Brain and nerves

Shown to raise response in panic disorder, with about 4 treated for one extra response in short trials that reviewers rated low quality.

Shown to reduce generalized anxiety symptoms more than placebo in short trials, with a moderate effect size of 0.50.

Shown to lengthen sleep by about an hour and shorten the time to fall asleep by 4 to 20 minutes in short trials, with more daytime drowsiness.

Shown to reduce migraine frequency and severity against a waiting list in two meta-analyses, with effects lasting more than a year in follow-up.

Compared with waiting list [2]; control conditions the source abstract does not describe [3]

Shown to raise response in adult depression, 62% against 51% on placebo in seven pooled trials, level with SSRIs.

Shown to raise smoking quit rates about 1.6 times over placebo, roughly 3 extra quitters per 100, and less than varenicline did.

Shown to reduce generalized anxiety symptoms more than placebo, with about 4 to 5 treated for one extra person improved in trials of 4 to 9 weeks.

Shown to improve attention, reaction time and driving lane control in sleep-deprived adults, compared with sleep loss without caffeine.

Shown to improve attention accuracy and reaction time slightly in rested adults, more at doses of 200 mg or more.

Shown to cut seizures in Dravet and Lennox-Gastaut syndromes, with drop seizures falling about 42% against 17% to 22% on placebo. These trials used prescription CBD.

Shown to reduce migraine by about 1.6 days a month more than placebo, a small effect that a meta-analysis rated high certainty.

Compared with placebo injections or infusions [1][2][3]

Shown to leave about 20% pain free 2 hours after rimegepant or ubrogepant, against 11% to 13% on placebo, about 1 extra pain-free person in 10 treated.

Compared with placebo [8][9][10]; triptans, indirectly [10]

Shown to reduce ADHD symptoms in children and teenagers against placebo, by a standardized difference of about 0.6 to 0.7 for clonidine and guanfacine.

Compared with placebo [4][5][6][7]; amphetamines, methylphenidate, atomoxetine and modafinil, in network comparisons [4]; placebo added to stimulants [5]

Shown to lower depression moderately to largely against waiting list and usual care, with effects still present 6 to 12 months later.

Compared with care as usual and waiting list [3]; control groups [4]

Shown to ease anxiety disorder symptoms moderately against pill or psychological placebo, with nearly three times the odds of responding.

Compared with psychological placebo [6][7]; pill placebo [6][7]; waiting list [7]

Shown to cut time to fall asleep by about 19 minutes and time awake at night by about 26 minutes against inactive comparisons, with little change in total sleep time.

Compared with inactive comparators [9]; no treatment [10]

Shown to lower depression and anxiety disorder symptoms against control conditions, with guided programs ahead of unguided ones right after treatment.

Compared with control treatments [13]; care as usual, waiting list, information control, psychological placebo or pill placebo [14]; face-to-face CBT [14]

Shown to improve memory scores modestly, most in older adults, with no change in people aged 11 to 31.

Shown to cut stroke or systemic embolism by about 19% and death by about 10% against warfarin in adults with atrial fibrillation.

Linked to 10% lower stroke at the highest fish intake than the lowest, and 6% lower for each 3 extra servings a week, in pooled cohorts.

Compared with the lowest fish intake category [8]; 3 fewer servings a week, in a dose-response model [9]

Linked to 18% lower cognitive impairment and 18% lower dementia at the highest fish intake than the lowest, in pooled observational studies of adults.

Compared with the lowest fish intake [14]; one fewer serving a week, in a dose-response model [15]

Linked to 17% to 22% lower risk of depression at the highest fish intake than the lowest, in pooled observational studies.

Compared with the lowest fish consumption [16][17]

Shown to lower stroke about 10% in adults, with no change in coronary heart disease. Effects were larger in people with low blood folate.

Shown to give at least 50% pain relief to about 32% of people with postherpetic neuralgia, against 13% to 17% on placebo.

Shown to give at least 50% pain relief to 38% on gabapentin against 21% on placebo, and to 31% on pregabalin 300 mg against 24%.

Shown to about double the share of people with drug-resistant focal epilepsy whose seizures fell by half, for both gabapentin and pregabalin as add-on treatment.

Shown to reduce symptoms of generalized anxiety disorder more than placebo on pregabalin, by about 2.8 points on the Hamilton anxiety scale.

Shown to reduce depressive symptoms with gardening and horticultural activities in two meta-analyses of trials, a moderate effect. A third found no significant mental health change in chronic illness.

Compared with comparison groups with no horticultural element [1]; control groups in randomized trials the abstract does not describe [2]; control groups in randomized and quasi-experimental studies [3]

Shown to raise wellbeing and other health measures with gardening in two meta-analyses, moderate effects, across trials and comparisons of gardeners with non-gardeners.

Compared with the same people before they began gardening, or non-gardeners [4]; comparison groups in the interventional and observational reviews it pooled [5]

Shown to raise cognition scores slightly in people with cognitive impairment or dementia, below the threshold for clinical significance.

Shown to ease chronic pain moderately (Hedges' g -0.42) against control treatments, with larger effects after 8 or more sessions.

