Low-Dose Naltrexone for Managing Pain and Autonomic Symptoms in Patients With Dysautonomia

Introduction  Low-dose naltrexone (LDN) has been studied in recent years as a novel off-label therapy for several conditions under the umbrella of dysautonomia, which is defined as disorders affecting the autonomic nervous system (ANS), including postural orthostatic tachycardia syndrome (POTS). Naltrexone has a paradoxical pain-reducing effect in low doses due to transient opioid receptor blockage that increases compensatory endogenous opioid signaling. It is also thought that LDN may improve autonomic symptoms by reducing microglial activation via TLR-4 antagonism and subsequently counteracting central sensitization. Patients with dysautonomia often experience comorbidities such as small fiber neuropathy and fibromyalgia. The goal of this study was to gain a better understanding of LDN's impact on autonomic symptoms and pain in patients with dysautonomia.  Methods In this chart review, we analyzed the records of 29 patients diagnosed with dysautonomia (general, POTS, or stiff person syndrome). Information collected included demographics, comorbidities, reasons for LDN prescription, LDN dose (initial and final), documented pain changes, and Composite Autonomic Symptom Score-31 (COMPASS-31). COMPASS-31 is a validated questionnaire used to measure autonomic symptom burden. COMPASS-31 scores (including subsections) were collected from patients during their initial visit to our tertiary care autonomic center, the visit when LDN was prescribed, and a follow-up visit three to nine months later. Student's t-test was used to determine statistical significance between COMPASS-31 scores from the initial visit and the LDN prescription visit, as well as between the LDN prescription visit and the follow-up visit.  Results  The most common reason for prescribing LDN to patients in this study was pain or fibromyalgia (61.11%), followed by orthostatic intolerance (27.78%). Improvement in pain was documented for seven patients (24.14%) at the follow-up visit after starting LDN. Most patients (86.21%) began LDN at a dose of 1 mg daily, but 11 subjects had an increased dose by their follow-up visit. No statistical significance was seen when comparing average COMPASS-31 total and subsection scores between the initial visit and the LDN prescription visit or between the LDN prescription visit and the follow-up visit. LDN therapy was largely tolerated with five patients reporting mild side effects. Conclusion  LDN may be prescribed for patients with dysautonomia either due to autonomic dysfunction or pain. Patients might show improvement in pain within a matter of months, but the reason why some respond better than others remains unclear. Future studies are needed to understand how LDN can impact autonomic symptoms on an individual level. With further investigation, we might discover predictors of a strong therapeutic effect from LDN in patients with dysautonomia.