A meta-analysis of the response to chronic L-dopa in patients with schizophrenia: therapeutic and heuristic implications.

Rationale: While it is generally believed that administration of the dopamine precursor levodopa ( L-dopa) exacerbates symptoms of schizophrenia, numerous reports suggest that adjunctive L-dopa may be beneficial. This body of literature has not been critically reviewed.

Objectives: On the basis of published studies, to determine whether L-dopa administered concomitantly with antipsychotic drugs provides a beneficial response in patients with schizophrenia.

Methods: This review examined 30 studies involving 716 patients. Due to wide methodological variability and limited statistical information, only five studies encompassing 160 patients could be included in a meta-analysis. The others were evaluated qualitatively.

Results: When L-dopa was added to antipsychotic drugs, the overall improvement was moderate ( d=0.71) and highly significant ( P<0.0001). There were 16 other studies in which L-dopa was added to antipsychotic drugs, but which did not meet criteria for inclusion in the meta-analysis. In these, worsening occurred in less than 20% of patients; the percentage of improved patients varied widely but had a central tendency around 50%.

Conclusions: . In patients already on antipsychotic drugs, the addition of L-dopa can be beneficial. Dopamine agonists merit further consideration as adjuncts to antipsychotic drugs in the treatment of schizophrenia.