Compared with control interventions the source abstract does not describe [13]; standard care, and other psychological interventions [14]

Shown to lower depression scores within 24 hours more than placebo, with racemic ketamine's effect lasting into follow-up in a meta-analysis of 49 trials. Used off-label.

Compared with saline placebo or midazolam [1]; placebo or active control in pooled trials [2][3]

Shown to reduce suicidal thoughts within a day of a single ketamine infusion, an effect lasting up to 3 days. The esketamine label states no reduction in suicide was shown.

Compared with saline or midazolam [7]; control infusions [8]; placebo spray added to standard care [4]

Shown to make a 50% seizure reduction about 5.8 times as likely as usual care in children with drug-resistant epilepsy, on low-certainty evidence, with adult results uncertain.

Compared with usual care [8]; control groups the source does not describe [9]; a further antiseizure medicine [10]

Shown to improve choice reaction time in the hour after a single 200 mg dose in adults. Simple reaction time and the Stroop test did not change.

Shown to lower relapse in bipolar disorder against placebo, by about 16% to 22% in pooled trials, while preventing mania less well than lithium.

Compared with placebo [1][2][3][4]; lithium [1][2]

Shown to improve bipolar depression modestly against placebo, with response about 1.27 times as likely, and in one pooled analysis only in more severe depression.

Compared with placebo [5][2][3][6]; lithium, olanzapine with fluoxetine, citalopram and inositol [6]

Shown to improve rated sleep quality in intensive care patients using eye masks, alone or with earplugs, in three reviews. Earplugs alone did not change sleep quality.

Compared with control groups in randomized trials the abstract does not describe [1]; control groups, including routine care, in randomized and nonrandomized studies [2]; comparison conditions the abstract does not describe [3]

Shown to lower anxiety, depression and distress in adults without a diagnosis, by about half a standard deviation, against no program or a waiting list.

Compared with no intervention [1]; control groups the source abstract does not describe [2]

Shown to ease disorder-specific symptoms more than no treatment and other active controls in pooled trials, and no differently from established treatments such as CBT or medication.

Compared with no treatment, minimal treatment, nonspecific and specific active controls, and evidence-based treatments [5]; waiting list, other active treatments, CBT and medication [6]

Shown to ease depression symptoms modestly against active control programs, and mindfulness-based cognitive therapy cut the risk of relapse within 60 weeks by about 31%.

Compared with active control programs [3]; no intervention and nonspecific active controls [1]; usual care and other active treatments including antidepressants [7]

Shown to ease chronic pain slightly in pooled trials rated low in quality. In back pain, an 8-week course matched CBT and beat usual care.

Compared with treatment as usual, passive controls, and education or support groups [8]; active control programs [3]; usual care and cognitive behavioral therapy [9]

Shown to reduce depression more than placebo in adults, with a higher response rate than SSRIs at two weeks and at the end of acute treatment.

Shown to reduce daytime sleepiness in adults with narcolepsy, about 3 points on the Epworth scale and 3 minutes longer awake on a lab test, but not cataplexy.

Compared with placebo [1][2][3]; sodium oxybate in one comparison [1]

Shown to reduce residual sleepiness in sleep apnea, about 2 to 3 points on the Epworth scale, with about three times the adverse events of placebo.

Compared with placebo, on top of CPAP [3][4][5]

Shown to improve cognitive test scores in rested healthy adults by a very small amount, an effect size near 0.1, with no clear advantage in any one domain.

Compared with placebo [9][10][11]

Shown to improve memory and overall test performance after an afternoon nap, a small to medium effect in three meta-analyses, similar across ages and nap lengths.

Compared with control conditions the abstract does not describe [1]; a no-nap control condition, and the same people before the nap [2]; a no-nap condition in randomized trials [3]

Shown to raise vigilance and alertness and to reduce felt fatigue after a nap, in three meta-analyses of nap studies.

Compared with control conditions the abstract does not describe [1]; a no-nap control condition, and the same people before the nap [2]; a no-nap condition in randomized trials [3]

Shown to lower depression and anxiety symptoms by a medium amount in trials across many groups, including people with major depression, in reviews rated low in quality.

Compared with usual care [13]; active controls such as usual care or a placebo tablet [14]

Shown to lower anxiety around heart procedures and in other adults in pooled trials, mostly against usual care or no intervention, with large and varied effects.

Compared with control groups the source abstracts do not describe [8][9]; nonactive controls: sham intervention, usual care, waiting list or psychoeducation [10]

Shown to improve sleep quality scores in pooled trials, mostly against usual care or no intervention, with large effects.

Compared with control groups the source abstract does not describe [11]; nonactive controls: sham intervention, usual care, waiting list or psychoeducation [10]; control groups the source abstract does not describe [12]

Shown to lengthen teenagers' sleep by about 25 to 77 minutes a night when school started later, in three reviews. Depressive symptoms fell slightly in pooled studies.

Compared with earlier school start times, as each study compared them [2]; the same students before the delay, and control schools in trials [3]; earlier school start times [4]

Shown to lower self-rated anxiety and depression symptoms in two meta-analyses, by small amounts for breathwork in general and larger amounts for heart rate variability biofeedback.

Compared with non-breathwork controls, active and inactive [2]; control conditions the source abstract does not describe [5]; inactive and active controls [3]

Shown to raise response in adult depression more than placebo. Head-to-head trials placed venlafaxine among the higher response rates and duloxetine level with other antidepressants.

