Fear, anxiety, and depression

What can be done

Actions rated on the strength-rating scale (A strong and replicated, B solid but limited, C weak or debated, D contested or failed), applied to the specific claim made.

• Context: About 322 million people live with depression and 470 million with an anxiety disorder, and only 27.6% of people who need anxiety treatment receive any (WHO, 2026a, WHO, 2026b). Disability from mental disorders rose from 80.8 million to 125.3 million healthy years lost between 1990 and 2019 (GBD 2019 Mental Disorders Collaborators, 2022).
• Ban highly hazardous pesticides (A). National bans on commonly ingested pesticides were followed by fewer pesticide suicides in five of six countries and fewer suicides overall in three (Gunnell et al., 2017). In Bangladesh, an estimated 35,071 suicides were averted with no apparent loss of farm output (Chowdhury et al., 2018).
• Collaborative care in primary care (A). A Cochrane review of 79 trials with 24,308 people found improvements in depression (SMD -0.34) and anxiety (SMD -0.30) in the short term (Archer et al., 2012).
• Evidence-based psychotherapy (A that it works, B for how much). Across 331 trials, all main therapies beat usual care with few differences between them (Cuijpers et al., 2021), but correcting for bias reduces the average effect from g = 0.70 to 0.31 (Cuijpers et al., 2019).
• Talking therapy delivered by trained, supervised lay health workers (B). Across 27 trials, the pooled effect was 0.49 (Singla et al., 2017). The Friendship Bench in Zimbabwe cut depression symptoms to 13.7% versus 49.9% (Chibanda et al., 2016), the Thinking Healthy Programme cut depression in new mothers to 23% versus 53% (Rahman et al., 2008), the Healthy Activity Program in India raised remission to 64% versus 39% (Patel et al., 2017), and Problem Management Plus reduced distress in Pakistan and Kenya (Rahman et al., 2016, Bryant et al., 2017). Effects faded or were absent in rural Zimbabwe (Haas et al., 2023), with peer-delivered Thinking Healthy (Sikander et al., 2019), with group Problem Management Plus in Jordan at 12 months and in Turkey (Bryant et al., 2022a, Bryant et al., 2022b, Acarturk et al., 2024), and in a youth adaptation of the Friendship Bench (Beji-Chauke et al., 2025), while distress stayed lower at 12 months for refugees in the Netherlands (de Graaff et al., 2024) and remote stepped care helped migrants in Italy (Purgato et al., 2025). Supervision and quality control appear to matter.
• Guided internet CBT (B). Across 39 trials with 9,751 people, guided and unguided internet CBT both outperformed controls, and guided versions did better for moderate or severe symptoms (Karyotaki et al., 2021).
• Antidepressants (B, size of benefit contested). All 21 antidepressants studied beat placebo across 522 trials (Cipriani et al., 2018), but the average gain over placebo was about 1.75 points on the Hamilton depression scale (Stone et al., 2022), and a reanalysis found discrepancies between published and unpublished trial data (Munkholm, Paludan-Müller, and Boesen, 2019).
• Scale up treatment (B, a model). For 36 countries, each dollar invested in scaling up treatment of depression and anxiety was projected to return 2.3 to 3.0 dollars in economic benefits, or 3.3 to 5.7 including health (Chisholm et al., 2016).
• Exercise (C). Walking or jogging was associated with moderate reductions in depression (g = -0.62), but confidence in the evidence is low (Noetel et al., 2024).
• Not shown to work: universal school mindfulness and individual workplace wellbeing offerings (D). A trial in 84 schools with 8,376 students found no benefit from mindfulness training (Kuyken et al., 2022), and school prevention programs in general have small effects, larger when targeted (Werner-Seidler et al., 2021). Workers who used individual wellbeing offerings such as resilience training and apps "appear no better off than nonparticipants" (C, a cross-sectional study) (Fleming, 2024), which points toward changing workload and job design instead.

Proposed and experimental methods

Methods that are proposed, under trial, approved in some places, or tried and then failed. Each shows a stage label and an evidence rating. A stage label shows how far a method has progressed, not whether it works. The stage labels are explained on the psychological factor page.

