Relative toxicity of mood stabilisers and antipsychotics: case fatality and fatal toxicity associated with self-poisoning

• Published in: BMC psychiatry Vol. 18; no. 1; pp. 399 - 8
• Main Authors: Ferrey, Anne E, Geulayov, Galit, Casey, Deborah, Wells, Claudia, Fuller, Alice, Bankhead, Clare, Ness, Jennifer, Clements, Caroline, Gunnell, David, Kapur, Navneet, Hawton, Keith
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 27-12-2018; BioMed Central; BMC
• Subjects: Adult; Antipsychotic agents; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Antipsychotic Agents - classification; Antipsychotics; Bipolar disorder; Carbamazepine; Chlorpromazine; Clozapine; Complications and side effects; Drug Overdose - etiology; Drug Overdose - prevention & control; Drug Overdose - psychology; Drug therapy; Drug toxicity; England; Fatalities; Female; Humans; Lamotrigine; Lithium; Medication Therapy Management; Mental disorders; Mental Disorders - complications; Mental Disorders - drug therapy; Mental Disorders - psychology; Mood; Mood stabilisers; Olanzapine; Overdose; Patients; Pharmacological research; Poisoning; Practice Patterns, Physicians; Psychiatry; Psychotropic drugs; Quetiapine; Risk Adjustment - methods; Risperidone; Self destructive behavior; Self-Injurious Behavior - prevention & control; Self-Injurious Behavior - psychology; Self-injury; Self-poisoning; Sodium; Sodium valproate; Statistical analysis; Suicidal behavior; Suicide; Suicide - prevention & control; Suicide - psychology; Suicide - statistics & numerical data; Suicides & suicide attempts; Toxicity; Tranquilizing Agents - administration & dosage; Tranquilizing Agents - adverse effects; Tranquilizing Agents - classification; Valproic acid; England; United Kingdom > UK; Antipsychotics; Mood stabilisers; Self-poisoning; Suicide; Drug toxicity
• ISSN: 1471-244X; 1471-244X
• DOI: 10.1186/s12888-018-1993-3

Bipolar and other psychiatric disorders are associated with considerably increased risk of suicidal behaviour, which may include self-poisoning with medication used to treat the disorder. Therefore, choice of medication for treatment should include consideration of toxicity, especially for patients at risk. The aim of this study was to estimate the relative toxicity of specific drugs within two drug categories, antipsychotics and mood stabilizers, using large-scale databases to provide evidence that could assist clinicians in making decisions about prescribing, especially for patients at risk of suicidal behaviour.
Two indices were used to assess relative toxicity of mood stabilisers and antipsychotics: case fatality (the ratio between rates of fatal and non-fatal self-poisoning) and fatal toxicity (the ratio between rates of fatal self-poisoning and prescription). Mood stabilisers assessed included lithium [reference], sodium valproate, carbamazepine, and lamotrigine, while antipsychotics included chlorpromazine [reference], clozapine, olanzapine, quetiapine and risperidone. Fatal self-poisoning (suicide) data were provided by the Office for National Statistics (ONS), non-fatal self-poisoning data by the Multicentre Study of Self-harm in England, and information on prescriptions by the Clinical Practice Research Datalink. The primary analysis focussed on deaths due to a single drug. Cases where the drug of interest was listed as the likely primary toxic agent in multiple drug overdoses were also analysed. The study period was 2005-2012.
There appeared to be little difference in toxicity between the mood stabilisers, except that based on case fatality where multiple drug poisonings were considered, carbamazepine was over twice as likely to result in death relative to lithium (OR 2.37 95% CI 1.16-4.85). Of the antipsychotics, clozapine was approximately18 times more likely to result in death when taken in overdose than chlorpromazine (single drug case fatality: OR 18.53 95% CI 8.69-39.52). Otherwise, only risperidone differed from chlorpromazine, being less toxic (OR 0.06 95% CI 0.01-0.47).
There was little difference in toxicity of the individual mood stabilisers. Clozapine was far more toxic than the other antipsychotics. The findings are relevant to prescribing policy, especially for patients at particular risk of suicidal behaviour.