Shown to lower anxiety scores in generalized anxiety disorder, by about 3.1 Hamilton points more than placebo on duloxetine and 2.7 on venlafaxine.

Shown to cut pain by half or more in painful diabetic neuropathy on duloxetine 60 mg, with about 5 treated for one extra person helped.

Linked to more dementia with low social participation and contact in two meta-analyses. Loneliness was linked in one and not significantly in the other.

Compared with people with more social participation and contact and less loneliness [5]; people with better social engagement [6]; people with more social activity and larger social networks [7]

Shown to reduce loneliness modestly in pooled randomized trials. Programs addressing how people think about social situations had the largest effects, and added chances to socialize did not.

Compared with control groups in randomized comparison studies [11]; control groups [12]; control groups in randomized trials, some without active controls [13]

Shown to reduce depression symptoms more than placebo in adults, by about 2 points on the Hamilton scale, with about 7 treated for one extra response.

Shown to reduce OCD symptoms by about 3 points more than placebo on the Yale-Brown scale in adults, with response about 1.8 times as likely.

Shown to raise response in generalized anxiety disorder, with about 7 treated for one extra response across antidepressants. Escitalopram lowered anxiety scores 2.45 points more than placebo.

Shown to match standard antidepressants for response in adults with mild to moderate or major depression, with fewer dropouts than on SSRIs, over 4 to 12 weeks.

Shown to lower depressive symptoms by a moderate amount and anxiety by a small amount in pooled trials, with smaller effects in trials with blinded assessment.

Compared with nonactive control conditions [17][18]; active controls such as usual care or a placebo tablet [19]

Shown to ease negative mood, anxiety and depressive feelings and raise positive mood after time in nature, in several meta-analyses rating study quality mostly low.

Compared with control conditions, mostly passive [7]; control groups [8]; built environments [9]; before the forest bathing, in the same people [6]; a 90-minute walk in an urban setting [10]

Shown to cut migraine frequency by about 1.2 attacks a month against placebo in adults, with about 4 treated for one extra person whose attacks halved.

Compared with placebo [1][2][3]; amitriptyline and other preventive drugs, in network comparisons [2]

Shown to improve self-rated sleep quality by a small to moderate amount in short trials of people with insomnia, with mixed results on measured sleep.

Shown to stop a migraine attack, with 28% pain free 2 hours after oral sumatriptan 50 mg against 11% on placebo.

Shown to differ within the class, with eletriptan and rizatriptan ranking above sumatriptan for pain freedom at 2 hours and naratriptan lowest.

Linked to fewer depressive and anxiety symptoms in people with a stronger sense of purpose in life, in two meta-analyses, moderate correlations.

Compared with people with a lower sense of purpose in life [13][14]

Shown to cut stroke by about 64% against placebo or no treatment in adults with nonvalvular atrial fibrillation, with fewer deaths in one review.

Shown to cut stroke by about 39% more than antiplatelet drugs in atrial fibrillation, and to halve stroke against aspirin in adults aged 75 or over.

Shown to ease depression symptoms by a small to moderate amount, against waiting list, usual care and attention controls, and against active exercise comparisons in older adults.

Compared with waiting list, treatment as usual and attention control [6]; inactive controls such as a waiting list or education booklets [7]; active controls such as walking or chair aerobics [7]

Shown to shorten the time to fall asleep by about 22 minutes on sleep-lab recordings in adults with insomnia, an effect the authors called small.

Shown to improve depression scores over placebo in two small trials of adults with depression, though the review authors judged the evidence too weak to be conclusive.

Shown to leave slightly more adults pain free 2 hours after 1,000 mg for a tension-type headache, with 22 treated for one extra person pain free.

Shown to leave 19% of adults pain free 2 hours after 1,000 mg for a migraine, against 10% on placebo.

Shown to halve migraine frequency in 41% against 17% with no acupuncture. Against sham acupuncture the difference was small, 50% against 41%.

Compared with no acupuncture or routine care [6]; sham acupuncture [6]; preventive migraine drugs [6]

Shown to halve headache frequency more often than routine care, 48% against 19% in the largest trial. Against sham acupuncture the difference was smaller, 51% against 43%.

Compared with routine care or treatment of acute headaches only [7]; sham acupuncture [7]

Shown to reduce clinician-rated ADHD symptoms more with amphetamines than with methylphenidate in head-to-head comparisons, in children and in adults.

Shown to raise math output by 7.8% and math accuracy by 3.0% on methylphenidate in children with ADHD, gains the authors called small.

Shown to cut binge eating by about 1.4 to 1.7 more days a week than placebo on lisdexamfetamine in adults with moderate to severe binge eating disorder.

Shown to raise nerve conduction speed in people with diabetic neuropathy when given by IV for 2 to 4 weeks. Most trials were poor quality.

Shown to lower nerve symptom scores in people with diabetic neuropathy over 5 weeks. Over 4 years, the main combined measure did not change.

Shown in very low quality evidence to make at least 50% pain relief about three times as likely as placebo, with about 4 treated for one extra responder.

Compared with placebo and other active treatments [6]

Shown to reduce migraine frequency against placebo in adults in a network meta-analysis, which ranked it above several other preventive drugs on weak evidence.

