Evidence behind the care
The key studies shaping how each condition is understood and treated here, gathered in one place and organized by topic. Each paper links to its free abstract on PubMed from the U.S. National Library of Medicine.
Depression
Read the full depression guide
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Esketamine Monotherapy in Adults With Treatment-Resistant Depression: A Randomized Clinical Trial
Janik et al. · JAMA Psychiatry · 2025
In this randomized trial, both esketamine nasal spray doses improved depression scores versus placebo at day 28, with benefit seen as early as 24 hours after the first dose, and the most common side effects were nausea, dissociation, dizziness and headache.
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Clemens et al. · Current Medical Research and Opinion · 2025
Using patient reported symptom ratings in the ESCAPE TRD trial, esketamine nasal spray produced higher remission and response rates than extended release quetiapine at both 8 and 32 weeks.
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Zaccoletti et al. · Lancet Psychiatry · 2026
Across 76 trials, staying on antidepressants and slowly tapering with therapy support both lowered relapse risk, while stopping quickly raised relapse risk similar to stopping at once.
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Kalfas et al. · JAMA Psychiatry · 2025
Across 50 trials, stopping an antidepressant caused about one extra mild symptom such as dizziness or nausea in the first week, well below the level of a major withdrawal syndrome.
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Bartoli et al. · Drugs & Aging · 2025
In 302 older adults with depression, vortioxetine did not improve symptoms, response, or remission more than standard SSRIs over six months.
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Kato et al. · Mol Psychiatry · 2021
Across forty trials with 8,890 patients, continuing the same antidepressant after remission lowered relapse to about 21 percent compared with about 40 percent on placebo.
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Bot et al. · J Affect Disord · 2026
In a real world cohort of 591 adults who started the SSRIs citalopram or sertraline, nearly half reached stable remission during follow up, most of them within the first year of treatment.
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Cipriani et al. · Lancet · 2018
Across 522 trials with more than 116,000 participants, every antidepressant beat placebo for symptom response, differences between individual drugs were modest, and only agomelatine and fluoxetine had fewer dropouts than placebo.
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Mishra et al. · J Affect Disord · 2025
In a trial of 150 patients with treatment resistant depression, adding pramipexole to sertraline lowered depression scores more than adding amantadine or quetiapine, with a similar rate of side effects across the three groups.
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Naudet et al. · BMC Med · 2025
This reanalysis of patient level data from 7 trials found esketamine plus an antidepressant had a statistically significant but small benefit over placebo, while raising rates of sedation, dissociation, and other adverse events.
Anxiety
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Kong et al. · Front Pharmacol · 2020
In this network meta analysis of 32 trials with more than 13000 adults with generalized anxiety disorder, duloxetine, escitalopram, paroxetine and venlafaxine doubled the odds of remission versus placebo while sertraline and a few others were as well tolerated as placebo.
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Hu et al. · JAMA Network Open · 2024
In this 8 week trial across several anxiety disorders, escitalopram and mindfulness training lowered patient reported anxiety to a similar degree by week 8, though the medication group improved faster in the first month and reported more side effects.
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Cardoner et al. · Front Pharmacol · 2025
Across 14 trials with nearly 5,000 patients, pregabalin reduced anxiety more effectively than SSRIs, SNRIs, and benzodiazepines, with fewer people stopping treatment.
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Christensen et al. · J Psychopharmacol · 2022
In an 8 week study of people with both severe depression and severe anxiety, vortioxetine was linked to meaningful improvement in anxiety symptoms and daily functioning.
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Chawla et al. · BMJ · 2022
Across 87 trials, SSRIs offered strong remission rates with the lowest risk of side effects among drug classes, and sertraline and escitalopram showed the best balance of benefit and tolerability.
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Caiazza et al. · Hum Psychopharmacol · 2026
Mirtazapine matched SSRIs for reducing anxiety symptoms in generalized anxiety disorder and was tolerated similarly to placebo, suggesting it may be a useful alternative when first line options are not suitable.
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Antidepressants versus placebo for generalised anxiety disorder (GAD)
Kopcalic et al. · Cochrane Database Syst Rev · 2025
A Cochrane review of 37 trials with more than 12,000 adults found antidepressants raised the treatment response rate by 41 percent over placebo, with similar overall dropout rates between the two groups.
