Prof. Lex Wunderink


Lex Wunderink Controversias Psiquiatria Barcelona
Talk Debate 2. Long term antipsychotic treatments can worsen life functional prognosis
Date Friday, April 21st, 2017
Time 16:45 - 17:15


Lex Wunderink, MD, is a clinical psychiatrist and head of the Department of Research and Education at Friesland Mental Health Services in The Netherlands. He is a research fellow at the University Medical Center Groningen, clinical director of the Friesland Early Intervention in Psychosis Program and the Northern Netherlands Consortium for Early Detection and Intervention. He completed his medical studies and his residency in psychiatry at the Erasmus University Medical Center in Rotterdam. He initiated one of the first large scaled assertive community care projects for the severely mentally ill in the early ’90s in the Rotterdam area.

His research and clinical work focus on the severely mentally ill, shifting from innovative care systems and assertive community treatment for the long-term severely mentally ill to treatment of first episode and high risk youth and detection and intervention in the early and prodromal phases of psychosis. His major research project, starting in 2002, was an RCT comparing the outcome of dose-reduction/discontinuation of antipsychotics with maintenance treatment in remitted first episode patients. Though the initial results did not ring the bell, the long-term results were striking, showing much better functional outcome in patients who received an early dose-reduction strategy compared to those who had been in maintenance treatment. These results inspired recently started replication studies in Copenhagen, Melbourne and The Netherlands.

At present his research is into the trajectories of the development of psychosis and associated severe mental illness, and the precursors of functional deficits. Other projects are development of a computerized adaptive screener for early detection and a trial on reduction of antipsychotic polypharmacy in long-term patients.

Lex Wunderink is head of residency training at Friesland MHS, authored or co-authored over 100 publications, is a reviewer for 7 peer-reviewed journals and an editorial board member of one. He is principal investigator, co-applicant or steering committee member of several national and international trials.


Background Long-term functional outcome of dose-reduction strategies in first episode psychosis (FEP) has not been studied before. Our study compared the 7-year outcome of an early antipsychotic dose-reduction/discontinuation (DR) strategy with maintenance treatment (MT). Primary outcome was recovery; relapse rates, functional and symptomatic remission were secondary outcomes.

Methods FEP patients (N=128) who were symptomatically remitted for 6 months during their first treatment year and who completed an 18 months trial comparing MT and DR were followed-up at 7 years. After completion of the trial treatment was left to the discretion of the attending clinician, during the five years until the 7 years follow-up. The original treatment strategy, MT or DR, and relevant baseline parameters were entered into a logistic regression analysis with symptomatic and functional remission and recovery at 7-years follow-up as dependent variables.

Results 103 patients were traced and willing to participate. DR-patients showed twice the recovery-rate of MT-patients (40% against 18%), OR 3.5 (P=.014). Symptomatic remission-rates were equal (69% and 67%). Better recovery-rates were attributable to higher functional remission-rates (46% vs. 20%) in DR. Predictors of recovery at 7 years of follow-up were DR strategy, less severe baseline negative symptoms and living together. During the last 2 years of follow-up the mean daily dose of antipsychotics in haloperidol equivalents was 2.20 mg in DR vs. 3.60 mg in MT (P=.031). Relapse-rates were initially higher in DR but leveled at 3 years; 61.5% relapsed in DR and 68.6% in MT in 7 years.

Conclusion DR strategy during the early stages of remitted FEP significantly improved 7-years outcome in terms of recovery and functional remission compared to maintenance treatment. Though initially the relapse-rates in DR were higher, these equaled those in MT from 3 years on to the end of the study. While the necessity of antipsychotic treatment to improve prognosis in FEP and to prevent relapse has been robustly demonstrated by many studies, we are faced with a dilemma concerning the drawbacks of long-term antipsychotic treatment on functional capacity. Though complete discontinuation is only feasible without relapse in a minority of patients, a personalized and guided dose-reduction strategy is clearly feasible and promotes functional recovery, doing justice to both sides of the dilemma.


[PDF] Alvarez-Jimenez M, et al. (2016). Beyond Clinical Remission in First Episode Psychosis: Thoughts on Antipsychotic Maintenance vs. Guided Discontinuation in the Functional Recovery Era. CNS Drugs. 2016 May;30(5):357-68. doi: 10.1007/s40263-016-0331-x.

[PDF] Wunderink L, et al. (2013). Recovery in Remitted First-Episode Psychosis at 7 Years of Follow-up of an Early Dose Reduction/Discontinuation or Maintenance Treatment Strategy.

[PDF] Wunderink L, Nienhuis FJ, Sytema S, Wiersma D. (2007). Predictive Validity of Proposed Remission Criteria in First-Episode Schizophrenic Patients Responding to Antipsychotics. Schizophr Bull. 2007 May; 33(3): 792–796.

[PDF] Wunderink L, Nienhuis FJ, Sytema S, Wiersma D. (2007). Guided discontinuation versus maintenance treatment in remitted first-episode psychosis: relapse rates and functional outcome. J Clin Psychiatry. 2007 May;68(5):654-61.