Prevention of suicide by clozapine in mental disorders: Systematic review

Background
Previous research has investigated the efficacy of clozapine in reducing suicidality in patients with schizophrenia and schizoaffective disorder. We aimed to systematically review published evidence, including studies concerning clozapine administration to treat: (a) refractory suicidality in other mental disorders, including bipolar disorder and borderline and other personality disorders; and (b) refractory cases of non-suicidal self-injury.
Method
We performed a PUBMED-search (last day: July 17, 2022) of English-language studies, combining the keywords “clozapine”, “suicidality”, and “suicide” with various psychopathological terms (e.g. “schizophrenia”). All duplications were eliminated.
Results
Fifty-one studies were eligible for inclusion in the review. Most studies suggest a superior anti-suicide effect of clozapine in schizophrenia/schizoaffective disorder, compared to other antipsychotics, or no antipsychotic therapy, which is not due to the close monitoring of patients for blood dyscrasias. No consensus exists as to whether other antipsychotic drugs share this effect. Discontinuation of clozapine is associated with increases in suicidality. Reductions in refractory suicidality/NSSI are observed in clozapine-treated patients with bipolar disorder or borderline personality disorder, but the evidence is limited. Potential biological underpinnings of the anti-suicide effect of clozapine include its unique profile of modulation of brain neurotransmitters; its non-selectivity for neurotransmitter receptors; specific genetic and hormonal factors; effects on neuroinflammation; and ability to elicit epileptiform activity.
Conclusion
The superior anti-suicide effect of clozapine in schizophrenia/schizoaffective disorder patients is well established. It may have a role in severe and refractory cases of suicidality and non-suicidal self-injury in patients with bipolar disorder or borderline personality disorder, but the level and quality of supporting evidence is limited.