Retrospective chart review of children on Low-Dose Naltrexone

Purpose

Low-dose naltrexone (LDN) is an opioid receptor antagonist that has shown beneficial effects for chronic pain management in adults. ‘Low dose’ refers to doses between 0.1 and 5 mg that have shown anti-inflammatory and antinociceptive effects (Parkitny & Younger, 2017). LDN targets toll-like receptor 4 (TLR4) on microglial cells, which cause nervous system inflammation through activating factors such as cytokines, interleukin (IL) 6, and tumor necrosis factor (TNF) (Younger et al., 2014). However, LDN usage remains unexplored in pediatric chronic pain. This is significant because between 15-35% of youth experience pain-related conditions such as abdominal pain and migraine, on top of other chronic pain conditions (Stancil et al., 2021; King et al., 2011). This study is the first to investigate the effects of LDN in a large cohort of children with chronic pain.

Methods

A retrospective chart review was conducted on a pediatric outpatient group at Cook Children’s Medical Center that received only LDN between January 2019 and June 2022. Functional disability inventory (FDI) and pain scores were analyzed at the initial and ‘best’ visit, i.e. the lowest FDI/pain score. The FDI is a 15-item questionnaire that measures limitations in children’s physical and psychosocial functioning. These questions include the patient’s ability to walk up the stairs, eat regular meals, and doing athletic activities. 284 total patients were prescribed LDN. Of these, 253 were excluded: 6 (2.3%) patients were prescribed LDN before March 1, 2018, 8 (3.1%) patients never started LDN, 86 (30.2%) patients had no follow-up data in the pain medicine clinic, and 153 (53.8%) patients were prescribed another medication in addition to LDN. In total, 31 patients were prescribed LDN and no other medications. Of those 31 patients, 25 had FDI scores and 23 had data for pain. Patients started LDN at an average age of 15.1 and ended LDN at an average age of 16.4. For FDI and pain scores, a Wilcoxon ranked sum test was performed since the data was ordinal and not normally distributed. IRB approval was obtained.

Results

Wilcoxon ranked sum test indicated FDI scores did significantly decrease from first (M=22.5) to best (M=16.4) (p<0.003). In contrast, the test did not reveal any significant differences between first (M=4.00) and best (M=3.52) pain scores (p<0.2).

Conclusion

The findings suggest that LDN may improve pain-related disability in pediatric patients, ultimately improving pain levels and psychosocial function. This also implies that LDN improves the daily functioning of children and allows them to complete routine tasks more efficiently. Results should be interpreted cautiously due to the retrospective study design and limited number of LDN-only cases available to review at this time. Additional prospective research should include whether LDN effects vary with age, or if certain diagnoses are more effectively treated with this medication.