Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Psychiatry
Published in: BMC Psychiatry 1/2019

Open Access 01-12-2019 | Schizophrenia | Research article

Patient characteristics, burden and pharmacotherapy of treatment-resistant schizophrenia: results from a survey of 204 US psychiatrists

Authors: Christoph U. Correll, Thomas Brevig, Cecilia Brain

Published in: BMC Psychiatry | Issue 1/2019

Login to get access

Abstract

Background

Minimal/non-response to antipsychotic treatment, and persistent positive symptoms despite treatment, are common among patients with schizophrenia. The aim of this study was to characterize a US treatment-resistant schizophrenia (TRS) population in terms of patient demographics, burden of symptoms, treatment history, and factors influencing therapeutic choice.

Methods

In an online survey, 204 psychiatrists self-selected and completed three patient records: two TRS and one schizophrenia (‘non-TRS’).

Results

Respondents reported that 29.5% of their schizophrenia caseload had TRS. Selected TRS (n = 408) vs non-TRS (n = 204) patients were more likely to be unemployed (74.5% vs 45.1%, p < 0.001), hospitalized at least once (93.4% vs 74.0%, p < 0.001), and to have physical/psychiatric comorbidities including obesity (40.2% vs 23.5%, p < 0.001) and depression (38.7% vs 25.0%, p = 0.001). Psychiatric symptoms were more frequent and severe in TRS, and interfered more with social and functioning domains. Of positive symptoms, eliminating delusions and hallucinations was considered most important to improve a patient’s long-term prognosis. In TRS, clozapine monotherapy was the most common treatment (15.9%), though ranked fifth of ten options to treat TRS. Psychiatrists typically increased the antipsychotic dose or added a second antipsychotic before initiating clozapine or switching antipsychotics. Antipsychotic switches were most commonly due to lack of efficacy (TRS = 71.4% vs non-TRS = 54.3%, p < 0.001) and intolerability (34.4% vs 38.4%, p = 0.22) with the prior antipsychotic. Persistent hallucinatory behavior was the top symptom leading to treatment switches in TRS (63.9% vs 37.1%, p < 0.001).