• Single-session interventions for youth depression and anxiety (Large trial, B). This builds on the agency findings in "Learned helplessness and low sense of control" in the psychological factors. One free, self-guided online session reduced depressive symptoms at three months compared with a supportive control in 2,452 U.S. adolescents (d = 0.18) (Schleider et al., 2022), and a meta-analysis of 50 randomized trials with 10,508 youths found an average effect of g = 0.32, larger for anxiety (0.56) than for depression (0.21, not significant) and larger against no treatment (0.41) than against active controls (0.14) (Schleider and Weisz, 2017). An umbrella review by the same research group found an effect of SMD = -0.25 across 12 meta-analyses (Schleider et al., 2025). An independent meta-analysis of self-administered sessions found small effects for anxiety (g = -0.24) and depression (g = -0.11), with wide prediction intervals that include no effect (Ball et al., 2026).
• Esketamine and intravenous ketamine for treatment-resistant depression (Approved but not scaled, B). These glutamate-acting drugs work within days. In a manufacturer-run withdrawal trial of 297 patients who had improved on esketamine nasal spray, continuing it reduced relapse among those in stable remission (26.7% versus 45.3%, a 51% lower risk, number needed to treat 6) (Daly et al., 2019), and the FDA approved it on March 5, 2019, for use only in certified clinics with at least two hours of monitoring after each dose (FDA, 2019). In a publicly funded, open-label trial of 403 patients, intravenous ketamine was noninferior to electroconvulsive therapy (ECT) (response 55.4% versus 41.2%), with memory loss after ECT and dissociation after ketamine, although more patients assigned to ECT withdrew before starting treatment (Anand et al., 2023). Misuse potential, cost, and clinic-only delivery limit access.
• Accelerated, MRI-guided magnetic brain stimulation (Approved but not scaled, B). Stanford Neuromodulation Therapy (SNT) compresses high-dose magnetic stimulation into 5 days and aims it using each person's brain scan. In a sham-controlled trial reported at a planned interim analysis with 29 treated patients, depression scores fell 52.5% with active treatment versus 11.1% with sham at 4 weeks (Cole et al., 2022), and a second trial by the same group with 48 patients found remission in 50.0% versus 20.8% at 1 month (Kratter et al., 2026). The FDA cleared the device on September 1, 2022 (FDA, 2022). Both trials are small and come from the developing group, and durability is not yet known.
• Zuranolone for postpartum depression (Approved but not scaled, B). Zuranolone is a neurosteroid pill taken for 14 days. In 196 women with severe postpartum depression, 50 mg daily improved the Hamilton depression score by 4.0 points more than placebo at day 15, with benefits also at days 3, 28, and 45, and somnolence, dizziness, and sedation were the most common side effects (Deligiannidis et al., 2023). The FDA approved it for postpartum depression in August 2023, found the evidence insufficient for major depressive disorder, and advised waiting at least 12 hours after a dose before driving (Psychiatric News, 2023).
• Psilocybin therapy for treatment-resistant depression (Large trial, B). One or two supervised doses of psilocybin are given with psychological support. In a developer-funded phase 2 trial of 233 adults, 25 mg reduced depression scores (MADRS) by 6.6 points more than 1 mg at week 3, but sustained response at 12 weeks was not supported, adverse events occurred in 77%, and suicidal ideation or behavior or self-injury occurred in all dose groups (Goodwin et al., 2022). In two phase 3 trials reported so far only in a company press release, 25 mg beat placebo by 3.6 points (258 dosed) and beat 1 mg by 3.8 points (581 dosed) at week 6, and the company expects to complete its FDA submission in the fourth quarter of 2026 (Compass Pathways, 2026). Participants can usually tell whether they received a psychedelic, and a systematic review concluded that effect sizes in psychedelic trials are likely overestimated because of this unblinding and high expectations (Muthukumaraswamy, Forsyth, and Lumley, 2021).
• Generative AI therapy chatbots (Early trial, B). In the first randomized trial of a generative AI therapy chatbot (Therabot), 210 adults with depression, anxiety, or high risk of eating disorders were assigned to the chatbot or a waitlist, chatbot users had significantly greater symptom reductions at 4 and 8 weeks, and staff intervened 15 times for safety concerns such as suicidal ideation and 13 times to correct inappropriate responses such as medical advice (Heinz et al., 2025). Average reductions were 51% for depression, 31% for anxiety, and 19% for body image and weight concerns (Dartmouth Technology Transfer Office, 2025). The trial was run by the developers, with a waitlist control and 8 weeks of follow-up. Illinois's Wellness and Oversight for Psychological Resources Act, signed in August 2025, bars the use of AI to provide mental health and therapeutic decision-making while allowing administrative and supplementary support for licensed professionals (IDFPR, 2025).
• Minimum age of 16 for social media accounts (Approved but not scaled, C). Australia's Online Safety Amendment (Social Media Minimum Age) Act 2024 (Federal Register of Legislation, 2024) took effect on December 10, 2025, and more than 4.7 million under-16 accounts were deactivated, removed, or restricted within days (Prime Minister of Australia, 2026). Three months later, the share of children under 16 holding an account had fallen from 52.4% to 42.1%, while 81.5% still used a platform with or without an account, and the regulator said it was too early to judge whether the intended outcomes had been achieved (eSafety Commissioner, 2026). No mental health outcome data have been reported, and some children said they felt less connected to peers while others reported less pressure to be online.
• Not shown to help: school bans on recreational phone use (Approved but not scaled, contested, C). In 1,227 English students aged 12 to 15 at 30 schools, restrictive policies were linked to 0.67 fewer hours of phone use and 0.54 fewer hours of social media use during school time, but not to better mental wellbeing (adjusted difference -0.48 points, 95% CI -2.05 to 1.06) or to less use over whole weekdays or weekends (Goodyear et al., 2025). The study was cross-sectional, so it cannot show cause.
• Reversed: MDMA-assisted therapy for PTSD (Failed or reversed, D). In a phase 3 trial of 104 adults, PTSD scores (CAPS-5) fell 23.7 points with MDMA versus 14.8 with placebo plus identical therapy (d = 0.7) (Mitchell et al., 2023). An FDA advisory committee voted 9 to 2 that efficacy had not been shown and 10 to 1 that benefits did not outweigh risks, citing functional unblinding, selection bias from prior MDMA use, and unanswered questions about heart and liver toxicity, and on August 9, 2024, the FDA declined approval and asked for another phase 3 trial (Walter and McKenzie, 2024). The journal Psychopharmacology then retracted three earlier MDMA therapy papers over protocol violations amounting to unethical conduct, particularly at one phase 2 trial site (Keshavan, 2024).

