Data on the prevalence of ASMs in PwID in England

Recent studies estimate that between one-third and one-fifth of PwID are prescribed ASMs and the percentage of PwID prescribed ASMs has continued to rise.^{Reference Mehta and Glover11–Reference Glover, Williams and Branford13} A 2019 Public Health England (PHE) report showed that between 2010 and the end of 2017 the proportion of PwID prescribed an ASM with a recorded recognised indication of epilepsy had fallen from 84.9% to 79.6%.^{Reference Mehta and Glover11} NHS Digital data shows the proportion receiving ASMs continues to rise with age for both those with a history of epilepsy and those without.¹²

Table 1 details 2020–2021 data from NHS Digital of the rate of ASM prescribing for PwID, both for those with epilepsy and those without. For both, the proportion of PwID receiving ASMs continues to rise throughout the age bands.¹² Unfortunately, the NHS Digital data does not indicate the numbers with both epilepsy and mental health conditions.¹²

Table 1

The age-related rate of antiseizure medication (ASM) prescribing for people with intellectual disability and epilepsy and those with intellectual disability but no epilepsy

Adapted data from NHS Digital.¹²

Multiple ASM use is also seen to increase with age, with a figure of 27.9% in children and young people and 43.3% in adults.^{Reference Monaghan, O'Dwyer and Luus10} A PHE study in 2015 found there was no consistent gender difference in the use of ASMs and that most prescribing (almost 100%) was long term.^{Reference Glover, Williams and Branford13}

Co-prescribing of ASMs with other psychotropic medications

Data from the 2019 PHE report suggest nearly half of PwID on ASMs are prescribed them in combination with other psychotropic medications (males 46.5%; 95% CI 48.6–44.4; and females 48.8%; 95% CI 51.1–46.4).^{Reference Mehta and Glover11}

Antipsychotic co-prescribing was noted in just over a quarter of females (25.2%; 95% CI 23–27.6) and males (28.5%; 95% CI 26.5–30.7). Approximately a fifth – males 19.8% (95% CI 18–21.7) and females 21.2% (95% CI 19.1–23.4) –were co-prescribed anxiolytics. Nearly a quarter of females were on co-prescribed antidepressants (23.3%; 95% CI 21.2–25.6) compared with approximately one in six males (15.8%; 95% CI 14.1–17.5). Antihypnotic co-prescribing was 6.2% (95% CI 5.1–7.6) in females and 5.7% (95% CI 4.7–6.9) in males.

There is no clear explanation of the high level of co-prescribing with ASMs, however, it is possible that when faced with a prescribing decision for mania or behavioural problems a history of epilepsy may steer the prescriber towards ASMs rather than antipsychotics or antidepressants. Alternatively, ASMs might be used in addition, as some antidepressants and antipsychotics can carry a risk of lowering the seizure threshold.

How complete are the data?

Most studies of ASM use in PwID are based on data generated by general practice prescribing systems. In January 2021 NHS Digital published data on several aspects of psychotropic and ASM prescribing by general practices for people identified as having intellectual disability along with comparison data for the rest of the registered population.¹² The data are on a large scale and document the years 2015–16 to 2019–20. They were collected as an addition to the data-set called ‘The Health and Care of People with Learning Disabilities’ that was introduced to support ‘Stopping Over-Medication of People with a Learning Disability, Autism or Both’ (STOMP).¹² Unfortunately, this does not give a full picture for England as the data collection process is not supported by one of the large commercial companies providing notes systems for general practice. The solution for bringing together a large single data-set has technical and financially challenges. The overall proportion of patients registered with general practitioners who were included varied over the 5 years from 56.2% to 60.3%. Coverage varied greatly between the current seven NHS regions, ranging from 19.5% to 87.8% in the most recent year, with coverage highest in the North-West, London and the South-East, and lowest in the East of England, the North-East and Yorkshire. There was similarly wide variation between clinical commissioning groups within regions. This means that the total figures quoted do not reflect England proportionately and have a regional bias. The measures used all reflect an end of year (31 March) position.

The behavioural effects of ASMs

Both positive and negative behavioural effects may be experienced by people with or without epilepsy when taking ASMs.^{Reference Nadkarni and Devinsky6} In general, sedating ASMs, such as sodium valproate and carbamazepine, possess anxiolytic, antimanic and sleep-promoting benefits but may cause fatigue, impaired attention and mood problems specifically, depression. Activating ASMs, such as felbamate and lamotrigine, may possess antidepressant and attention-enhancing efficacy but may cause anxiety, insomnia and agitation.

A retrospective, cohort study of 246 PwID and epilepsy at the long-stay department of an epilepsy centre in the Netherlands found a statistically significant lower use of antidepressants when prescribed lamotrigine for epilepsy.^{Reference Leunissen, de la Parra and Tan14} They also found significantly less prescriptions of anxiolytics in patients using ASMs with mood-stabilising properties (carbamazepine, valproic acid and lamotrigine).

A study comparing the psychiatric and behavioural side-effects profile of older and newer ASMs in a large specialty practice-based sample of patients diagnosed with epilepsy found that psychiatric and behavioural side-effects occurred in 17.2% of patients and led to lack of tolerance in 13.8% of patients.^{Reference Chen, Choi and Hirsch15} However, this study was not specific to PwID.

