Naltrexone for Severe Eye-Gouging in Down Syndrome

We present the case of a profoundly intellectually disabled, nonverbal woman in her 40s with Down syndrome who experienced life-long severe self-injurious behavior (SIB), including chronic eye-gouging that resulted in blindness. She had been unsuccessfully treated for SIB with decades of polypharmacy, including neuroleptics, antidepressants, and anxiolytics, but ultimately showed complete resolution of SIB with naltrexone therapy.

Case

“Ms. B” carried a diagnosis of Down syndrome. She was nonverbal, and while formal neuropsychological testing was not available, the evidence from history and clinical interview suggested profound intellectual disability. In addition to intellectual disability, the patient suffered from severe violent outbursts and SIB that had begun in early childhood. Of particular importance, her SIB took the form of chronic eye-rubbing and gauging. This symptom persisted for decades, was recalcitrant to treatment, and resulted in the patient blinding herself from chronic abrasion and infection. Aggressive and violent outbursts were common in her younger years but improved with age and neuroleptic management. She was first reported to have been seen by a psychiatric practitioner at 30 years old; however, numerous caregiver transfers and a complex psychosocial history resulted in considerable uncertainty about many historical details.

At the time of presentation, Ms. B was in the care of her foster mother. Details of why she was in foster care were vague; however, it was reported to be related to her intense special care needs rather than specific issues in the household of her biological family. Her foster mother was experienced with caring for intellectually disabled individuals and was an excellent support. Ms. B received nursing assistance for medication management and activities of daily living. She lived at home with her foster mother.

No specific family history of mental illness was known to providers. There was no known history of early-life trauma or neglect, though this cannot be known definitively, since the patient had undergone numerous housing and care transfers. To our knowledge, she had not been psychiatrically hospitalized, and despite chronic eye-gauging SIB, there was no known history of suicidality. She carried no other primary psychiatric diagnoses. Down syndrome had been confirmed early in life by genetic testing. There was no suspicion of any history of substance use, legal history, or homelessness.

At presentation, Ms. B was being treated with escitalopram (10 mg), paliperidone (3 mg daily), and buspirone (15 mg b.i.d.). The rational for this medication regimen was reported by her foster mother to be unclear. A primary concern had been aggression and self-injury. Despite long-term polypharmacy, she persisted in having constant, daily self-injurious eye rubbing and gouging that resulted in frequent infection. Aggressive behaviors, however, were well controlled on this regimen at the time, though no change in medication had occurred in recent history, and thus it is unknown whether this abatement in aggression was due to the natural history of her condition or medications.

Ms. B presented with her foster mother to an outpatient community care clinic for general medication management. After a few introductory appointments, her foster mother’s primary concern remained self-injurious behaviors, as well as unnecessary polypharmacy. Given the lack of SIB improvement despite numerous neuroleptics, anxiolytics, antidepressants, and other medication families, naltrexone was initiated at 25 mg and quickly titrated to 50 mg. Within 1 month of medication initiation, SIB had ceased entirely. The patient had no further eye gouging and no subsequent infections of the eye. No other SIBs were present. Escitalopram was decreased and discontinued with no adverse effects on mood, anxiety, SIB, aggression, or behavioral symptoms; then, buspirone was tapered and discontinued over 2 months without any adverse effects. The patient remained on paliperidone (3mg) and naltrexone with persistent resolution in her baseline severe SIB and continued resolution of aggression. There were no side effects of naltrexone pharmacotherapy per her foster mother’s report, and none were apparent on examination.

Discussion

This case evidences the potential severity of SIBs in adults with intellectual disability. Naltrexone was chosen in this case due to failure of approved medications commonly used for SIB in intellectual disability. The risks and benefits were carefully weighed and, in particular, given the seriousness of this form of self-injury, as well as the long-term risks of unnecessary polypharmacy, naltrexone was considered a safe and low-risk option. The options, risks, and benefits were discussed at length with the patient’s foster mother.

Naltrexone was considered with full awareness of the fact that it is not a Food and Drug Administration (FDA)-approved medication and with attention to the large number of anecdotal reports in the literature suggesting safety and potential efficacy in a range of forms of self-injurious populations. Evidence of naltrexone efficacy in SIB in the heterogeneous population of intellectually disabled adults is limited with few double-blind placebo-controlled studies. As a result of limited data, for example, a recent Cochrane Review concluded that recommendations could not be made for use of naltrexone for SIB in intellectual disability (1). Notably, three of the albeit small studies suggested clinical benefits. Safety, efficacy, dosing, and population variability in the use of naltrexone for SIB in intellectual disability requires further empirical study (1).

Despite limited data, naltrexone is frequently used off-label in self-injuring intellectual disabled patients due to the high side-effect burden of many of the other medications often utilized. Aripiprazole and risperidone are approved for behavioral treatment in autism, but there is little formal guidance for SIB management in these populations.

SIB pathophysiology is not well understood. Dysregulation of a number of neurotransmitters has been linked with SIB, including dopamine, endogenous opioid, serotonin, glutamate, and GABA systems (2). For example, the caudate nucleus, which is heavily innervated by dopaminergic neurons, has been shown to be abnormal in cases of SIB associated with a wide range of neurodevelopmental conditions (3). Glutamate works in a regulatory relationship with dopamine between the basal ganglia and prefrontal cortex and has been implicated in animal studies of SIB (4).

Endogenous opioid theories of SIB are particularly relevant in the case of naltrexone. For example, one theory speculates that endogenous opioids stimulated by pain result in down-regulation of receptors culminating in the phenomenon of “pain addiction” (2, 5). SIB may be related to hypothalamus-pituitary-adrenal dysfunction that involves dysfunction of the stress-related substance proopiomelanocortin, which is an endogenous opioid precursor. Naltrexone, a centrally acting opioid blocker that is FDA-approved for alcohol and opioid dependence, may act on this system to provide relief of self-injurious urges (6). Further exploration of SIB in intellectual disability is clearly warranted. This report adds to the evidence of potential benefit for naltrexone in severe SIB in intellectual disabled adults.

Key Points/Clinical Pearls