Click to Enlarge: Source: Primary Care Companion For CNS Disorders
HOUSTON – Although clozapine is the only pharmacologic intervention approved for treating patients with schizophrenia or schizoaffective disorder who have had suicidal behaviors or inadequate response to other antipsychotics, the medication is underutilized in veterans with these mental health issues, according to a new study.
The study published in The Primary Care Companion for CNS Disorders evaluated whether a history of suicide attempt increases the odds of receiving clozapine treatment in veterans with schizophrenia or schizoaffective disorder.1
The researchers obtained electronic health record data for 134,692 veterans with schizophrenia or schizoaffective disorder treated at any U.S. VAMC between Jan. 1, 2000, and Jan. 31, 2021. Logistic regression was applied to estimate odds ratios for clozapine treatment in suicide attempters compared to nonattempters.
Knowing the extent to which clozapine is being prescribed in a high-risk population such as suicide attempters with schizophrenia or schizoaffective disorder is the first step in designing initiatives to increase the use of this proven intervention by prescribers, according to the study.
“Caring for the mental health of our veterans, including preventing suicide, is a top priority for the VA,” Olaoluwa Okusaga, MD, MScPHR, associate professor at Baylor College of Medicine and staff psychiatrist at the Michael E. DeBakey VAMC in Houston, told U.S. Medicine. “In the previous two years, we’ve made some important progress in suicide prevention. We recognize that our veterans with conditions such as schizophrenia and related disorders are at special risk, and this research points the way towards care that reduces this risk and improves veterans’ lives.”
“Clozapine is used to treat patients with schizophrenia when other medicines don’t work well or there is a risk of suicidal behavior, but clozapine is often underprescribed. We wanted to evaluate how we were doing treating veterans with these conditions.”
The study found that 3,407 patients had a documented history of suicide attempt, while 6,867 patients had received clozapine treatment. Also, 9.4% of suicide attempters (321 patients) versus 5.0% of nonattempters (6,546 patients) had received clozapine treatment. Prior suicide attempt (compared to no prior suicide attempt) was associated with almost twice the odds of being prescribed clozapine.
The patients were predominantly male (92%) and white (55%), with a mean age of 59 years. Suicide attempters were almost five years younger on average, had a slight female and white predominance, and were more likely to have been divorced.
“While VA’s healthcare professionals appropriately prescribe clozapine as a treatment for those veterans with these disorders who have attempted suicide, we have progress to make ensuring that treatment-resistant cases are also being prescribed clozapine,” Okusaga wrote in an email. “Our findings were similar to a smaller British study that found only about half of those diagnosed with treatment-resistant schizophrenia cases had ever been treated with clozapine. I’m confident our research will improve how veterans with schizophrenia or schizoaffective disorder are treated.”2
Patients with schizophrenia or schizoaffective disorder are at higher risk for suicide attempts. Suicide attempt rates are up to 20.3% in those with schizophrenia and 46.8% in those with schizoaffective disorders, according to a systematic review using Scopus and PubMed databases.3
Research and clinical experience highly support the prescription of clozapine, which is superior to other antipsychotics as a therapy for treatment-resistant schizophrenia and schizoaffective disorder with risk of suicidal behavior.4 Clozapine can and does play a key role in caring for veterans with special risks, Okusaga wrote. In the United States, it has been estimated that one-third of suicides among patients with schizophrenia or schizoaffective disorder may be prevented if treated with clozapine, according to the study.
More Use of Clozapine?
“Our study proves that the veterans who need clozapine the most are getting it, but it is also a wakeup call that we need to prescribe clozapine more often for treatment-resistant schizophrenia in order to provide veterans with the best possible care from the latest medical data,” Okusaga explained.
Clinicians involved in the care of veterans with psychotic disorders should consider prescribing clozapine, as it is the best evidence-based treatment for patients with treatment resistance or suicidal behavior, he added.
“My personal recommendation to every healthcare professional who is involved in the care of patients with schizophrenia or schizoaffective disorder, especially prescribers, is they should be comfortable prescribing clozapine,” Okusaga wrote in an email. “Too often I see a reluctance to prescribe clozapine either because of logistical issues—like registering the patient in the REMS program, weekly blood draw and ANC monitoring—or because of potential side effects. To date, though, no medication has been able to beat clozapine in terms of symptom control and lowering all-cause mortality.”
“Additionally, we’ve found that patients are more likely to stay on clozapine than many other medications we prescribe, despite the logistical challenges involved. Bottom line, we need to continue to emphasize that, despite the side effects, risk to affected veterans is reduced when those with treatment resistance in schizophrenia or schizoaffective disorder take clozapine.”
Although expanding the use of clozapine involves a risk of increased side effects, the net benefits in suicide reduction and secondary enhancements, such as potential for improved cognition, adherence and quality of life, must be considered, according to the study.
Among the study’s strengths, data was collected from a larger nationwide cohort of patients than has previously been assessed in this subject area. The study combined data from both inpatient and outpatient centers, more accurately reflecting real-world conditions. However, it was not possible to stratify prescribing odds across individual centers.
Further limitations of this study include the strong male predominance of the sample (which limits the generalizability of the findings) and the lack of information on duration of treatment, mean dosage and adjunctive therapy. In addition, suicide attempts could have been underreported in electronic medical records, as some patients might not have reported their suicide attempt(s) either because they were not asked directly or felt embarrassed. Also, the study didn’t have data on deaths from suicide.
- Jones GH, Mitchell BG, Bernard J, Walder A, Okusaga OO. History of Suicide Attempt and Clozapine Treatment in Veterans With Schizophrenia or Schizoaffective Disorder. Prim Care Companion CNS Disord. 2022 Nov 1;24(6):21m03231. doi: 10.4088/PCC.21m03231. PMID: 36343352.
- Beck K, McCutcheon R, Stephenson L, et al. Prevalence of treatment-resistant psychoses in the community: A naturalistic study. Journal of Psychopharmacology. 2019;33(10):1248-1253. doi:10.1177/0269881119855995
- Álvarez A, Guàrdia A, González-Rodríguez A, Betriu M, Palao D, Monreal JA, Soria V, Labad J. A systematic review and meta-analysis of suicidality in psychotic disorders: Stratified analyses by psychotic subtypes, clinical setting and geographical region. Neurosci Biobehav Rev. 2022 Dec;143:104964. doi: 10.1016/j.neubiorev.2022.104964. Epub 2022 Nov 17. PMID: 36403792.
- Gammon D, Cheng C, Volkovinskaia A, Baker GB, Dursun SM. Clozapine: Why Is It So Uniquely Effective in the Treatment of a Range of Neuropsychiatric Disorders? Biomolecules. 2021 Jul 15;11(7):1030. doi: 10.3390/biom11071030. PMID: 34356654; PMCID: PMC8301879.
