Breakthrough Clinical Results
Myriad Genetics announced a post-hoc analysis of the PRIME study, revealing that patients with Major Depressive Disorder (MDD) treated based on GeneSight test results experienced faster initial remission and response. The benefits persisted over six months. The PRIME Care study, involving 1,944 U.S. Veterans, demonstrated that GeneSight results improved treatment outcomes, with patients more likely to achieve remission over 24 weeks. The post-hoc analysis further showed a 27% higher likelihood of remission and a 21% higher likelihood of response at any given time during the study period for patients using the GeneSight test.
Key Highlights
- Treatment informed by the GeneSight test led to faster initial remission and response in patients with MDD.
- The benefit of GeneSight-informed treatment persisted over six months.
- Patients using the GeneSight test were 27% more likely to achieve remission and 21% more likely to experience a response.
- The PRIME Care study included 1,944 U.S. Veterans with depression.
Incidence and Prevalence
Global Estimates of Depression Incidence and Prevalence
Depression is currently the second largest contributor to non-fatal disease burden globally. Recent epidemiological studies provide comprehensive insights into the global burden of this mental health condition.
Global Prevalence
In 2019, individuals with documented depression globally increased to 290,185,742, representing a 0.59% increase from 182,183,358 in 1990. According to 2021 meta-analyses examining studies during the early pandemic period: - One analysis found a pooled prevalence of 25.6% across 37 studies (N = 47,677) - Another reported a pooled prevalence of 27% (95% confidence interval: 9%-45%)
The National Comorbidity Survey estimated the prevalence of current (30-day) major depression at 4.9%, while lifetime major depression was estimated at 17.1%.
Regional Variations
The World Mental Health Surveys across 27 countries found varying depression prevalence rates: - Nigeria (21.6%) - New Zealand (17.4%) - South Africa (15.0%) - US (12.5%)
Without accounting for measurement differences, the estimates were: - New Zealand (17.8%) - United States (13.5%) - South Africa (9.8%) - Nigeria (3.1%)
European studies have shown higher prevalence rates compared to US and Canadian community studies from the 1980s.
Demographic Patterns
Gender Disparities: Females consistently bear a heavier burden for depression. According to the Global Burden of Disease Study 2019, females had higher incidence rates than males (RR: 1.602). In a Korean study (2014-2019), depression prevalence in women was 2.76 times greater than in men (6.34% vs. 2.29%).
Age Patterns: Seniors and middle-aged populations carry the highest burden of mental disorders. The incidence and disability-adjusted life years of depression were highest in the 60-64 age group. The global prevalence of major depression in the elderly was 13.3% (95% CI: 8.4-20.3%).
Vulnerable Populations
- The pooled prevalence of depression among displaced people was 26.4% (95% CI; 22.2-31.1)
- Among men who have sex with men (MSM), prevalence was 35% (95% CI 31%-39%)
- For MSM living with HIV, prevalence was higher at 47% (95% CI 39%-55%)
- In Pakistan, the prevalence is 45.9%
- Post-stroke depression in India showed a pooled prevalence of 55% (95% CI 43%, 65%)
Socioeconomic Factors
Both high- and low-socio-demographic-index countries were found to be high-risk regions for depressive disorders. The pooled prevalence was higher among developing countries (40.78%) than developed countries (17.05%).
Recent Trends
The age-standardized DALY rate of depression has started to decrease compared with trends related to anxiety disorders. However, the COVID-19 pandemic significantly increased depression rates, with a 2024 cross-sectional study finding 37.0% of COVID-19 patients reported depressive symptoms.
These findings highlight the significant and varied burden of depression globally, with important disparities across regions, demographics, and socioeconomic factors.
Key Unmet Needs and Target Populations for Depression Treatment
Major Unmet Needs
Major depressive disorder (MDD) is a leading cause of disability worldwide and expected to be the leading cause of overall global burden of disease by 2030. A significant unmet need exists for patients with treatment-resistant depression (TRD), affecting approximately 30-40% of individuals with MDD who do not respond to initial monotherapy. An estimated 44% do not respond to two consecutive antidepressant therapies, and 33% do not respond to up to four antidepressants. Over 15% of all patients with MDD remain refractory to any treatment intervention.
There is an urgent need for better biomarkers for treatment response in TRD. Although some evidence exists for biomarkers like IL-6, CRP, BDNF, most results are either single-study reports or show conflicting outcomes.
The need for personalized treatment algorithms with higher remission rates and fewer side effects is critical, as is the development of precision drugs for specific patient subgroups. The heterogeneous nature of clinical depression necessitates condition-specific sequencing algorithms embracing both drug and non-drug strategies.
Target Populations
Older Adults
Older individuals face unique challenges with depression treatment, showing lower response and remission rates and poorer tolerability to antidepressants. They were also less likely to have accessed mental healthcare during the pandemic, suggesting age-related barriers to treatment access.
