Around the world, people living in objectively difficult circumstances who experience symptoms of generalized anxiety disorder (GAD) do not qualify for a diagnosis because their worry is not ‘excessive’ relative to the context. We carried out the first large-scale, cross-national study to explore the implications of removing this excessiveness requirement.

Data come from the World Health Organization World Mental Health Survey Initiative. A total of 133 614 adults from 12 surveys in Low- or Middle-Income Countries (LMICs) and 16 surveys in High-Income Countries (HICs) were assessed with the Composite International Diagnostic Interview. Non-excessive worriers meeting all other DSM-5 criteria for GAD were compared to respondents meeting all criteria for GAD, and to respondents without GAD, on clinically-relevant correlates.

Removing the excessiveness requirement increases the global lifetime prevalence of GAD from 2.6% to 4.0%, with larger increases in LMICs than HICs. Non-excessive and excessive GAD cases worry about many of the same things, although non-excessive cases worry more about health/welfare of loved ones, and less about personal or non-specific concerns, than excessive cases. Non-excessive cases closely resemble excessive cases in socio-demographic characteristics, family history of GAD, and risk of temporally secondary comorbidity and suicidality. Although non-excessive cases are less severe on average, they report impairment comparable to excessive cases and often seek treatment for GAD symptoms.

Individuals with non-excessive worry who meet all other DSM-5 criteria for GAD are clinically significant cases. Eliminating the excessiveness requirement would lead to a more defensible GAD diagnosis.

Despite their documented efficacy, substantial proportions of patients discontinue antidepressant medication (ADM) without a doctor's recommendation. The current report integrates data on patient-reported reasons into an investigation of patterns and predictors of ADM discontinuation.

Face-to-face interviews with community samples from 13 countries (n = 30 697) in the World Mental Health (WMH) Surveys included n = 1890 respondents who used ADMs within the past 12 months.

10.9% of 12-month ADM users reported discontinuation-based on recommendation of the prescriber while 15.7% discontinued in the absence of prescriber recommendation. The main patient-reported reason for discontinuation was feeling better (46.6%), which was reported by a higher proportion of patients who discontinued within the first 2 weeks of treatment than later. Perceived ineffectiveness (18.5%), predisposing factors (e.g. fear of dependence) (20.0%), and enabling factors (e.g. inability to afford treatment cost) (5.0%) were much less commonly reported reasons. Discontinuation in the absence of prescriber recommendation was associated with low country income level, being employed, and having above average personal income. Age, prior history of psychotropic medication use, and being prescribed treatment from a psychiatrist rather than from a general medical practitioner, in comparison, were associated with a lower probability of this type of discontinuation. However, these predictors varied substantially depending on patient-reported reasons for discontinuation.

Dropping out early is not necessarily negative with almost half of individuals noting they felt better. The study underscores the diverse reasons given for dropping out and the need to evaluate how and whether dropping out influences short- or long-term functioning.

To investigate the occurrence of traumatic stress symptoms (TSS) among healthcare workers active during the COVID-19 pandemic and to obtain insight as to which pandemic-related stressful experiences are associated with onset and persistence of traumatic stress.

This is a multicenter prospective cohort study. Spanish healthcare workers (N = 4,809) participated at an initial assessment (i.e., just after the first wave of the Spain COVID-19 pandemic) and at a 4-month follow-up assessment using web-based surveys. Logistic regression investigated associations of 19 pandemic-related stressful experiences across four domains (infection-related, work-related, health-related and financial) with TSS prevalence, incidence and persistence, including simulations of population attributable risk proportions (PARP).

Thirty-day TSS prevalence at T1 was 22.1%. Four-month incidence and persistence were 11.6% and 54.2%, respectively. Auxiliary nurses had highest rates of TSS prevalence (35.1%) and incidence (16.1%). All 19 pandemic-related stressful experiences under study were associated with TSS prevalence or incidence, especially experiences from the domains of health-related (PARP range 88.4–95.6%) and work-related stressful experiences (PARP range 76.8–86.5%). Nine stressful experiences were also associated with TSS persistence, of which having patient(s) in care who died from COVID-19 had the strongest association. This association remained significant after adjusting for co-occurring depression and anxiety.

TSSs among Spanish healthcare workers active during the COVID-19 pandemic are common and associated with various pandemic-related stressful experiences. Future research should investigate if these stressful experiences represent truly traumatic experiences and carry risk for the development of post-traumatic stress disorder.

