Low-Dose Naltrexone for Severe Fibromyalgia Syndrome: A Report of a Case With Two-Year Follow-Up

Abstract

Fibromyalgia syndrome (FMS) is characterized by diffuse musculoskeletal pain associated with daytime fatigue, sleep disturbance, cognitive deficits, and often further somatic symptoms. While some patients with FMS respond to standard treatment with amitriptyline, pregabalin, or duloxetine in combination with outpatient multimodal pain management, there are still many who do not benefit sufficiently from this treatment or suffer intolerable side effects. Effective treatment options are therefore needed to supplement conventional therapies. Naltrexone is used in many countries as an off-label therapy in low doses for several chronic immunomodulatory disorders, including FMS. However, the strength of evidence from previous randomized controlled trials is low. I report a patient with severe FMS who did not respond to conventional therapy. Instead, low-dose naltrexone (LDN) (4.5 milligrams per day) resulted in a significant and sustained improvement in most FMS symptoms. The results of this case report suggest that an off-label use of LDN in severe refractory FMS may be a viable option. However, the information base is currently limited, and studies are conflicting.

Keywords: fatigue; fibromyalgia; neurology; neurophysiology; pain management; pharmacology; sleep disorder; widespread pain.

Figure 1. Widespread Pain Index of the patient.

At the initial assessment, painful areas were the left shoulder, right shoulder, left arm, right arm, left forearm, right forearm, neck, upper back, left hip, right hip, left thigh, right thigh, left leg, right leg, left jaw, right jaw, and chest. Areas not included were the abdomen and lower back. The Widespread Pain Index (WPI) was 17/19, indicating a high prevalence of pain across multiple body regions. The figure is a free drawing, filled in by the patient to mark the areas of pain.

Figure 2. Pain intensity and Fibromyalgia Impact Questionnaire (FIQR) follow-up: February 2023 to April 2025.

The revised Fibromyalgia Impact Questionnaire (FIQR, grey line) is a specific questionnaire designed to quantify the disability caused by fibromyalgia syndrome (FMS). A comprehensive analysis of the data from February to August 2023 revealed a value exceeding 70 points (severe impairment). Following the administration of low-dose naltrexone (LDN) 4.5 mg, a decline of 35 points was observed in April 2025, indicating mild severity. The maximum level of pain (blue line) was reduced from a mean of 90 to 55 on the 0-100 Numeric Rating Scale, while the mean level of pain (orange line) decreased from 70 to 30.

Figure 3. Fibromyalgia severity score and Patient Health Questionnaire for Depression and Anxiety 4 (PHQ-4) follow-up: February 2023 to April 2025.

Following the administration of low-dose naltrexone (LDN) 4.5 mg, the total symptom severity score for fibromyalgia syndrome (FMS) (blue line) exhibited a marked improvement, decreasing from nine points on a scale of 12 (severe, pervasive, continuous life-disturbing problems) from February to August 2023 to six points (slight or mild problems) in April 2025. The Patient Health Questionnaire for Depression and Anxiety (PHQ-4, orange line) demonstrated a decline from seven (moderate psychological impairment) to five out of 12 points (mild psychological impairment) over the same time period.