Stress and anxiety
ICD-10 F41.945 drugs
Drugs used for this condition
- CChamomile (Matricaria chamomilla / recutita, flowers)Add-on therapy · Herbal preparation, EMA HMPC traditional herbal medicinal productChamomile has moderate evidence for mild anxiety symptoms. Amsterdam et al. RCT (J Clin Psychopharmacol 2009) with chamomile extract 220 mg 1–5 times daily for 8 weeks in 57 patients with mild–moderate GAD showed a meaningful reduction in Hamilton anxiety scores vs placebo. Later studies by the same group gave mixed results, and no systematic review reaches a confident positive conclusion. EMA HMPC recognises chamomile for mild nervous tension within traditional-use status. NICE CG113 recommends CBT and SSRIs first-line for GAD – chamomile is only an add-on for mild symptoms. If chamomile was prescribed as monotherapy for diagnosed GAD or panic disorder in place of standard treatment, consider seeking a second opinion.
- CPassionflower (Passiflora incarnata, aerial parts)Add-on therapy · Herbal sedative, EMA HMPC traditional herbal medicinal productPassionflower is used for mild nervous tension and transient anxiety. EMA HMPC in 2014 confirmed traditional-use status based on 30 years of European practice. The Miyasaka Cochrane review 2007 pooled 2 RCTs in GAD and preoperative anxiety – conclusion: data are too sparse to recommend passionflower as monotherapy for anxiety disorders. Several small comparator trials showed effect comparable to low-dose oxazepam in GAD, but methodology was weak and samples small. NICE CG113 (2019) does not mention passionflower. For episodic anxiety before dental procedures or public speaking a short course of 250–500 mg of extract is acceptable. If passionflower was offered for diagnosed anxiety disorder or panic attacks as a replacement for psychotherapy and SSRIs, consider seeking a second opinion.
- CSaffron (Crocus sativus stigma extract)Add-on therapy · Herbal antidepressant supplement, standardised affron® and Safr'Inside® extractsSaffron has been studied in mild anxiety symptoms in several RCTs. The Marx 2019 meta-analysis combined trials with anxiety symptoms and showed moderate reduction in anxiety scores vs placebo, with effect size comparable to the antidepressant signal. Certified affron® and Safr'Inside® extracts at 28–30 mg/day over 8 weeks gave a positive signal. No data exist in diagnosed GAD or panic disorder; trials enrolled people with mild anxiety symptoms without a formal diagnosis. NICE CG113 does not mention saffron. For mild episodic anxiety an 8–12-week course is acceptable as an add-on to core measures – CBT, sleep normalisation and physical activity. In diagnosed anxiety disorder replacing standard care with saffron is not justified.
- DL-lysineCase-by-case decision · Essential amino acidL-lysine for anxiety and stress has been studied mainly in combination with L-arginine rather than on its own. Two small randomized, double-blind, placebo-controlled trials (108 and 29 participants) reported lower trait and state anxiety and reduced cortisol during psychosocial stress in healthy adults with elevated anxiety, using about 2.64 to 3 g of each amino acid per day. Both trials came from a single research group linked to an amino acid manufacturer and have not been independently replicated. EFSA has not substantiated any L-lysine health claim, including stress-related ones. For L-lysine as a standalone agent, benefit in anxiety is not established, and no harm is documented at the doses studied.
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.
- DApigeninNot recommended · Flavonoid from chamomile, parsley and celery; supplement for sleep and «anti-ageing»; not registered as a drug by AEMPS or EMA; EFSA has not approved related health claimsApigenin is a flavonoid found in chamomile, parsley, and celery. It is sold as a calming supplement and promoted for stress and anxiety. Studies have not shown a convincing benefit for this use: the data come from lab work and small trials without reliable results in people. For anxiety and chronic stress, other approaches work, mainly psychotherapy (cognitive behavioral therapy first) and, when indicated, medication prescribed by a doctor. Do not take apigenin in place of a treatment with proven benefit, since that can delay care for a condition that needs it.