This study investigates associations of several dimensions of childhood adversities (CAs) with lifetime mental disorders, 12-month disorder persistence, and impairment among incoming college students.

Data come from the World Mental Health International College Student Initiative (WMH-ICS). Web-based surveys conducted in nine countries (n = 20 427) assessed lifetime and 12-month mental disorders, 12-month role impairment, and seven types of CAs occurring before the age of 18: parental psychopathology, emotional, physical, and sexual abuse, neglect, bullying victimization, and dating violence. Poisson regressions estimated associations using three dimensions of CA exposure: type, number, and frequency.

Overall, 75.8% of students reported exposure to at least one CA. In multivariate regression models, lifetime onset and 12-month mood, anxiety, and substance use disorders were all associated with either the type, number, or frequency of CAs. In contrast, none of these associations was significant when predicting disorder persistence. Of the three CA dimensions examined, only frequency was associated with severe role impairment among students with 12-month disorders. Population-attributable risk simulations suggest that 18.7–57.5% of 12-month disorders and 16.3% of severe role impairment among those with disorders were associated with these CAs.

CAs are associated with an elevated risk of onset and impairment among 12-month cases of diverse mental disorders but are not involved in disorder persistence. Future research on the associations of CAs with psychopathology should include fine-grained assessments of CA exposure and attempt to trace out modifiable intervention targets linked to mechanisms of associations with lifetime psychopathology and burden of 12-month mental disorders.

Major depressive disorder (MDD) is characterised by a recurrent course and high comorbidity rates. A lifespan perspective may therefore provide important information regarding health outcomes. The aim of the present study is to examine mental disorders that preceded 12-month MDD diagnosis and the impact of these disorders on depression outcomes.

Data came from 29 cross-sectional community epidemiological surveys of adults in 27 countries (n = 80 190). The Composite International Diagnostic Interview (CIDI) was used to assess 12-month MDD and lifetime DSM-IV disorders with onset prior to the respondent's age at interview. Disorders were grouped into depressive distress disorders, non-depressive distress disorders, fear disorders and externalising disorders. Depression outcomes included 12-month suicidality, days out of role and impairment in role functioning.

Among respondents with 12-month MDD, 94.9% (s.e. = 0.4) had at least one prior disorder (including previous MDD), and 64.6% (s.e. = 0.9) had at least one prior, non-MDD disorder. Previous non-depressive distress, fear and externalising disorders, but not depressive distress disorders, predicted higher impairment (OR = 1.4–1.6) and suicidality (OR = 1.5–2.5), after adjustment for sociodemographic variables. Further adjustment for MDD characteristics weakened, but did not eliminate, these associations. Associations were largely driven by current comorbidities, but both remitted and current externalising disorders predicted suicidality among respondents with 12-month MDD.

These results illustrate the importance of careful psychiatric history taking regarding current anxiety disorders and lifetime externalising disorders in individuals with MDD.

The most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries.

Face-to-face interviews with community samples totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents.

3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2–4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness.

ADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population sample from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them.

Although non-suicidal self-injury (NSSI) is an issue of major concern to colleges worldwide, we lack detailed information about the epidemiology of NSSI among college students. The objectives of this study were to present the first cross-national data on the prevalence of NSSI and NSSI disorder among first-year college students and its association with mental disorders.

Data come from a survey of the entering class in 24 colleges across nine countries participating in the World Mental Health International College Student (WMH-ICS) initiative assessed in web-based self-report surveys (20 842 first-year students). Using retrospective age-of-onset reports, we investigated time-ordered associations between NSSI and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-IV) mood (major depressive and bipolar disorder), anxiety (generalized anxiety and panic disorder), and substance use disorders (alcohol and drug use disorder).

NSSI lifetime and 12-month prevalence were 17.7% and 8.4%. A positive screen of 12-month DSM-5 NSSI disorder was 2.3%. Of those with lifetime NSSI, 59.6% met the criteria for at least one mental disorder. Temporally primary lifetime mental disorders predicted subsequent onset of NSSI [median odds ratio (OR) 2.4], but these primary lifetime disorders did not consistently predict 12-month NSSI among respondents with lifetime NSSI. Conversely, even after controlling for pre-existing mental disorders, NSSI consistently predicted later onset of mental disorders (median OR 1.8) as well as 12-month persistence of mental disorders among students with a generalized anxiety disorder (OR 1.6) and bipolar disorder (OR 4.6).