Conclusions

According to psychiatrists, symptoms have a greater clinical burden on patients with TRS than non-TRS. TRS is commonly managed by antipsychotic dose increases/combinations, with clozapine the fifth preference despite being the only approved TRS medication. New treatments are needed for patients who do not respond to available antipsychotics.
Appendix
Available only for authorised users
Literature
1.
Kahn RS, Sommer IE, Murray RM, Meyer-Lindenberg A, Weinberger DR, Cannon TD, et al. Schizophrenia. Nat Rev Dis Primers. 2015;1:15067.PubMedCrossRef
2.
Lehman AF, Lieberman JA, Dixon LB, McGlashan TH, Miller AL, Perkins DO, et al. American Psychiatric Association; Steering Committee on Practice Guidelines. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004;161(2 Suppl):1–56.PubMed
3.
Tiihonen J, Mittendorfer-Rutz E, Majak M, Mehtälä J, Hoti F, Jedenius E, et al. Real-world effectiveness of antipsychotic treatments in a nationwide cohort of 29 823 patients with schizophrenia. JAMA Psychiatry. 2017;74:686–93.PubMedPubMedCentralCrossRef
4.
Taipale H, Mehtälä J, Tanskanen A, Tiihonen J. Comparative effectiveness of antipsychotic drugs for rehospitalization in schizophrenia – a nationwide study with 20-year follow-up. Schizophr Bull. 2018;44:1381–7.PubMedCrossRef
5.
Carbon M, Correll CU. Clinical predictors of therapeutic response to antipsychotics in schizophrenia. Dialogues Clin Neurosci. 2014;16:505–24.PubMedPubMedCentral
6.
7.
Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry. 2012;13:318–78.PubMedCrossRef
8.
Howes OD, McCutcheon R, Agid O, de Bartolomeis A, van Beveren NJ, Birnbaum ML, et al. Treatment-resistant schizophrenia: treatment response and resistance in psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology. Am J Psychiatry. 2017;174:216–29.PubMedCrossRef
9.
Conley RR, Kelly DL. Management of treatment resistance in schizophrenia. Biol Psychiatry. 2001;50:898–911.PubMedCrossRef
10.
Meltzer HY. Treatment-resistant schizophrenia – the role of clozapine. Curr Med Res Opin. 1997;14:1–20.PubMedCrossRef
11.
12.
Lally J, MacCabe JH. Antipsychotic medication in schizophrenia: a review. Br Med Bull. 2015;114:169–79.PubMedCrossRef
13.
Wimberley T, Støvring H, Sørensen HJ, Horsdal HT, MacCabe JH, Gasse C. Predictors of treatment resistance in patients with schizophrenia: a population-based cohort study. Lancet Psychiatry. 2016;3:358–66.PubMedCrossRef
14.
Iasevoli F, Giordano S, Balletta R, Latte G, Formato MV, Prinzivalli E, et al. Treatment resistant schizophrenia is associated with the worst community functioning among severely-ill highly-disabling psychiatric conditions and is the most relevant predictor of poorer achievements in functional milestones. Prog Neuro-Psychopharmacol Biol Psychiatry. 2016;65:34–48.CrossRef
15.
Kennedy JL, Altar CA, Taylor DL, Degtiar I, Hornberger JC. The social and economic burden of treatment-resistant schizophrenia: a systematic literature review. Int Clin Psychopharmacol. 2014;29:63–76.PubMedCrossRef
16.
Flyckt L, Löthman A, Jörgensen L, Rylander A, Koernig T. Burden of informal care giving to patients with psychoses: a descriptive and methodological study. Int J Soc Psychiatry. 2013;59:137–46.PubMedPubMedCentralCrossRef
17.
Ong HC, Ibrahim N, Wahab S. Psychological distress, perceived stigma, and coping among caregivers of patients with schizophrenia. Psychol Res Behav Manag. 2016;9:211–8.PubMedPubMedCentralCrossRef
18.
Brain C, Kymes S, DiBenedetti DB, Brevig T, Velligan DI. Experiences, attitudes, and perceptions of caregivers of individuals with treatment-resistant schizophrenia: a qualitative study. BMC Psychiatry. 2018;18:253.PubMedPubMedCentralCrossRef
19.
Mouchlianitis E, McCutcheon R, Howes OD. Brain-imaging studies of treatment-resistant schizophrenia: a systematic review. Lancet Psychiatry. 2016;3:451–63.PubMedPubMedCentralCrossRef
20.
Gillespie AL, Samanaite R, Mill J, Egerton A, MacCabe JH. Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? A systematic review. BMC Psychiatry. 2017;17:12.PubMedPubMedCentralCrossRef
21.
Lally J, Ajnakina O, Di Forti M, Trotta A, Demjaha A, Kolliakou A, et al. Two distinct patterns of treatment resistance: clinical predictors of treatment resistance in first-episode schizophrenia spectrum psychoses. Psychol Med. 2016;46:3231–40.PubMedCrossRef
22.
Howes OD, Kapur S. A neurobiological hypothesis for the classification of schizophrenia: type A (hyperdopaminergic) and type B (normodopaminergic). Br J Psychiatry. 2014;205:1–3.PubMedCrossRef
23.
Mouchlianitis E, Bloomfield MAP, Law V, Beck K, Selvaraj S, Rasquinha N, et al. Treatment-resistant schizophrenia patients show elevated anterior cingulate cortex glutamate compared to treatment-responsive. Schizophr Bull. 2016;42:744–52.PubMedCrossRef
24.
Chouinard G, Samaha AN, Chouinard VA, Peretti CS, Kanahara N, Takase M, Iyo M. Antipsychotic-induced dopamine supersensitivity psychosis: pharmacology, criteria, and therapy. Psychother Psychosom. 2017;86:189–219.PubMedCrossRef
25.
26.
27.
Siskind D, Siskind V, Kisely S. Clozapine response rates among people with treatment-resistant schizophrenia: data from a systematic review and meta-analysis. Can J Psychiatr. 2017;62:772–7.CrossRef
28.
29.
Stroup TS, Gerhard T, Crystal S, Huang C, Olfson M. Geographic and clinical variation in clozapine use in the United States. Psychiatr Serv. 2014;65:186–92.PubMedCrossRef
30.
