Clozapine in the management of persistent destructive behaviour in a 17-year-old boy with intellectual disability

Abstract

The management of challenging and refractory destructive behaviour in young patients with intellectual disability (ID) is a major issue faced by families, carers and healthcare professionals who support them. Often, paediatricians and psychiatrists use various behavioural and psychopharmacological approaches, including polypharmacy. We report on one such patient who benefitted greatly from a trial of clozapine, resulting in less aggression, improved quality of life and potentially huge cost savings. We conclude that clozapine may represent a beneficial though seldom-used option for severe, destructive behaviour in young people with ID.

Background

Young people with intellectual disability have levels of psychopathology 3–4 times that of the normal population.¹ Both carer stress and costs of care are directly related to severity of comorbid emotional and behavioural problems,² rather than level of intellectual disability (ID). This case report describes severe emotional and behavioural problems in a young man with ID who received an inpatient trial of clozapine.

Case presentation

The patient was a 17-year-old boy with diagnoses of moderate ID, severe autism spectrum disorder (ASD) and epilepsy, living 3 days a week with his parents and 10-year-old brother, and 4 days in respite care. ASD was diagnosed at age 2.5 years, with no abnormalities on genetic testing and no reported family history of ID or psychiatric illness. Communication was primarily with single words, simple phrases or the use of picture cards.

He was admitted to manage severe destructive behaviours, primarily an autistic preoccupation with barren room surfaces. He would rip fittings from walls and ceilings at home and school, including lights, power points and built-in furniture. He had bitten through live wires and attempts to stop him were met with attacks of biting, hitting or pinching, frequently causing injury. These behaviours worsened over the previous 3 years. Sometimes, he would lash out violently for no apparent reason. Due to his size and forcefulness, his parents were physically unable to manage the aggression and they worried about the safety of his younger brother.

The patient also appeared unhappy. Previously he enjoyed family activities and amused himself looking up favourite singers on digital devices. He lost interest in this and repeatedly smashed computer screens. At times there were concerns about preoccupations with internal stimuli, prompting consideration of psychosis or a prodrome as a differential diagnosis, bearing in mind the complexity in diagnosing psychosis with comorbid ASD and severe ID. His sleep was erratic, sometimes waking in the middle of the night, breaking things or running away. Junk food was his only apparent pleasure, resulting in weight gain.

As a child he was happier and more manageable. There was less aggression and he tolerated the stimuli of being in school classrooms but remained socially isolated. He used 1–2 word verbal communication, but could write or type more complex messages. At 13 he was diagnosed with complex partial epilepsy; treated with carbamazepine resulting in seizure frequency once every 3–4 months. They were brief and self-limiting, aside from one long seizure (45 min) 3 years ago. When his aggressive behaviour worsened at 14, carbamazepine was changed to topiramate, with little improvement in behaviour and no change to seizure frequency.

Although some aspects of behaviour management were considered less than ideal at home and in the respite facility, the consistency of his behaviour across these and the school environment, made this an unlikely major contributor to the presentation. Further, environmental and behavioural management approaches had little impact on the behaviour.

Time in respite care was increased, while his school classroom eventually became spartan and barren with one teacher and one other student. He had few pleasures apart from food, making reward systems challenging. Occupational and speech therapy interventions were ceased due to risk of injury and his limited participation.

The patient saw a developmental paediatrician regularly, with less frequent community psychiatry reviews. Monitoring of challenging behaviour was facilitated with the Developmental Behaviour Checklist-Monitoring.³ He received a variety of psychotropics, including antidepressants for obsessive behaviours (citalopram, escitalopram, clomipramine, fluoxetine, mirtazapine) stimulants for impulsivity (methylphenidate, dexamphetamine), antipsychotics for aggression in ASD (risperidone, aripiprazole, quetiapine, chlorpromazine), clonidine for aggression and sleep and melatonin for sleep. Some were given at maximum recommended doses and in combination. No significant decline in aggressive behaviour occurred with any of these medications.

There is some evidence for usage of clozapine in ASD and severe behavioural disturbance, when not improved with first-line antipsychotics. In one case series, Beherec and colleagues⁴ treated six patients (age range 14–34) with clozapine over 8–12 months. They reported an average twofold reduction in number of days of aggression and a decrease in total number of psychotropics used. In another case series, Kiani and colleagues⁵ presented findings for clozapine usage in five patients with ID and severe challenging behaviour. They noted improvements in symptoms, quality of life and transition to the community.

Consequently, admission to an adolescent psychiatry ward for a trial of clozapine was jointly requested by the patient’s community paediatrician and psychiatrist.

Treatment

Due to risks of aggression to other inpatients and staff, the patient needed a separate ward area and 2:1 nurse staffing. Staffing permission was obtained from senior administrators. As he was turning 18 during the admission but lacked capacity to consent and his parents had never applied to the guardianship tribunal, the patient was presented to the state mental health tribunal. Involuntary treatment was approved on grounds of irrational behaviour and irritable mood as symptoms of a mental illness. His parents were seen regularly to discuss goals of treatment, treatment progression and to obtain consent.

Medications on admission were clonidine 300 μg/day in four divided doses, aripiprazole 15 mg mane, quetiapine 600 mg/day in three divided doses, mirtazapine 60 mg nocte, topiramate 200 mg two times per day and metformin 1 g two times per day. Physical examination was unremarkable apart from obesity, with an admission weight of 94 kg (body mass index (BMI) 32.7, 98th centile BMI-for-age). Precommencement clozapine investigations followed the widely used Australian National Clozapine Titration Guide,⁶ which also aided in the identification and management of clozapine-related side effects. All investigations were normal; however, the echocardiogram was delayed until several weeks into clozapine initiation as he needed a general anaesthetic because of poor cooperation. Parental informed consent to commence clozapine with a delayed baseline echocardiogram was obtained following discussion of the risks.

