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Adjunctive Therapy With Levodopa May Be Beneficial in Patients with Schizophrenia

The addition of levodopa (L-dopa) to treatment appears moderately beneficial in patients with schizophrenia who are already taking antipsychotic drugs (APDs), according to a new study.

Previous research results are conflicting regarding the effect of L-dopa, a dopamine precursor, on schizophrenic symptoms. While some findings show that administration of L-dopa exacerbates symptoms, other studies report that L-dopa as an adjunctive therapy is beneficial in treatment-resistant patients.

Led by George E. Jaskiw, MD, of the Louis Stokes Cleveland Department of Veterans Affairs Medical Centre, Brecksville, Ohio, United States, researchers performed an analysis of data collected from 30 previous studies to determine whether L-dopa administered concomitantly with antipsychotic drugs provides a beneficial response in patients with schizophrenia.

The studies were identified through a computer based literature search, and involved a total of 716 patients. Due to considerable methodological variability between studies, 5 (160 patients) were included in a meta-analysis and the remaining studies were evaluated qualitatively.

Meta analysis results showed that the effect sizes (Cohen's d) for the L-dopa response were heterogeneous and all were in the same direction. The overall composite effect size was moderate (d = .71) and highly significant (P < .00001).

In the 16 other studies in which L-dopa was added to antipsychotic drugs, a plot of the percentage of patients who improved against sample size showed that studies with a small sample size had a wide improvement range, but with a central tendency around 50%.

Alternatively, a plot of sample size against the percentage of patients who worsened when L-dopa was added to antipsychotic drugs demonstrated that less than 20% of patients showed worsening.

Regarding the clinical implications of the study, the investigators say that there is no evidence that administering L-dopa to APD-free patients is therapeutic, and conclude that high dose L-dopa should not be administered to APD-free patients without a highly compelling reason. Additionally, any role of L-dopa as an adjunct for schizophrenics with an inadequate APD response remains to be defined.

"We are not recommending that clinicians routinely combine L-dopa with typical or atypical APDs for patients with schizophrenia who are poor or partial treatment responders," the researchers said. "Nonetheless, further evaluation of L-dopa and other DA agonists as adjunctive treatments for schizophrenia is certainly warranted."


Psychopharmacology (Berl) 2004 Feb;171:4:365-74. Epub 2003 Dec 11. "A meta-analysis of the response to chronic l-dopa in patients with schizophrenia: therapeutic and heuristic implications"

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