Amisulpride - dose, plasma concentration, occupancy and response: implications for therapeutic drug monitoring

Objective: To evaluate the relationships between dose, plasma concentration, pharmacological activity and clinical outcome to evaluate the appropriateness of therapeutic drug monitoring (TDM) in patients receiving amisulpride. Method: Literature search of Embase, Medline and PubMed databases. Results: Amisulpride plasma concentration is closely correlated with dose (r2 = 0.96, P < 0.0001), dopamine occupancy, response and with extra-pyramidal symptoms (EPS). Dose is correlated with response, dopamine occupancy and EPS. Optimal clinical response was found at doses of 400-800 mg/day, corresponding to plasma levels of approximately 200-500 ng/ml. EPS appears to be more reliably predicted by a plasma level above 320 ng/ml than by a particular dose. Conclusion: The effects and safety of amisulpride in the treatment of schizophrenia and schizoaffective disorder are predicted by daily dose. The plasma concentration threshold for response appears to be approximately 200 ng/ml. EPS are more reliably predicted by plasma level than by dose. TDM for patients prescribed amisulpride is thus of some clinical value.