Compared with placebo [7]; candesartan, fluoxetine, propranolol, topiramate and valproate, in network comparisons [7]

Shown to cut chronic tension-type headaches by about 4.8 a month against placebo with tricyclic antidepressants, which also reduced headaches more than SSRIs.

Compared with placebo, SSRIs and behavioral therapy [9]

Shown to about double quit rates against placebo with nortriptyline in a Cochrane review of six trials.

Compared with placebo [14]; bupropion [14]

Shown to lower stroke, heart attack or vascular death slightly more than aspirin, 5.32% against 5.83% a year, in people with artery disease.

Shown to cut stroke in the next 90 days to 8.2% against 11.7% on aspirin alone after a minor stroke or TIA in one of two trials.

Shown to cut repeat ischemic stroke in the first 6 weeks by about 60%, with no further benefit seen after 12 weeks.

Shown to cut stroke by about 22% against no treatment in atrial fibrillation, less than warfarin or apixaban did in direct comparisons.

Shown to lower depression scores in people with mental disorders, mostly anxiety disorders, though a second statistical model did not confirm the effect.

Shown to make a 50% seizure reduction about six times as likely as drug therapy alone in drug-resistant epilepsy, though less often than the classic ketogenic diet in children.

Compared with a usual diet with the same antiseizure drugs [1]; standard care with no diet therapy [2]; usual care [3]; standard drug therapy alone [4]; the classic ketogenic diet and a low glycemic index diet [5]; the classic ketogenic diet [6]

Shown to cut relapse within a year to 27% on an antipsychotic against 64% on placebo in people with schizophrenia, about 1 fewer relapse per 3 treated.

Shown to reduce mania symptoms more than placebo for both quetiapine and aripiprazole, by a standardized mean difference of 0.37, and less than haloperidol.

Shown to reduce depressive symptoms in bipolar depression more than placebo on quetiapine 150 or 300 mg a day, without a clear gain in response or remission rates.

Shown to improve sleep quality and add about 48 minutes of sleep against placebo, mostly in people with anxiety or depression, with frequent side effects.

Shown to produce small improvements in behavioral symptoms of dementia on aripiprazole, with effect sizes of 0.12 to 0.20, against a higher death rate than placebo.

Shown to lower irritability scores by about 6 points more than placebo on aripiprazole in children and adolescents with autism over 8 weeks.

Shown to improve stress slightly in healthy and at-risk adults over 4 weeks or more, with no change in depression or anxiety. Bayer funded the review.

Shown to cut seizures during alcohol withdrawal, with a risk ratio of 0.16 against placebo in three studies.

Shown to stop prolonged seizures more often than placebo when given by vein in hospital, with lorazepam ahead of diazepam.

Shown to lower episodic migraine by about 1.5 headaches a month on propranolol against placebo, with 40% against 23% halving their migraine days in one trial.

Shown to reduce limb tremor in essential tremor on propranolol, rated Level A in one evidence review and clinically useful in another.

Shown to cut migraine attacks by about 2 a month against a waiting list in children and adolescents, in five small trials.

Compared with waiting list [4]

Shown to reduce tension-type headache with a medium to large effect (d 0.73) that lasted about 15 months, more than headache monitoring, placebo or relaxation.

Compared with headache monitoring, placebo, and relaxation therapies [5]

Shown to reduce self-reported stress and anxiety with a large effect (Hedges' g 0.83) against control conditions, in a meta-analysis of 24 studies.

Compared with control conditions the source abstract does not describe [9]

Shown to lower new episodes of seasonal depression in adults with a history of it, with 84% staying depression-free against 72% on placebo.

Shown to reduce ADHD symptoms in adults by a moderate amount in a Cochrane review of six small trials rated low quality. Not an approved use.

Shown to lower stroke from 3.4% to 1.9% and total cardiovascular events from 8.0% to 5.7% against placebo, with no significant change in deaths.

Shown to lower anxiety in people with anxiety disorders across 8 small studies, with a confidence interval close to zero.

Shown to reduce monthly migraine days with atogepant, with a 50% responder rate about 1.7 times placebo's. Rimegepant every other day cut 0.8 more days than placebo.

Compared with placebo [5][6]

Shown to reduce migraine days by a small amount in a meta-analysis of 5 trials, a result the authors called preliminary.

Compared with control conditions the source abstract does not describe [8]

Shown to improve memory in children exposed to alcohol before birth when choline was given in pregnancy, though each pooled result rests on 2 trials.

Shown to raise quit rates against placebo, with about 1.9 times the odds, in a Cochrane review of six small trials, with frequent dry mouth and sedation.

Compared with placebo [8]

Shown to make severe opioid withdrawal less likely and completing withdrawal more likely than placebo, with results similar to a methadone taper but more low blood pressure.

Compared with placebo and reducing doses of methadone [9]

Shown to reduce migraine frequency and attack duration in adults with migraine, across 6 small studies. Severity did not change.

Linked to 24% lower risk of depression at the highest coffee intake than the lowest, and 8% lower per daily cup, in observational studies.

Compared with the lowest consumption level [11]

Shown to keep anxiety lower than control conditions for up to 12 months, and past 12 months for generalized anxiety, social anxiety and PTSD, in mostly low-quality trials.

