Substance abuse is associated with increased extrapyramidal symptoms in schizophrenia: a meta-analysis

Psychoactive substances (PAS) may interact with antipsychotics in the development of extrapyramidal symptoms (EPS) in schizophrenia. PAS exert acute and chronic impacts on the basal ganglia. Clinical data have been gathered about the effects of PAS on EPS in schizophrenia, producing inconsistent results. This meta-analysis sought to determine whether PAS enhance EPS in schizophrenia patients.

A search of the literature using computerized engines was undertaken. Studies were retained in the analysis if: (i) they included schizophrenia patients with and without substance abuse; and (ii) they comprised a measure of EPS using valid instruments.

Sixteen studies available were identified, involving 3479 patients. The composite analysis revealed a small and positive effect size (g=0.260), suggesting increased EPS in substance-abusing patients. Cocaine was associated with the largest effect size estimate (g=0.613). Dual diagnosis patients were more frequently males than single diagnosis patients. Thus, we performed a sub-analysis of studies with no confounders (e.g. age, sex and/or symptoms). The pooling of these 10 studies produced a moderate and positive effect size (g=0.401).

Our results show that PAS negatively impact on EPS in schizophrenia, especially when potential confounding factors are controlled. Cocaine emerged as the PAS with the most deleterious effects on EPS in schizophrenia. Our results have implications for the prevention of EPS in schizophrenia and for the design of future studies on the topic.