- DAshwagandha (Withania somnifera)Not recommended · Dietary supplements, plant adaptogens (local classification)Ashwagandha (Withania somnifera) is an Ayurvedic adaptogen, the most studied over-the-counter supplement for stress reduction. Meta-analyses from 2014–2022 (Pratte, Salve, Lopresti) based on 8–12 small clinical trials show significant reductions in the Perceived Stress Scale (PSS-10) and a 20–30% reduction in salivary cortisol versus placebo. The effect is dose-dependent: the most common dose is 300–600 mg of standardized KSM-66 extract (5% withanolides) once or twice daily. Evidence quality is moderate: small samples (60–130 participants), short studies (8–12 weeks), and high risk of bias. NICE and APA guidelines for anxiety and stress do not currently include ashwagandha. It is relatively safe in healthy adults, but rare cases of drug-induced liver injury and thyroid stimulation have been reported; ashwagandha is contraindicated in hyperthyroidism, autoimmune disease, and pregnancy. For persistent stress, it is more useful to address sleep, physical activity, and screen for an anxiety disorder or depression. If ashwagandha is taken on its own for stress, do not expect miracles; for marked symptoms, consult a clinician.
- DBacopa monnieri (brahmi)Not recommended · Plant nootropic adaptogen from Ayurvedic medicine, supplement. Not registered as medicine in EU or AEMPSBacopa monnieri (brahmi) is an Ayurvedic herb sold as a supplement for calmness and for easing stress and anxiety. There is no convincing evidence that it lowers anxiety or helps people cope with stress. For persistent anxiety, what actually helps is psychotherapy (especially cognitive behavioral therapy) and, when needed, medication prescribed by a doctor – worth discussing with a clinician.
- DEleutherococcus senticosus («Siberian ginseng»)Not recommended · Plant adaptogen, supplement. In EU – traditional herbal medicinal product (EMA HMPC); OTC tincture in RussiaEleutherococcus is sold as a «natural anti-stress» for office workers and students. Several small RCTs showed mild reductions in stress questionnaire scores. EFSA 2010 approved no health claim. EMA HMPC 2014 recognises «traditional use for symptoms of weakness» but not «stress relief». NICE 2022 and SEP 2014 list SSRIs and CBT for anxiety disorders; eleutherococcus is not mentioned. If eleutherococcus was recommended for clinically significant anxiety instead of psychotherapy and an antidepressant, consider seeking a second opinion.
- DFabomotizoleNot recommended · Other anxiolytics (local classification)Fabomotizole is an anxiolytic sold and promoted in Russia for relief of stress and anxiety. Convincing benefit for this use has not been shown: international guidelines and reviews do not mention the drug, and the available data are too weak to support an effect. In this use the substance is well tolerated and carries no known harm, but there is little reason to expect help from it. For persistent anxiety, psychotherapy (cognitive behavioral therapy in particular) and medicines with an established evidence base, chosen by a doctor, are what work.
- DGamma-aminobutyric acid (GABA)Not recommended · Inhibitory CNS neurotransmitter; as a supplement – amino acid for oral useGamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the nervous system, and as a supplement it gets marketed for relieving stress and anxiety. Good-quality studies have not shown a clear benefit for this use: oral GABA crosses the blood-brain barrier poorly, and there is no solid evidence base for a calming effect. For anxiety and chronic stress, the approaches with proven benefit are psychotherapy (cognitive behavioral therapy first) and, where indicated, medication prescribed by a doctor. Do not take this supplement instead of treatment with proven benefit, since that can mean missing care that actually works.
- DGlycine (as a marketed «nootropic»)Not recommended · Other psychostimulants and nootropics (local classification)Glycine is an amino acid sold as a mild nootropic and calming aid, including for stress and anxiety. Studies have not shown a convincing benefit for this use: there is no solid evidence base behind taking glycine for anxiety or stress. For marked or persistent anxiety, the approaches with real support are psychotherapy (cognitive behavioral therapy first) and, when a doctor decides, medications with proven efficacy. The substance itself is harmless in this role, but do not take it in place of therapy with proven benefit, since that can mean missing treatment that actually helps.
