Naltrexone use for self-injurious behavior in patients with developmental disabilities

Self-injurious behavior (SIB) is a serious problem seen in individuals with developmental disabilities (DD). Evidence-based options for the treatment of SIB in patients with DD are limited and no medication is approved for this indication. Non-pharmacotherapeutic options including environmental change and behavioral therapy are generally recommended for use as first line therapy. However, these options are sometimes inadequate.¹ Despite lack of strong evidence, a variety of medications are used for SIB in DD. These include: antipsychotics (typical and atypical), antiepileptic drugs (e.g. divalproex, carbamazepine, etc.), lithium, and antidepressants (particularly selective serotonin reuptake inhibitors). First line agents include atypical antipsychotics (e.g. risperidone, olanzapine) and mood stabilizers (e.g. divalproex, carbamazepine).² However, if a patient fails to respond to these agents or has contraindications to these options, other agents may occasionally be utilized. One such agent is the opioid antagonist naltrexone. Using naltrexone for the treatment of SIB comes from the theory that SIB is influenced by the release of endogenous opioids. Therefore, blocking the effects of these opioids could attenuate these behaviors. This article briefly summarizes the evidence for safety and efficacy of naltrexone for SIB in DD.

STUDY 1

Casner et al. conducted a retrospective study of institutionalized patients (mean = 35.3 y/o) in Texas treated with naltrexone for SIB over a 5-year period. SIB was defined as bodily harm resulting in tissue damage and lasting for at least one year. Specific behaviors included head banging, self-biting, hitting, scratching, hair pulling, and skin picking. A total of 56 individuals received naltrexone during the study period. The majority of these patients were categorized as having severe-to-profound mental retardation. Doses ranged from 25–300 mg/day (mean = 96.8 mg/day) and treatment duration ranged from 3–87 months (mean = 36.5 months). Fifty-six percent of the patients were considered by the interdisciplinary treatment team to have responded (based on objective data or clinical impressions). However, a more objective analysis by the authors indicated that only 13 patients were considered strict “objective responders”. Objective responders were defined as patients with at least a 50% reduction in SIB with a statistically significant difference from baseline. One patient had a transient elevation in liver enzymes that resolved following medication discontinuation. Another patient had an increase in blood pressure following increasing his dose to 150 mg/day. The hypertension was treated successfully with propranolol and his dose was ultimately maintained at 300 mg/day for 2 years. Overall, this study has many shortcomings including being uncontrolled. However, it does demonstrate that naltrexone may be a beneficial option for DD patients with SIB.³

STUDY 2

Willemsen-Swinkels et al. conducted a double-blind, placebo-controlled crossover study of patients in an assisted living facility in the Netherlands. Seventeen subjects with DD and SIB were treated with either naltrexone 100 mg or placebo for four weeks followed by a washout period then a 4 week crossover treatment with the other agent. Patients were then enrolled in long term treatment with 50 mg/day or 150 mg/day. This study found there were no differences in naltrexone treatment compared to placebo. Staff members (no mention of blinding) were asked whether they believed each patient behaved better on naltrexone or on placebo. Approximately half of the subjects were deemed better on placebo and half better on naltrexone. Safety issues were uncommon. One patient displayed a worsening in behavior (i.e. acting out) and SIB secondary to the initiation of naltrexone that resolved following the discontinuation of naltrexone. Another patient complained of significant nausea and three others were observed by staff to be sedated while on 150 mg/day. The authors concluded there is no evidence to support the use of naltrexone for this indication. However, this study has several limitations including lack of blinding, multiple changes in protocol, and variable process for determining efficacy.⁴

NOTABLE CASES/STUDIES

Multiple case reports and case series describe the use of naltrexone for the treatment of SIB. One case report described the use of naltrexone for a 3-year old with head banging and repeated ear-slapping that ultimately resolved following addition of naltrexone. Naltrexone treatment was continued for three years in doses up to 50 mg/day.⁵ Another study described a 28 y/o female patient with a profound decrease in SIB during naltrexone use that persisted even after discontinuation (follow-up of 6 months).⁶ One report summarized the case of a 24 y/o patient with a severe intellectual disability and autism whose SIB worsened significantly with the addition of naltrexone and returned to baseline following naltrexone discontinuation.⁷ Another notable study summarized the available literature up to 2003 and quantified the response of individuals with DD treated for SIB. This study found that 80% of the 86 subjects described had relative improvements in symptoms. Additionally 47% of patients had at least a 50% reduction in symptoms from baseline, as determined by study authors.⁸

CONCLUSION AND APPLICATION TO CLINICAL PRACTICE

Overall, the literature suggests that naltrexone is an option clinicians should be aware of for the treatment of SIB in patients with DD. Its use should be considered when first line agents (e.g. atypical antipsychotics, divalproex, carbamazepine) have failed or are contraindicated. Available studies use a variety of starting doses. In adults, 50 mg/day is the most common starting dose. Studies in children and adolescents most commonly use a dose of 0.5–2 mg/kg/day (starting doses vary). Titration generally occurs fairly slowly with a normal maximum dose of 100 mg/day (one report of 300 mg/day). Response is generally seen within days of initiation. However, some studies report decreasing symptoms over a period of months. Baseline target symptoms should be recorded as occurrences of SIB/hour or rated based on severity. If specific target symptoms of SIB are not resolving, discontinuation is warranted.

It is important to note that this is an off-label use and is not without its potential dangers. Contraindications to use include existing liver dysfunction or current or projected use of opioids. The package insert contains a boxed warning for hepatotoxicity when used at higher than therapeutic doses. Hepatic enzymes should be monitored at baseline and periodically thereafter (e.g. at 1 month, then every 6–12 months). The most common adverse effects to monitor include gastrointestinal upset and insomnia. As with any pharmacotherapy, it is important to weigh the risks and benefits and continuously monitor for appropriateness.