Abstract: The previous version of this review included no trials. We identified two trials that could be included from the 2015 and 2017 searches. They randomised 30 in- and outpatients with schizophrenia in the USA and Germany. Overall, the risk of bias was unclear, mainly due to poor reporting: allocation concealment was not described; generation of the sequence was not explicit; studies were not clearly blinded; and outcome data were not fully reported. Findings were sparse. One study reported on the primary outcomes and found that significantly more participants allocated to procyclidine (anticholinergic) had not improved to a clinically important extent compared with those allocated to isocarboxazid (MAO-inhibitor) after 40 weeks' treatment (1 RCT, n = 20; RR 4.20, 95% CI 1.40 to 12.58; very low quality evidence); that there was no evidence of a difference in the incidence of any adverse effects (1 RCT, n = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence); or acceptability of treatment (measured by participants leaving the study early) (1 RCT, n = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence). The other trial compared anticholinergic withdrawal with anticholinergic continuation and found no evidence of a difference in the incidence of acceptability of treatment (measured by participants leaving the study early) (1 RCT, n = 10; RR 2.14, 95% CI 0.11 to 42.52; very low quality evidence). No trials reported on social confidence, social inclusion, social networks, or personalised quality of life — outcomes designated important to patients. No studies comparing either i. anticholinergics with placebo or no treatment, or ii. studies of anticholinergic withdrawal, were found that reported on the primary outcome 'no clinically important improvement in TD symptoms and adverse events'. Based on currently available evidence, no confident statement can be made about the effectiveness of anticholinergics to treat people with antipsychotic-induced tardive dyskinesia. The same applies for the withdrawal of such medications. Whether the withdrawal of anticholinergics may benefit people with antipsychotic-induced TD should be evaluated in a parallel-group, placebo-controlled randomised trial, with adequate sample size and at least 6 weeks of follow-up.

Plain-language summary: . The review includes two small randomised studies with a total of 30 people with schizophrenia who had also developed antipsychotic-induced tardive dyskinesia. Participants in one study received either the anticholinergic drug procyclidine or isocarboxacid, an antidepressant drug. One participant group in the other study was withdrawn from the anticholinergic drug biperiden whereas the other group of participants continued taking biperiden. . There were sparse findings from two small and poorly reported trials. It is uncertain whether giving anticholinergic drugs is helpful in the treatment of tardive dyskinesia for people who are taking antipsychotic medication. It is also uncertain whether the withdrawal of anticholinergic medication improves the symptoms of tardive dyskinesia. . Available evidence is very low or low quality, limited, and small scale. It is not possible to recommend these drugs or the withdrawal of these drugs as a treatment for tardive dyskinesia. To fully investigate whether the withdrawal of anticholinergic drugs has any positive effects for people with tardive dyskinesia, we need more high quality research data. This plain language summary was adapted by the review authors from a summary originally written by Ben Gray, Senior Peer Researcher, McPin Foundation (mcpin.org).