Compared with care as usual, relaxation, psychoeducation, pill placebo, supportive therapy or waiting list [8]

Shown to improve insomnia severity, sleep efficiency and sleep onset when delivered over the internet, by amounts similar to those reported for face-to-face CBT.

Compared with control conditions the source abstract does not describe [12]

Shown to ease chronic pain, disability and distress slightly more than usual treatment. Against other active treatments the benefit was very small and did not last.

Compared with treatment as usual [15]; active control treatments [15]

Linked to 22% fewer people with depressive symptoms at 7,000 steps a day than at 2,000, in one meta-analysis of three cohorts.

Compared with 2,000 steps a day [4]

Linked to 38% less dementia at 7,000 steps a day than at 2,000, in one meta-analysis of two cohorts.

Compared with 2,000 steps a day [4]

Shown to ease depressive and anxiety symptoms in the short term, in one meta-analysis of 9 small studies of cocoa-rich products.

Compared with control conditions the abstract does not describe [7]

Linked to better social-emotional, behavioral and overall development scores in children whose mothers ate more seafood in pregnancy, with inconsistent results for overall cognition.

Compared with children whose mothers ate less seafood in pregnancy [13]

Shown to lower depression symptoms modestly in people with symptoms, with EPA-rich formulas only. Not shown to prevent depression.

Linked to about 30% lower autism risk and lower ADHD odds in children whose mothers took folic acid, in observational studies.

Shown to give at least 50% pain relief to about 22% to 24% of people with fibromyalgia on pregabalin, against about 14% on placebo.

Shown to reduce the percentage of heavy drinking days on gabapentin in adults with alcohol use disorder, with other drinking outcomes not clearly different from placebo.

Shown to lower self-rated stress with horticultural therapy in one meta-analysis, without changing physiological measures. A community gardening trial found larger falls in stress and anxiety.

Compared with a control group the abstract does not describe [6]; a waiting list for a community garden plot [7]

Shown to raise fullness ratings after higher-protein meals in tightly controlled preload studies of healthy adults.

Compared with diets with less protein

Shown to reduce generalized anxiety scores more than placebo over 4 to 12 weeks, by about 2.5 to 3.5 points on the Hamilton anxiety scale.

Shown to raise cognitive test scores by 4 points on the Mini-Mental State Examination when added to drug treatment for vascular dementia, in one meta-analysis of Chinese trials.

Shown to relieve an acute migraine attack compared with sham in a Cochrane review of 3 small trials, at low quality. It did not prevent attacks.

Shown to lower pain from lab pain tests in healthy volunteers (Hedges' g 0.54 to 0.76), mainly in people who respond strongly to suggestion.

Compared with no intervention [15]

Shown to reduce anxiety more than control conditions, with the average treated person improving more than 79% of controls, and more when combined with other psychological treatment.

Compared with control conditions the source abstract does not describe [18]

Shown to improve anxiety, memory and intelligence scores modestly in iron-deficient children and menstruating adults, with no effect in those without deficiency.

Shown to lower restless legs scores about 5 points and double the share who improved, pooling oral and intravenous iron.

Shown to lower depression scores in treatment-resistant depression by about 4 to 7 points more than placebo on a 60-point scale after 4 weeks.

Compared with placebo nasal spray, with or without a new oral antidepressant [4]; placebo in pooled trials [1][2]

Shown to delay relapse in people who had improved on esketamine, about half the hazard of relapse after a switch to placebo spray.

Compared with switching to placebo nasal spray, with the oral antidepressant continued [4]

Shown to improve self-rated sleep onset, daytime function and sleep quality modestly in people of all ages.

Shown to make a halving of seizure frequency about 1.8 times as likely as placebo when added to other drugs in drug-resistant focal epilepsy.

Compared with placebo added to existing seizure drugs [7][4]

Shown to lower anxiety in pooled trials, including state anxiety after a single session and trait anxiety after a course of treatment.

Compared with control conditions in randomized studies the source abstract does not describe [12]; active treatments [2]

Shown to lower depressive symptoms against control groups in a meta-analysis of 17 trials, with a moderate pooled effect.

Compared with control groups the source abstract does not describe [15]

Shown to ease anxiety in adults with health conditions against time-matched control programs, and an 8-week course matched escitalopram in one trial of anxiety disorders.

Compared with active control programs matched for time and attention [3]; escitalopram 10 to 20 mg [4]

Shown to improve sleep quality slightly more than time-matched control programs in one meta-analysis, and no differently from established sleep treatments.

Compared with nonspecific active controls matched for time and attention [10]; evidence-based sleep treatments [10]

Shown to lower cortisol in pooled trials. Blood cortisol fell only in people with a physical illness, and saliva cortisol did not fall significantly in one review.

Compared with control groups [15]; inactive controls and active controls [16]

Shown to improve thinking skills very slightly in one meta-analysis, mainly executive function and working memory, against inactive comparisons such as a waiting list.

Compared with inactive comparators [19]

Shown to shorten time to fall asleep about 7 minutes and add about 8 minutes of sleep in people with primary sleep disorders.

Shown to improve sleep quality scores about 1.2 points in adults with other conditions, with results varying by condition and no clear change in cancer.

