One Intervention for Many: Solving the Challenge of Managing Mental Health Across the Broad Spectrum of Childhood Epilepsy

Abstract

Clinical Effectiveness of the Psychological Therapy Mental Health Intervention for Children with Epilepsy in Addition to Usual Care Compared with Assessment-Enhanced Usual Care Alone: A Multicentre, Randomised Controlled Clinical Trial in the UK

Bennett SD, Cross JH, Chowdhury K, Ford T, Heyman I, Coughtrey AE, Dalrymple E, Byford S, Chorpita B, Fonagy P, Moss-Morris R, Reilly C, Smith JA, Stephenson T, Varadkar S, Blackstone J, Quartly H, Hughes T, Lewins A, Moore E, Walji F, Welch A, Whelan E, Zacharia A, D'Oelsnitz A, Shah M, Xu L, Vezyroglou A, Mitchell K, Nizza IE, Ganguli P, Shafran R. Lancet. 2024;403(10433):1254–1266. doi: 10.1016/S0140-6736(23)02791-5.

Background: Mental health difficulties are common in children and young people with chronic health conditions, but many of those in need do not access evidence-based psychological treatments. The study aimed to evaluate the clinical effectiveness of integrated mental health treatment for children and young people with epilepsy, a common chronic health condition known to be associated with a particularly high rate of co-occurring mental health difficulties. Methods: We conducted a parallel-group, multicenter, open-label, randomized controlled trial of participants aged 3–18 years, attending epilepsy clinics across England and Northern Ireland who met diagnostic criteria for a common mental health disorder. Participants were randomized (1:1; using an independent web-based system) to receive the Mental Health Intervention for Children with Epilepsy (MICE) in addition to usual care, or assessment-enhanced usual care alone (control). Children and young people in both groups received a full diagnostic mental health assessment. MICE was a modular psychological intervention designed to treat common mental health conditions in children and young people using evidence-based approaches such as cognitive behavior therapy and behavioral parenting strategies. Usual care for mental health disorders varied by site but typically included referral to appropriate services. Participants, along with their caregivers, and clinicians were not masked to treatment allocation but statisticians were masked until the point of analysis. The primary outcome, analyzed by modified intention-to-treat, was the parent-report Strengths and Difficulties Questionnaire (SDQ) at 6 months post-randomization. The study is complete and registered with ISRCTN (57823197). Findings: Precisely, 1401 young people were potentially deemed eligible for study inclusion. Following the exclusion of 531 young people, 870 participants were assessed for eligibility and completed the SDQ, and 480 caregivers provided consent for study inclusion between May 20, 2019, and January 31, 2022. Between August 28, 2019, and February 21, 2022, 334 participants (mean ages 10.5 years [SD 3.6] in the MICE group vs 10.3 [4.0] in the control group at baseline) were randomly assigned to an intervention using minimization balanced by age, primary mental health disorder, diagnosis of intellectual disability, and autistic spectrum disorder at baseline. One hundred and sixty-eight (50%) of the participants were female and 166 (50%) were male. One hundred and sixty-six participants were randomly assigned to the MICE group and 168 were randomly assigned to the control group. At 6 months, the mean SDQ difficulties for the 148 participants in the MICE group was 17.6 (SD 6.3) and 19.6 (6.1) for the 148 participants in the control group. The adjusted effect of MICE was −1.7 (95% CI −2.8 to −0.5; p = .0040; Cohen's d, 0.3). Fourteen (8%) patients in the MICE group experienced at least 1 serious adverse event compared with 24 (14%) in the control group. Sixty-eight percent of serious adverse events (50 events) were admission due to seizures. Interpretation: MICE was superior to assessment-enhanced usual care in improving symptoms of emotional and behavioral difficulties in young people with epilepsy and common mental health disorders. The trial therefore shows that mental health comorbidities can be effectively and safely treated by a variety of clinicians, utilizing an integrated intervention across ages and in the context of intellectual disability and autism. The evidence from this trial suggests that such a model should be fully embedded in epilepsy services and serve as a model for other chronic health conditions in young people.

Commentary

Mental health comorbidities are exceedingly common and high impact among people with epilepsy across the age spectrum, ¹ as they are associated with poor quality of life, increased mortality risk, and other outcomes particularly relevant to pediatric epilepsy including poor caregiver mental health ² and poor school performance. ³ Population-based research demonstrated up to 60% of children with epilepsy are impacted by mental health difficulties, ⁴ and many children experience more than one type of mental health difficulty. ⁵ This problem is further compounded by poor access to specialty mental health care for people with epilepsy overall, ⁶ and arguably greater need for mental health professionals to manage children with epilepsy than adults. While it is often appropriate for adults with common mental health comorbidities such as anxiety or depression to be managed via pharmacotherapies such as antidepressants prescribed by neurologists or primary care physicians, in children, evidence-based care recommendations often favor psychological interventions for mental health difficulties, which typically require specially trained mental health clinicians. ⁵ Successful models of psychological care in epilepsy clinics have been developed and evaluated, but these models rely on specialty psychologists.^7,8

