Abstract: We included 14 studies investigating the use of cholinergic drugs compared with placebo published between 1976 and 2014. All studies involved small numbers of participants (five to 60 people). Three studies that investigated the new cholinergic Alzheimer drugs for the treatment of TD are new to this update. Overall, the risk of bias in the included studies was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, studies were not clearly blinded, we are unsure if data are incomplete, and data were often poorly or selectively reported. We are uncertain about the effect of new or old cholinergic drugs on no clinically important improvement in TD symptoms when compared with placebo; the quality of evidence was very low (RR 0.89, 95% CI 0.65 to 1.23; 27 people, 4 RCTs). Eight trials found that cholinergic drugs may make little or no difference to deterioration of TD symptoms (low-quality evidence, RR 1.11, 95% CI 0.55 to 2.24; 147 people). Again, due to very low-quality evidence, we are uncertain about the effects on mental state (RR 0.50, 95% CI 0.10 to 2.61; 77 people, 5 RCTs), adverse events (RR 0.56, 95% CI 0.15 to 2.14; 106 people, 4 RCTs), and leaving the study early (RR 1.09,95% CI 0.56 to 2.10; 288 people 12 RCTs). No study reported on social confidence, social inclusion, social networks, or personalised quality of life. TD remains a major public health problem. The clinical effects of both older cholinergic drugs and new cholinergic agents, now used for treating Alzheimer's disease, are unclear, as too few, too small studies leave many questions unanswered. Cholinergic drugs should remain of interest to researchers and currently have little place in routine clinical work. However, with the advent of new cholinergic agents now used for treating Alzheimer's disease, scope exists for more informative trials. If these new cholinergic agents are to be investigated for treating people with TD, their effects should be demonstrated in large well-designed, conducted and reported randomised trials.

Plain-language summary: . We searched for trials in July 2015 and April 2017, using the Cochrane Schizophrenia Group's register of trials. The review includes 14 studies investigating the use of cholinergic drugs compared with placebo. All studies randomised small numbers of participants (five to 60 people) with schizophrenia or other chronic mental illnesses who had also developed antipsychotic-induced tardive dyskinesia. . We found the effects of both older and newer cholinergic drugs to be unclear as too few and too small studies are available and do not yield great evidence and leave many questions unanswered. . The available evidence is weak, limited, and small scale. It is not possible to recommend these drugs as a treatment for tardive dyskinesia based on our findings. To fully investigate whether the use of cholinergic drugs have any positive effects for people with tardive dyskinesia, there would have to be well-designed, larger, longer-term studies, particularly on new cholinergic drugs currently being used for treating Alzheimer’s disease. Ben Gray, Senior Peer Researcher, McPin Foundation. http://mcpin.org/