict of interest | Not stated | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "Randomised" Comment: No other information about method of randomisation, so we were unable to assess risk of bias. We established contact with the lead author who no longer has access to the data or protocols. |
| Allocation concealment (selection bias) | Unclear risk | Quote: "Randomised" Comment: No other information about method of allocation concealment, so we were unable to assess risk of bias.We established contact with the lead author who no longer has access to the data or protocols. |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "Double blind" Quote: "Blinded medication was provided in identical‐appearing grey tablets so that all patients received the same total number of capsules." |
| Blinding of outcome assessment (detection bias) Efficacy | Low risk | Quote: "Blinded raters evaluated the patients" |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "Seven patients (35%) in each of the valproate‐treated groups and 9 (47%) in the lithium standard‐titration group discontinued the study medication before the conclusion of the trial." Comment: Both groups have a > 30% dropout rate. However, dropout rates are comparable (less than a two‐fold difference). |
| Selective reporting (reporting bias) | High risk | Comment: Means and standard deviations of all outcomes are not reported. We established contact with the lead author who no longer has access to these data. |
| Other bias | Low risk | Comment: None identified |