- DHawthorn (Crataegus monogyna / laevigata)Not recommended · Medicinal plant; EMA HMPC well-established use for mild nervous tension and traditional use in mild chronic heart failure; standardised WS 1442 extract (Crataegutt)Hawthorn tincture sits under EMA HMPC as traditional use for mild nervous tension and sleep disturbances, usually in combinations with valerian, passionflower and lemon balm. No quality RCTs of hawthorn alone in anxiety disorders exist; the perceived effect mostly reflects the ritual of taking the product and the herbal combination. AEMPS registers these combinations as traditional herbal medicines – a status, not evidence of efficacy by modern standards. For pronounced or persistent anxiety, the evidence supports psychotherapy and, when indicated, physician-prescribed SSRIs or SNRIs. If hawthorn was offered as a substitute for anxiety treatment, consider seeking a second opinion from a psychiatrist or psychotherapist.
- DHoly basil, tulsi (Ocimum sanctum, Ocimum tenuiflorum)Not recommended · Plant adaptogen from Ayurvedic medicine, supplement. Not registered as medicine in EU or AEMPSTulsi (holy basil) is sold as an «Ayurvedic adaptogen» against stress and anxiety. Evidence base is weak: several small Indian RCTs showed heterogeneous results on stress scales; no large international RCTs. EFSA 2010 approved no health claim for tulsi. NICE 2022 and SEP 2014 list SSRIs and CBT for anxiety disorders; tulsi is in no international guideline. If tulsi was recommended for clinically significant anxiety instead of psychotherapy and an antidepressant, consider seeking a second opinion. Important: high-dose tulsi extracts have caused isolated drug-induced liver injury cases.
- DL-theanineNot recommended · Amino acid from green tea leaves (Camellia sinensis), supplementL-theanine is the main marketing claim from supplement makers: promises to «relieve stress», «remove anxiety» and «relax without drowsiness». A single RCT (Hidese 2019, Nutrients, 30 people) found reduced STAI anxiety under acute stress in healthy adults. The Williams 2020 systematic review confirms only a short-term effect under situational stress, with no data on chronic anxiety or clinical anxiety disorders. EFSA 2011 did not approve a health claim. NICE CG113 lists SSRIs and CBT first-line for anxiety disorders; L-theanine is not mentioned. If L-theanine was recommended for panic attacks, GAD or social phobia instead of psychotherapy referral, consider seeking a second opinion.
- DLion's mane (Hericium erinaceus)Not recommended · Medicinal mushroom, supplement. AEMPS does not register as medicineLion's mane (Hericium erinaceus) is an edible mushroom whose extract is sold as a supplement for stress and anxiety. Convincing benefit for this use has not been shown: there is no solid evidence of a meaningful anti-anxiety effect in people. For stress and anxiety, what actually helps is psychotherapy (cognitive behavioral therapy first of all) and, when needed, medication with proven effectiveness chosen by a doctor. Lion's mane should not be taken instead of such treatment, since that can mean missing care that genuinely works.
- DLion's Mane Mushroom (Hericium erinaceus)Not recommended · Medicinal mushroom; in supplements – dried mycelium or fruiting body of Hericium erinaceus. Marketed on iHerb, Amazon, and in Spanish herbolarios as a «natural nootropic», nerve growth factor (NGF) stimulant, and remedy for dementia, anxiety, and ADHD. AEMPS does not register it as a medicine; AESAN classifies it as a complemento alimenticio without therapeutic indication. FDA has no approved indication.Lion's mane is marketed as a «natural anxiolytic» and «adaptogen» for stress and anxiety. The double-blind RCT by Nagano (Biomed Res 2010) in 30 menopausal Japanese women with anxiety and poor sleep reported lower ICED and DBSO scores after 4 weeks of cookies containing 2 g/day of lion's mane powder. The sample is tiny, the population specific, no confirmatory RCTs exist, and major anxiety guidelines do not list lion's mane. NICE recommends cognitive behavioural therapy for generalised anxiety and panic disorder as first-line, and SSRIs (sertraline, escitalopram, paroxetine) or SNRIs (venlafaxine, duloxetine) in moderate-severe disease; Spanish SEPyN holds a comparable algorithm. None of these guidelines refer to «adaptogens», a marketing term coined in 1940s Soviet science without an accepted definition. If «stress» reflects burnout, the answer is rest and workload review, not a supplement; if anxiety interferes with work and sleep, consider seeking a second opinion with a primary-care physician or psychiatrist – guidelines do not propose lion's mane.
