Anticholinergics vs Placebo for Neuroleptic-Induced Parkinsonism

Neuroleptic-induced parkinsonism is a common and distressing early onset adverse effect of treatment with antipsychotic drugs. It is associated with poor compliance and, therefore, an increased risk of relapse. We assessed the role of anticholinergic drugs as adjunctive therapy with standard antipsychotic medication in the pharmacological treatment of parkinsonism.

The aim of this systematic review was to assess the effects of anticholinergic drugs compared with placebo for antipsychotic-induced parkinsonism in people with schizophrenia.

We searched Cochrane Schizophrenia Group’s Register of Trials on October 2013 and again in May 2016.

We included all randomized clinical trials comparing any adjunctive anticholinergic drug with adjunctive placebo for people with schizophrenia experiencing neuroleptic-induced parkinsonism.

Review authors independently selected trials, assessed methodological quality, and extracted data. We used a random effect meta-analysis. Where possible, we calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) with 95% CIs for continuous measures.

There were 2 small trials including people with antipsychotic-induced parkinsonism to adjunctive placebo or adjunctive anticholinergic drugs (orphenadrine and procyclidine).

For the outcomes of “Parkinsonism—clinically important change in the medium term” we found no data. The proxy measure of ratings on the Extrapramidal Symptom Rating Scale (at 24 weeks) were highly skewed and difficult to interpret (1 randomized controlled trial [RCT], n = 48, very low quality). No trial reported “General functioning—clinically important change.” Regarding adverse effects, one very small trial (n = 24) reported no adverse effects in either group (vs orphenadrine, low-quality data). Regarding general mental state, we found no usable data. The proxy measure of ratings of hostile suspiciousness factor of the Brief Psychiatric Rating Scale showed no difference (vs procyclidine, n = 48, 1 RCT, MD 0.1, 95% CI −0.19 to 0.39, very low-quality data). No trial reported quality of life. For leaving the study early, more people left early from the placebo groups (n = 72, 2 RCTs, RR 0.14, 95% CI 0.03 to 0.58, moderate quality data).

This review highlights the need for well-designed, conducted, and reported clinical trials to support the common use of anticholinergic drugs in the treatment of antipsychotic-induced parkinsonism. Antipsychotic-induced parkinsonism occurs frequently, yet clinician’s current decisions for treatment are based on consensus guidelines and long-established clinical practice rather than good quality evidence from randomized trials. Full details are reported in Dickenson et al.¹