Shown to reduce jet lag after flights crossing five or more time zones when taken near bedtime at the destination. Doses above 5 mg did no better.

Shown to improve sleep onset or sleep time in children with autism, cerebral palsy, atopic dermatitis or other neurologic conditions. No data in typically developing young children.

Shown to lower depressive symptoms slightly in perimenopausal women with depressive symptoms, with no benefit in women not selected for them.

Shown to lower insomnia severity by about 6 points more than placebo at 6 weeks on low-dose mirtazapine, with no difference from placebo from 12 weeks.

Shown to reduce sleepiness on night shifts in people diagnosed with shift work disorder, about 1 point on a 10-point scale. No trials tested shift workers without the disorder.

Compared with placebo [6][7][8]

Shown to keep sleep-deprived healthy people awake and to hold memory and executive function better than placebo, though repeated doses did not prevent decline over longer deprivation.

Compared with placebo [12]

Shown to improve depression scores and remission modestly when added to standard treatment, in unipolar and bipolar depression, an off-label use.

Compared with placebo added to standard treatment [15][16]

Shown to improve global cognition and memory slightly over 3 years in US adults 60 and older, all in one trial of one product.

Shown to raise days abstinent by about 9 percentage points and lower relapse slightly in alcohol dependence, with no change in heavy drinking days.

Shown to lower depression scores slightly when added to treatment, mainly in bipolar disorder.

Shown to improve cognitive performance during night shifts after a nap, mostly from 30 minutes after waking, in one meta-analysis. Memory dipped right after waking.

Compared with control conditions without a nap [4]

Shown to give at least half pain relief to 53% on tramadol against 30% on placebo in small nerve pain trials the reviewers rated low quality.

Shown to lower headache recurrence within 72 hours of emergency migraine treatment, with 9 treated to prevent one, using one injected dose of dexamethasone.

Linked to 18% less depression at half the guideline amount and 25% less at the guideline amount, in one meta-analysis of cohorts, with smaller gains beyond.

Compared with adults reporting no activity [15]

Shown to lower stroke about 14% and death about 12% with a potassium salt substitute, mostly from one trial in older rural Chinese adults at high stroke risk.

Shown to lower depression and anxiety in adults with diagnosed disorders, with effect sizes varying widely. Anxiety did not change in children.

Shown to improve cognitive test scores in older adults with cognitive impairment and in young adults in two meta-analyses of small trials. Home-use devices showed no significant effect.

Shown to lower anxiety (SMD -0.82) in pooled trials that mixed placebo and no-treatment comparisons, with very high heterogeneity.

Compared with a placebo group or blank control, pooled together [4]

Linked to more new depression at both short and long sleep in one meta-analysis of seven cohorts.

Compared with people with normal sleep duration [9]

Shown to lower positive mood and raise negative mood when sleep was cut or skipped, in one meta-analysis of 64 experimental studies.

Compared with control conditions the source does not describe [10]

Shown to impair attention after total sleep loss in pooled experiments, and 14 nights of 6 hours or less in bed caused growing deficits in one trial.

Compared with a baseline test in the same people, or a control group [11]; 8 hours in bed a night [12]

Shown to lower self-rated stress by a small to moderate amount against inactive controls such as a waiting list, in one meta-analysis.

Compared with inactive non-breathwork controls [2]

Shown to lower self-rated stress slightly more than active control conditions. In one trial, 5 minutes a day of cyclic sighing lifted mood more than mindfulness meditation.

Compared with active non-breathwork controls [2]; mindfulness meditation for the same time [4]

Linked to small improvements in depression, anxiety and stress after quitting, in a Cochrane review of mostly cohort data rated very low to moderate in certainty.

Compared with people who continued to smoke [19]

Shown to reduce social anxiety and panic symptoms more than placebo in the venlafaxine trials behind its approval, five in social anxiety and two in panic disorder.

Linked to more depression with loneliness, a moderate effect in one meta-analysis of 88 studies and a positive link in all ten longitudinal studies of older adults in a review.

Compared with people with lower loneliness scores [8]; less lonely older adults [9]

Shown to raise response in panic disorder in adults, with about 7 treated with an antidepressant for one extra response.

Shown to raise response in social anxiety disorder in adults, about 1.65 times as likely as on placebo, in evidence a Cochrane review rated very low quality.

Shown to improve PTSD symptoms in adults, with 58% responding on an SSRI against 35% on placebo.

Shown to lower relapse in people who had improved: about 22 fewer relapses per 100 on a continued SSRI than after a switch to placebo.

Shown to reduce premenstrual symptoms in women with PMS or PMDD by a moderate amount, more with daily dosing than with dosing in the luteal phase only.

Shown to raise remission from binge eating in bulimia nervosa across antidepressants, with about 9 treated for one extra remission. The SSRI trials were all of fluoxetine.

Shown to lower PMS anxiety, depression, mood and behavioral symptoms modestly against placebo. One small trial found physical and behavioral gains but no mood change.

Shown to lower stress, anxiety and depression in pooled trials of tai chi and of qigong, against waiting list and varied controls, in trials with methodological limits.

