A novel approach to measuring response and remission in schizophrenia in clinical trials.
Pharmaceutical companies conduct clinical trials to show the efficacy and safety of new medications for the treatment of schizophrenia. After the new medications are marketed, clinicians treating patients with schizophrenia discover that a considerable number of patients do not respond to these new medications. The goals of the review are to examine the methodology and design of recent antipsychotic clinical trials, identify common flaws, and propose guidelines to fix the flaws and improve the quality of future clinical trials of antipsychotic medications.



A review of recent antipsychotic clinical trials was conducted using a PubMed search. Ten recent trials published in the past four years were reviewed and their methods analyzed and critiqued.



The authors identified six major methodological flaws that may explain the suboptimal response in many patients after a drug is approved. Most of the flaws are related to eligibility criteria, the misuse of the Positive and Negative Syndromes Scale (PANSS) and the lack of consensus on how to define remission, response and exacerbation in schizophrenia. Proposed guidelines for a more rigorous use of the PANSS are presented and recommendations are proposed for using uniform criteria for remission, response and exacerbation in schizophrenia.



The authors recommend using standardized diagnostic interviews to screen patients for eligibility criteria and using the PANSS according to the author's recommendations and the proposed guidelines. Uniform criteria to define remission, response and exacerbation are recommended for clinical trials examining the efficacy and safety of antipsychotic drugs in schizophrenia.
Chief of Psychiatry, William R. Sharpe, Jr. Hospital. Clinical Professor of Psychiatry, West Virginia School of Osteopathic Medicine. Adjunct faculty, School of Public Health, West Virginia University (WVU), USA. Electronic address: ahmed.s.aboraya@wv.gov.
Ahmed
A
Aboraya
Dept. of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Germany Ismaningerstr. 22, 81675 München, Germany.
Stefan
S
Leucht
The Sydney Souers Professor and Chairman Department of Psychiatry and Behavioral Neuroscience Saint Louis University School of Medicine St. Louis MO, USA.
Henry A
HA
Nasrallah
Department of Psychiatry and Psychotherapy, Technische Universität München, München, Germany.
Myrto
M
Samara
Parc Sanitari Sant Joan de Déu Dr. Antoni Pujadas, 42 08830 - Sant Boi de Llobregat Barcelona, Spain.
Josep Maria
JM
Haro
Atlanticare Regional Medical Center 1925 Pacific Ave Atlantic City, NJ, USA.
Ahmed
A
Elshazly
Editor-in-Chief, International Journal of Mental Health & Addiction Consultant, Kuwait Center for Autism, Kuwait.
Masood
M
Zangeneh
D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods*; D006801:Humans; D017410:Practice Guidelines as Topic; D058996:Quality Improvement; D012074:Remission Induction; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome
D014150:Antipsychotic Agents
Clinical trials; Exacerbation; Rating scales; Remission; Response; Structured Clinical Interview