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Müller et al. · Eur Arch Psychiatry Clin Neurosci · 2026
A network meta analysis of 100 trials with more than 28,000 adults found most anxiety medicines eased symptoms more than placebo, while tolerability differed widely across medicines.
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Bakay et al. · Health Care Women Int · 2025
In this 11 year review, postpartum women with generalized anxiety disorder reached a 78.8% response rate and a 63.6% remission rate after 8 weeks of paroxetine treatment.
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Duan et al. · Psychiatry Res Neuroimaging · 2025
In a network meta analysis of 8 randomized trials, high frequency rTMS showed higher response and remission rates than other active brain stimulation therapies for generalized anxiety disorder.
ADHD
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Ostinelli et al. · Lancet Psychiatry · 2025
Across 113 trials with nearly 15000 adults, stimulants were the only treatment shown to reduce core ADHD symptoms with good acceptability while atomoxetine also worked but had more dropouts.
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Pharmacological interventions for ADHD: a systematic review and dose effect network meta analysis
Nourredine et al. · Lancet Psychiatry · 2026
In this 2026 dose response analysis, stimulant benefits leveled off above certain doses in adults while side effect related dropouts rose with higher doses, suggesting higher doses add risk without extra benefit.
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Zhang et al. · BMJ · 2025
In a Swedish study of more than 148000 people newly diagnosed with ADHD, starting medication was linked with lower rates of suicidal behavior, substance misuse, traffic accidents, and criminality over two years.
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Capusan et al. · BMJ Ment Health · 2026
People with ADHD who also had a substance use disorder were about twice as likely to stop their ADHD medication within a year, with young men and those on lower doses most affected.
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Rutledge-Jukes et al. · Cureus · 2024
Across eleven randomized trials, lisdexamfetamine reduced both inattentive and hyperactive ADHD symptoms more than placebo, and higher doses did not improve symptoms further.
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Muneer et al. · Psychopharmacol Bull · 2026
Across five randomized trials in 1,968 people, centanafadine lowered ADHD symptom scores more than placebo and showed a generally acceptable side effect profile.
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Weisler et al. · CNS Spectrums · 2006
In a four week controlled trial, extended release mixed amphetamine salts lowered adult ADHD symptom scores, most side effects reported were mild or moderate, and vital signs and heart tracings showed no major changes.
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Isfandnia et al. · Neuroscience & Biobehavioral Reviews · 2024
A 2024 review of many trials found that longer term stimulant and non stimulant medications improved focus and thinking skills in people with ADHD, with the stimulant helping in all areas tested and the non stimulant helping in most areas.
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Chapman et al. · Cureus · 2026
Viloxazine extended release reduced ADHD symptoms in adolescents and adults with a favorable tolerability profile.
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Oliva et al. · J Clin Psychiatry · 2026
Higher doses of methylphenidate and mixed amphetamine salts improved ADHD symptoms and supported abstinence in adults with co occurring stimulant use disorder.
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Bellato et al. · J Am Acad Child Adolesc Psychiatry · 2025
Across 17 randomized trials, amphetamines, methylphenidate, and atomoxetine each improved quality of life more than placebo in people with ADHD, not just core symptoms.
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Current nonstimulant medications for adults with attention deficit/hyperactivity disorder
Brancati et al. · Expert Rev Neurother · 2024
Atomoxetine showed significant efficacy for adult ADHD as the guideline supported second line option, while bupropion, viloxazine, guanfacine and tricyclic antidepressants also showed evidence of benefit for personalizing treatment.
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Mick et al. · Eur Neuropsychopharmacol · 2013
In trials of stimulants for adult ADHD, average resting heart rate rose by about six beats per minute and systolic blood pressure by about two points, so heart health monitoring is part of ongoing care.
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Farhat et al. · Lancet Psychiatry · 2025
Across 102 randomized trials, ADHD medications caused only small increases in blood pressure and pulse while guanfacine lowered them, so blood pressure and heart rate monitoring is advised during treatment with any of these medications.