Compared with varied control groups, including some nonrandomized studies [12]; waiting list [13]; lectures and structured movement alone [13]

Shown in two trials of older adults with insomnia to improve sleep against no intervention or sleep education, by modest amounts on wrist-worn sleep measures.

Compared with no intervention [14]; a sleep seminar education control [15]

Shown to lower stroke from 6.2% to 4.2%, coronary heart disease from 3.9% to 2.8% and deaths from 11.0% to 9.8% as first-line low-dose treatment.

Shown to lower salivary cortisol slightly in forest groups in one meta-analysis, and serum cortisol fell after forest visits in two small trials in men.

Compared with urban groups [1]; people with lower greenspace exposure [2]; the group sent to a city area [3]; the day before forest therapy, in the same men [4]

Linked to more physical activity and restoration with more blue space nearby or more contact with it, in one meta-analysis. Living closer was not linked to restoration.

Compared with people living farther from, with less, or with less contact with blue space [13]; comparisons the source does not describe [14]

Shown to cut monthly migraine days modestly against placebo in chronic migraine, with the most dropouts for side effects among the treatments compared.

Compared with placebo, botulinum toxin and acupuncture [4]

Shown to make a halving of seizures about 2.7 times as likely as placebo when added to other drugs, with more effect at higher doses and more withdrawals.

Compared with placebo added to existing seizure drugs [6]

Shown to reduce binge episodes by about 1.3 a week and weight by about 4.9 kg against placebo in binge eating disorder, with more withdrawals for safety reasons.

Compared with placebo, with or without psychotherapy [9]

Shown to lower total alcohol consumption against placebo in adults with alcohol dependence, with no trial powered to show health benefits.

Compared with placebo, and indirectly nalmefene, naltrexone and acamprosate [10]

Shown to reduce depression symptoms more than placebo in adults. Response matched SSRIs in one meta-analysis and ranked among the lower rates in another.

Shown to leave 59% pain free 2 hours after a 6 mg sumatriptan injection against 15% on placebo, a larger effect than by mouth.

Shown to match or exceed NSAIDs, aspirin and acetaminophen for headache relief at 2 hours, and to outperform lasmiditan, rimegepant and ubrogepant in a network analysis.

Shown to leave 28% pain free at 2 hours on sumatriptan plus naproxen against 8% on placebo, more than either drug alone.

Shown to leave 48% pain free 15 minutes after a 6 mg sumatriptan injection for a cluster headache attack, against 17% on placebo.

Shown to raise pain freedom in adolescents with migraine, with 6 treated for one extra pain free, and 13 in younger children.

Shown to raise the share of women free of menstrual migraine when frovatriptan was taken around the period, with about 4 to 7 treated for one extra.

Shown to lower depression scores against placebo in people with depression or depressive symptoms, with effect sizes varying widely across reviews.

Shown to raise the share of people reporting better sleep, about 37% more than placebo, in adults with or without sleep problems. Most studies had method problems.

Shown to improve overall premenstrual symptoms and premenstrual depression over placebo in women with PMS, in mostly low-quality trials from a 1999 review.

Shown to lower depressive symptom scores in adults with depression, in small trials with high heterogeneity.

Linked to better memory and verbal fluency in older volunteers in 16 of 17 studies in one review. One large US cohort found no link with cognitive impairment.

Compared with older adults who did not volunteer [5]; retired seniors who did not volunteer or volunteered only on and off [6]; people who volunteered 0 hours a year [4]

Linked to 23% less dementia in people with a stronger sense of purpose in life, in one meta-analysis of six samples followed up to 17 years.

Compared with people with a lower sense of purpose in life [12]

Shown to lower depression scores when added to usual treatment in people with mental health problems, in a meta-analysis of small studies with high heterogeneity.

Shown to ease anxiety slightly against no treatment in one meta-analysis of 8 small trials, in people with raised anxiety. No effect appeared in diagnosed anxiety disorders.

Compared with no treatment [4]

Shown to ease anxiety more than active comparisons in small pooled trials. In one trial of generalized anxiety disorder, Kundalini yoga beat stress education but fell short of CBT.

Compared with active comparators the source abstract does not describe [4]; stress education [5]; cognitive behavioral therapy [5]

Shown to improve self-rated sleep quality in older adults against inactive controls such as a waiting list, in one meta-analysis.

Compared with inactive controls such as a waiting list or education booklets [7]

Shown to improve self-rated sleep quality over placebo in short trials of eszopiclone and zolpidem, by more than zaleplon, melatonin or ramelteon.

Shown to keep improving sleep against placebo across 6 to 8 months of use in four trials of eszopiclone and zolpidem in adults with chronic insomnia.

One trial found adding 5-HTP to fluoxetine for 12 weeks lowered OCD symptoms more than fluoxetine plus placebo in 60 adults.

Small trials found 5-HTP improved sleep scores in older adults who slept poorly, raised REM sleep in Parkinson's disease, and cut sleep terrors in children.

One small crossover trial found lisinopril lowered days with migraine by 21% against placebo in adults with 2 to 6 attacks a month.

Limited evidence: low-quality trials found a small drop in depression scores, 1.69 points on the Hamilton scale, against sham acupuncture, and a moderate drop against no treatment.