- DMagnesium (oral salts: citrate, glycinate, oxide, sulfate)Not recommended · Mineral supplements. MacromineralsHigh-quality RCTs are absent. Small studies showed a weak effect on subjective stress in healthy adults, not exceeding placebo under controlled conditions. International psychiatry societies (APA, NICE mental health) do not include magnesium in anxiety treatment guidelines. Clinically significant anxiety or depression requires specialist consultation.
- DMelissa officinalis (leaf extract)Not recommended · Herbal sedative, EMA HMPC traditional herbal medicinal productLemon balm is often marketed as a «universal anti-stress» remedy, even for full-blown anxiety disorders. EMA HMPC limits its indication to mild nervous tension and does not extend it to GAD, panic disorder or social anxiety. No positive RCTs exist in diagnosed anxiety disorders. NICE CG113 (2019) does not mention lemon balm. The standard of care is CBT and SSRIs/SNRIs when needed. If lemon balm was offered for panic attacks, GAD or severe stress as a replacement for psychotherapy and prescribed medication, consider seeking a second opinion. For episodic nervousness before a difficult task a short course is acceptable, but it is a symptomatic measure.
- DOxytocinNot recommended · Posterior pituitary hormonesOxytocin is a hormone used in medicine to induce labor and to manage postpartum hemorrhage. Nasal and injectable forms are marketed for relationships, intimacy, and anxiety reduction. These uses have been studied: large RCTs and meta-analyses of oxytocin for anxiety and social behavior, including a double-blind placebo-controlled autism trial (Sikich, NEJM 2021), showed no benefit. International guidelines do not support nasal oxytocin for anxiety. For anxiety, proven help comes from psychotherapy and, where indicated, SSRIs; oxytocin should not replace them.
- DPregnenoloneNot recommended · Endogenous C21 steroid precursor; sold as a supplement on iHerb and Amazon; not registered as a drug in the EUPregnenolone is a steroid hormone that the body uses as a precursor to other hormones. It is sold as a supplement for stress and anxiety, marketed for calm and mental clarity. Convincing benefit for this use has not been shown: there is no solid evidence that it eases anxiety. For stress and anxiety, other approaches help – psychotherapy (cognitive behavioral therapy first of all), regular sleep and physical activity, and, when symptoms are pronounced, medication prescribed by a doctor.
- DRhodiola rosea (golden root)Not recommended · Plant adaptogen, supplement. In EU – traditional herbal medicinal product per EMA HMPC monographRhodiola rosea is widely sold as a «natural anti-stress» and «adaptogen for emotional burnout». Several small RCTs showed moderate reductions in stress scores in students before exams and workers with burnout. EMA HMPC 2012 recognised rhodiola as a traditional herbal medicinal product «for relief of stress symptoms», but this designation does not require efficacy evidence – only 30 years of traditional use. EFSA 2010 approved no health claim for rhodiola. NICE 2022 and SEP 2014 list SSRIs and CBT for anxiety disorders; rhodiola is not mentioned. If rhodiola was recommended for GAD, panic attacks or clinically significant anxiety instead of psychotherapy and an antidepressant, 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 sold as a «natural anti-stress» promising tonic effect without drowsiness. No evidence base: no significant RCTs with anxiety and stress scale endpoints. EMA HMPC 2024 does not include «stress reduction» in approved traditional indications. NICE 2022 and SEP 2014 list SSRIs and CBT for anxiety disorders; schisandra is not mentioned. If schisandra was recommended for clinically significant anxiety, consider seeking a second opinion.
- DSelank (Thr-Lys-Pro-Arg-Pro-Gly-Pro)Not recommended · Anxiolytics (local classification). Russian development.Selank is a synthetic peptide promoted as a remedy for stress and anxiety. Convincing benefit for this use has not been shown: there is no solid evidence base beyond a few small studies. For anxiety and chronic stress, approaches with proven effect help – psychotherapy (including cognitive behavioral therapy) and, when a doctor decides it fits, antidepressants such as SSRIs or SNRIs.
- DValeriana officinalis (root extract)Not recommended · Herbal sedative, EMA HMPC traditional herbal medicinal productValerian is often sold as a «natural alternative to benzodiazepines» for anxiety and stress. EMA HMPC explicitly limits this position to mild nervous tension, not anxiety disorders. No positive RCTs exist in generalized anxiety disorder, panic disorder or social phobia. NICE CG113 (2019) on anxiety disorders does not include valerian in the management algorithm. The standard remains CBT and SSRIs/SNRIs when needed. Valerian's effect on anxiety symptoms matches placebo in most comparisons. If valerian was offered as a replacement for a prescribed benzodiazepine or antidepressant in a diagnosed anxiety disorder, consider seeking a second opinion. For ordinary episodic nervousness before a public talk or a difficult conversation a short course is acceptable, but it is a symptomatic measure.
- F5-hydroxytryptophan (5-HTP)Not recommended · Direct serotonin precursor, supplement (not registered as medicine in EU or US)5-HTP is sold as a «natural anxiolytic» on the hypothesis: serotonin regulates anxiety; raising brain serotonin reduces anxiety. Logic is correct (basis of SSRIs), but direct transfer to a 5-HTP supplement fails: oral 5-HTP is significantly converted to serotonin in the periphery (platelets, GI tract), causing nausea and tachycardia, while only a fraction reaches the CNS. NICE 2022 and SEP 2014 list SSRIs and CBT first-line for anxiety disorders. Main risk: combination with SSRIs, tramadol or triptans – serotonin syndrome. If 5-HTP was recommended for GAD or panic attacks instead of a psychiatric consultation, consider seeking a second opinion.
- FAripiprazoleNot recommended · Atypical antipsychotic – dopamine partial agonistAripiprazole is an antipsychotic. It is prescribed for schizophrenia, bipolar disorder, as an add-on to antidepressants for treatment-resistant depression, and for autism spectrum disorder in children (APA 2020 and NICE NG178 guidelines). For acute stress or anxiety, aripiprazole has no proven efficacy: no clinical studies of such use exist. The drug has serious side effects: akathisia (a distressing sensation of inner restlessness), metabolic syndrome, pathological gambling and other compulsive behaviors (FDA warning, 2016). If aripiprazole was prescribed for these indications, consider seeking a second opinion.
- FCitalopramNot recommended · SSRI (selective serotonin reuptake inhibitor)Citalopram is an SSRI antidepressant. It is prescribed for depression and panic disorders (APA 2022 and NICE NG222 guidelines). For mood stabilization or workplace stress, citalopram does not work: no clinical studies of such use exist. The drug has serious risks: dose-dependent QT-interval prolongation (FDA warning, 2011; maximum dose limited to 40 mg, 20 mg in older adults), sexual dysfunction, discontinuation syndrome, and increased suicide risk in young adults (FDA boxed warning). If citalopram was prescribed for stress or mood stabilization, consider seeking a second opinion.
- FClobazamNot recommended · 1,5-benzodiazepine antiepilepticClobazam is a long-acting benzodiazepine. It is prescribed for Lennox-Gastaut syndrome and focal epilepsy (AAN 2018 guidelines); a short course for anxiety in adults is described in the AEMPS Ficha Técnica, but with caution. For regular use in stress and anxiety in people without epilepsy or an anxiety disorder, clobazam is not used: the risks far outweigh the benefit. Regular benzodiazepine use causes tolerance, physical dependence, abuse risk, sedation, and a severe withdrawal syndrome on abrupt discontinuation (tremor, anxiety, insomnia, and in severe cases seizures). The FDA boxed warning for benzodiazepines flags high dependence risk and dangerous consequences when combined with opioids. If clobazam was prescribed for stress, consider seeking a second opinion.
