Despite their awareness of the efficacy of clozapine, psychiatrists in Israel underuse the medication for treatment-resistant schizophrenia, with barriers to initiation including concerns about tolerance, compliance, and difficulty adhering with blood monitoring, according to a study published in Psychiatry Research.

Researchers in this study used nationwide data from questionnaires completed by 295 Israeli psychiatrists to examine psychiatrists’ familiarity, awareness, and attitudes regarding the use of clozapine. Participants used a scoring system to answer questions regarding clozapine procedures, including familiarity with clozapine guidelines, properties of the drug, prescriptions, and their own attitudes regarding specialized clozapine resources.

Related Articles

Approximately half of respondents (53.3%) reported initiating clozapine treatment, according to the guidelines, while 33% reported administering clozapine only after ≥3 unsuccessful antipsychotic treatments. Counterintuitively, the ready availability of specialized clozapine treatment resources, such as clozapine clinics, was associated with delayed clozapine treatment initiation (36.9% rate of initiation with additional clozapine resources vs 58.9% without; P<.001), as well as lower rates of clozapine administration.

Continue Reading

Barriers to initiation included the psychiatrists’ concerns regarding side effects (overall: 64.1%; specifically: agranulocytosis 71.3%, myocarditis 34.2%, electrocardiogram changes 18.0%, diabetes 9.5%, constipation 4.7%, and hypersalivation 3.4%), patients’ concerns regarding side effects (83.4%), and psychiatrists’ concerns regarding patient compliance (82%). Respondents reported the burden of adhering to blood monitoring as the primary reason for avoiding clozapine initiation (94%).

Although the study was limited by being a cross-sectional sample of Israeli psychiatrists, so that generalizability is unclear, the data was collected from approximately 20% of all psychiatrists, and the distribution of gender, age, and expertise level was representative of the total population. Investigators concluded that the executive allocation of resources to encourage, facilitate, and support the use of clozapine does not increase the appropriate guideline-recommended use of clozapine.


Daod E, Krivoy A, Shoval G, et al. Psychiatrists’ attitude towards the use of clozapine in the treatment of refractory schizophrenia: A nationwide survey Psychiatry Res. 2019;275:155-161.