Association between epilepsy and challenging behaviour in PwID

A 2021 study tried to identify whether there is an association between epilepsy and challenging behaviour in PwID by carrying out a systematic review of published data.^{Reference Akrout Brizard, Limbu and Baeza-Velasco9} They showed no significant association between epilepsy and challenging behaviour. However, the authors warned that the findings were contradictory and must be interpreted with caution because of the difficulty in pooling data from varied studies, which is likely to introduce confounding. Where significant differences were found, effect sizes are small and may not be clinically significant, and there are major methodological flaws in the included studies, which should be addressed in future large-scale properly controlled studies.

Prescribing ASMs for the management of challenging behaviours for PwID

A 2008 systematic review of the effectiveness of mood stabilisers and ASMs for the management of behaviour problems in PwID concluded that although there is some support for the use of lithium and some ASMs for the management of behaviour problems in adults with intellectual disability, they could only find one randomised controlled trial (RCT) relating to a non-ASM (lithium) and two non-RCTs, one on lithium and the other on carbamazepine.^{Reference Deb, Chaplin and Sohanpal16} In addition, one prospective non-controlled trial on sodium valproate and three retrospective case series studies were discovered, of which one considered the efficacy of lithium, one valproate and one topiramate. In the selected studies all the ASMs were add-ons to existing medication.

A recent UK-based 2020 study highlighted significant differences in the understanding, confidence and approaches to managing challenging behaviour in PwID and epilepsy between different professional groups, such as neurologists and psychiatrists.^{Reference Kinney, Chester and Tromans17} A best practice checklist was proposed to provide a structured framework. The framework outlines various aspects of assessing and managing challenging behaviour in PwID and epilepsy.^{Reference Kinney, Chester and Tromans17} It gives prompts to enquire into the specifics of domains of biological factors (history taking, clinical examination and physical investigations), psychological and behavioural factors and social factors.^{Reference Kinney, Chester and Tromans17}

Why is addressing ASM prescribing in PwID important?

First, the Learning Disability Mortality Review Programme (LeDeR), which is an ongoing national inquiry in England of all deaths in PwID aged 4–74 years, showed one of the most frequently prescribed groups of medications were ASMs prescribed to almost half of all PwID who had died prematurely.¹⁸ Around a quarter were on valproate.¹⁸

Second, PwID on ASMs appear to have high levels of multimorbidity and polypharmacy.^{Reference Sun, Perera and Henley19} In particular, those over 40 years of age are more vulnerable to proportionate increases in polypharmacy and multimorbidity while inversely effected by level of service and care, compared with their younger peers^{Reference Watkins, Henley and Sun20}

Third, concerns about long-term side-effects relating to issues such as bone and bowel health need considering.^{Reference Winterhalder, McCabe and Young21,Reference Maslen, Hodge and Tie22}

Who should ‘own’ the problem?

Any proactive and constructive work to rationalise ASM prescribing needs all key stakeholders across epilepsy, intellectual disability and mental health to collaborate.^{Reference Watkins, Linehan and Brandt23} An unresolved challenge globally has been how should PwID and epilepsy be supported, which is an important challenge to address in order to understand ASM prescribing in this population.^{Reference Shankar and Perera24} Clinical presentations can lead to diagnostic overshadowing leading to a range of situations of neglect, misdiagnosis and overprescribing.^{Reference Watkins, O'Dwyer and Kerr25} There are concerns about unmet training needs across all health and social stakeholder groups which should be inclusive of the needs of this population and require addressing.^{Reference Lines, Henley and Winterhalder26}

Practice recommendations for review of long-term ASM prescribing

For most PwID the prescribing of ASMs is long term.^{Reference Branford, Sun and Shankar3} Ideally where ASMs are being prescribed for an indicated and appropriate condition, for example bipolar or epilepsy, the relevant National Institute for Health and Care Excellence guidance needs to be considered. Specifically, where seizures are an issue clinicians should follow the advice in epilepsy-specific best practice guidelines.

For PwID who receive ASMs solely for behavioural issues (i.e. non-psychiatric indications or in the absence of epilepsy) ASMs should be initiated or continued only if there is recognised and documented evidence that psychological or other interventions alone did not produce change within an agreed time; treatment for any coexisting mental or physical health problem has not lead to a reduction in the behaviour; or the risk to the person or others is very severe (for example, because of violence, aggression or self-injury). The evidence to support this is modest and there needs to be recognition that the aetiology can be diverse, with the best available evidence for aggression being for valproate use for aggressive behaviour in paediatric populations.^{Reference Munshi, Oken and Guild27} Further, where possible, ASMs should only be offered in combination with psychological or other evidenced interventions.

For PwID with a history of epilepsy who are taking ASMs and not experiencing any symptoms, consider reducing or discontinuing long-term prescriptions of ASM. This would need to include reviewing the person's condition after reducing or discontinuing a prescription and considering referral to a psychiatrist experienced in working with PwID.

There needs to be annual review and documentation of the reasons for continuing the prescription if it is not reduced or discontinued. Figure 1 provides a decision-support flow chart of the above information for clinicians to consider in practice.

Fig. 1

Decision-support flow chart for review of antiseizure medication in people with intellectual disabilities.