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; Christoph U Correll

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, Christoph U Correll

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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.

Original language	English
Pages (from-to)	216-229
Journal	The American Journal of Psychiatry
Volume	174
Issue number	3
Early online date	6 Dec 2016
DOIs	https://doi.org/10.1176/appi.ajp.2016.16050503
Publication status	Published - 1 Mar 2017

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Treatment-Resistant Schizophrenia_HOWES_Accepted8SEp2016_GREEN AAMAccepted author manuscript, 1.58 MB

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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., ... Correll, C. U. (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

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

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.",

author = "Howes, {Oliver D} and Rob McCutcheon and Ofer Agid and {de Bartolomeis}, Andrea and {van Beveren}, {Nico J M} and Birnbaum, {Michael L} and Bloomfield, {Michael A P} and Bressan, {Rodrigo A} and Buchanan, {Robert W} and Carpenter, {William T} and Castle, {David J} and Leslie Citrome and Daskalakis, {Zafiris J} and Michael Davidson and Drake, {Richard J} and Serdar Dursun and Ebdrup, {Bj{\o}rn H} and Helio Elkis and Peter Falkai and Fleischacker, {W Wolfgang} and Ary Gadelha and Fiona Gaughran and Glenth{\o}j, {Birte Y} and Ariel Graff-Guerrero and Hallak, {Jaime E C} and Honer, {William G} and James Kennedy and Kinon, {Bruce J} and Lawrie, {Stephen M} and Jimmy Lee and Leweke, {F Markus} and MacCabe, {James H} and McNabb, {Carolyn B} and Herbert Meltzer and Hans-J{\"u}rgen M{\"o}ller and Shinchiro Nakajima and Christos Pantelis and {Reis Marques}, Tiago and Gary Remington and Rossell, {Susan L} and Russell, {Bruce R} and Siu, {Cynthia O} and Takefumi Suzuki and Sommer, {Iris E} and David Taylor and Neil Thomas and Alp {\"U}{\c c}ok and Daniel Umbricht and Walters, {James T R} and John Kane and Correll, {Christoph U}",

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doi = "10.1176/appi.ajp.2016.16050503",

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journal = "The American Journal of Psychiatry",

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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 & Correll, CU 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

TY - JOUR

T1 - Treatment-Resistant Schizophrenia

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

AU - Correll, Christoph U

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.

U2 - 10.1176/appi.ajp.2016.16050503

DO - 10.1176/appi.ajp.2016.16050503

M3 - Article

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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