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Safety of Stimulants Across Patient Populations: A Meta Analysis
Oliva et al. · JAMA Netw Open · 2025
Across 93 randomized trials, stimulants including methylphenidate, lisdexamfetamine and other amphetamines raised the risk of overall adverse events compared with placebo.
PTSD
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Hoppen et al. · JAMA Psychiatry · 2025
A network meta analysis of 70 randomized trials found trauma focused cognitive behavioral therapies produced the largest PTSD symptom reductions in children and teens, with benefits holding through two years of follow up.
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Leithner et al. · Psychological Medicine · 2026
A Bayesian meta analysis of 55 trials found psychosocial interventions strongly reduced PTSD symptoms in adults in lower income countries, with trauma focused treatments working best as first line care.
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Doubly Randomized Preference Trial of Prolonged Exposure Versus Sertraline for Treatment of PTSD
Zoellner et al. · Am J Psychiatry · 2019
Both prolonged exposure therapy and sertraline produced large lasting improvements in PTSD symptoms, and patients who received the treatment they preferred did better overall.
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Hien et al. · J Consult Clin Psychol · 2015
Adding sertraline to Seeking Safety therapy led to greater and longer lasting reduction in PTSD symptoms than therapy with placebo, in people with both PTSD and alcohol use disorder.
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Pharmacotherapy for post traumatic stress disorder (PTSD)
Williams et al. · Cochrane Database Syst Rev · 2026
Across 66 trials, SSRIs improved PTSD symptoms more than placebo with moderate certainty evidence, while dropout rates from side effects stayed low at about 9 percent.
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Kotochinsky et al. · J Psychiatr Res · 2026
Adding brexpiprazole to an SSRI lowered clinician rated PTSD symptoms across four trials, though it also raised weight and sleepiness, with no overall rise in total side effects.
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Pharmacotherapy for post-traumatic stress disorder: systematic review and meta-analysis
Jia et al. · Ther Adv Psychopharmacol · 2025
A meta analysis of 52 trials found medicines improved core PTSD symptoms with a 39 percent response rate, and antidepressants showed slightly stronger effects than antipsychotics.
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Costa et al. · J Psychiatr Res · 2020
A network meta analysis of 58 trials found paroxetine, venlafaxine, fluoxetine and sertraline each reduced PTSD symptoms more than placebo.
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Fortney et al. · JAMA Psychiatry · 2025
A large pragmatic trial of primary care patients found that brief written exposure therapy and SSRI medication produced similar PTSD symptom improvement, while patients who did not respond to an SSRI improved more after switching to venlafaxine than after adding exposure therapy.
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Hicks et al. · Psychol Trauma · 2026
A randomized trial of veterans with PTSD and alcohol use disorder found that adding topiramate to prolonged exposure therapy did not cause meaningful cognitive problems and may support better treatment response.
OCD
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Eghdami et al. · Front Psychiatry · 2024
Across six trials with 195 adults, adding NAC to ongoing SSRI therapy modestly lowered OCD symptom scores with no increase in adverse events compared to placebo, though longer studies are still needed.
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Mindfulness for obsessive-compulsive disorder: a systematic review and meta-analysis
Perin et al. · Brazilian Journal of Psychiatry · 2026
Across six randomized trials, mindfulness based treatments reduced OCD symptoms as well as established CBT including exposure and response prevention, with equal dropout rates in both groups.
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Exner et al. · Journal of Anxiety Disorders · 2024
In a randomized trial of 74 outpatients, metacognitive therapy reduced OCD symptoms as well as exposure and response prevention by end of treatment, and both groups showed similarly low dropout.
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Memantine Augmentation in Obsessive-Compulsive Disorder: A Systematic Review and Meta-analysis
Lyndon et al. · CNS Drugs · 2026
Pooling six trials, this review found that adding memantine to standard treatment did not clearly reduce OCD symptoms more than placebo, so it is not supported for routine use.
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Mirzazadeh et al. · BMC Psychiatry · 2025
Both groups improved on escitalopram, and adding memantine offered no extra symptom benefit apart from time management.
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Zemestani et al. · Behavior Modification · 2022
Adding either talk therapy approach to a stable SSRI dose produced larger symptom reductions than staying on the SSRI alone.
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Gualtieri et al. · J Clin Med · 2025
Higher SSRI doses reduced OCD symptoms more than standard doses in treatment resistant patients, with side effects that were generally mild.
