We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CIs). We assumed that people who left early had no improvement. We assessed risk of bias and created 'Summary of findings' tables using GRADE.
MAIN RESULTS: We included 31 RCTs of 24 interventions with 1278 participants; 22 of these trials were newly included in this 2017 update. Five trials are awaiting classification and seven trials are ongoing. All participants were adults with chronic
psychiatric disorders, mostly
schizophrenia, and
antipsychotic-induced TD. Studies were primarily of short (three to six6 weeks) duration with small samples size (10 to 157 participants), and most (61%) were published more than 20 years ago. The overall risk of bias in these studies was unclear, mainly due to poor reporting of allocation concealment, generation of the sequence, and blinding.Nineteen of the 31 included studies reported on the primary outcome 'No clinically important improvement in TD symptoms'. Two studies found moderate-quality evidence of a benefit of the intervention compared with 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. However, due to small sample sizes we cannot be certain of these effects.We consider the results for the remaining interventions to be inconclusive: Low- to very low-quality 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 low- to very low-certainty evidence of no 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).None of the included studies reported on the other primary outcome, 'no clinically significant extrapyramidal adverse effects'.
AUTHORS' CONCLUSIONS: