Chronic fatigue
Persistent fatigue over weeks or months in the absence of confirmed medical causes (anaemia, hypothyroidism, depression, iron or B12 deficiency, chronic infections). Distinct from chronic fatigue syndrome / myalgic encephalomyelitis.
ICD-10 R5337 drugs
Also known as: Unspecified fatigue
Drugs used for this condition
Marketing claims without evidence base
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
- DAscorbic acidNot recommended · Vitamins. AntioxidantsAscorbic acid (vitamin C) is widely offered and marketed as a remedy for tiredness – in supplements, effervescent tablets and vitamin blends. For chronic fatigue this use has no convincing benefit: there is no quality evidence that taking vitamin C relieves fatigue in people who are not deficient in it. Persistent fatigue responds to a different approach – finding the cause (poor sleep, anemia, thyroid problems, depression and other conditions) and treating that cause with a doctor. Do not take this product instead of a treatment with proven benefit, or you may miss a condition that needs real care.
- DAstragalus root (Astragalus membranaceus; Huang Qi in traditional Chinese medicine)Not recommended · Root of the perennial legume Astragalus membranaceus and its extracts. In traditional Chinese medicine, Huang Qi is used to «tonify Qi»; modern marketing sells it as an «immune modulator», a «longevity and telomere supplement», and supportive care in oncology. Neither AEMPS nor EMA registers it as a medicine; the EMA HMPC has not published a dedicated monograph on astragalus. AESAN classifies it as a complemento alimenticio. FDA has issued no approval.Astragalus is often sold as an «adaptogen» for chronic fatigue, burnout, and post-viral syndrome. No high-quality RCTs with hard endpoints (validated fatigue scales, return-to-work rates, objective tests – ESR, thyroid hormones) exist for astragalus in chronic fatigue. The term «adaptogen» is a marketing construct from 1940s Soviet toxicology and is absent from the European Pharmacopoeia and Spanish AEMPS framework. NICE NG206 for myalgic encephalomyelitis/chronic fatigue syndrome recommends an individualised plan of energy management (pacing), psychological support, gradual return to activity, and treatment of comorbidities; neither astragalus nor «adaptogens» appear in the guideline. If fatigue lasts over 6 months and impairs function, consider seeking a second opinion – iron deficiency, hypothyroidism, depression, long COVID, sleep apnoea, untreated coeliac disease, and occult infection should be ruled out.
- DBeta-1,3/1,6-D-glucan (yeast or oat)Not recommended · Polysaccharide immunomodulator. Oat beta-glucan is a dietary fibre with EFSA-approved cholesterol health claim. Yeast beta-glucan (Wellmune) is a supplement with immunity marketing without EFSA approvalBeta-1,3/1,6-D-glucan is a polysaccharide from the cell wall of baker's yeast or from oats. Supplements market it for chronic fatigue and immune support. For chronic fatigue, beta-glucan has not shown convincing benefit, and there is no good clinical evidence for this use. Persistent fatigue calls for finding the cause (anemia, hypothyroidism, iron or B12 deficiency, sleep problems, depression) and treating that. Beta-glucan is harmless here, but it should not replace treatment your doctor has chosen, since that can mean missing a condition that does respond to therapy.
- DBifidobacterium longumNot recommended · Probiotic, Bifidobacterium genus bacteria. Supplement in Russia and Spain; marketing segment of «psychobiotics» promising gut-brain axis effects. AEMPS does not register it as a medicineBifidobacterium longum is a probiotic strain sold as an energy supplement and promoted for chronic fatigue. For this use the data fall short: there is no solid evidence base that the strain relieves chronic fatigue. When fatigue persists, what helps is finding the cause with a doctor (anemia, thyroid problems, sleep disorders, depression) and treating that. Don't use this supplement in place of a proper workup and a treatment with proven benefit
- DBiotinNot recommended · Vitamin B7 (H). Water-soluble vitamin, cofactor of four carboxylases. AEMPS registers biotin as a medicine for treating confirmed deficiency; in multivitamins and mono-supplements – dietary supplementBiotin (vitamin B7) is a water-soluble vitamin marketed as a supplement for energy and against fatigue. There is no convincing evidence that biotin helps with chronic fatigue – the data for this use are lacking, and biotin deficiency is very rare in people on a normal diet. For persistent fatigue it makes more sense to look for the cause with a doctor: check sleep, thyroid function, iron and B12 levels, and emotional state.
- DCordyceps (Cordyceps sinensis, Cordyceps militaris)Not recommended · Medicinal mushroom of Tibetan and Chinese medicine, supplement. AEMPS does not register as medicineCordyceps (the fungi Cordyceps sinensis and Cordyceps militaris) is sold as a supplement for energy and chronic fatigue, often with promises of better stamina. There is no convincing evidence that it helps with chronic fatigue: the data come from small, low-quality studies, and major clinical guidelines do not include it for this use. When fatigue persists, the more useful step is to look for a cause with a doctor (anemia, thyroid problems, iron or vitamin D deficiency, poor sleep, depression) and to work on sleep and gradual physical activity.
- DCyanocobalaminNot recommended · Vitamins. Haemopoietic stimulantsCyanocobalamin is a form of vitamin B12, often promoted as a remedy for fatigue and an energy boost, including for people without a B12 deficiency. In patients with normal B12 levels, no convincing benefit for chronic fatigue has been shown – there is no evidence base for this use. When fatigue persists, the useful step is to look for the cause: check sleep, thyroid, iron and B12 levels, and rule out depression or chronic illness before choosing treatment. B12 makes sense when a deficiency is confirmed, but it does not replace addressing the actual cause of the fatigue.
- DD-riboseNot recommended · Pentose monosaccharide; complemento alimenticio with a claimed role in energy metabolismD-ribose is marketed as a universal remedy for chronic fatigue and fibromyalgia, promising «cellular energy». The marketing basis is an open-label pilot by Teitelbaum (2006) in 41 people without placebo control. This is not an evidence level that supports a recommendation. No double-blind RCTs in fibromyalgia or chronic fatigue syndrome are in the Cochrane Library. NIH ODS rates the fatigue data on D-ribose as insufficient. Persistent fatigue requires workup (ferritin, B12, TSH, depression and sleep screening), not a supplement.
- DEleutherococcus senticosus («Siberian ginseng»)Not recommended · Plant adaptogen, supplement. In EU – traditional herbal medicinal product (EMA HMPC); OTC tincture in RussiaEleutherococcus is the top-selling adaptogen in Russia as a «natural energiser» for «weakness and exhaustion». Evidence base in chronic fatigue syndrome: small RCTs with heterogeneous results; no Cochrane systematic review. EMA HMPC 2014 recognises «traditional use for symptoms of weakness» without requiring evidence. NICE ME/CFS 2021 (NG206) recommends pacing and multidisciplinary follow-up; eleutherococcus is not mentioned. If eleutherococcus was recommended for persistent fatigue without workup (ferritin, TSH, HbA1c, depression and sleep apnoea screening), consider seeking a second opinion.
- DGlycine (as a marketed «nootropic»)Not recommended · Other psychostimulants and nootropics (local classification)Glycine is an amino acid sold as a nootropic and promoted for chronic fatigue, with the promise of restoring energy and focus. There is no solid evidence that it helps with chronic fatigue, so no proven benefit for this use. Lasting tiredness usually has a treatable cause worth finding: sleep quality and schedule, deficiencies (iron, vitamin B12, thyroid), chronic conditions, mood, so it is worth discussing symptoms with a doctor and running basic tests. Glycine is harmless in this role, but do not take it instead of proper workup and treatment that does work, or you may miss the real cause.
- DLecithin (soy or sunflower phosphatidylcholine)Not recommended · Phospholipid mixture, dietary supplement. A mass OTC «memory drug» and «hepatoprotector» in Russia. Essentiale (Sanofi, essential phospholipids) is a separate regulated medicine, registered by AEMPS and in Russia for NAFLDLecithin (soy or sunflower phosphatidylcholine) is a source of phospholipids sold as an "energy" supplement and promoted for chronic fatigue. Studies have not shown a clear benefit for this use, and reliable evidence for it is lacking. Persistent fatigue responds to finding and treating its cause instead – anemia, thyroid problems, iron or vitamin B12 deficiency, sleep disorders, depression – along with better sleep and regular activity. The substance itself is harmless here, but do not take it in place of a proper workup and treatment that works, or you may miss the real cause.
- DLevocarnitine (L-carnitine)Not recommended · Amino acid derivative; cofactor for long-chain fatty acid transport into mitochondriaL-carnitine is marketed for chronic fatigue based on its role in energy production. Healthy adults on a normal diet have normal carnitine levels and do not gain energy from supplementation. NIH ODS states directly: convincing evidence of benefit in chronic fatigue or fibromyalgia is lacking. Persistent fatigue requires workup (ferritin, B12, TSH, depression and sleep screening), not a supplement.
- DMethylcobalaminNot recommended · Active coenzyme form of vitamin B12Methylcobalamin is an active form of vitamin B12. For chronic fatigue it is often marketed as a supplement for energy and alertness. In people without a B12 deficiency, no convincing benefit for this condition has been shown, and there is no reliable evidence for such use. When fatigue persists, it makes sense to look for the cause with a doctor: check sleep, thyroid, iron and B12 levels, rule out depression and other conditions, and treat whatever is found. Methylcobalamin is harmless in this role, but it should not be taken instead of treatment with proven benefit, or you may miss the care you actually need.
- DNicotinamide mononucleotide (NMN)Not recommended · Dietary supplements, NAD+ precursors (local classification)Nicotinamide mononucleotide (NMN) is a NAD+ precursor marketed as an anti-fatigue and energy supplement. For chronic fatigue it has not shown convincing benefit: there is no solid evidence for this use. What actually helps is finding and treating the cause of the tiredness (sleep, iron and vitamin D deficiencies, thyroid problems, depression), and chronic fatigue syndrome is managed with paced activity and supportive care under medical supervision. Do not take NMN instead of an approach with proven benefit, so you don't miss the treatment you need.
- DNicotinamide riboside (NR)Not recommended · Dietary supplements, NAD+ precursors (local classification)Nicotinamide riboside (NR) is a form of vitamin B3 sold as an energy supplement and marketed for chronic fatigue. NR has not shown convincing benefit for this condition – there is no evidence base for this use. With ongoing fatigue, the more useful step is to find the cause with a doctor: checking sleep, deficiencies (iron, B12, vitamin D), thyroid function, mood, and chronic illness, then treating what turns up. NR is harmless in this role, but do not take it instead of proper evaluation and treatments with proven benefit, or you risk missing the real cause.
- DPyrroloquinoline quinone (PQQ)Not recommended · Dietary supplements, redox cofactors (local classification)Pyrroloquinoline quinone (PQQ) is a compound with antioxidant properties, sold as a supplement "for energy" and marketed as a way to relieve chronic fatigue. PQQ has not shown convincing benefit for this condition, and there is no good-quality evidence that it works here. With persistent fatigue, the first step is to find and treat the underlying cause (sleep, iron deficiency, thyroid problems, depression, chronic illness) together with a doctor. PQQ is safe in this use, but it does not replace treatments with proven benefit, and relying on it instead of proper workup and care delays real help.
- DRhodiola rosea (golden root)Not recommended · Plant adaptogen, supplement. In EU – traditional herbal medicinal product per EMA HMPC monographRhodiola is sold as a «natural energiser» for office workers with burnout and patients with chronic fatigue. Several small RCTs in 50–100 subjects showed moderate reductions in fatigue scores at 200–600 mg/day of standardised SHR-5 extract. No Cochrane systematic review on rhodiola in chronic fatigue syndrome. EMA HMPC 2012 recognises «traditional use for symptoms of weakness» without requiring evidence. NICE ME/CFS 2021 (NG206) recommends pacing and multidisciplinary follow-up; rhodiola is not in guidelines. If rhodiola was recommended for persistent fatigue without workup (ferritin, TSH, HbA1c, depression and sleep apnoea screening), consider seeking a second opinion.
- DSchisandra chinensis (magnolia berry)Not recommended · Plant adaptogen, supplement. In EU – EMA HMPC assessment 2024; OTC tincture in RussiaSchisandra is traditionally used in Russia as a tonic for mental and physical fatigue. Evidence base in chronic fatigue: small RCTs with small samples and heterogeneous results. EMA HMPC 2024 recognises «traditional use for symptoms of weakness» without requiring evidence. NICE ME/CFS 2021 (NG206) recommends pacing for chronic fatigue; schisandra is not mentioned. If schisandra was recommended for persistent fatigue without workup, consider seeking a second opinion.
- DTaurineNot recommended · Sulfur-containing amino acid, supplement and energy-drink ingredient. In Russia registered as a medicine (Dibicor) for T2DM and CHFTaurine is marketed as a «natural energiser» for office workers and people with chronic fatigue. No evidence base for efficacy in chronic fatigue syndrome (ME/CFS), long COVID or burnout. EFSA 2009 approved no health claim. NICE ME/CFS 2021 (NG206) recommends pacing and multidisciplinary follow-up; taurine supplements are not mentioned. If taurine was recommended for persistent fatigue without workup (ferritin, TSH, HbA1c, depression and sleep apnoea screening), consider seeking a second opinion.
- DTurkey tail (Trametes versicolor, Coriolus versicolor)Not recommended · Medicinal mushroom. In Japan PSK (Krestin) approved as chemotherapy adjuvant for gastric cancer since 1977. In EU and AEMPS not registered as medicine; sold as supplementTurkey tail is a medicinal mushroom (Trametes / Coriolus versicolor) and the source of the polysaccharides PSK and PSP. It gets promoted as an immune supplement and for chronic fatigue. No convincing benefit has been shown for chronic fatigue itself: there is no solid evidence base for this use. What actually helps with persistent fatigue is finding and treating the cause (for example anemia, thyroid problems, sleep disorders, or depression), and for chronic fatigue syndrome, working on sleep, activity pacing, and symptoms together with a clinician. Don't take this supplement in place of treatment with proven benefit, or you risk missing the care you need.
- DUrolithin A (ellagitannin metabolite, mitophagy activator)Not recommended · Ellagitannin metabolite, supplement. Formed by gut microbiota from ellagitannins in pomegranates, walnuts and raspberries. Synthetic form Mitopure (Amazentis) is patented and sold in EU and USUrolithin A as Mitopure (Amazentis) is actively sold as a «natural mitophagy activator» in age-related muscle loss and chronic fatigue. Liu 2022 (Cell Reports Medicine) RCT in 88 middle-aged adults showed 12% muscle endurance improvement on 6-minute walk test at 1000 mg/day × 16 weeks vs placebo; Andreux 2019 (Nat Metab) RCT in 60 elderly – mitochondrial function biomarker increase. Sample sizes small; no multicentre RCTs with functional status, mortality or hospitalisation endpoints. In chronic fatigue syndrome (ME/CFS) NICE 2021 (NG206) recommends pacing and multidisciplinary follow-up; urolithin A is not mentioned. If urolithin A was recommended for persistent fatigue without workup (ferritin, TSH, HbA1c, depression and sleep apnoea screening), consider seeking a second opinion from a general practitioner.
- DVitamin B12 (cobalamin)Not recommended · Water-soluble B-vitamin; cofactor of methionine synthase and methylmalonyl-CoA mutaseVitamin B12 (cobalamin) is a water-soluble vitamin needed for blood formation and nerve function. For chronic fatigue it is often taken and marketed as an energy booster, yet no convincing benefit has been shown for this use in people who are not B12-deficient. When fatigue persists, the useful step is to find its cause with a doctor: check sleep, thyroid, iron levels, mood, and other conditions. The vitamin itself is harmless here, but it should not replace proper evaluation and treatment with proven benefit, or the real cause may be missed.
- FAmitriptylineNot recommended · Tricyclic antidepressants (TCA)Amitriptyline is a tricyclic antidepressant with marked sedative and anticholinergic effects. In Spain it is licensed for major depressive disorder, neuropathic pain, prevention of chronic tension-type headache and migraine in adults, and nocturnal enuresis in children aged 6 and over (Tryptizol SmPC, section 4.1). Chronic fatigue is not on this list. It is still often prescribed for fatigue: in PatientsLikeMe data (2011), only 9% of 1197 people taking amitriptyline did so for its licensed indication, the rest off-label, including the fibromyalgia and chronic fatigue syndrome community. There are no randomised trials of amitriptyline for chronic fatigue or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). NICE NG206 (2021) advises against offering any medicine or supplement to cure ME/CFS and notes that these patients may tolerate medicines less well. The European EUROMENE consensus (2021) lists tricyclics such as amitriptyline only to relieve accompanying pain and sleep problems, not fatigue itself. The drug itself very commonly causes drowsiness and lethargy and commonly causes fatigue, along with dry mouth, constipation and orthostatic hypotension. Urinary retention, acute angle-closure glaucoma, QT prolongation and arrhythmias are possible, and an adult dose of 750 mg or more can cause severe poisoning (SmPC, sections 4.4, 4.8, 4.9). It is contraindicated after a recent myocardial infarction, with heart block or rhythm disorders, severe liver disease and with MAO inhibitors. The AGS Beers Criteria 2023 advise avoiding amitriptyline in older adults. In patients under 25, antidepressants increase the risk of suicidal behaviour. Alcohol and sedatives add to the drowsiness. If amitriptyline was prescribed for fatigue, it is reasonable to discuss the goal, the dose and a tapering plan with your doctor: stopping abruptly after long use can cause headache, malaise and insomnia.
- FBuprenorphine (transdermal)Not recommended · Opioid analgesic – partial μ-opioid receptor agonistTransdermal buprenorphine is an opioid analgesic, a partial μ-receptor agonist in patch form. It is prescribed for moderate-to-severe chronic pain when other drugs are ineffective (AEMPS Ficha Técnica). For chronic fatigue without a confirmed pain syndrome, buprenorphine is strictly not indicated. The drug has serious risks: opioid dependence (FDA boxed warning), respiratory depression, constipation, nausea, QT prolongation, fall and fracture risk in older adults, and withdrawal syndrome on abrupt discontinuation. If a buprenorphine patch was prescribed for fatigue, seek a second opinion immediately.
- FCytoflavin (succinic acid, nicotinamide, riboflavin, inosine complex)Not recommended · Other metabolic agents (local classification)Cytoflavin is a Russian combination of succinic acid, nicotinamide, riboflavin, and inosine. It is not included in international clinical guidelines, and the FDA, EMA, and AEMPS have not approved it. Cytoflavin is prescribed for the Soviet-era diagnoses asthenic syndrome, nervous-system exhaustion, post-infectious asthenia, and dyscirculatory encephalopathy, none of which exist in ICD-11 or international neurology. There are no independent international clinical studies with endpoints on validated fatigue or cognitive scales. For chronic-fatigue complaints, the workup should include anemia, B12 deficiency, hypothyroidism, depression, obstructive sleep apnea, and chronic infections: the cause is often one of these. For dizziness attributed to blood pressure, check blood pressure, hemoglobin, and rule out cardiac arrhythmia. If cytoflavin was prescribed for asthenia or after an acute respiratory infection, consider seeking a second opinion.
- FDeflazacortNot recommended · Systemic glucocorticoid (oxazoline derivative)Deflazacort is a systemic corticosteroid. It is prescribed for Duchenne muscular dystrophy, autoimmune diseases, and acute exacerbations of asthma (AEMPS Ficha Técnica). For chronic fatigue without a confirmed diagnosis, deflazacort is not indicated. The drug has serious risks on long-term use: adrenal suppression, steroid diabetes, osteoporosis, immunosuppression, psychiatric disturbances, cataract, and hypertension. If deflazacort was prescribed for fatigue without a confirmed diagnosis, seek a second opinion immediately.
- FDexamethasoneNot recommended · GlucocorticoidsDexamethasone is a potent systemic corticosteroid. It is prescribed for acute autoimmune crises, severe allergic reactions, cerebral edema, chemotherapy, and as part of protocols for severe infections (bacterial meningitis, severe oxygen-requiring COVID-19 per RECOVERY 2021). For chronic fatigue without a confirmed diagnosis, dexamethasone is not indicated. The drug has a catastrophic risk profile on long-term use: HPA axis suppression (dangerous withdrawal syndrome), steroid diabetes, osteoporosis with fractures, avascular necrosis of bones, immunosuppression with risk of severe infections, psychiatric disturbances (psychosis, insomnia), cataract, and hypertension. If dexamethasone was prescribed for chronic fatigue without a confirmed diagnosis, seek a second opinion immediately.
- FDuloxetineNot recommended · SNRIDuloxetine is an SNRI antidepressant. It is prescribed for major depression, generalized anxiety disorder, diabetic peripheral neuropathy, and fibromyalgia (APA 2022, NICE NG222). For ordinary chronic fatigue without a confirmed diagnosis, duloxetine is not indicated. The drug has serious risks: nausea (common, up to 25%), sexual dysfunction, elevated blood pressure, hepatotoxicity, discontinuation syndrome on abrupt stopping, and increased suicide risk in young people (FDA boxed warning). If duloxetine was prescribed for fatigue, consider seeking a second opinion.
- FIron oral (salts: sulfate, bisglycinate, fumarate, gluconate, polymaltose; heme iron polypeptide, lactoferrin)Not recommended · Oral iron preparations; antianaemic agentsThis refers to chronic fatigue WITHOUT confirmed iron deficiency. Here iron gives no benefit, and taking it without an indication risks constipation, nausea, and iron overload. If iron deficiency is confirmed by tests (ferritin and so on), iron is indicated and effective, but those are separate indications: iron deficiency anemia and iron deficiency without anemia. Fatigue should first prompt checking iron stores, not taking iron blindly.
- FLicorice root (Glycyrrhiza glabra, root and rhizome; including deglycyrrhizinated DGL)Not recommended · Root of Glycyrrhiza glabra and related Glycyrrhiza uralensis and Glycyrrhiza inflata species. Supplements come as root extract, candy, tea, alcoholic tincture, and deglycyrrhizinated form (DGL, without glycyrrhizin). Marketing promotes licorice as «adrenal support», a remedy for «adrenal fatigue», and a «natural remedy for viruses and gastritis». EMA HMPC published a European herbal monograph (2013) with traditional uses in cough, dyspepsia, and skin irritation; AEMPS does not register it as a medicine; AESAN classifies it as a complemento alimenticio. FDA grants GRAS status as a food additive but in 2017 warned consumers of cardiac arrhythmia risk with intake above 56 g/day of black licorice candy in people over 40.Licorice root is central to the marketing concept of «adrenal fatigue». The hypothesis: chronic stress «depletes» the adrenals, cortisol output falls, weakness, morning sluggishness, and salt cravings appear, and licorice «supports» the adrenals through 11-beta-HSD2 inhibition and prolonged endogenous cortisol action. Endocrinology has rejected this concept. The Endocrine Society Statement 2016 and the Spanish SEEN confirm: «adrenal fatigue» is not a recognised diagnosis. Chronic fatigue has other causes – iron and B12 deficiency, hypothyroidism, depression, sleep disorders, myalgic encephalomyelitis/chronic fatigue syndrome, long COVID, uncontrolled diabetes. Real adrenal insufficiency – Addison's disease, secondary hypocortisolism – is confirmed in the lab (cosyntropin test, morning cortisol, ACTH) and treated with hydrocortisone or prednisolone replacement per protocol, not with licorice root. Taking licorice for «adrenal fatigue» is dangerous: prolonged cortisol action produces hypertension and hypokalaemia and masks the actual causes of fatigue.
- FMethylprednisoloneNot recommended · Systemic glucocorticoidMethylprednisolone is a systemic corticosteroid. It is prescribed for acute autoimmune crises, severe allergic reactions, cerebral edema, and severe autoimmune disease flares (EULAR 2023, AEMPS Ficha Técnica). For chronic fatigue without a confirmed diagnosis, methylprednisolone is not indicated. The drug has serious risks on long-term use: adrenal suppression, steroid diabetes, osteoporosis with fractures, avascular bone necrosis, immunosuppression, psychiatric disturbances, cataract, and hypertension. If methylprednisolone was prescribed for fatigue, seek a second opinion immediately.
- FNaloxoneNot recommended · Antidotes, opioid receptor antagonistsNaloxone is an opioid receptor antagonist. It is prescribed for opioid overdose reversal (heroin, fentanyl, oxycodone) and in combination with buprenorphine for opioid use disorder (FDA, ASAM 2020). Naloxone at very low doses (LDN, low-dose naltrexone, 1.5–4.5 mg) is promoted in alt circles for chronic fatigue, fibromyalgia, and autoimmune diseases. Clinical studies of low-dose naltrexone (a related drug) in fibromyalgia are small and heterogeneous; for chronic fatigue, an evidence base is essentially absent. International clinical guidelines do not include naloxone/naltrexone for chronic fatigue. If naloxone or LDN was recommended for fatigue, consider seeking a second opinion.
- FNoopept (N-phenylacetyl-L-prolylglycine ethyl ester)Not recommended · Nootropics (local classification). Russian development.For non-clinical chronic fatigue, noopept is used as a «tonic nootropic». Independent RCTs with validated fatigue scale endpoints (FSS, MFI-20) in healthy adults do not exist. Absent from international guidelines.
- FPrednisoloneNot recommended · GlucocorticoidsCorticosteroids for "getting back on one's feet," chronic fatigue, subjective weakness, or asthenia are not supported by any international guideline. Short-term improvement on prednisolone is the drug's euphoric effect, not treatment of a cause. Upon discontinuation, state worsens below baseline due to withdrawal syndrome. Prolonged use produces cumulative complications: osteoporosis, steroid-induced diabetes, Cushing syndrome, adrenal insufficiency. Chronic fatigue requires differential workup: anaemia, B12 deficiency, hypothyroidism, depression, chronic infections – treat the cause.
- FResveratrolNot recommended · Dietary supplements, plant polyphenols (local classification)For non-clinical fatigue, resveratrol is sold as an «antioxidant with tonic effect». RCTs with validated fatigue scale endpoints (FSS, MFI-20) in healthy adults are unavailable. Resveratrol is absent from international asthenia and chronic fatigue guidelines.
- FTapentadolNot recommended · Opioid analgesic with dual mechanismTapentadol is an opioid analgesic with additional norepinephrine reuptake inhibitor activity. It is prescribed for moderate-to-severe chronic pain when other drugs are ineffective (AEMPS Ficha Técnica). For chronic fatigue without a confirmed pain syndrome, tapentadol is strictly not indicated. The drug has serious risks: opioid dependence formation (FDA boxed warning), respiratory depression (life-threatening, especially combined with other CNS depressants), serotonin syndrome with other serotonergic drugs, sedation, constipation, and nausea. If tapentadol was prescribed for fatigue, seek a second opinion immediately.
How to read tiers A–F
Evidence tiers belong to the drug-indication pair, not to the drug as a whole: the same substance can be A for one condition and F for another.
- AStrong evidence – first or second line in international guidelines
- BRecommended in selected cases
- CStudy data contradict each other
- DBenefit not proven, no documented harm
- FDocumented harm, or risk without benefit