Howes OD, Vergunst F, Gee S, McGuire P, Kapur S, Taylor D. Adherence to treatment guidelines in clinical practice: study of antipsychotic treatment prior to clozapine initiation. Br J Psychiatry. 2012;201:481–5.PubMedCrossRef
31.
Najim H, Heath D, Singh P. Antipsychotic prescribing before clozapine in a community psychiatric hospital: a case note review. Psychiatr Danub. 2013;25(Suppl 2):S165–70.PubMed
32.
Bachmann CJ, Aagaard L, Bernardo M, Brandt L, Cartabia M, Clavenna A, et al. International trends in clozapine use: a study in 17 countries. Acta Psychiatr Scand. 2017;136:37–51.PubMedCrossRef
33.
Nielsen J, Dahm M, Lublin H, Taylor D. Psychiatrists’ attitude towards and knowledge of clozapine treatment. J Psychopharmacol. 2010;24:965–71.PubMedCrossRef
34.
Gee S, Vergunst F, Howes O, Taylor D. Practitioner attitudes to clozapine initiation. Acta Psychiatr Scand. 2014;130:16–24.PubMedCrossRef
35.
Dold M, Fugger G, Aigner M, Lanzenberger R, Kasper S. Dose escalation of antipsychotic drugs in schizophrenia: a meta-analysis of randomized controlled trials. Schizophr Res. 2015;166:187–93.PubMedCrossRef
36.
Loebel A, Silva R, Goldman R, Watabe K, Cucchiaro J, Citrome L, Kane JM. Lurasidone dose escalation in early nonresponding patients with schizophrenia: a randomized, placebo-controlled study. J Clin Psychiatry. 2016;77:1672–80.PubMedCrossRef
37.
Gallego JA, Bonetti J, Zhang J, Kane JM, Correll CU. Prevalence and correlates of antipsychotic polypharmacy: a systematic review and meta-regression of global and regional trends from the 1970s to 2009. Schizophr Res. 2012;138:18–28.PubMedPubMedCentralCrossRef
38.
Correll CU, Gallego JA. Antipsychotic polypharmacy: a comprehensive evaluation of relevant correlates of a long-standing clinical practice. Psychiatr Clin North Am. 2012;35:661–81.PubMedPubMedCentralCrossRef
39.
Galling B, Roldán A, Hagi K, Rietschel L, Walyzada F, Zheng W, et al. Antipsychotic augmentation vs. monotherapy in schizophrenia: systematic review, meta-analysis and meta-regression analysis. World Psychiatry. 2017;16:77–89.PubMedPubMedCentralCrossRef
40.
Correll CU, Rubio JM, Inczedy-Farkas G, Birnbaum ML, Kane JM, Leucht S. Efficacy of 42 pharmacologic cotreatment strategies added to antipsychotic monotherapy in schizophrenia: systematic overview and quality appraisal of the meta-analytic evidence. JAMA Psychiatry. 2017;74:675–84.PubMedPubMedCentralCrossRef
41.
McCutcheon R, Beck K, Bloomfield MAP, Marques TR, Rogdaki M, Howes OD. Treatment resistant or resistant to treatment? Antipsychotic plasma levels in patients with poorly controlled psychotic symptoms. J Psychopharmacol. 2015;29:892–7.PubMedPubMedCentralCrossRef
42.
McCutcheon R, Beck K, D’Ambrosio E, Donocik J, Gobjila C, Jauhar S, et al. Antipsychotic plasma levels in the assessment of poor treatment response in schizophrenia. Acta Psychiatr Scand. 2018;137:39–46.PubMedCrossRef
43.
Byerly M, Fisher R, Whatley K, Holland R, Varghese F, Carmody T, et al. A comparison of electronic monitoring vs. clinician rating of antipsychotic adherence in outpatients with schizophrenia. Psychiatry Res. 2005;133:129–33.PubMedCrossRef
44.
Carbon M, Correll CU. Thinking and acting beyond the positive: the role of the cognitive and negative symptoms in schizophrenia. CNS Spectr. 2014;19(Suppl 1):38–52.PubMed
45.
Leucht S, Leucht C, Huhn M, Chaimani A, Mavridis D, Helfer B, et al. Sixty years of placebo-controlled antipsychotic drug trials in acute schizophrenia: systematic review, bayesian meta-analysis, and meta-regression of efficacy predictors. Am J Psychiatry. 2017;174:927–42.PubMedCrossRef
46.
Fusar-Poli P, Papanastasiou E, Stahl D, Rocchetti M, Carpenter W, Shergill S, McGuire P. Treatments of negative symptoms in schizophrenia: meta-analysis of 168 randomized placebo-controlled trials. Schizophr Bull. 2015;41:892–9.PubMedCrossRef
47.
Millan MJ, Agid Y, Brüne M, Bullmore ET, Carter CS, Clayton NS, et al. Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov. 2012;11:141–68.PubMedCrossRef
48.
Khaykin E, Eaton WW, Ford DE, Anthony CB, Daumit GL. Health insurance coverage among persons with schizophrenia in the United States. Psychiatr Serv. 2010;61:830–4.PubMedCrossRefPubMedCentral
49.
Metadata
Title
Patient characteristics, burden and pharmacotherapy of treatment-resistant schizophrenia: results from a survey of 204 US psychiatrists
Authors
Christoph U. Correll
Thomas Brevig
Cecilia Brain
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2019
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-019-2318-x

Other articles of this Issue 1/2019

BMC Psychiatry 1/2019 Go to the issue

Research article

“I just wish it becomes part of routine care”: healthcare providers’ knowledge, attitudes and perceptions of screening for maternal mental health during and after pregnancy: a qualitative study

Research article

Cognitive behavioral treatment for depressed adolescents: results from a cluster randomized controlled trial of a group course

Correction

Correction to: Classification, substrate specificity and structural features of D-2-hydroxyacid dehydrogenases: 2HADH knowledgebase

Research article

Satisfaction of psychiatric inpatients in China: clinical and institutional correlates in a national sample

Research article

Cognitive insight and quality of life among psychiatric outpatients

Research article

Cognitive predictors of treatment outcome for exposure therapy: do changes in self-efficacy, self-focused attention, and estimated social costs predict symptom improvement in social anxiety disorder?