Treatment-Resistant Schizophrenia: Treatment Response 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 Fleischacker; Ary 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

doi:10.1176/appi.ajp.2016.16050503

Treatment-Resistant Schizophrenia: Treatment Response 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

Department of Clinical Medicine

280 Citations (Scopus)

Abstract

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 of minimum adherence 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 language	English
Journal	The American Journal of Psychiatry
Volume	174
Issue number	3
Pages (from-to)	216-229
Number of pages	14
ISSN	0002-953X
DOIs	https://doi.org/10.1176/appi.ajp.2016.16050503
Publication status	Published - 1 Mar 2017

Keywords

Antipsychotic Agents/therapeutic use
Brief Psychiatric Rating Scale/statistics & numerical data
Drug Resistance
Humans
Practice Guidelines as Topic
Psychometrics
Randomized Controlled Trials as Topic
Schizophrenia/diagnosis
Schizophrenic Psychology

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Howes, O. D., McCutcheon, R., Agid, O., de Bartolomeis, A., van Beveren, N. J. M., Birnbaum, M. L., Bloomfield, M. A. P., Bressan, R. A., Buchanan, R. W., Carpenter, W. T., Castle, D. J., Citrome, L., Daskalakis, Z. J., Davidson, M., Drake, R. J., Dursun, S., Ebdrup, B. H., Elkis, H., Falkai, P., ... Kane, J. (2017). Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology. The American Journal of Psychiatry, 174(3), 216-229. https://doi.org/10.1176/appi.ajp.2016.16050503

Howes, OD, McCutcheon, R, Agid, O, de Bartolomeis, A, van Beveren, NJM, Birnbaum, ML, Bloomfield, MAP, Bressan, RA, Buchanan, RW, Carpenter, WT, Castle, DJ, Citrome, L, Daskalakis, ZJ, Davidson, M, Drake, RJ, Dursun, S, Ebdrup, BH, Elkis, H, Falkai, P, Fleischacker, WW, Gadelha, A, Gaughran, F, Glenthøj, BY, Graff-Guerrero, A, Hallak, JEC, Honer, WG, Kennedy, J, Kinon, BJ, Lawrie, SM, Lee, J, Leweke, FM, MacCabe, JH, McNabb, CB, Meltzer, H, Möller, H-J, Nakajima, S, Pantelis, C, Reis Marques, T, Remington, G, Rossell, SL, Russell, BR, Siu, CO, Suzuki, T, Sommer, IE, Taylor, D, Thomas, N, Üçok, A, Umbricht, D, Walters, JTR & Kane, J 2017, 'Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology', The American Journal of Psychiatry, vol. 174, no. 3, pp. 216-229. https://doi.org/10.1176/appi.ajp.2016.16050503

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abstract = "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 of minimum adherence 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.",

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T2 - Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology

AU - Howes, Oliver D

AU - McCutcheon, Rob

AU - Agid, Ofer

AU - de Bartolomeis, Andrea

AU - van Beveren, Nico J M

AU - Birnbaum, Michael L

AU - Bloomfield, Michael A P

AU - Bressan, Rodrigo A

AU - Buchanan, Robert W

AU - Carpenter, William T

AU - Castle, David J

AU - Citrome, Leslie

AU - Daskalakis, Zafiris J

AU - Davidson, Michael

AU - Drake, Richard J

AU - Dursun, Serdar

AU - Ebdrup, Bjørn H

AU - Elkis, Helio

AU - Falkai, Peter

AU - Fleischacker, W Wolfgang

AU - Gadelha, Ary

AU - Gaughran, Fiona

AU - Glenthøj, Birte Y

AU - Graff-Guerrero, Ariel

AU - Hallak, Jaime E C

AU - Honer, William G

AU - Kennedy, James

AU - Kinon, Bruce J

AU - Lawrie, Stephen M

AU - Lee, Jimmy

AU - Leweke, F Markus

AU - MacCabe, James H

AU - McNabb, Carolyn B

AU - Meltzer, Herbert

AU - Möller, Hans-Jürgen

AU - Nakajima, Shinchiro

AU - Pantelis, Christos

AU - Reis Marques, Tiago

AU - Remington, Gary

AU - Rossell, Susan L

AU - Russell, Bruce R

AU - Siu, Cynthia O

AU - Suzuki, Takefumi

AU - Sommer, Iris E

AU - Taylor, David

AU - Thomas, Neil

AU - Üçok, Alp

AU - Umbricht, Daniel

AU - Walters, James T R

AU - Kane, John

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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 of minimum adherence 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.

AB - 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 of minimum adherence 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.

KW - Antipsychotic Agents/therapeutic use

KW - Brief Psychiatric Rating Scale/statistics & numerical data

KW - Drug Resistance

KW - Humans

KW - Practice Guidelines as Topic

KW - Psychometrics

KW - Randomized Controlled Trials as Topic

KW - Schizophrenia/diagnosis

KW - Schizophrenic Psychology

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DO - 10.1176/appi.ajp.2016.16050503

M3 - Review

C2 - 27919182

SN - 0002-953X

VL - 174

SP - 216

EP - 229

JO - The American Journal of Psychiatry

JF - The American Journal of Psychiatry

IS - 3

ER -

Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology

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