What is the recommended approach to using Naltrexone (opioid receptor antagonist) for treating self-harm behaviors in patients with a history of psychiatric comorbidities?

Naltrexone for Self-Harm: Evidence-Based Approach

Naltrexone at doses of 25-50 mg daily may be considered as an adjunctive treatment for non-suicidal self-injury (NSSI) in patients with psychiatric comorbidities, particularly borderline personality disorder, when standard treatments have failed, though the evidence base remains limited and requires careful patient selection. 1, 2

Mechanism and Rationale

Naltrexone blocks endogenous opioid receptors, theoretically reducing the positive reinforcement that occurs when self-injury triggers endorphin release 1. By preventing this neurochemical reward, the compulsive urge to self-harm may diminish over time 1, 2.

Evidence Quality and Strength

The evidence supporting naltrexone for self-harm is substantially weaker than for its FDA-approved indications (opioid and alcohol dependence):

• A 2024 systematic review identified only a small number of studies supporting naltrexone 25-50 mg/day for decreasing or eliminating self-injurious behaviors in NSSI patients 2
• One case report demonstrated complete cessation of self-injurious behavior over 32 weeks in a patient with borderline personality disorder and dysthymia after failing neuroleptics, antidepressants, and valproate 1
• Contradictory evidence exists: A double-blind, placebo-controlled study in two profoundly mentally retarded adults showed no measurable effects on self-injurious behavior over 12-18 weeks 3

The quality of evidence is low, consisting primarily of case reports and small uncontrolled studies 2. No large randomized controlled trials have been conducted 2.

Patient Selection Criteria

Ideal candidates for naltrexone trial in self-harm:

• Patients with borderline personality disorder or other severe personality disorders exhibiting chronic NSSI 1, 2
• Failed trials of first-line treatments (SSRIs, mood stabilizers, antipsychotics, dialectical behavior therapy) 1
• No current opioid use or requirement for opioid analgesia 4
• Highly motivated patients willing to engage in concurrent psychotherapy 5, 6
• No acute hepatitis or decompensated cirrhosis 4

Critical Pre-Treatment Screening

Before initiating naltrexone for self-harm, verify:

• Complete opioid abstinence for at least 7-10 days to avoid precipitating withdrawal 4, 5
• Baseline liver function tests, as naltrexone carries hepatotoxicity risk 4
• Screen for depression, anxiety, and suicidal ideation, as naltrexone may worsen depression 4
• Confirm patient is not pregnant (naltrexone is contraindicated in pregnancy) 4
• Assess renal function; reduce dose by 50% if moderate-to-severe renal impairment present 4

Dosing Protocol for Self-Harm

Start with 25 mg daily, increasing to 50 mg daily if tolerated after 1 week 1, 2. This represents low-dose naltrexone (LDN) compared to the standard 50-100 mg used for opioid dependence 4, 2.

• Monitor liver function tests at baseline and every 3-6 months 4
• Assess efficacy after 8-12 weeks of treatment 1
• Naltrexone must be combined with intensive psychotherapy and behavioral interventions—medication alone is insufficient 5, 6

Monitoring Parameters

• Frequency and severity of self-harm episodes (weekly assessment) 1
• Depressive symptoms and suicidal ideation (particularly in patients under 24 years) 4
• Liver enzymes every 3-6 months 4
• Treatment adherence and motivation level 5, 6

When to Discontinue

Stop naltrexone if:

• No reduction in self-harm frequency after 12 weeks at therapeutic dose 1, 2
• Emergence of significant depression or suicidal ideation 4
• Liver function tests show elevation >3x upper limit of normal 4
• Patient requires opioid analgesia for pain management 4

Critical Safety Warnings

• Patients who discontinue naltrexone have markedly decreased opioid tolerance and face increased risk of overdose death if they use opioids 4
• Naltrexone blocks pain relief from opioid medications, creating a management challenge if acute pain or surgery occurs 4
• For elective procedures requiring opioids, hold oral naltrexone 2-3 days prior 4
• Educate patients about the increased sensitivity to opioids after naltrexone discontinuation 4

Common Pitfalls to Avoid

• Do not use naltrexone as monotherapy—it only works when combined with comprehensive psychotherapy and behavioral interventions 5, 6, 1
• Do not initiate without confirming complete opioid abstinence, as this will precipitate severe withdrawal 4, 5
• Do not expect rapid results—therapeutic effects may take 8-12 weeks to manifest 1
• Do not ignore the limited evidence base—this is an off-label use with minimal high-quality data 2

Alternative Considerations

Given the weak evidence for naltrexone in self-harm, prioritize evidence-based treatments first:

• Dialectical behavior therapy (DBT) remains the gold standard for borderline personality disorder with self-harm 1
• SSRIs for comorbid depression and anxiety 1
• Mood stabilizers (valproate, lithium) for affective instability 1
• Antipsychotics for severe emotional dysregulation 1

Naltrexone should be reserved for treatment-refractory cases where standard interventions have failed 1, 2.