The International Journal of Neuropsychopharmacology


Evidence-based pharmacotherapy of schizophrenia

Stefan Leuchta1 c1, Stephan Heresa1, Werner Kisslinga1 and John M. Davisa2

a1 Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, München, Germany

a2 Department of Psychiatry, University of Illinois at Chicago, IL, USA


We describe the pharmacological treatment of schizophrenia and have arranged the manuscript as a simple algorithm which starts from the choice of an antipsychotic drug for an acutely ill patient and concludes with the most important questions about maintenance treatment. In acutely ill patients the choice of drug is mainly based on pragmatic criteria. Among many strategies used for agitated patients, haloperidol plus promethazine is the best examined one. In case of persistent depression or negative symptoms treatment includes antidepressants, and some second-generation antipsychotic drugs (SGAs) have been found somewhat superior to first-generation antipsychotic drugs (FGAs) in these domains. If an antipsychotic is suspected to be ineffective, several factors need to be checked before action is taken. Few trials have addressed strategies such as switching the drug or increasing the dose in case of non-response. Clozapine remains the gold-standard for treatment-refractory patients, while none of the numerous augmentation strategies that have been examined by randomized controlled trials can be generally recommended. Maintenance treatment with antipsychotic drugs effectively reduces relapse rates. Small, not definitive, studies have shown that withdrawing antipsychotics from patients who have been stable for up to 6 yr leads to more relapses than continuing medication. In effect, continuous treatment is more effective than intermittent strategies. The identification of optimum doses for relapse prevention with FGAs has proven difficult, and there is little randomized data on SGAs. Although the randomized evidence on a superiority of depot compared to oral treatment is not ideal, this approach suggests obvious advantages in assuring compliance.

(Received March 15 2010)

(Reviewed May 26 2010)

(Revised October 11 2010)

(Accepted October 28 2010)

(Online publication January 06 2011)


c1 Address for correspondence: S. Leucht, M.D., Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 München, Germany. Tel.: 49-89-4140-4249 Fax: 49-89-4140-4888 Email: