Medication I — Autonomic / Cardiovascular

9. Medication I — autonomic / cardiovascular

This section describes medications and basic measures used in a disorder of circulatory regulation (dysautonomia) — in particular in postural tachycardia syndrome (POTS), which frequently occurs in the context of Long COVID and ME/CFS. Important up front: the available studies are almost all small (11–54 people), mostly designed as short-term cross-over investigations and carried out predominantly in "classic" POTS, not specifically in people with Long COVID or ME/CFS [5][10]. None of the substances named is approved in Germany for treating POTS — all are used off-label [10][11]. The therapy is fundamentally symptom-oriented and individual; in ME/CFS with exertion intolerance (PEM) these agents only ease circulatory symptoms and do not replace pacing [10].

Safety frame (applies to all the following substances): choice, dosing, tapering in and out and monitoring belong strictly in a doctor's hands. Agents affecting heart rate and blood pressure generally require baseline diagnostics (among them ECG, blood-pressure/pulse course) and follow-up checks. Do not stop or up-dose beta-blockers, ivabradine and pyridostigmine on your own. Interactions (e.g. further heart-rate-lowering agents, CYP3A4 interactions) and individual contraindications are to be checked by a doctor beforehand. This text is not an instruction for self-medication and promises no cure.

Basic therapy: salt and fluids

Best evidenced is volume/salt loading. In a controlled cross-over diet study (n=14 women with POTS) a high-salt diet (300 mmol ≈ 6.9 g sodium/day, corresponding to ≈ 17.5 g table salt) increased blood volume, lowered the standing heart rate and the noradrenaline raised on standing [7]. This study dose is considerably higher than the usual intake and was given under study conditions — such a high salt intake should not happen on one's own but only with medical guidance. Professional societies (Heart Rhythm Society) recommend, as a guide, about 10–12 g table salt (≈ 3–4 g sodium) and 2–3 litres of fluid daily [7]. Buffered electrolyte mixtures are gentler on the stomach than pure table salt. Contraindications/caution: heart failure, kidney disease, arterial hypertension; in these constellations an increased salt/fluid intake is potentially dangerous and defensible only after consulting a doctor. Acute i.v. saline infusions (1–2 l) improve symptoms in the short term (hours to days) but, because of infection and thrombosis risk (especially with an indwelling catheter), are explicitly not recommended as a long-term therapy [7].

Lowering the heart rate

Propranolol (low dose). Non-selective beta-blocker, CNS-penetrating, lowers the heart rate; by blocking β2-mediated vasodilation, peripheral vascular resistance can rise. In a randomised cross-over study (n=54) a low dose (20 mg) lowered the standing heart rate from 108 to 86/min and improved symptoms; a higher dose (80 mg) lowered the pulse more but did not improve symptoms further and in part worsened them (light-headedness, "brain fog", shortness of breath) — hence the principle "less is more" [2]. A small RCT (n=11) reported an acutely improved maximal oxygen uptake [3] (small sample, single finding — of limited reliability). Safety: off-label (approved among others for hypertension, angina); caution with low baseline blood pressure; in asthma/COPD non-selective beta-blockers are generally contraindicated because of bronchoconstriction, or defensible only in exceptional cases. Fatigue/tiredness is a generally known side effect documented for beta-blockers as a drug class – not an ME/CFS-specific effect. It carries more weight in ME/CFS and Long COVID, however, because fatigue is already pronounced there [2][5]. Do not stop abruptly (rebound tachycardia/blood-pressure rise possible); watch for bradycardia and AV conduction disturbances. Cardioselective beta-blockers (metoprolol, bisoprolol, nebivolol) have a much weaker, mostly retrospective evidence base (class IIb recommendation) [5].