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Coelho et al. · JAMA Netw Open · 2025
Across 27 randomized trials, glutamatergic medications lowered OCD symptom scores more than placebo when used alone or added to standard care.
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Öst et al. · Cogn Behav Ther · 2026
A review of 47 studies with more than 2800 participants found that benefits from cognitive behavior therapy for OCD remained strong about two and a half years after treatment ended, with response rates near 70 percent both right after treatment and at follow up.
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Woodson et al. · Bull Menninger Clin · 2025
Adults with OCD did as well in a virtual partial hospital program as in residential care, with both forms of intensive treatment showing effective results.
Weight Management
Read the full weight management guide
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Tirzepatide as Compared with Semaglutide for the Treatment of Obesity
Aronne et al. · New England Journal of Medicine · 2025
In the first direct randomized trial of the two leading weekly injections, tirzepatide produced about 20 percent average weight loss over 72 weeks versus about 14 percent with semaglutide, and more people on tirzepatide reached higher weight loss milestones.
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Omeh et al. · Expert Review of Endocrinology and Metabolism · 2026
Across 23 trials with more than 14000 people, tirzepatide 10 or 15 mg matched sleeve gastrectomy for total body weight loss, while semaglutide showed moderate results and orlistat showed only a small effect.
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Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes
Lincoff et al. · New England Journal of Medicine · 2023
In a trial of more than 17,000 adults with established heart disease and excess weight but no diabetes, semaglutide reduced major heart events by about 20 percent compared with placebo.
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Horn et al. · Lancet · 2026
In a large 72 week trial in adults with obesity and type 2 diabetes, a once daily oral pill called orforglipron reduced body weight and blood sugar more than placebo, with mostly mild to moderate stomach side effects.
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Moiz et al. · Ann Intern Med · 2026
Tirzepatide and semaglutide produced the largest weight loss across 38 trials, while stomach related side effects stayed common and no new safety signals appeared.
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Khera et al. · JAMA · 2016
Phentermine plus topiramate ranked strongest among older approved oral agents with the most patients reaching at least 5 percent weight loss, while more patients stopped naltrexone plus bupropion or liraglutide over side effects.
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Munawar et al. · Cureus · 2025
Tirzepatide produced greater weight loss than semaglutide across seven direct comparison studies totaling nearly 29,000 participants.
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Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment
Wharton et al. · N Engl J Med · 2025
Once daily oral orforglipron reduced body weight significantly more than placebo over 72 weeks, with mostly mild to moderate gastrointestinal side effects.
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Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity
Jastreboff et al. · N Engl J Med · 2026
In this phase 3 trial of 2,339 adults with obesity, once weekly retatrutide produced an average 25 percent weight loss at 80 weeks on the highest dose versus 3.9 percent with placebo, and it also eased knee osteoarthritis pain and sleep apnea events, with gastrointestinal effects being the most common side effects.
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Ciudin et al. · Adv Ther · 2026
Across trials comparing three injectable weight medications in people with obesity and no diabetes, tirzepatide 10 and 15 mg produced greater weight and waist reduction than liraglutide and semaglutide, while all three showed a comparable safety profile.
Medications
Read the full medications guide
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Mirtazapine versus other antidepressive agents for depression
Watanabe et al. · Cochrane Database of Systematic Reviews · 2011
Across 29 randomized trials with nearly 5,000 participants, mirtazapine appeared to improve symptoms sooner than SSRIs for some patients. It caused more sleepiness, appetite increase, and weight gain, but less nausea and sexual dysfunction than SSRIs.
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Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression
Rush et al. · The New England Journal of Medicine · 2006
After an initial SSRI had failed, switching to bupropion SR, sertraline, or venlafaxine XR produced similar overall results. This supports bupropion as one reasonable next step, not as a universally better option.
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Nelson et al. · The American Journal of Psychiatry · 2009
Across placebo controlled trials, adding an atypical antipsychotic helped more patients reach response and remission when their antidepressant alone had not done enough. The benefit had to be weighed against a higher burden of side effects.