NSSI is common among first-year college students and is a behavioral marker of various common mental disorders.

Depressive and anxiety disorders are highly comorbid, which has been theorized to be due to an underlying internalizing vulnerability. We aimed to identify groups of participants with differing vulnerabilities by examining the course of internalizing psychopathology up to age 45.

We used data from 24158 participants (aged 45+) in 23 population-based cross-sectional World Mental Health Surveys. Internalizing disorders were assessed with the Composite International Diagnostic Interview (CIDI). We applied latent class growth analysis (LCGA) and investigated the characteristics of identified classes using logistic or linear regression.

The best-fitting LCGA solution identified eight classes: a healthy class (81.9%), three childhood-onset classes with mild (3.7%), moderate (2.0%), or severe (1.1%) internalizing comorbidity, two puberty-onset classes with mild (4.0%) or moderate (1.4%) comorbidity, and two adult-onset classes with mild comorbidity (2.7% and 3.2%). The childhood-onset severe class had particularly unfavorable sociodemographic outcomes compared to the healthy class, with increased risks of being never or previously married (OR = 2.2 and 2.0, p < 0.001), not being employed (OR = 3.5, p < 0.001), and having a low/low-average income (OR = 2.2, p < 0.001). Moderate or severe (v. mild) comorbidity was associated with 12-month internalizing disorders (OR = 1.9 and 4.8, p < 0.001), disability (B = 1.1–2.3, p < 0.001), and suicidal ideation (OR = 4.2, p < 0.001 for severe comorbidity only). Adult (v. childhood) onset was associated with lower rates of 12-month internalizing disorders (OR = 0.2, p < 0.001).

We identified eight transdiagnostic trajectories of internalizing psychopathology. Unfavorable outcomes were concentrated in the 1% of participants with childhood onset and severe comorbidity. Early identification of this group may offer opportunities for preventive interventions.

Major depressive disorder (MDD) is a leading cause of morbidity and mortality. Shortfalls in treatment quantity and quality are well-established, but the specific gaps in pharmacotherapy and psychotherapy are poorly understood. This paper analyzes the gap in treatment coverage for MDD and identifies critical bottlenecks.

Seventeen surveys were conducted across 15 countries by the World Health Organization-World Mental Health Surveys Initiative. Of 35 012 respondents, 3341 met DSM-IV criteria for 12-month MDD. The following components of effective treatment coverage were analyzed: (a) any mental health service utilization; (b) adequate pharmacotherapy; (c) adequate psychotherapy; and (d) adequate severity-specific combination of both.

MDD prevalence was 4.8% (s.e., 0.2). A total of 41.8% (s.e., 1.1) received any mental health services, 23.2% (s.e., 1.5) of which was deemed effective. This 90% gap in effective treatment is due to lack of utilization (58%) and inadequate quality or adherence (32%). Critical bottlenecks are underutilization of psychotherapy (26 percentage-points reduction in coverage), underutilization of psychopharmacology (13-point reduction), inadequate physician monitoring (13-point reduction), and inadequate drug-type (10-point reduction). High-income countries double low-income countries in any mental health service utilization, adequate pharmacotherapy, adequate psychotherapy, and adequate combination of both. Severe cases are more likely than mild-moderate cases to receive either adequate pharmacotherapy or psychotherapy, but less likely to receive an adequate combination.

Decision-makers need to increase the utilization and quality of pharmacotherapy and psychotherapy. Innovations such as telehealth for training and supervision plus non-specialist or community resources to deliver pharmacotherapy and psychotherapy could address these bottlenecks.

There is a substantial proportion of patients who drop out of treatment before they receive minimally adequate care. They tend to have worse health outcomes than those who complete treatment. Our main goal is to describe the frequency and determinants of dropout from treatment for mental disorders in low-, middle-, and high-income countries.

Respondents from 13 low- or middle-income countries (N = 60 224) and 15 in high-income countries (N = 77 303) were screened for mental and substance use disorders. Cross-tabulations were used to examine the distribution of treatment and dropout rates for those who screened positive. The timing of dropout was examined using Kaplan–Meier curves. Predictors of dropout were examined with survival analysis using a logistic link function.