To overcome some of these barriers, Bennett et al ⁹ developed and evaluated an epilepsy-tailored, evidence-based psychological intervention designed to address multiple simultaneous mental health comorbidities adapted from the Approach to Therapy for Children with Anxiety, Depression, Trauma, or Conduct Problems (MATCH-ADTC). The specific intervention tested, Mental Health Intervention for Children with Epilepsy (MICE), is a personalized intervention with up to 20 weekly sessions over 6 months and up to 2 subsequent booster sessions. MICE is remotely delivered by epilepsy service clinicians without prior formal psychological therapy experience (including nurses and pediatricians). Intervention sessions are delivered to the caregiver, the child and caregiver, or the child alone, depending upon the problem targeted for an individual session and the child's age and intellectual capacity.

Bennett et al ⁹ report the results of a randomized clinical effectiveness trial comparing the MICE intervention to usual care enhanced by a psychiatric diagnostic interview among 334 children with epilepsy followed for one year. The study was conducted among children ages 3–18 years who had elevated parent-reported scores on the Strengths and Difficulties Questionnaire (SDQ) and met the Diagnostic and Statistical Manual-5 criteria for primary disorder(s) in the following categories: anxiety, depression, disruptive behavior, or trauma. Children with caregiver-reported intellectual disability or an autism spectrum diagnosis were included as long as the impairment was not so severe that they could not access the measures or intervention. Usual care included sharing psychiatric diagnostic interview results with the epilepsy care team and referrals to available local or community mental health resources. The trial demonstrated a significant improvement in behavioral difficulties at 6 months in the MICE group compared to the control (primary outcome parent-reported change in the SDQ Total Difficulties score). The benefit was durable, with a slightly higher effect size in favor of MICE at 12 monthst than at 6 months. Improvement in a child anxiety and depression scale was also observed at 6 and 12 months, as well as improved caregiver anxiety and depression measures at 6 months.

This was an extremely well-designed and conducted study, with multiple important implications for epilepsy care which may be also extended to other chronic childhood diseases and potentially adapted for adults with epilepsy. Most importantly, multiple features of the intervention design may facilitate broad dissemination of this intervention and potentially surmount barriers often faced in attempting to implement interventions previously tested in only a narrow sample of patients, rather than a more typical patient group for the clinical setting. Robust patient and caregiver/parent involvement throughout multiple stages of the research project ¹⁰ likely enhanced the intervention's broad applicability and relevance. The significant clinical outcomes achieved across such a mixed sample including a wide pediatric age range, multiple different mental health comorbidities, and individuals with autism and intellectual disability deserve great notice, suggesting a single intervention may address the bulk of mental health difficulties in a pediatric epilepsy setting and thus be well-worth investment to adopt the intervention. Furthermore, remote intervention delivery and delivery by clinicians from within the epilepsy care service without significant previous therapy experience enhance the feasibility of intervention adoption by epilepsy clinics and centers. Similar interventions are desperately needed for adult epilepsy care settings as well, particularly to address behavioral issues among adults with epilepsy and intellectual disability or autism, for whom mental health and behavioral difficulties are commonly raised by families in clinical settings but are rarely addressed, and for whom evidence in this area is scarce to nonexistent.

Despite these strengths and the potential for dissemination of MICE, some aspects of the intervention design are also threats to broad dissemination. First, while the epilepsy care setting-based intervention clinicians were typically not psychologists, they underwent an extensive training program to deliver the MICE intervention, including a 5-day intensive training followed by weekly supervised therapy delivery for 6 months and a half-day booster training after 6 months. ¹⁰ This level of time commitment for training and the expertise needed to deliver this type of training may be difficult for health systems or epilepsy centers to replicate, and further dissemination of the MICE intervention materials would be needed before this could be adopted by centers more globally. Also, the cost of delivering this intervention is unclear at present, as is its financial sustainability in settings reliant on insurance billing such as most centers in the United States. Lack of clear financial sustainability/inability to bill for evidence-based mental health interventions in epilepsy has been a barrier to implementating other psychological interventions in epilepsy, including some epilepsy self-management programs. Future directions indicated in the publication by Bennett et al ⁹ will help partly address these concerns/shed light on key factors related to dissemination: namely, the forthcoming full health economic analysis, and the in-process implementation across England.

In all, the MICE trial is a landmark epilepsy trial demonstrating the effectiveness of an integrated mental healthcare model broadly applicable to children served in epilepsy care settings and which successfully addresses a variety of mental health care difficulties. It is an invitation for the entire field of epilepsy to move forward in adopting solutions to address mental health comorbidity in epilepsy care settings.