Patients with Medical Comorbidities
Patients with serious medical illnesses and psychiatric conditions represent an important target population. Studies show 51.6% of certain TRD patients had serious medical illnesses including cancer (19.4%) or end-organ disease (22.6%), while 45.2% had major neurocognitive disorder.
Socioeconomically Disadvantaged Groups
Socioeconomic factors significantly affect access to novel therapies. Having both education less than a bachelor's degree and household income less than $75,000 reduced chances of esketamine initiation by 37%. The treatment gap is worse for individuals with socioeconomic disadvantage.
Patients with Benzodiazepine Dependency
45.2% of TRD patients had benzodiazepine long-term use (BLTU), with less than 5% successfully withdrawing during one-year follow-up. Persistent BLTU was associated with higher depression severity, anxiety, impaired sleep, lower functioning, decreased cognitive abilities, and higher work impairment.
Regional Populations
Studies in Latin America (Mexico, Colombia, Brazil, and Argentina) found 29% of MDD patients met criteria for TRD, with higher proportions in public versus private healthcare sites. In Taiwan, TRD was defined in 11.2% of patients with unipolar depression and 37.1% of patients with pharmaceutically treated depression.
Emerging Treatment Approaches
Novel treatment approaches being investigated include repetitive Transcranial Magnetic Stimulation (rTMS), accelerated intermittent Theta Burst Stimulation (aiTBS), deep brain stimulation, esketamine targeting the glutamatergic system, and combined treatments such as rTMS with internet-based Cognitive Behavioral Therapy (iCBT).
The COVID-19 pandemic has exacerbated treatment gaps in MDD care, highlighting the need for effective digital interventions that can overcome access barriers while maintaining treatment efficacy.
Recent Studies
Recent Depression Studies: Interventions, Safety, and Efficacy
Chinese Older Adult Collaborations in Health (COACH) Study (2022)
The COACH intervention provided algorithm-driven treatment for depression and hypertension by village primary care doctors with support from village lay workers and psychiatrist consultations. Among 2,365 adults aged ≥60 with hypertension and significant depressive symptoms, participants showed greater reduction in depressive symptoms (Cohen's d = -1.43; p < 0.001) and greater likelihood of achieving hypertension control (odds ratio = 18.24; p < 0.001) compared to enhanced care-as-usual. For safety outcomes, 36 participants died of natural causes (22 in COACH arm, 14 in control), and 40 COACH participants discontinued antidepressant medication due to side effects.
Transcranial Pulse Stimulation (TPS) Study (2023)
This single-blinded randomised controlled trial tested TPS intervention in 30 adults with major depressive disorder. The intervention consisted of six 30-minute TPS sessions completed in 2 weeks. Outcomes measured depression, cognition, anhedonia, and daily living activities at baseline, post-intervention, and 3-month follow-up. The study aimed to determine if TPS could be considered a top treatment option for MDD.
Mindful Living Group (MLG) Study (2023)
The MLG intervention, based on Eastern body-mind wisdom and Western trauma healing theory, was delivered to 31 individuals with COVID-19 pandemic-related traumatic stress through 10 weekly 2-hour online sessions. Efficacy outcomes showed significant improvements in depression (F = 42.78, p < 0.001) and anxiety (F = 23.40, p < 0.001), with increased mindfulness, posttraumatic growth, self-efficacy, and social support. Mindfulness showed significant negative correlations with both depression and anxiety.
Happy Older Latinos are Active (HOLA) Study (2025)
The HOLA health promotion intervention targeted older Latinos at risk for depression or anxiety disorders. Among 60 participants aged 60+ with subthreshold symptoms, a significantly higher proportion of HOLA participants experienced clinically significant reduction in anxiety symptoms (60% vs. 26.7% in control). The intervention, delivered by a community health worker, demonstrated good feasibility with enrollment targets met and high acceptability with 69% session attendance.
Magnesium Chloride plus Vitamin D Study (2025)
This study tested oral supplementation with magnesium chloride (1300 mg) plus vitamin D (4000 IU) for depression related to long-COVID. The combination significantly reduced Beck Depression Inventory scores from 28.8±3.7 to 9.2±7.5 (p<0.01), with 73.2% of subjects reaching clinical improvement compared to 34.5% in the vitamin D only control group (p=0.006).
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) Study (2024)
Clinical trials (phases I and I/II) with 78 participants confirmed good short-term safety and tolerability with no serious adverse events reported and no drop-outs for this psychedelic treatment for depression.
Low-Dose Prazosin Study (2024)
This randomized, double-blind, placebo-controlled study of low-dose prazosin (0.5-1 mg/day) as augmentation therapy for depression with trauma history found adverse reactions in 20.0% of the prazosin group versus 24.1% in placebo. The prazosin group had lower incidence of sleeplessness or nightmares (3.3% vs. 20.7%) but higher incidence of orthostatic hypotension (16.7% vs. 0%).