This article was published on May 14, 2022
The reason it is important for mental health clinicians to explicitly identify some patients with schizophrenia as being “treatment-resistant” is that this will (or, should) trigger a process of evaluation and treatment that should not be delayed. On other pages on this website, we’ll discuss what that specific evaluation and treatment should consist of.
What do we mean by “treatment-resistant” schizophrenia?
I don’t like the term “treatment-resistant” schizophrenia but it is widely used and is convenient.
Experts don’t always agree on when to call a case of schizophrenia “treatment-resistant”. Many practice guidelines use the following definition:
Schizophrenia is considered to be “treatment-resistant” if it has not responded to at least two antipsychotic trials of sufficient dose and duration. (Howes et al., 2017; Kinon, 2019).
1. At least TWO antipsychotic trials
(Some, but not all, experts add that at least one of those antipsychotics should have been a second-generation antipsychotic.)
How is sufficient dose and duration—an adequate treatment trial—defined for this purpose?
2. Sufficient duration: 6 weeks or more (at a sufficient dose)
3. Sufficient dose: The dose of the antipsychotic should have been equivalent to 600 mg or more of chlorpromazine.
For an explanation of equivalent doses of antipsychotics, please see the following articles on this website:
Second-Generation Antipsychotics: Dose Equivalents
Dose equivalents of long-acting injectable second-generation antipsychotics
4. Adherence: Obviously, an adequate treatment trial would need one more thing—that the patient actually took the medication! That has to be verified in some way—if necessary, by plasma levels or by using a long-acting injectable antipsychotic.
How common is it?
A review of studies of first-episode psychosis reported the worrisome statistic that nearly a quarter of patients with first-episode psychosis or schizophrenia develop treatment-resistant schizophrenia (Siskind et al., 2022).
And, if those who later relapse are included, about one-third of patients are “treatment-resistant” (Siskind et al., 2022).
Are you surprised by how common “treatment-resistant” schizophrenia is?
When is schizophrenia more likely to be treatment-resistant?
The most consistently reported predictor of schizophrenia becoming treatment-resistant is a younger age of onset (Smart et al., 2021).
Related Pages
Let’s explicitly identify patients with “treatment-resistant” schizophrenia
Second-generation antipsychotics: Dose equivalents
Dose equivalents of long-acting injectable second-generation antipsychotics
References
Elkis H, Buckley PF. Treatment-Resistant Schizophrenia. Psychiatr Clin North Am. 2016 Jun;39(2):239-65. doi: 10.1016/j.psc.2016.01.006. Epub 2016 Mar 30. PMID: 27216902.
Howes OD, McCutcheon R, Agid O, de Bartolomeis A, van Beveren NJ, Birnbaum ML, Bloomfield MA, 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 JE, Honer WG, Kennedy J, Kinon BJ, Lawrie SM, Lee J, Leweke FM, MacCabe JH, McNabb CB, Meltzer H, Möller HJ, 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 JT, Kane J, Correll CU. Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology. Am J Psychiatry. 2017 Mar 1;174(3):216-229. doi: 10.1176/appi.ajp.2016.16050503. Epub 2016 Dec 6. PMID: 27919182; PMCID: PMC6231547.
Lally J, Gaughran F. Treatment resistant schizophrenia – review and a call to action. Ir J Psychol Med. 2019 Dec;36(4):279-291. doi: 10.1017/ipm.2018.47. Epub 2018 Nov 27. PMID: 30477599.
Nucifora FC Jr, Woznica E, Lee BJ, Cascella N, Sawa A. Treatment resistant schizophrenia: Clinical, biological, and therapeutic perspectives. Neurobiol Dis. 2019 Nov;131:104257. doi: 10.1016/j.nbd.2018.08.016. Epub 2018 Aug 29. PMID: 30170114; PMCID: PMC6395548.
Siskind D, Orr S, Sinha S, Yu O, Brijball B, Warren N, MacCabe JH, Smart SE, Kisely S. Rates of treatment-resistant schizophrenia from first-episode cohorts: systematic review and meta-analysis. Br J Psychiatry. 2022 Mar;220(3):115-120. doi: 10.1192/bjp.2021.61. PMID: 35049446.
Smart SE, Kępińska AP, Murray RM, MacCabe JH. Predictors of treatment resistant schizophrenia: a systematic review of prospective observational studies. Psychol Med. 2021 Jan;51(1):44-53. doi: 10.1017/S0033291719002083. Epub 2019 Aug 29. PMID: 31462334; PMCID: PMC7856410.
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