Compared with no treatment, waiting list or treatment as usual [16]; sham acupuncture [16]; antidepressant medication [16]

One small trial found sleepiness scores improved 4.4 points on amphetamine-dextroamphetamine and 5.0 on modafinil, without showing the two were equivalent.

Limited evidence: two cohort studies linked terazosin, doxazosin or alfuzosin to lower Parkinson risk or fewer Parkinson events than tamsulosin, in men. No trial has tested this.

Compared with men taking tamsulosin [17][18]

Limited evidence: citicoline and choline alfoscerate improved cognitive scores in people with dementia or mild cognitive impairment, in studies of poor quality with risk of bias.

Small trials found citicoline raised a memory score in older adults with memory impairment, and alpha-GPC raised one attention score in young men.

One trial found losartan lowered stroke by 25% against atenolol in adults with high blood pressure and an enlarged left ventricle, at similar blood pressure.

Small trials found candesartan lowered migraine days against placebo, with about 40% of people having at least half as many.

One trial found viloxazine lowered adult ADHD symptoms 3.7 points more than placebo over 6 weeks.

Compared with placebo [6]

Small trials found a single dose of atomoxetine improved stopping a started action in healthy volunteers, mostly in those who did worst on placebo, with no effect on learning.

Compared with placebo, in crossover designs [7][8]

The label reports that aripiprazole reduced tic scores more than placebo in two trials of 8 and 10 weeks in patients aged 6 to 18.

Small trials found 300 mg a day for 12 weeks improved delayed word recall in adults over 55, while other memory tasks did not change.

Small trials found bacopa lowered anxiety and self-reported stress scores against placebo in older and middle-aged adults.

Small trials found response in social anxiety disorder about 4 times as likely on a benzodiazepine as on placebo, in 132 people.

Small trials found propranolol removed physical symptoms of stage fright in musicians and raised performance quality as scored by critics.

One pilot trial found 4,200 mg a day cut brain swelling by more than 75% in 60% of patients against 26% on placebo during radiotherapy.

One small trial found verapamil lowered attack frequency in episodic cluster headache against placebo over 14 days.

One trial found 64% halved their migraine days on atogepant against 39% on topiramate, and 12% stopped for side effects against 30%.

Compared with topiramate at the highest tolerated dose of 50 to 100 mg a day [7]

One trial found galcanezumab 300 mg cut weekly cluster attacks by 8.7 against 5.2 on placebo, with 71% responding against 53%.

Compared with placebo [11]

Limited evidence: two low-quality trials suggested several sessions of neck manipulation eased cervicogenic headache pain more than massage.

Compared with massage [7]

One trial found caffeinated coffee helped people take in new information and offset fatigue against decaffeinated coffee, with no change in working memory or mood.

Compared with decaffeinated coffee [12]; people drinking no coffee [13]

Limited evidence: a systematic review described better sleep quality and quality of life in a few trials, without pooled estimates.

Small studies found plasma noradrenaline rose 530% and dopamine 250% during an hour in 14°C water, and people reported feeling more alert after a 5-minute immersion.

Limited evidence: lowered depression scores about 2 points, below the 3 points counted as a meaningful change.

One trial found stroke or systemic embolism at 1.6% a year on apixaban against 3.7% on aspirin, with no significant rise in major bleeding.

A systematic review found the caffeine dose in a typical energy drink can improve mental performance, with little evidence that taurine, ginseng or other added ingredients contribute.

Compared with caffeine alone or placebo, in the studies reviewed [5]

One small trial found sublingual epitalon raised a urine melatonin marker 1.7-fold in women aged 40 to 50 with low levels. No health outcome was measured.

Small trials found L-methylfolate added to antidepressants raised response and lowered symptoms in adults with major depression.

Limited evidence: added to a preventive drug, ginger lowered headache severity at 3 months. Reviewers call any acute or preventive benefit too uncertain.

Small trials found 3 g of glycine before bed improved self-rated sleep and next-day fatigue in people with poor or shortened sleep.

Limited evidence: a sham-controlled pilot in 15 people with mild Alzheimer's disease and an uncontrolled study of 12 adults reported better sleep while grounded at night.

Compared with sham grounding [1]; before grounding, in the same people [2]

One uncontrolled study of 12 adults found saliva cortisol at night fell after 6 weeks of sleeping grounded, and self-reported stress eased.

Compared with before grounding, in the same people [2]

One trial found better global cognitive scores after 3 months of sessions in 63 healthy adults over 64, compared with a control group that received no treatment.

One trial found better neurological function and quality of life after 40 sessions in people 6 to 36 months after a stroke, with no change during an untreated waiting period.

Limited evidence: cognitive test scores were higher 1 month after 20 sessions in 42 people with Alzheimer's disease than in 30 untreated patients, in a non-randomized study.

One trial of 200 women found a 15-minute hypnosis session before breast surgery lowered pain at discharge from 48 to 22 on a 100-point scale against empathic listening.

Compared with nondirective empathic listening as an attention control [16]

Limited evidence: iodine slightly raised cognitive scores in iodine-deficient children, with each result resting on one trial.

One trial found 27% in remission at 8 weeks on esketamine against 18% on quetiapine, each added to an SSRI or SNRI, in treatment-resistant depression.

Compared with extended-release quetiapine, each added to an SSRI or SNRI [5]