Treatment-ResistantSchizophrenia: TreatmentResponse and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology

Oliver D. Howes*, Rob McCutcheon, Ofer Agid, Andrea De Bartolomeis, Nico J.M. Van Beveren, Michael L. Birnbaum, Michael A.P. Bloomfield, Rodrigo A. Bressan, Robert W. Buchanan, William T. Carpenter, David J. Castle, Leslie Citrome, Zafiris J. Daskalakis, Michael Davidson, Richard J. Drake, Serdar Dursun, Bjørn H. Ebdrup, Helio Elkis, Peter Falkai, W. Wolfgang FleischackerAry Gadelha, Fiona Gaughran, Birte Y. Glenthøj, Ariel Graff-Guerrero, Jaime E.C. Hallak, William G. Honer, James Kennedy, Bruce J. Kinon, Stephen M. Lawrie, Jimmy Lee, F. Markus Leweke, James H. MacCabe, Carolyn B. McNabb, Herbert Meltzer, Hans Jürgen Möller, Shinchiro Nakajima, Christos Pantelis, Tiago Reis Marques, Gary Remington, Susan L. Rossell, Bruce R. Russell, Cynthia O. Siu, Takefumi Suzuki, Iris E. Sommer, David Taylor, Neil Thomas, Alp Üçok, Daniel Umbricht, James T.R. Walters, John Kane, Christoph U. Correll

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

667 Scopus citations


Objective: Research and clinical translation in schizophrenia is limited by inconsistent definitions of treatment resistance and response. To address this issue, the authors evaluated current approaches and then developed consensus criteria and guidelines. Method: A systematic review of randomized antipsychotic clinical trials in treatment-resistant schizophrenia was performed, and definitions of treatment resistance were extracted. Subsequently, consensus operationalized criteria were developed through 1) a multiphase, mixed methods approach, 2) identification of key criteria via an online survey, and 3) meetings to achieve consensus. Results: Of 2,808 studies identified, 42 met inclusion criteria. Of these, 21 studies (50%) did not provide operationalized criteria. In the remaining studies, criteria varied considerably, particularly regarding symptom severity, prior treatment duration, and antipsychotic dosage thresholds; only two studies (5%) utilized the same criteria. The consensus group identified minimum and optimal criteria, employing the following principles: 1) current symptoms of a minimum duration and severity determined by a standardized rating scale; 2) moderate or worse functional impairment; 3) prior treatment consisting of at least two different antipsychotic trials, each for a minimum duration and dosage; 4) systematic monitoring of adherence and meeting ofminimumadherence criteria; 5) ideally at least one prospective treatment trial; and 6) criteria that clearly separate responsive from treatment-resistant patients. Conclusions: There is considerable variation in current approaches to defining treatment resistance in schizophrenia. The authors present consensus guidelines that operationalize criteria for determining and reporting treatment resistance, adequate treatment, and treatment response, providing a benchmark for research and clinical translation.

Original languageEnglish (US)
Pages (from-to)216-229
Number of pages14
JournalAmerican Journal of Psychiatry
Issue number3
StatePublished - Mar 2017

ASJC Scopus subject areas

  • Psychiatry and Mental health


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