“Clozapine Keeps Patients Alive”: Starting This Antipsychotic Sooner

CONFERENCE REPORTER
“Large studies have really corroborated the fact that clozapine keeps patients alive,” said Jonathan M. Meyer, MD, at the 2023 Annual Psychiatric Times™ World CME Conference.

Many patients with schizophrenia in their first episode are treatment resistant from onset and starting clozapine early increases response, Meyer stressed to attendees. In fact, each new failed antipsychotic trial reduces the rate of clozapine response by 8% to 11%, and each psychiatric hospitalization reduces chance of clozapine response by 4% to 8%. Delaying patients getting clozapine is going to limit the extent of response.^1-6

Clozapine has several evidence-based uses.^7-9 They include:

1. Treatment-resistant schizophrenia. The response rate is greater than or equal to 40%.

2. Schizophrenia and suicidality. Clozapine proved superior to olanzapine in the head-to-head InterSePT trial. In a meta-analysis of 24 studies, mortality rate ratios were 44% lower in patients continuously treated with clozapine compared to other antipsychotics and mortality was highest in periods after clozapine discontinuation (HR: 2.65, 95% CI 1.47–4.78).

3. Schizophrenia patients with persistent impulsive aggression. Clozapine’s impact is independent of its effect on psychosis symptoms.

4. Treatment-resistant mania. Meyer considered this a niche use.

5. Parkinson disease psychosis. Another niche use, clozapine can be used in Parkinson disease at very low doses of 25-50 mg.

Meyer urged other clinicians not to wait to try clozapine with patients, as waiting 4 years from time of treatment resistance decreases the extent of clozapine response. One study found that of the 162 patients with schizophrenia who took clozapine, 14.0% discontinued due to intolerance of clozapine or due to nonadherence, 16.0% showed minimal or no improvement, 34.5% showed moderate improvement, and 34.5% showed marked improvement. The mean delay of clozapine initiation for the entire sample was 29 months.¹⁰

However, even if delayed start decreases the effectiveness of clozapine, he did urge clinicians to initiate the antipsychotic anyways. “Do not deprive people of being on clozapine simply because they have been ill for a long time. That is not the patient's fault,” said Meyer.

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References

1. Siskind D, Orr S, Sinha S, et al. Rates of treatment-resistant schizophrenia from first-episode cohorts: systematic review and meta-analysis. Br J Psychiatry. 2022;220(3):115-120.

2. Harvey PD, Rosenthal JB. Treatment resistant schizophrenia: course of brain structure and function. Prog Neuropsychopharmacol Biol Psychiatry. 2016;70:111-116.

3. Emsley R, Chiliza B, Asmal L, Harvey BH. The nature of relapse in schizophrenia. BMC Psychiatry. 2013;13:50.

4. Kane JM. Treatment strategies to prevent relapse and encourage remission. J Clin Psychiatry. 2007;68 Suppl 14:27-30.

5. Nielsen J, Nielsrn RE, Correl CU. Predictors of clozapine response in patients with treatment-refractory schizophrenia: results from a Danish Register Study. J Clin Psychopharmacol. 2012;32(5):678-683.

6. Yoshimura B, Yada Y, So R, et al. The critical treatment window of clozapine in treatment-resistant schizophrenia: secondary analysis of an observational study. Psychiatry Res. 2017;250:65-70.

7. Vanasse A, Blais L, Courteau J, et al. Comparative effectiveness and safety of antipsychotic drugs in schizophrenia treatment: a real-world observational study. Acta Psychiatr Scand. 2016;134(5):374-384.

8. Vermeulen JM, van Rooijen G, van de Kerkhof MPJ, et al. Clozapine and long-term mortality risk in patients with schizophrenia: a systematic review and meta-analysis of studies lasting 1.1-12.5 years. Schizophr Bull. 2019;45(2):315-329.

9. Meyer JM, Stahl SM. The Clozapine Handbook. Cambridge University Press, 2019.

10. Üçok A, Çikrikçili U, Karabulut S, et al. Delayed initiation of clozapine may be related to poor response in treatment-resistant schizophrenia. Int Clin Psychopharmacol. 2015;30(5):290-295.