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Bauer et al. · The Journal of Clinical Psychiatry · 2009
In 493 patients whose antidepressant had not worked well enough, adding quetiapine XR reduced depressive symptoms more than placebo over 6 weeks, with separation visible by the first week. Dry mouth, sleepiness, and stopping because of side effects were more common with quetiapine.
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Crossley et al. · The Journal of Clinical Psychiatry · 2007
Two combined analyses of randomized trials found lithium significantly more effective than placebo as an add on to antidepressants for depression. Evidence that lithium speeds up the onset of benefit was more modest.
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Calabrese et al. · The Journal of Clinical Psychiatry · 1999
Lamotrigine improved several measures of bipolar depression compared with placebo, with improvement appearing by week 3. Note: this studied lamotrigine on its own for bipolar depression, not as an add on for unipolar depression.
Erectile Dysfunction
Read the full erectile dysfunction guide
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Oral sildenafil in the treatment of erectile dysfunction
Goldstein et al. · N Engl J Med · 1998
In two trials totaling 861 men, 69 percent of attempts at intercourse succeeded with sildenafil versus 22 percent with placebo. Headache, flushing, and indigestion were the most common side effects.
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Tsertsvadze et al. · Ann Intern Med · 2009
Across short term trials, PDE5 inhibitors improved erections in 67 to 89 percent of men versus 27 to 35 percent with placebo. Head to head trials found no clear winner among sildenafil, vardenafil, and tadalafil.
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Flibanserin for Premenopausal Hypoactive Sexual Desire Disorder: Pooled Analysis of Clinical Trials
Simon et al. · J Womens Health · 2019
Pooling the VIOLET, DAISY, and BEGONIA trials in 2,465 premenopausal women, flibanserin modestly increased satisfying sexual events and desire scores versus placebo. Dizziness and sleepiness were the most common side effects.
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Katz et al. · J Sex Med · 2013
In 1,087 premenopausal women treated for 24 weeks, nightly flibanserin improved desire and reduced distress versus placebo. About 1 in 10 stopped treatment because of side effects.
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Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials
Kingsberg et al. · Obstet Gynecol · 2019
In two identical trials of 1,267 premenopausal women, on demand bremelanotide improved desire and reduced distress versus placebo. Nausea, flushing, and headache were the most common side effects.
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Berman et al. · J Urol · 2003
In 202 postmenopausal women, sildenafil improved arousal and satisfaction versus placebo, but only in women without low desire. It did not help desire itself.
Substance Use
Read the full substance use guide
Cannabis (marijuana)
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Meta analysis of the Association Between the Level of Cannabis Use and Risk of Psychosis
Marconi et al. · Schizophrenia Bulletin · 2016
People who used cannabis heavily were more likely to develop psychosis, and the more someone used, the higher the risk appeared to be.
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Gobbi et al. · JAMA Psychiatry · 2019
Teens who used cannabis were more likely to develop depression as young adults, were about half again as likely to have thoughts of suicide, and were more than three times as likely to attempt suicide. As an observational study it cannot prove cause.
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Kedzior et al. · BMC Psychiatry · 2014
Across 31 studies, people with anxiety disorders were more likely to use cannabis, and people who had used cannabis at the start of the studies showed a small increase in anxiety later on.
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Marijuana Use, Respiratory Symptoms, and Pulmonary Function: A Systematic Review and Meta analysis
Ghasemiesfe et al. · Annals of Internal Medicine · 2018
Smoking cannabis was linked to more coughing, mucus, wheezing, and shortness of breath, although the studies did not prove lasting lung damage.
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Storck et al. · Heart · 2025
Cannabis use was linked to higher chances of heart attack, stroke, and death from heart disease, though many of the underlying studies had important quality limits.
Alcohol
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Li et al. · Addiction · 2020
People with alcohol use disorders were 57 percent more likely to develop depressive symptoms later on.
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Alcohol use and death by suicide: A meta analysis of 33 studies
Isaacs et al. · Suicide and Life-Threatening Behavior · 2022
Across more than 10 million people in 33 studies, alcohol use was linked to a 94 percent higher risk of dying by suicide.
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A meta analysis of acute use of alcohol and the risk of suicide attempt
Borges et al. · Psychological Medicine · 2017
Drinking shortly before a suicide attempt was linked to much higher odds of making an attempt, with risk climbing as the amount of alcohol rose.
