Primary Care Underutilizes Specialist-Recommended Medications for ME/CFS

A retrospective study of 571 patients shows limited use of targeted pharmacotherapy and high reliance on dietary supplements.

For Doctors in a Hurry

Researchers investigated whether general practitioners underuse specialist-recommended pharmacologic therapies for managing myalgic encephalomyelitis/chronic fatigue syndrome symptoms.
This retrospective study analyzed the medical records of 571 patients referred to a specialty clinic between 2018 and 2022.
Only 68.3 percent of patients used specialist-recommended medications, while 72.2 percent reported using dietary supplements for symptom management.
The researchers concluded that potentially effective medications are underprescribed, leading many patients to rely on supplements to manage their symptoms.
Improving clinician education regarding available treatment options and standardized guides may enhance the management of this debilitating multisystem disease.

Bridging the Management Gap in Myalgic Encephalomyelitis

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem disease with an estimated prevalence of 0.89% (95% CI 0.60 to 1.33) based on 1994 Centers for Disease Control and Prevention criteria [1]. The condition is clinically defined by profound exhaustion and post-exertional malaise, a significant exacerbation of symptoms following minimal physical or cognitive exertion [2]. The underlying etiology remains unknown, and the prognosis is often poor, with fewer than 5% of patients returning to their pre-illness activity levels [3]. Because no medications have received regulatory approval for ME/CFS, clinicians must rely on off-label pharmacological strategies and symptom management for issues such as orthostatic intolerance (the inability to maintain an upright posture without symptoms) and sleep dysfunction [2, 4]. While behavioral interventions like cognitive behavioral therapy (a psychological approach targeting thought patterns) have demonstrated cost-effectiveness in some adult populations, pharmacological trials for agents like sodium oxybate or micronutrients remain limited in scope [5, 4]. To understand how frequently these medical therapies are implemented in general practice before patients reach specialty care, researchers recently conducted a retrospective analysis of prescribing patterns.

Quantifying the Clinical Practice Gap

To evaluate the current state of medical management for this condition, researchers conducted a retrospective analysis of clinical records from 571 patients diagnosed with ME/CFS. These individuals were referred to a single specialty clinic in Minnesota between 2018 and 2022. The study sought to determine which pharmacologic therapies and dietary supplements patients were utilizing at the time of their initial consultation, providing a window into the prescribing patterns of general practitioners. The clinical profile of the cohort reflects the complex nature of ME/CFS, a multisystem neurologic disease. Patients presented with hallmark characteristics, including profound fatigue and a marked decrease in functional capacity. Beyond simple exhaustion, the researchers documented core symptoms such as unrefreshing sleep and postexertional malaise, a specific phenomenon where symptoms worsen significantly after physical or mental activity. The clinical presentation also frequently included cognitive impairment and orthostatic intolerance (the inability to maintain an upright posture without developing symptoms like dizziness or tachycardia). Identifying effective management strategies has become increasingly urgent, as the prevalence of ME/CFS has risen exponentially in the wake of the COVID-19 pandemic. Despite this growing patient population, the findings indicate a significant gap between specialist recommendations and primary care implementation. While specialists have successfully utilized various pharmacologic therapies to address the multisystem symptoms of the disease, data from these 571 patients suggest that targeted medical interventions remain underutilized in the broader medical field.

Current Prescribing Patterns and Underutilized Therapies

The retrospective analysis revealed that 68.3% of patients had been prescribed at least one medication potentially used for ME/CFS management prior to their specialty consultation. However, the use of pharmacotherapy for comprehensive symptom management was largely limited to specific categories. The most frequently prescribed medications included serotonin-norepinephrine reuptake inhibitors, which are often used to address both mood and chronic pain pathways. Other common prescriptions identified in the patient histories were gabapentin, an anticonvulsant frequently utilized for neuropathic pain, and tricyclic antidepressants. While these medications are common in general practice, their use in this cohort was primarily restricted to the management of pain and anxiety rather than the broader autonomic, cognitive, or sleep-related symptoms of the disease. By ascertaining the specific medications patients had already tried at the time of their initial consultation, the researchers established a baseline of pre-specialty care. The findings indicate that while pharmacologic therapies have been used successfully by ME/CFS specialists to address the complex clinical presentation of the condition, such targeted therapies remain underutilized in the general medical field. For the practicing physician, this highlights an opportunity to expand the therapeutic armamentarium beyond basic pain management, incorporating off-label strategies to address autonomic dysfunction and sleep architecture before referring patients to specialized centers.

Patient Reliance on Dietary Supplements

The analysis revealed a high prevalence of self-managed care through non-prescription interventions. A total of 72.2% of patients reported having taken at least one dietary supplement prior to their specialty consultation, a figure that slightly exceeds the 68.3% of patients who had been prescribed pharmacologic treatments. This widespread use of over-the-counter products suggests that patients are actively seeking relief for their multisystem symptoms outside of traditional pharmaceutical channels. The researchers identified that the most common supplements used by this cohort were vitamin D, vitamin B12 and B complex, and fish oil. While these are frequently utilized by the general population, they may be specifically targeted by ME/CFS patients attempting to address profound fatigue and cognitive impairment. The high rate of supplement use highlights a significant clinical trend where patients resort to dietary interventions to manage symptoms in the absence of targeted pharmacotherapy. This reliance on supplements likely reflects a compensatory strategy by patients navigating a debilitating illness without access to a comprehensive medical treatment plan. For the practicing physician, these findings underscore the importance of discussing non-prescription intake during routine consultations. A patient's heavy reliance on supplements like B complex and fish oil may serve as a clinical indicator of unmet therapeutic needs, prompting the physician to explore more rigorous, evidence-based symptom management strategies.

Implications for Primary Care Management

The retrospective analysis of 571 patients referred to the Minnesota specialty clinic between 2018 and 2022 indicates a substantial gap between specialist recommendations and current primary care practice. Although 68.3% of patients had tried at least one medication for their symptoms, these interventions were largely limited to serotonin-norepinephrine reuptake inhibitors, gabapentin, and tricyclic antidepressants, which are primarily utilized for the management of comorbid pain and anxiety. The researchers concluded that potentially helpful medications for ME/CFS are being underprescribed in the general medical field, particularly those targeting the core physiological disruptions of the disease. This underutilization of targeted pharmacotherapy likely contributes to the high reliance on non-prescription interventions, as 72.2% of patients reported using dietary supplements such as vitamin D, vitamin B12, and fish oil to manage their condition in the absence of specialized medical guidance. Addressing this practice gap is increasingly urgent as the prevalence of the disease has risen exponentially following the COVID-19 pandemic. The study authors emphasize that better education of clinicians about available treatment options and treatment guides may improve management of this debilitating multisystem neurologic disease. By integrating established treatment protocols into primary care, physicians can move beyond basic pain management and more effectively address the profound fatigue, orthostatic intolerance, and decreased functional capacity that characterize the illness. Utilizing clinical treatment guides (standardized protocols that outline evidence-based pharmacologic pathways) can provide primary care providers with the necessary framework to prescribe specialist-recommended therapies, ultimately reducing the patient's reliance on self-managed supplement regimens and improving long-term clinical outcomes.

Study Info

Underuse of Pharmacologic Therapies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Before Specialist Evaluation.

Stephanie L Grach, Jaime Seltzer, Michael R Mueller, Chris A Aakre, et al.

Journal Annals of family medicine

Published April 29, 2026