In a large population-based cohort study, we found that people with epilepsy have an elevated self-harm risk compared to those without the condition. There was a fivefold elevation in risk in the first year following diagnosis and a threefold increased risk persisting beyond this first year. Among people with epilepsy, those most likely to self-harm included people with comorbid mental illness diagnoses, previous psychiatric referral, previous hospitalization for any reason, or five or more consultations with their GP in the previous year. Individuals treated with none or multiple AEDs, including those who had recently augmented treatment, were at increased risk of self-harm, compared to those prescribed AED monotherapy.

We report the first published estimates for elevated self-harm risk in people with incident epilepsy in which self-harm cases were ascertained using both primary and secondary care records. Our estimates are slightly higher than those reported in earlier studies that included only individuals who presented to hospital with self-harm [4, 5] and estimates from the study using the predecessor to the CPRD, prior to linkage availability (OR 2.35, 95% CI 1.67–3.29), thus including only self-harm episodes that were recorded in primary care [6]. Previous studies did not restrict to an incident epilepsy cohort; therefore, inclusion of individuals with prevalent epilepsy may have resulted in prevalent-user bias [11]. This may have diluted the period of highest risk, close to the time of incident epilepsy diagnosis.

Among people with epilepsy, we found that elevated self-harm risk was associated with prior diagnosis of any mental illness or referral to psychiatric services. This corroborates with evidence reported from general population studies in which mental illness is associated with a 6- to 14-fold increased risk of self-harm, dependent on the specific diagnosis [4]. Within the epilepsy cohort, a fivefold increased risk of self-harm was associated with history of alcohol and substance misuse. It is possible that these individuals experience a high frequency of seizures, caused by the alcohol or substance misuse, or due to non-compliance with treatment as a result of a disordered lifestyle. This could contribute to the increased self-harm risk experienced by these individuals. A bidirectional relationship between attempted suicide, which includes self-harm, and epilepsy has been suggested previously [25].

Having five or more face-to-face general practice consultations in the previous year was associated with elevated self-harm risk, compared to people who attend up to four times per year. Clinicians should be alert to the risk of self-harm in individuals who present regularly, which may be in relation to epilepsy severity or comorbid conditions. Importantly, clinicians can use these frequent interactions to discuss self-harm risk with patients in this group.

The use of multiple AEDs is a result of treatment augmentation, due to inadequate seizure control; or during a period of switching to an alternative monotherapy due to lack of tolerance or for other reasons such as pregnancy [22]. The elevated self-harm risk observed during use of multiple AEDs is likely to be an indication of more severe epilepsy with an associated higher seizure frequency, which is not controlled by AED monotherapy. Furthermore, individuals who have many seizures may experience consequent psychosocial difficulties, including inability to drive or absence from work or social activities, which may exacerbate the stigma associated with epilepsy [26]. Additionally, some individuals may become despondent if AED treatment requires augmentation, despite compliance with monotherapy. This may result in difficulty coping and the condition may be perceived as a burden to the individual, both of which are known motivators of suicidal behaviour [27]. Indeed, we observed an elevated risk of self-harm associated with recent augmentation of AED treatment. We have previously identified the need to examine the risk associated with individual AEDs using carefully designed, new-user studies [28]. This was not the aim of this study; therefore, the study design does not allow us to comment on individual AEDs.

Self-harm risk was also elevated for people who were not prescribed an AED in the 90 days prior to the index self-harm case date (OR 1.47, 95% CI 1.01–2.12). On entry to the incident epilepsy cohort, all individuals were prescribed an AED. Therefore, those individuals without AED prescription on the self-harm case date may have gradually stopped taking AEDs because they became seizure free. In the UK, the National Institute for Health and Care Excellence (NICE) recommends that AED withdrawal should only be considered following a 2-year absence of seizures [21]. Given that the median time since epilepsy diagnosis on self-harm case date was approximately 2 years, it is unlikely that all of those who had no recent AED prescription withdrew their AED on the advice of a clinician. It is possible that some of those individuals were non-compliant with their medication regimen. This may be motivated by undesirable adverse events, beliefs about medication and illness, comorbid mental illness or lifestyle choices, all of which may potentially contribute to elevated self-harm risk.

Healthcare professionals involved in the care of people with epilepsy could instigate conversations about self-harm risk, especially if the described risk factors are present. These include mental health problems, and extend to both the clinicians responsible for the mental health services and those working in general primary care settings. Furthermore, GPs should consider discussing self-harm risk management in people who consult frequently. Further research could investigate whether any technological prompts could aid this during consultations.

Strengths and limitations

This is the first published study to estimate self-harm risk among people with epilepsy in a large, linked primary care patient cohort, including 11,690 people with incident epilepsy. Linkage to HES maximized self-harm case ascertainment. The Read codes used to identify self-harm cases were verified by clinicians and have been used in other studies [15, 29]. To mitigate confounding by previous self-harm, we restricted the incident epilepsy cohort to include only those persons with no prior recorded history of self-harm in either their primary or secondary healthcare records. It is still possible, however, that individuals had a self-harm event prior to this look-back period and before their CPRD records began. Furthermore, we recognize that not all people who have a self-harm episode will present to healthcare services and those who do represent the “tip of the iceberg” of self-harm events [30]. However, our inclusion of self-harm reported to both primary and secondary care builds upon those studies which used only one of those sources to ascertain self-harm [4,5,6]. As people with epilepsy attend the GP more often than those who do not, there may have been more opportunity to report self-harm and they may be asked about self-harm as per the WHO recommendations [7]. This would overestimate the magnitude of elevated self-harm risk in people with epilepsy compared to those without the condition.

It is not possible to accurately determine the type of epilepsy from UK general practice data; therefore, this is something we could not examine in this study. Epilepsy type may influence risk of self-harm [31]. It would, therefore, be beneficial to compare self-harm risk among people with different epilepsy subtypes, particularly whether having symptomatic epilepsy (and therefore underlying brain pathology) has an influence on self-harm risk.