As none of his pre-existing medications, aside from mirtazapine for sleep and topiramate for seizure control were beneficial, they were ceased. Clonidine was ceased over 2 weeks. Clozapine was then commenced while aripiprazole and quetiapine were both ceased in a cross-taper. The patient was taking clozapine 200 mg/day by the time quetiapine and aripiprazole were stopped. Clozapine was further titrated to 300 mg/day. Topiramate was changed to lamotrigine under guidance of a neurologist, due to its lower propensity towards behavioural disturbance as an adverse effect. While clozapine was commenced, lamotrigine was added and titrated to 100 mg two times per day, then topiramate was ceased over 2 months. During the medication adjustment period, significant changes in his presentation appeared only once clozapine reached 300 mg/day. Thereafter, he remained an inpatient when he required clozapine observations and he returned to community care at a new group home on other days.

Outcome and follow-up

During his 4.5-month long inpatient admission, the patient often stayed in the courtyard watching passers-by or sang to himself while flapping his arms. He tore four mattresses, broke numerous light fittings, pulled apart built-in furniture and pulled a basin and taps off the wall. Nine staff assaults were recorded and five on objects. The worst incident led to a nurse needing 1 week off work with a facial injury.

When the clozapine dose reached 300 mg/day (clozapine level: 217 μg/L (RR: 350–600), norclozapine 261 μg/L), observations by his parents, inpatient staff and group home staff indicated he was ‘calmer’, ‘happier’, ‘more settled’ and ‘sleeping better’. Assaultive incidents and property destruction stopped, apart from one incident of smashing windows in his group home, coinciding with an unexpectedly low clozapine level of 68 μg/L. He was able to participate in simple outings and cognitive capacity improved. Side effects included daytime sedation which abated with time and mild constipation which was managed with over-the-counter aperients.

The patient was discharged to his community group home and the public clozapine clinic in his area. He remained well with substantially improved behaviour after 4-month follow-up but had gained 13 kg. No seizures were noted during the admission or follow-up period.

Perspectives from the patient’s family at 4-month follow-up

His mother noted happier mood and improved social inclusion. He managed to attend a café with his younger brother every weekend, without incident.

Perspectives from other healthcare staff at 4-month follow-up

His psychologist, who saw him weekly, noted more meaningful and socially complex exchanges, with better understanding of cues and improved recognition of emotional states in himself and others. Overall, aggression had reduced in frequency and intensity, while unpredictable aggression towards people had stopped altogether. He had numerous opportunities to wander from his group home but only absconded once and was easily redirected.

Discussion

This case raises numerous issues, namely: the process of inpatient admission and management, the suitability and efficacy of clozapine treatment, its apparent effects on behaviour and adaptation, and cost-effectiveness. We discuss these in turn.

The psychiatric admission of a teenager with severe neurodevelopmental disabilities can engender resistance from medical, nursing and administrative staff. Reasons may include concerns about protracted inpatient stays and physical assaults on staff and patients. Potential solutions are to request expert consultations, conduct extra supervision, up-skill medical and nursing staff via specialised courses in neuropsychiatry and promote reflective practice. Another solution involves constructing purpose-built inpatient units for adolescents with neurodevelopmental disabilities and comorbid mental illness. These exist in the USA and may serve as a model to explore.⁷

In this case, clozapine was not used to treat schizophrenia, its usual indication. However, there is some evidence that clozapine may be useful in other psychiatric conditions and as an antiviolence agent.⁸

Treatment ‘success’ in this patient arguably points towards clozapine. Confounders included the patient’s new group home environment and the introduction of lamotrigine while clozapine was titrated. However, multiple prior environmental changes, both for school and living conditions, failed to bring about desired behavioural changes. Furthermore, no discernible benefits in aggressive behaviour were observed with his previous anticonvulsants carbamazepine or topiramate and the new annual seizure frequency is indeterminate given the limited follow-up duration. Also, improvement only began when clozapine reached a blood level typically associated with symptomatic improvement.

It remains to be seen if the reduction in aggressive behaviour is sustained long-term. Indeed, further improvements may be possible, in keeping with current knowledge that the full effects of clozapine may gradually emerge over a duration up to 12 months.⁹

From a financial perspective, using clozapine in cases where there are frequent presentations owing to ‘treatment-resistance’ may afford massive cost savings to both of Australia’s healthcare and disability services, the latter of which is funded by the federal National Disability Insurance Scheme (NDIS). Prior to admission, the patient’s NDIS funding amounted to around $A1 million annually, largely because of constant 2-to-1 staff supervision. At 4-month follow-up post-clozapine treatment, this was still the case although night staffing had eased with one active (awake) and one inactive staff member within premises. Over the long-term such as 10–20 years, potential savings could amount to millions in taxpayer dollars per patient.

Learning points.

• Clozapine may be an efficacious and cost-effective choice for psychiatrists when managing such patients who fall into the ‘treatment-resistant’ group.

• Clozapine does not necessarily have to be a last-resort option nor is its titration and side-effect monitoring any different in this patient group, from patients with schizophrenia.

• A medium to long-duration inpatient admission may be necessary to titrate clozapine, however, benefits including reduction in polypharmacy, improved quality of life and potential for large cost-savings are factors in its favour.