Treatment Database

A tricyclic antidepressant taken at low doses at night for fibromyalgia pain and poor sleep. A Cochrane review found useful pain relief in a minority of patients; it remains a mainstay of clinical practice.

A JAK1/JAK2 inhibitor that lowered deaths in hospitalized COVID-19. It is being tested for Long COVID with cognitive impairment in the phase 3 REVERSE-LC trial, with no results yet. Carries a boxed warning.

An orally bioavailable, blood-brain-barrier-permeable small molecule with dual anti-inflammatory and insulin-sensitizing properties. Bezisterim selectively inhibits inflammation-driven ERK signaling and modulates NF-κB activation, reducing downstream expression of inflammatory cytokines.

Second-generation H1 antihistamines aimed at mast cell activation in Long COVID. Observational studies report symptom improvement, and a trial of loratadine with famotidine (STIMULATE-ICP) is ongoing.

A mast cell stabilizer that reduces the release of histamine and other mediators from activated mast cells. Oral cromolyn is FDA-approved for mastocytosis on the basis of four small randomized controlled trials (32 evaluable patients), and it is a standard treatment for mast cell activation syndrome (MCAS).

A low-dose cyclobenzaprine tablet dissolved under the tongue, FDA-approved for fibromyalgia in 2025 and aimed at unrefreshing sleep. Two of three phase 3 trials reduced daily pain, with better sleep and less fatigue.

A human IgG1 antibody fragment that selectively blocks the neonatal Fc receptor (FcRn), accelerating the degradation of pathogenic IgG autoantibodies. Investigated for dysautonomia and post-exertional malaise in PC-POTS (post-COVID POTS).

An H2 receptor antagonist that may prevent SARS-CoV-2 spike protein entry into endothelial cells and attenuates cytokine storm. In combination with H1 antihistamines, up to 72% of Long COVID patients showed symptom reduction (Glynne et al.).

A synthetic mineralocorticoid that expands blood volume by increasing sodium and water retention in the kidneys. It is used off-label for POTS and other forms of orthostatic intolerance to reduce dizziness, lightheadedness and tachycardia on standing.

An SSRI that also acts on sigma-1 receptors. A 399-person placebo-controlled trial (2026) found a modest reduction in Long COVID fatigue; given early in COVID-19, it did not prevent Long COVID. It has many drug interactions.

A nerve-pain medicine related to pregabalin, used for fibromyalgia pain and sleep. In a Cochrane review, about 35% of patients had substantial pain relief, versus 21% on placebo.

Guanfacine, an ADHD medicine, plus the antioxidant NAC, proposed by Yale researchers for Long COVID brain fog. In a 12-patient case series, 8 improved; there are no placebo-controlled trials. Guanfacine lowers blood pressure, which matters in POTS.

A selective HCN4 channel blocker that reduces heart rate by blocking the funny current of the sinus node. A randomized double-blind placebo-controlled crossover trial (Taub et al. 2021, n=22 hyperadrenergic POTS) demonstrated significant reductions in heart rate and improvements in quality of life.

A dual-action mast cell stabilizer and H1 receptor antagonist. Superior to second-generation antihistamines alone due to its combined mechanism. In the Harvard/Stanford TREATME Study, 24% (n=50) reported moderate to much better improvement. Must be compounded in the US.

A biguanide antidiabetic agent investigated for Long COVID prevention and ME/CFS treatment. The COVID-OUT RCT demonstrated early metformin use reduced Long COVID incidence by ~41% at 10 months.

An alpha-1 adrenergic agonist that increases peripheral vascular resistance, used for orthostatic hypotension (OH) and neuropathic POTS. A double-blind placebo-controlled crossover study in 20 patients found midodrine improved postural tachycardia in neuropathic POTS but not hyperadrenergic POTS.

An oral COVID-19 antiviral. Three placebo-controlled trials, including the largest, RECOVER-VITAL (n=959), found no benefit for established Long COVID; evidence for prevention during acute infection is not settled. It has many drug interactions.

An extracorporeal procedure removing and replacing plasma to eliminate autoantibodies, inflammatory mediators, and microclots. The España-Cueto et al.

Beta-adrenergic receptor antagonists used off-label for POTS, inappropriate sinus tachycardia (IST), autonomic symptoms, anxiety, and migraines in Long COVID. Low-dose propranolol (20 mg daily) has the most evidence for POTS, particularly hyperadrenergic POTS.

An acetylcholinesterase inhibitor that boosts acetylcholine signaling, including at autonomic ganglia, strengthening the reflexes that regulate heart rate and blood pressure. It is used off-label for POTS and orthostatic intolerance and has been studied for exercise intolerance in ME/CFS.

An mTOR inhibitor used to prevent transplant rejection. An uncontrolled pilot in 86 ME/CFS patients taking a low weekly dose found reduced fatigue and PEM; placebo-controlled trials are underway.

A synthetic double-stranded RNA TLR3 agonist. The Phase III RCT (n=234, Strayer et al. PLoS One 2012) showed a statistically significant 21.3% improvement in exercise treadmill tolerance on ITT analysis (p=0.047).

GLP-1 medicines for diabetes and weight loss being explored for Long COVID, MCAS and POTS. Evidence so far is an uncontrolled MCAS case series and clinician reports; a 1,058-person placebo-controlled Long COVID trial is underway.

An anesthetic injection near the stellate ganglion in the neck, intended to reset the sympathetic nervous system. Case series and uncontrolled cohorts in Long COVID report relief; there is no randomized trial.

An antidepressant widely used at low doses for sleep. A meta-analysis found modestly longer measured sleep but more side effects than placebo. It is untested in ME/CFS and Long COVID and can cause low blood pressure on standing.