(March 19, 2019) Individuals with severe mental illness die up to 25 years sooner than those without mental illness. This disparity has been worsening in recent years due to lack of improvement in mortality rates for severe mental illness compared to other chronic diseases. Cardiovascular disease, suicide, and self-harm behaviors are the three major contributors to this mortality gap.
Research published last month in Schizophrenia Bulletin indicates that continuous clozapine treatment for individuals with schizophrenia may have long-term benefits in lowering overall mortality rates, compared to treatment with other antipsychotic medications. The results suggest that although long-term clozapine usage may increase the risk of developing cardiovascular disease, that risk may be outweighed by the reduced likelihood that those taking it will die by suicide.
Based on a systematic review and meta-analysis that evaluates results from a combination of published research to determine an overall effect, the authors examined the long-term effects of clozapine use on mortality risk — a topic of substantial clinical interest. Clozapine was withdrawn from international markets in 1975 due to its association with agranulocytosis, a life-threatening blood condition. However, this side effect is extremely rare and can be mitigated with blood monitoring of the individual while on the medication. Although it was re-introduced to the market in 1990, in the last 30 years, doctors have been prescribing clozapine at a rate that remains significantly below recommended levels.
Clozapine is the most effective anti-psychotic medication for individuals with schizophrenia who are treatment-resistant, and the only medication approved by the Federal Drug Administration for reducing suicide and self-harm behaviors among individuals with psychotic disorders. However, like other anti-psychotic medications, clozapine has side effects including weight gain and high blood sugar that may increase an individual’s risk of developing cardiovascular disease.
In 22 published studies that included a long-term follow-up, the authors found that continuous clozapine treatment is associated with a decreased mortality rate for individuals with schizophrenia. This was not the case for individuals who had been treated with clozapine at a single point in time or intermittently, indicating that continuous treatment with clozapine is most beneficial for increasing life expectancy.
The authors conclude that physicians’ clozapine prescribing practices need to be re-examined: “The concern of clinicians that prescribing clozapine will increase the long-term mortality risk of schizophrenia patients by inducing cardiovascular-related adverse effects is not empirically supported in the current systematic review and meta-analysis.”
To learn more about the under-utilization of clozapine in the United States, read the Treatment Advocacy Center 2015 report Clozapine for treating schizophrenia, a comparison of the states.
References:
Elizabeth Sinclair
Director of Research
Treatment Advocacy Center