Sources cited on this page

1. WHO: Over a billion people living with mental health conditions (2025) B Moderate: agency estimate
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38. Keshavan, M. (2024, August 11). Three MDMA therapy papers retracted over ethics violations. STAT. link B Moderate
39. Kratter, I. H., Austelle, C. W., Lissemore, J. I., Wada, M., Geoly, A., Chaiken, A., et al. (2026). Stanford neuromodulation therapy for treatment-resistant depression: A randomized controlled trial confirming efficacy, and an EEG study providing insight into mechanism of action and a potentially predictive biomarker of efficacy. World Psychiatry, 25(1), 105-116. link B Moderate
40. Mitchell, J. M., Ot'alora G., M., van der Kolk, B., Shannon, S., Bogenschutz, M., Gelfand, Y., et al. (2023). MDMA-assisted therapy for moderate to severe PTSD: A randomized, placebo-controlled phase 3 trial. Nature Medicine, 29(10), 2473-2480. link D Contested
41. Muthukumaraswamy, S. D., Forsyth, A., & Lumley, T. (2021). Blinding and expectancy confounds in psychedelic randomized controlled trials. Expert Review of Clinical Pharmacology, 14(9), 1133-1152. link B Moderate
42. Schleider, J. L., & Weisz, J. R. (2017). Little treatments, promising effects? Meta-analysis of single-session interventions for youth psychiatric problems. Journal of the American Academy of Child and Adolescent Psychiatry, 56(2), 107-115. link B Moderate
43. Schleider, J. L., Zapata, J. P., Rapoport, A., Wescott, A., Ghosh, A., Kaveladze, B., et al. (2025). Single-session interventions for mental health problems and service engagement: Umbrella review of systematic reviews and meta-analyses. Annual Review of Clinical Psychology, 21(1), 279-303. link B Moderate
44. Walter, K., & McKenzie, H. (2024, August 9). FDA rejects Lykos' MDMA-assisted PTSD therapy after negative adcomm. BioSpace. link B Moderate
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Every source for this factor is listed on the psychological factor page.