A Cochrane review [Abstract] 1 included 31 RCTs of 24 interventions with a total of 1278 participants. All participants were adults with chronic psychiatric disorders, mostly schizophrenia, and antipsychotic-induced TD. Studies were primarily of short (3 to 6 weeks) duration. Nineteen of the 31 included studies reported on the primary outcome 'No clinically important improvement in TD symptoms'. Two studies found benefit of the intervention vs. placebo: valbenazine (RR 0.63, 95% CI 0.46 to 0.86, 1 RCT, n = 92) and extract of Ginkgo biloba (RR 0.88, 95% CI 0.81 to 0.96, 1 RCT, n = 157), respectively. Some evidence of a benefit was found for buspirone (RR 0.53, 95% CI 0.33 to 0.84, 1 RCT, n = 42), dihydrogenated ergot alkaloids (RR 0.45, 95% CI 0.21 to 0.97, 1 RCT, n = 28), hypnosis or relaxation, (RR 0.45, 95% CI 0.21 to 0.94, 1 study, n = 15), pemoline (RR 0.48, 95% CI 0.29 to 0.77, 1 RCT, n = 46), promethazine (RR 0.24, 95% CI 0.11 to 0.55, 1 RCT, n = 34), insulin (RR 0.52, 95% CI 0.29 to 0.96, 1 RCT, n = 20), branched chain amino acids (RR 0.79, 95% CI 0.63 to 1.00, 1 RCT, n = 52), and isocarboxazid (RR 0.24, 95% CI 0.08 to 0.71, 1 RCT, n = 20). There was no evidence of difference between intervention and placebo or no treatment for the following interventions: melatonin (RR 0.89, 95% CI 0.71 to 1.12, 2 RCTs, n = 32), lithium (RR 1.59, 95% CI 0.79 to 3.23, 1 RCT, n = 11), ritanserin (RR 1.00, 95% CI 0.70 to 1.43, 1 RCT, n = 10), selegiline (RR 1.37, 95% CI 0.96 to 1.94, 1 RCT, n = 33), oestrogen (RR 1.18, 95% CI 0.76 to 1.83, 1 RCT, n = 12), and gamma-linolenic acid (RR 1.00, 95% CI 0.69 to 1.45, 1 RCT, n = 16).
Comment: The quality of evidence is downgraded by study quality (inadequate or unclear allocation concealment), imprecise results (few patients and wide confidence intervals) and indirectness (most are very old studies).
Another Cochrane review [Abstract] 2 included 3 studies with 80 inpatients with schizophrenia. They were aged 18 to 71 years and followed up for a period 9 to 26 weeks. Overall, pyridoxal 5 phosphate (P5P) produced a significant improvement in tardive dyskinesia symptoms when compared with placebo, assessed by a change in Extrapyramidal Symptoms Rating Scale (ESRS) scores from baseline to the end of the first phase of the included studies (RR 19.97, CI 2.87 to 139.19; 2 RCTs, n = 65). The endpoint tardive dyskinesia score (a measure of its severity) assessed with the ESRS, was significantly lower among participants on P5P (MD -4.07, CI -6.36 to -1.79; 2 RCTs, n = 60).It was unclear whether P5P led to more side effects (RR 3.97, CI 0.20 to 78.59; 2 RCTs, n = 65) or caused deterioration in tardive dyskinesia symptoms when compared to placebo (RR 0.16, CI 0.01 to 3.14; 2 RCTs, n = 65). Five patients on P5P and none on placebo withdrew from the study because they were not willing to take more medications (RR 8.72, CI 0.51 to 149.75; 2 RCTs, n = 65).There was no significant difference in the Positive and Negative symptoms Scale (PANSS) between participants taking P5P and those taking placebo. For the positive symptoms: (MD -1.50, CI -4.80 to 1.80; 1 RCT, n = 15). For the negative symptoms: (MD -1.10, CI -5.92 to 3.72; n = 15, 1 RCT).
Comment: The quality of evidence is downgraded by imprecise results (few patients and wide confidence intervals) and indirectness (short follow-up time).
The third Cochrane review [Abstract] 3 included 14 studies, which involved small numbers of patients (5 to 60 people). Only 4 studies had a duration longer than 6 weeks. The effect of new or old cholinergic drugs on no clinically important improvement in TD symptoms as compared with placebo is not clear (RR 0.89, 95% CI 0.65 to 1.23; 4 RCTs, n=27). Eight trials found that cholinergic drugs may make little or no difference to deterioration of TD symptoms (RR 1.11, 95% CI 0.55 to 2.24; n=147). The effects on mental state is not clear, either (RR 0.50, 95% CI 0.10 to 2.61; 5 RCTs, n=77), as seen also for adverse events (RR 0.56, 95% CI 0.15 to 2.14; 4 RCTs, n=106) and leaving the study early (RR 1.09,95% CI 0.56 to 2.10; 12 RCTs, n=288).
Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment), indirectness (short follow-up time), imprecise results (few patients and wide confidence intervals) and indirectness (short follow-up time).
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