Is there evidence to support the use of low-dose Naltrexone (Naltrexone) for the treatment of anxiety, depression, and/or Attention Deficit Hyperactivity Disorder (ADHD)?

From the Guidelines

Low dose naltrexone (LDN) is not recommended for anxiety, depression, or ADHD due to limited research support and insufficient evidence. While some preliminary studies suggest LDN (typically 1-4.5mg daily) may help with certain inflammatory conditions and possibly some mood disorders through its anti-inflammatory effects and endorphin modulation, the existing research is mostly small-scale, with few randomized controlled trials focusing on these specific conditions 1. The most recent and highest quality study, published in 2019, does not mention LDN as a treatment option for ADHD, instead highlighting the efficacy of stimulant medications and nonstimulant medications like atomoxetine, extended-release guanfacine, and extended-release clonidine 1.

Key Points to Consider

• Standard treatments like SSRIs, SNRIs, or stimulants have much stronger evidence bases for anxiety, depression, and ADHD
• LDN is typically prescribed off-label, requires compounding by specialty pharmacies, and may cause side effects like sleep disturbances, headaches, or gastrointestinal issues
• Patients should not discontinue current effective treatments in favor of LDN without medical supervision
• The 2019 clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents does not support the use of LDN for ADHD 1

Important Considerations for Treatment

• Stimulant medications have an effect size of around 1.0 for the treatment of ADHD, while nonstimulant medications like atomoxetine, extended-release guanfacine, and extended-release clonidine have effect sizes of around 0.7 1
• The choice of medication should be guided by the clinician's prescription choice, taking into account the characteristics of each medication and the patient's specific needs
• Patients should be closely monitored for potential side effects and adjustments to treatment should be made as needed, under the guidance of a healthcare provider 1

From the Research

Research on Low-Dose Naltrexone

• There is some research on the use of low-dose naltrexone (LDN) for various conditions, including anxiety, depression, and ADHD 2, 3, 4, 5.
• A 2018 review of LDN discussed its potential benefits in reducing glial inflammatory response and upregulating endogenous opioid signaling, which may be relevant to conditions such as fibromyalgia, Crohn's disease, and multiple sclerosis 2.
• A 2021 study found that LDN did not alter the activity of the endogenous opioid system involving proopiomelanocortin neurons, suggesting that its mechanisms may be independent of this system 3.
• A 2017 randomized controlled trial found that LDN augmentation showed some benefit for patients with major depressive disorder who were partially responsive to dopaminergic antidepressants 4.

Anxiety and Depression

• The 2017 study mentioned above found that LDN augmentation reduced symptoms of depression in patients with major depressive disorder 4.
• However, there is limited research specifically on the use of LDN for anxiety, and more studies are needed to fully understand its potential benefits and mechanisms 2, 3.

ADHD

• A 2011 study found that adjunctive atomoxetine (not LDN) was effective in reducing symptoms of anxiety and ADHD in adult patients with comorbid generalized anxiety and ADHD 6.
• There is currently no direct research on the use of LDN for ADHD, and more studies are needed to explore its potential benefits and mechanisms for this condition.

Chronic Pain

• A 2024 retrospective study found that LDN was associated with a statistically significant reduction in pain scores in adult chronic pain patients, although the clinical significance is unclear due to the high discontinuation rate 5.