Ivabradine. Selective inhibitor of the I_f channel in the sinus node; lowers the heart rate in a purely sinus-node-specific way without a drop in blood pressure, without a negative effect on heart contractility and without bronchoconstriction — an advantage over beta-blockers [1][8]. The best evidence comes from a randomised, double-blind, placebo-controlled cross-over study in hyperadrenergic POTS (n=22): the standing heart rate fell from 94 to 78/min, physical and social function improved, without relevant hypotension [1]. Safety: in the EU/Germany, ivabradine is approved only for symptomatic chronic heart failure and stable angina pectoris (coronary heart disease); use in inappropriate sinus tachycardia and in POTS is off-label (corrected: inappropriate sinus tachycardia is not an approved indication but a guideline-supported off-label use) [8]. Side effects: flashes of light/phosphenes (~3 % in the SHIFT study), bradycardia, increased atrial-fibrillation risk; contraindicated in pregnancy (teratogenic in animal studies), reliable contraception needed. Relevant interactions with strong CYP3A4 inhibitors and with verapamil/diltiazem (contraindicated or to be avoided) [1][8]. For Long COVID, the protocol of the randomised COVIVA study (ivabradine in post-COVID POTS/inappropriate sinus tachycardia; 2:1 active:placebo, ~40 evaluable people) was published in 2025; efficacy results are still pending. In addition, the larger platform study RECOVER-AUTONOMIC is studying POTS in Long COVID [9].

Pyridostigmine (Mestinon). Acetylcholinesterase inhibitor, strengthens the vagal "brake" on the heart and thereby lowers the heart rate without a rise in blood pressure. In a randomised cross-over study (n=17) 30 mg lowered the standing heart rate after 2 h from 111 to 100/min and improved the symptom score [4]; a retrospective case series (n=203) reported improvement in ~50 % [5] (retrospective, without a control group — only of limited reliability). Safety: off-label (approved for myasthenia gravis); typical side effects are abdominal cramps, nausea, diarrhoea, increased salivation/sweating — favourable with accompanying gastroparesis/constipation, unfavourable with diarrhoea [4][5]. Caution/contraindication with mechanical gastrointestinal or urinary-tract obstruction and with asthma (cholinergic bronchoconstriction/bradycardia possible).

Stabilising blood pressure and volume

Midodrine. A prodrug; its metabolite is a peripheral alpha-1 agonist that constricts vessels and veins, increases venous return and reduces venous "pooling". The approval rests on orthostatic hypotension (RCT n=171) [6]; in POTS there is cross-over evidence for less pooling [5]. Short duration of action (~4 h). Safety: off-label in POTS; characteristic are goose bumps, scalp tingling, urinary retention and above all a rise in blood pressure when lying down (supine hypertension) — the last dose should be several hours before lying down. Contraindications include severe organic heart disease, acute kidney disease, urinary retention, phaeochromocytoma, thyrotoxicosis; blood-pressure checks (also when lying down) are recommended [6].

Fludrocortisone. Synthetic mineralocorticoid; increases sodium/water retention and plasma volume. The evidence is weak and inconsistent — a placebo-controlled study in neurally mediated hypotension/chronic fatigue showed no advantage over placebo (class IIb recommendation) [5]. Safety: off-label; potassium loss (regular potassium checks recommended), oedema, high blood pressure, headache; blood-pressure checks and caution with longer use (mineralo-/glucocorticoid effects). Only sensible with sufficient salt and fluid intake [5].

Assessment

Overall, the evidence is limited and comes from small short-term studies; the most reliable are low-dose propranolol, ivabradine (hyperadrenergic POTS), pyridostigmine and salt/volume loading [1][2][4][7]. All statements concern the short-term symptom relief of circulatory complaints; proof of a lasting or disease-modifying benefit in Long COVID/ME/CFS is lacking, and none of the substances cures the underlying disease. The German AWMF S1 guideline Long/Post-COVID explicitly names POTS/dysautonomia and points to a symptom-oriented, individual therapy; the BfArM maintains an expert group on off-label use [10][11]. All statements do not replace medical advice; choice, dosing and monitoring belong in a doctor's hands.