Chlorpromazine Dose-Response Investigated for Schizophrenia
An updated review regarding the dose response effects of the antipsychotic drug chlorpromazine found that in some cases of schizophrenia, lower dosages may impart similar effects to higher ones, with low doses being favored due to the debilitating side effects associated with higher dosages.
Researchers from England and the Netherlands searched the Cochrane Schizophrenia Group's Study-Based Register of Trials on three different occasions (December '08, October '14, and December '16). They collected all relevant randomized controlled trials (RTCs) comparing doses of chlorpromazine in individuals with schizophrenia.
The final analysis included five studies with 1,132 participants. The longest trial only lasted for six months and the researchers found that all included trials carried at least a moderate risk of bias. Low, medium and high doses were defined as ≤400mg/day, 401mg/day to 800mg/day, and >800mg/day, respectively.
When low-dose chlorpromazine was compared to medium-dose chlorpromazine, no clear benefit was seen with one dose over another with regards to global and mental state outcomes. In addition, the likelihood of leaving the study early was no different between the two groups.
One study comparing low-dose to high-dose chlorpromazine in 416 individuals found clear evidence of greater improvement regarding global state in the higher-dose group, with significantly fewer individuals in the lower dose improving (RR 1.13, 95% CI 1.01 to 1.25). However, a significantly greater risk of extrapyramidal symptoms was identified in the high-dose group (RR 0.43. 95% CI 0.32 to 0.59).
There was a noticeable difference between the number of people leaving the study from each group for any reason, with significantly more people leaving from the high-dose group (RR 0.60, 95% CI 0.40 to 0.89, moderate-quality evidence). Compared to the medium- and high-dose groups, more individuals in the low-dose group left the study due to deterioration in behavior (RR 2.70, 95% CI 1.34 to 5.44, low-quality evidence).
The researchers highlight that although chlorpromazine is 1 of the 5 medicines listed by the World Health Organization (WHO) Model List of Essential Medicines used in psychotic disorders, and has been used for over 50 years, there is a dearth of high-grade evaluative studies concerning dosing. The gradual trend toward recommending lower dosages of chlorpromazine has arisen not due to trial based evidence, but rather clinical experience and consensus.
The authors of the study note how this approach to dosing lacks scientific rigor and does not, ‘allow for proper dissemination of information that would assist clinicians to find the optimum treatment dosage for their patients.' They go on to state that future medications should have data available from high-quality trials and studies to provide optimum treatment to patients in the shortest amount of time.
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