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Llamosas-Falcón et al. · Hepatology International · 2023
The more alcohol people drank, the higher their chances of developing serious liver scarring and dying from it, with no clearly safe amount identified.
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Wood et al. · The Lancet · 2018
Drinking more alcohol was linked to higher risks of stroke, heart failure, fatal high blood pressure disease, aortic aneurysm, and dying from any cause once drinking passed about 100 grams of alcohol per week.
Cocaine
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Sabé et al. · Progress in Neuro-Psychopharmacology & Biological Psychiatry · 2021
Across all studies pooled, a large share of people who use cocaine had experienced psychosis symptoms like intense paranoia or hallucinations while using.
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Moçambique et al. · Brazilian Journal of Psychiatry · 2022
In this review of 2,252 cocaine users, about 44 percent had suicidal thoughts and about 28 percent had attempted suicide.
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Cardiovascular Risks of Simultaneous Use of Alcohol and Cocaine A Systematic Review
van Amsterdam et al. · Journal of Clinical Medicine · 2024
Mixing cocaine with alcohol is even harder on the heart than cocaine alone, and the mix creates a byproduct called cocaethylene that greatly raises the risk of sudden cardiac death.
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Cocaine and Marijuana Use Among Young Adults With Myocardial Infarction
DeFilippis et al. · Journal of the American College of Cardiology · 2018
Among young adults who had a heart attack, those who used cocaine or marijuana had roughly double the risk of dying from heart problems compared to people who did not use.
Methamphetamine
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McKetin et al. · EClinicalMedicine · 2019
A review of 149 studies found methamphetamine use linked to much higher odds of psychosis, violence, depression, and suicidal behavior.
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Cohen-Laroque et al. · Schizophrenia Research · 2024
Psychosis caused by methamphetamine can look just as severe as schizophrenia, with hallucinations and delusions that are just as intense.
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A systematic review of risk factors for methamphetamine associated psychosis
Arunogiri et al. · Australian and New Zealand Journal of Psychiatry · 2018
The more often and more heavily someone uses methamphetamine, the more likely they are to develop psychotic symptoms.
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Curran et al. · Journal of the American Heart Association · 2022
In a study of over 20 million hospital patients, methamphetamine use raised the overall risk of heart and blood vessel disease by about 32 percent.
Opioids
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Prescription Opioid Duration, Dose, and Increased Risk of Depression in 3 Large Patient Populations
Scherrer et al. · Annals of Family Medicine · 2016
In three large patient groups, people who took prescription opioids for longer periods and at higher doses were more likely to develop depression.
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Initiation of Opioid Prescription and Risk of Suicidal Behavior Among Youth and Young Adults
Fine et al. · Pediatrics · 2022
In a nationwide study of nearly 2 million Swedish youth, those who started a prescription opioid had more than double the risk of suicidal behavior compared to young people who did not.
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Fleischauer et al. · MMWR · 2017
A CDC report tracking rising hospital stays for a life threatening heart valve infection linked to injection drug use.
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Increases in Drug and Opioid Involved Overdose Deaths: United States, 2010 to 2015
Rudd et al. · MMWR · 2016
A CDC report documenting the sharp rise in US overdose deaths driven by opioids, showing overdose is one of the leading ways opioid use kills.
Nicotine (tobacco and vaping)
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Hu et al. · Frontiers in Medicine · 2025
Current smokers were more likely to develop major depression, schizophrenia, and bipolar disorder. As an observational study it cannot prove smoking caused them.
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Proposal for the Inclusion of Tobacco Use in Suicide Risk Scales: Results of a Meta Analysis
Echeverria et al. · International Journal of Environmental Research and Public Health · 2021
Across about 2.5 million people followed over time, current smokers had a higher risk of dying by suicide and of having suicidal thoughts than people who did not smoke.
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Obisesan et al. · JAMA Network Open · 2019
People who vaped, especially daily, were more likely to report depression, although this one time snapshot cannot show whether vaping came first.
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Hackshaw et al. · BMJ · 2018
Even smoking just one cigarette a day carried a surprisingly large share of the heart disease and stroke risk of smoking 20 a day, so cutting back is not nearly as protective as quitting.
