Bipolar disorder and other psychiatric disorders are associated with a significantly increased risk of suicidal behavior, which may include self-poisoning due to the use of drugs to treat the disease. Therefore, the choice of treatment should include considerations for toxicity, especially in patients at risk.
The objective of this study was to assess the relative toxicity of specific drugs in antipsychotics and mood stabilizers, using large databases to provide evidence to help clinicians make prescribing decisions, particularly in patients at risk of suicide.
method
The relative toxicity of mood stabilizers and antipsychotics was assessed using two indicators: case fatality rate (fatal and non-fatal self-poisoning ratio) and fatal toxicity (ratio between fatal self-poisoning and prescription). Mood stabilizers assessed included lithium, sodium valproate, carbamazepine, and lamotrigine, while antipsychotics included chlorpromazine, clozapine, olanzapine, quetiapine, and risperidone.
Fatal self-poisoning (suicide) data were provided by the UK Office for National Statistics (ONS), non-fatal e-poisoning data were provided by the UK Multicentre Self-Harm Research Centre, and prescribing information was provided by the Clinical Practice Research DataLink (CPRD). The main analysis focused on deaths caused by a single drug, but also on the case of major toxic substances that could be overdose by multiple drugs. The study period was 2005-2012.
outcome
1. Mood stabilizer
During the eight-year study period (2005-2012), 59 suicidal deaths in England were due to single-drug poisoning, and 37 were taking multiple drugs, with mood stabilizers listed as the top subjects. Of these 96 deaths, 55% were male and 45% were female; data came from 3083 deaths from poisoning suicide that occurred during the study period. Of the 59 deaths, 7% were aged 15-24, 61% were aged 25-54 and 32% were over 55 years of age.
During the same period, 687 cases of nonfatal self-harm using mood stabilizers were identified through a multicentric self-harm study conducted in the UK. Data obtained from CPRD show that an average of 46,860 mood stabilizer prescriptions were surveyed each year between 2005 and 2012.
The results showed that toxicity between mood stabilizers appeared to vary little, and carbamazepine was more than twice as likely to cause death relative to lithium in addition to taking into account the case fatality rate of multiple drug poisonings (or 2.37 95% ci 1.16-4.85).
2. Antipsychotic drugs
During the study period, 143 people committed suicide as a result of poisoning with a single drug, and another 61 had evidence of multiple drugs, but antipsychotics were listed as the top respondents. Of the 204 deaths, 66% were male and 34% female. The data came from 3,083 suicides involving self-poisoning. In terms of age distribution, 6% of people aged 15-24 years, 80% of deaths among people aged 25-54 years and 14% of deaths among people over 55 years of age.
In the UK's Multicentre Study of Self-Harm, there were 1631 non-fatal incidents of self-poisoning involving the taking of antipsychotic drugs. During the same period, 32,758 patients took antipsychotic drugs each year.
In antipsychotics, clozapine is about 18 times more likely to cause death than chlorpromazine when overdose (monotherapy case fatality: or 18.53, 95% ci 8.69-39.52). Otherwise, only risperidone differs from the control drug chlorpromazine, which is less toxic (or 0.06, 95% ci 0.01-0.47).
Table 2 Case fatality index
Table 3 Fatal toxicity index
conclusion
The toxicity of mood stabilizers did not vary much across all individuals. Clozapine is far more toxic than other antipsychotic drugs. These findings have some implications for prescribing policies, particularly for patients at particular risk of suicide.