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. 2018 Dec 27;18(1):399.
doi: 10.1186/s12888-018-1993-3.

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

Anne E Ferrey  1   2 , Galit Geulayov  3 , Deborah Casey  3 , Claudia Wells  4 , Alice Fuller  5 , Clare Bankhead  5 , Jennifer Ness  6 , Caroline Clements  7 , David Gunnell  8 , Navneet Kapur  7 , Keith Hawton  3
Affiliations

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

Anne E Ferrey et al. BMC Psychiatry. .

Abstract

Background: 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.

Method: 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.

Results: 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).

Conclusions: 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.

Keywords: Antipsychotics; Drug toxicity; Mood stabilisers; Self-poisoning; Suicide.

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Conflict of interest statement

Ethics approval and consent to participate

The monitoring systems for self-harm in Oxford and Derby have approval from local Health /Psychiatric Research Ethics Committees to collect data on self-harm for local and multicentre projects. Self-harm monitoring in Manchester is part of a clinical audit system, and has been ratified by the local Research Ethics Committee. All three monitoring systems are fully compliant with the Data Protection Act of 1998. All centres have approval under Section 251 of the National Health Services (NHS) Act 2006 (formerly Section 60, Health and Social Care Act 2001) to collect patient identifiable information without patient consent.

We also obtained specific Independent Scientific Advisory Committee (ISAC) approval from the CPRD (protocol number 14_064R2) and also from ONS to obtain mortality data.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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