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Kim et al. · International Journal of Chronic Obstructive Pulmonary Disease · 2025
People who both vaped and smoked regular cigarettes were more likely to have COPD, a serious long term lung disease, and to report mental health problems than people who used neither.
Benzodiazepines and sedatives
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Hamadieh et al. · BMC Psychiatry · 2026
Combining 21 studies, people prescribed benzodiazepines were more than twice as likely to attempt or die by suicide. An association does not prove the medication caused it.
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Penninkilampi et al. · CNS Drugs · 2018
Across 15 studies with about 159,000 dementia cases, benzodiazepine use was linked to about a 39 percent higher chance of dementia, even after accounting for early dementia symptoms. This is observational and not proof of cause.
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Mortality associated with anxiolytic and hypnotic drugs A systematic review and meta analysis
Parsaik et al. · Australian and New Zealand Journal of Psychiatry · 2016
Pooling 25 studies of over 2.3 million patients, people using sleep or anti anxiety drugs had 43 percent higher mortality than non users, and benzodiazepine users specifically had 60 percent higher mortality.
Hallucinogens
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Murrie et al. · Schizophrenia Bulletin · 2020
Among people who had already experienced hallucinogen induced psychosis, about 1 in 4 later received a schizophrenia diagnosis. The hallucinogen evidence was limited and strongly influenced by PCP cases.
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Pharmacological Treatment of Hallucinogen Persisting Perception Disorder (HPPD): A Systematic Review
Neven et al. · Harvard Review of Psychiatry · 2025
A review of 31 studies found hallucinogen use can leave some people with lingering visual disturbances and flashbacks that may last a year or more and seriously burden daily life.
MDMA (ecstasy, molly)
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Ecstasy (MDMA) and memory function: a meta analytic update
Laws et al. · Human Psychopharmacology · 2007
Across 26 studies, people who used ecstasy recreationally scored worse on short term and long term memory tests, especially verbal memory. Other drug use may have played a role.
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The pharmacology and toxicology of 'ecstasy' (MDMA) and related drugs
Kalant · CMAJ · 2001
This review identified over 87 ecstasy related deaths from dangerously high body temperature, muscle breakdown, heart rhythm problems, and liver failure, noting the toxic dose range overlaps the typical recreational dose.
Kratom
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Kratom use and mental health: A systematic literature review and case example
Bachu et al. · Journal of Addictive Diseases · 2023
This review of published cases found kratom use linked to new or worsening psychotic and manic symptoms, especially in people who already had a psychiatric condition.
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Prevalence of Kratom Use Disorder Among Kratom Consumers
Smith et al. · Journal of Addiction Medicine · 2024
In a survey of 2,061 kratom users, about 1 in 4 met criteria for a kratom use disorder, most often marked by tolerance and withdrawal symptoms.
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Kratom Withdrawal: A Systematic Review with Case Series
Stanciu et al. · Journal of Psychoactive Drugs · 2019
Stopping regular kratom use can trigger withdrawal similar to opioid withdrawal, including depressed mood and anxiety.
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Kratom (Mitragyna Speciosa) Liver Injury: A Comprehensive Review
Schimmel et al. · Drugs · 2020
Kratom use can injure the liver, typically showing up as jaundice and abnormal liver tests within weeks of use, which usually improves after stopping but can occasionally become severe.
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Characteristics of deaths associated with kratom use
Corkery et al. · Journal of Psychopharmacology · 2019
Among 156 kratom associated deaths reviewed, most involved other substances too, and the toxic and fatal dose levels of kratom are still poorly understood.
Inhalants
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Garakani et al. · The American Journal on Addictions · 2016
Reviewing 91 published cases, heavy nitrous oxide misuse was linked to nerve damage, psychosis, and in some reports death, along with spinal cord injury in most cases.
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Boyce et al. · Epidemiologia · 2025
Among emergency department patients with recent nitrous oxide use, about half had psychotic symptoms and about a third had suicidal thoughts or self harm.
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Yücel et al. · Journal of Psychiatry and Neuroscience · 2010
Brain scans showed teenagers who used inhalants like toluene long term had more damage to the brain's wiring than cannabis users or people who did not use, which may explain lasting behavior and mental health problems.