- FClonidineNot recommended · Central α2-adrenergic agonistClonidine is an alpha-2 agonist used for hypertension (as a non-first-line drug) and for ADHD in children (ESC/ESH 2023 and AAP 2019 guidelines). For acute stress or anxiety control in adults, clonidine is not used: no clinical studies of such use exist. The drug has serious risks: pronounced sedation, orthostatic hypotension (fall risk), paradoxical bradycardia, a severe rebound syndrome on abrupt discontinuation (sharp blood-pressure spike, sometimes above baseline, FDA boxed warning), and formation of drug dependence. If clonidine was prescribed for stress, consider seeking a second opinion.
- FDoxazosinNot recommended · Long-acting selective α1-adrenoceptor antagonistDoxazosin is an alpha-1 blocker used for hypertension (as a non-first-line drug; the ALLHAT 2000 trial showed it underperforms diuretics on hard endpoints) and for benign prostatic hyperplasia. For post-traumatic stress disorder with nightmares, prazosin (a related drug) is used off-label (APA 2017 and VA/DoD 2023 guidelines). Doxazosin is not included in that recommendation and is not used for anxiety control outside HTN, BPH, or PTSD. The drug has serious risks: a first-dose phenomenon with severe orthostatic hypotension and syncope (especially in older adults), paradoxical rebound hypertension on abrupt discontinuation, and fall risk. If doxazosin was prescribed for anxiety or nightmares, consider seeking a second opinion.
- FEscitalopramNot recommended · Selective serotonin reuptake inhibitors (SSRIs)Escitalopram is an SSRI antidepressant. It is prescribed for depression, generalized anxiety disorder, panic disorder, and social anxiety (APA 2022 and NICE NG222 guidelines). For workplace stress reduction or concentration improvement, escitalopram does not work: no clinical studies of such use exist. The drug has serious risks: sexual dysfunction (often persistent), QT-interval prolongation (FDA warning, 2011; limited to 20 mg in older adults), discontinuation syndrome on abrupt stopping, and increased suicide risk in young adults (FDA boxed warning). If escitalopram was prescribed for stress or concentration, consider seeking a second opinion.
- FFluoxetineNot recommended · Selective serotonin reuptake inhibitorsFluoxetine (Prozac) is an SSRI antidepressant. It is prescribed for depression, anxiety disorders, OCD, bulimia, and PMDD (APA 2022 and NICE NG222 guidelines). For energy, weight loss, or productivity in people without a psychiatric diagnosis, fluoxetine does not work: no clinical studies of such use exist. The 1990s Prozac marketing campaigns created the myth of a happiness pill, but no evidence base supports it. The drug has serious risks: sexual dysfunction (often persistent after discontinuation), hyponatremia, nausea, headache, and increased suicide risk in young adults under 24 (FDA boxed warning). If fluoxetine was prescribed for energy or weight loss, consider seeking a second opinion.
- FGabapentinNot recommended · Gabapentinoids (antiepileptics)Gabapentin for non-clinical anxiety or stress is not mentioned in APA or NICE mental health guidelines. Off-label use is widespread but unjustified – efficacy is doubtful and dependence/abuse risks are real. Since 2018, gabapentin and pregabalin are Schedule 3 controlled substances in the UK.
- FHypericum perforatumNot recommended · Antidepressants. Other antidepressants of herbal originSt. John's wort is widely sold as a natural calming remedy for nerves, stress, anxiety and sleep. For these conditions its benefit is not proven: there are no clinical trials in anxiety disorders or insomnia, only isolated case reports with no effect. The herb's proven niche is mild-to-moderate depression, not anxiety or sleep. It is also far from harmless: it speeds up the breakdown of many medicines and weakens them – oral contraceptives, warfarin, immunosuppressants, HIV drugs – and combined with SSRI antidepressants it can trigger serotonin syndrome and raises skin sensitivity to sunlight. Taking it for nerves or sleep, especially alongside other medicines, carries real risk with no proven benefit.
- FL-tryptophanNot recommended · Essential amino acid, precursor of serotonin, melatonin and niacin. In the UK registered by MHRA as Optimax for resistant depressionL-tryptophan is sold as a «natural anxiolytic» on the «tryptophan → serotonin → anxiety reduction» hypothesis. Evidence in anxiety disorders is weak: a significant fraction of tryptophan goes to the kynurenine pathway rather than serotonin, and CNS effect is unpredictable. NICE CG113 lists SSRIs and CBT first-line for anxiety disorders. Main risk: combination with SSRIs, tramadol or triptans – serotonin syndrome. EMS (eosinophilia-myalgia syndrome) after the 1989 outbreak, which had fatalities and led to an FDA over-the-counter ban, continues to be reported in isolated cases. Unproven benefit against documented harm is a net-minus, so it is not recommended. If L-tryptophan was recommended for GAD or panic attacks instead of a psychiatric consultation, consider seeking a second opinion.
- FMethylthioninium chloride (methylene blue)Not recommended · Antidotes (V03AB17). The drug has one FDA-approved indication – methaemoglobinaemia. Biohacker use is off-label.Methylene blue (methylthioninium chloride) is a dye and a drug approved for methemoglobinemia and, in some countries, for cyanide poisoning. In biohacker channels, methylene blue is marketed as a mitochondrial support agent for energy, concentration, and stress reduction. There are no published clinical studies in healthy adults with endpoints on validated stress, anxiety, or cognitive scales. The FDA, EMA, and AEMPS have not approved methylene blue for these uses. Methylene blue is a monoamine oxidase inhibitor: combining it with SSRI, SNRI, or TCA antidepressants or with triptans can cause life-threatening serotonin syndrome. In people with G6PD deficiency it can trigger hemolytic anemia. If methylene blue was recommended for energy or stress, consider seeking a second opinion, especially if you take antidepressants.
- FOndansetronNot recommended · 5-HT3 serotonin receptor antagonistOndansetron is a serotonin 5-HT3 receptor antagonist. It is prescribed for nausea and vomiting from chemotherapy or radiotherapy, postoperative nausea, and acute gastroenteritis in children (ASCO 2024 and AAP 2018 guidelines). For stress nausea or anxiety vomiting, ondansetron is not used: no clinical studies of such use exist. The drug carries a risk of dose-dependent QT-interval prolongation and Torsades de pointes (FDA warning, 2012; doses above 16 mg IV are not recommended). If nausea is anxiety-related, other approaches work: breathing techniques, psychotherapy, and, when indicated, treatment of an anxiety disorder. If ondansetron was prescribed for nervous nausea, consider seeking a second opinion.
- FPaliperidoneNot recommended · Atypical antipsychotic – active metabolite of risperidonePaliperidone is an antipsychotic, the active metabolite of risperidone. It is prescribed only for schizophrenia and schizoaffective disorder (APA 2020 guidelines). For acute stress, paliperidone does not work: no clinical studies of such use exist. The drug has serious side effects: extrapyramidal symptoms (tremor, muscle stiffness), QT-interval prolongation, hyperprolactinemia, metabolic syndrome. In elderly patients with dementia, it increases mortality (FDA boxed warning). If paliperidone was prescribed for stress, consider seeking a second opinion.
- FParoxetineNot recommended · Selective serotonin reuptake inhibitor (SSRI)Paroxetine is an SSRI antidepressant. It is prescribed for depression, generalized anxiety disorder, panic disorder, social anxiety, and post-traumatic stress disorder (APA 2022 and NICE NG222 guidelines). For emotional regulation or workplace stress, paroxetine does not work: no clinical studies of such use exist. Paroxetine has the most severe discontinuation syndrome among SSRIs: abrupt stopping causes dizziness, brain-zaps, nausea, and anxiety, sometimes lasting weeks. Other risks: sexual dysfunction, weight gain, teratogenicity (FDA category D, risk of fetal cardiac defects), and increased suicide risk in young adults (FDA boxed warning). If paroxetine was prescribed for emotional regulation, consider seeking a second opinion.
- FPicamilon (nicotinoyl-GABA)Not recommended · Nootropics and vasoactive agents (local classification). Russian development.Picamilon (nicotinoyl-GABA) is a Soviet-era drug marketed in Russia as a mild tranquilizer with a vascular component for stress, anxiety, and reduced productivity. It is not included in any international clinical guidelines; the FDA, EMA, and AEMPS have not approved picamilon, and the FDA banned its sale as a dietary supplement in the US in 2015 because it is an unregistered drug. There are no independent clinical studies in humans with endpoints on validated anxiety or stress scales. For persistent stress or anxiety, it is more useful to see a clinician for a diagnostic workup (generalized anxiety disorder, depression, sleep disorders), where evidence-based treatments are available. If picamilon was prescribed for stress, consider seeking a second opinion.
- FPregabalinNot recommended · Gabapentinoids (antiepileptics)Pregabalin (Lyrica) is an antiepileptic drug prescribed for neuropathic pain, fibromyalgia, generalized anxiety disorder, and partial epilepsy. For stress, insomnia, or emotional tension outside these indications, pregabalin is dangerous. The drug is a controlled substance in the US (Schedule V), the UK (Schedule 3 since 2019), and Russia (prescription-only with special requirements since 2019) because of abuse and dependence potential. In patients with a history of substance use disorder, the risk of pregabalin dependence is significant. On black markets in Eastern Europe and the CIS, Lyrica is one of the most popular illicit drugs. Abrupt discontinuation causes a severe withdrawal syndrome: anxiety, insomnia, tachycardia, and sometimes seizures. If pregabalin was prescribed for stress or sleep, consider seeking a second opinion.
- FRisperidoneNot recommended · Atypical antipsychotic – dopamine and serotonin receptor antagonistRisperidone is an antipsychotic, not an anxiolytic. It is prescribed for schizophrenia, bipolar disorder, and behavioral problems in children with autism spectrum disorder (APA 2020 and NICE NG178 guidelines). For acute stress, risperidone does not work: no clinical studies of such use exist. The drug has serious side effects: extrapyramidal symptoms (tremor, muscle stiffness), metabolic syndrome, hyperprolactinemia. In elderly patients with dementia, it increases mortality (FDA boxed warning). If risperidone was prescribed for stress, consider seeking a second opinion.
- FSertralineNot recommended · Selective serotonin reuptake inhibitors (SSRIs)Sertraline is an SSRI antidepressant. It is prescribed for depression, generalized anxiety disorder, panic disorder, OCD, PTSD, social anxiety, and PMDD (APA 2022, NICE NG222, and WFSBP 2023 guidelines). For burnout or productivity improvement in people without a psychiatric diagnosis, sertraline does not work: no clinical studies of such use exist. Sertraline is one of the most prescribed SSRIs, but this does not mean it is safe for everyone. Risks: sexual dysfunction (often persistent after discontinuation), gastrointestinal upset, hyponatremia, discontinuation syndrome, and increased suicide risk in young adults (FDA boxed warning). For genuine burnout, other approaches work: workload review, psychotherapy, sleep normalization; for confirmed depression or anxiety, sertraline can help, but that is a diagnosis-based prescription. If sertraline was prescribed for productivity, consider seeking a second opinion.
- FVenlafaxineNot recommended · SNRI (serotonin-norepinephrine reuptake inhibitor)Venlafaxine is an SNRI antidepressant. It is prescribed for depression, generalized anxiety disorder, panic disorder, and social anxiety (APA 2022 and NICE NG222 guidelines). For acute stress or productivity improvement, venlafaxine does not work: no clinical studies of such use exist. The drug has serious risks: dose-dependent blood-pressure elevation, QT-interval prolongation, one of the most severe discontinuation syndromes among antidepressants (abrupt stopping causes brain-zaps, dizziness, nausea, anxiety), sexual dysfunction, and increased suicide risk in young adults (FDA boxed warning). If venlafaxine was prescribed for stress, consider seeking a second opinion.
- FZiprasidoneNot recommended · Atypical antipsychotic – indole derivativeZiprasidone is an antipsychotic. It is prescribed only for schizophrenia and bipolar disorder (APA 2020 guidelines). For acute stress or emotional regulation, ziprasidone does not work: no clinical studies of such use exist, no evidence base supports it. The drug has severe side effects: substantial QT-interval prolongation (greater than most antipsychotics), and risk of DRESS syndrome, a severe skin reaction (FDA warning, 2014). If ziprasidone was prescribed for stress or emotional regulation, consider seeking a second opinion.
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