Dropout rates are high, both in high-income (30%) and low/middle-income (45%) countries. Dropout mostly occurs during the first two visits. It is higher in general medical rather than in specialist settings (nearly 60% v. 20% in lower income settings). It is also higher for mild and moderate than for severe presentations. The lack of financial protection for mental health services is associated with overall increased dropout from care.

Extending financial protection and coverage for mental disorders may reduce dropout. Efficiency can be improved by managing the milder clinical presentations at the entry point to the mental health system, providing adequate training, support and specialist supervision for non-specialists, and streamlining referral to psychiatrists for more severe cases.

Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.

To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.

We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054).

To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).

Previous work has identified associations between psychotic experiences (PEs) and general medical conditions (GMCs), but their temporal direction remains unclear as does the extent to which they are independent of comorbid mental disorders.

In total, 28 002 adults in 16 countries from the WHO World Mental Health (WMH) Surveys were assessed for PEs, GMCs and 21 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders. Discrete-time survival analyses were used to estimate the associations between PEs and GMCs with various adjustments.

After adjustment for comorbid mental disorders, temporally prior PEs were significantly associated with subsequent onset of 8/12 GMCs (arthritis, back or neck pain, frequent or severe headache, other chronic pain, heart disease, high blood pressure, diabetes and peptic ulcer) with odds ratios (ORs) ranging from 1.3 [95% confidence interval (CI) 1.1–1.5] to 1.9 (95% CI 1.4–2.4). In contrast, only three GMCs (frequent or severe headache, other chronic pain and asthma) were significantly associated with subsequent onset of PEs after adjustment for comorbid GMCs and mental disorders, with ORs ranging from 1.5 (95% CI 1.2–1.9) to 1.7 (95% CI 1.2–2.4).

PEs were associated with the subsequent onset of a wide range of GMCs, independent of comorbid mental disorders. There were also associations between some medical conditions (particularly those involving chronic pain) and subsequent PEs. Although these findings will need to be confirmed in prospective studies, clinicians should be aware that psychotic symptoms may be risk markers for a wide range of adverse health outcomes. Whether PEs are causal risk factors will require further research.

One important aspect of the societal burden of mental disorders is the extent to which these problems cause disability.

To assess days out of role associated with commonly occurring mental disorders in comparison with physical disorders in Portugal.

National cross-sectional survey, with home interviews carried out with 3849 adult (aged 18+) respondents (57.3% response rate).

Twelve-month prevalence for any mental disorder was 21.8%, any physical disorder 55.1% and any disorder 63.1%, with an average of 2.3 disorders per respondent with a disorder. Close to one out of every 10 respondents (9.2%) reported at least one day totally out of role in the past month (median of 6.4 days/any). The 18 conditions accounted for 78.2% of all days out of role, with 20.2% because of mental disorders and 59.2% because of physical disorders.

Mental disorders account for a substantial proportion of all role disability in the Portuguese population. Early detection and intervention would have a positive societal effect. Owing to highly frequent comorbidity, simultaneous management of mental and physical disorder comorbidities is advised for greater effect.

The patterns of comorbidity among mental disorders have led researchers to model the underlying structure of psychopathology. While studies have suggested a structure including internalizing and externalizing disorders, less is known with regard to the cross-national stability of this model. Moreover, little data are available on the placement of eating disorders, bipolar disorder and psychotic experiences (PEs) in this structure.

We evaluated the structure of mental disorders with data from the World Health Organization Composite International Diagnostic Interview, including 15 lifetime mental disorders and six PEs. Respondents (n = 5478–15 499) were included from 10 high-, middle- and lower middle-income countries across the world aged 18 years or older. Confirmatory factor analyses (CFAs) were used to evaluate and compare the fit of different factor structures to the lifetime disorder data. Measurement invariance was evaluated with multigroup CFA (MG-CFA).

A second-order model with internalizing and externalizing factors and fear and distress subfactors best described the structure of common mental disorders. MG-CFA showed that this model was stable across countries. Of the uncommon disorders, bipolar disorder and eating disorder were best grouped with the internalizing factor, and PEs with a separate factor.

These results indicate that cross-national patterns of lifetime common mental-disorder comorbidity can be explained with a second-order underlying structure that is stable across countries and can be extended to also cover less common mental disorders.