Mental health has become one of the most urgent and complex public health challenges of our era. Today, more than 1 billion people globally live with some form of a mental health disorder.1 Among young people, the situation is equally concerning: 1 in 7 adolescents experience a mental health condition during the critical period of emotional, cognitive, and social development.2 Alcohol and substance use disorders affect an additional 400 million individuals worldwide,3 with prevalence projected to rise in the coming years as economic instability, social isolation, and chronic stress continue to heighten vulnerability.
Stigma is often a large part of why individuals don’t seek diagnosis. Globally, 75% of those with mental, neurological, or substance use disorders receive no treatment at all.4 Access disparities are compounded by gender differences: women are significantly more likely to experience depression and anxiety, while men face higher rates of early-onset schizophrenia and substance use disorders. Yet despite the breadth and depth of the crisis, mental health accounts for only 2% of domestic government healthcare spending worldwide.5 This global deprioritization creates a disconnect that leaves millions without support.
The consequences reverberate far beyond emotional well-being. Mental health conditions now account for more years lived in poor health than cardiovascular disease, respiratory disease, diabetes, kidney disease, and cancer combined.5 They also intensify the difficulty of treating nearly every chronic illness, compounding healthcare needs, complicating clinical decision-making, and driving higher utilization of healthcare resources. Because mental health influences the trajectory of so many other conditions, improving mental health outcomes is not only a clinical imperative but a foundational step in reducing the global burden of disease.
Against this backdrop, clinical research holds immense promise. New treatment modalities—including digital therapeutics, precision psychiatry approaches, neuromodulation tools, and next-generation psychopharmacology—offer opportunities to transform care. But these innovations cannot move forward without successful clinical trials, and mental health trials face some of the steepest recruitment and retention challenges in medicine. Understanding and addressing these obstacles is critical to developing more effective therapies and improving the lives of those living with mental health conditions.
Why It’s So Hard to Recruit for Mental Health Trials
Recruitment and retention for mental health studies present distinct complexities shaped by human experience, clinical variability, and operational realities. Unlike in other therapeutic areas—where symptoms often follow clearer biological pathways or where patients are already embedded in structured care systems, mental health trials must navigate layered barriers that influence willingness, eligibility, and ability to participate.
Stigma remains one of the most powerful deterrents. Individuals may hesitate to seek treatment or participate in research because they fear judgment, labeling, or confidentiality breaches. Even when someone is interested in contributing to scientific advancement, concerns about how their data will be used or how their mental health status will be perceived can significantly restrict engagement. This reluctance can reduce the pool of potential participants and disproportionately exclude individuals from communities where mental health stigma remains especially strong.
Symptom variability adds an additional layer of complexity. Many mental health conditions fluctuate significantly over time. Individuals who appear eligible during initial outreach may later experience changes in symptom severity that temporarily disqualify them from participation. This fluidity can disrupt scheduling, complicate protocol adherence, and contribute to frustration or disengagement among participants.
High screen-fail ratios are common. Strict inclusion criteria—such as stable medication regimens, specific symptom thresholds, comorbid conditions, or safety considerations—can disqualify many otherwise interested individuals. Because mental illness doesn’t follow a linear treatment path, it can make it extremely difficult to capture the right cohort at the right moment.
Operational challenges further impede recruitment. As stated above, mental health care pathways are often fragmented, with many individuals receiving minimal or inconsistent care across different settings and providers. Unlike areas such as oncology or cardiology, there is still no standardized, predictable, or structured pathway in which patients with mental health conditions can get referred into clinical trials.
Retention presents its own difficulties. Even after enrollment, participants may face emotional fatigue, transportation challenges, caregiving responsibilities, or other life stressors that hinder their ability to continue in a study. Dropout rates in mental health trials often exceed those in many physical health studies because participants must balance both the demands of the trial and the pressures of daily life while managing their symptoms.
Finally, site capacity constraints can limit progress. Many research sites still lack dedicated psychiatric research staff, or the specialized training necessary to manage complex assessments, safety monitoring requirements, and nuanced patient communication. Even highly experienced clinicians may face overwhelming workloads that limit their ability to support participants effectively.
All these barriers demonstrate the need for smarter, patient-first recruitment strategies that reflect both human needs and operational realities.
A Deeper View into the Patient Experience
One emerging and scientifically grounded strategy involves the use of burden indices to quantify and address the factors that influence participant decision-making and site operations. Tools such as the Patient Burden Index (PBI) and Site Burden Index (SBI) provide structured ways to evaluate stress points that may undermine enrollment or contribute to dropout.
The Patient Burden Index evaluates the real-world demands placed on participants throughout the course of a trial. For individuals already navigating mental health challenges, like depression, anxiety, PTSD, bipolar disorder, or schizophrenia, seemingly manageable tasks can become substantial barriers. Requirements such as frequent site visits, long travel distances, invasive procedures, extensive questionnaires, digital monitoring expectations, or lifestyle restrictions may significantly influence a participant’s willingness or ability to stay engaged.
High PBI scores can predict where participants might struggle or disengage, enabling sponsors to make more informed decisions early in the trial design process. For example, if the frequency of site visits is disproportionately burdensome, adjustments such as remote assessments, simplified procedures, or transportation support may substantially improve feasibility. Understanding participant burden can also guide tailored outreach, helping potential participants see how the study aligns with their needs and how the research team intends to support them.
Predicting and addressing these burdens leads to:
- More realistic expectations for enrollment timelines
- Greater feasibility and accuracy in forecasting recruitment
- More empathetic communication that aligns with participant concerns
- Better retention strategies informed by likely pain points
By anticipating where drop-offs may occur, trials can adapt to meet participants’ needs rather than expecting participants to adapt to rigid structures that may be unsustainable.
Ground Your Site Strategy in Operational Reality
The Site Burden Index offers an equally important lens into the operational environment. Mental health trial sites frequently manage high patient volumes with limited resources. Screening processes are often lengthy and multi-layered, assessments may be time-intensive, and safety monitoring can demand frequent check-ins or staff intervention.
Quantifying this burden helps sponsors identify which sites are best equipped to manage a protocol’s requirements and where additional support may be needed. Sites with high burden scores may face workflow bottlenecks, have limited staffing, or require more training to manage complex eligibility assessments. By understanding these dynamics early, sponsors can set more realistic enrollment expectations, reduce screen failures, and allocate operational support where it will meaningfully improve participant flow.
Together, PBI and SBI offer a more complete understanding of the ecosystem in which mental health research takes place, enabling trial designs that are more inclusive, more achievable, and more efficient.
Tailor Your Patient Engagement for the Realities of Mental Health
In addition to scientific modeling, mental health trials require engagement strategies that reflect the lived experiences of participants. Each diagnosis is unique and comes with a decision-making pattern that reflects that. Recruitment efforts that overlook these nuances risk disengagement, misunderstandings, or reinforcement of harmful stereotypes.
Best practice is to have professionals who are trained in behavioral health communication help patients navigate the emotional and logistical challenges that often accompany trial participation. For individuals who may feel uncertain, overwhelmed, or hesitant, having a knowledgeable and empathetic point of contact like a Patient Companion can make the process more approachable. Professionals like these can help address stigma, clarify complex screening procedures, normalize symptom fluctuations, and troubleshoot practical challenges such as transportation or scheduling.
When these supportive approaches are paired with burden insights from tools like PBI, the recruitment experience becomes more aligned with patient realities. Participants feel better informed, less anxious, and more confident in their decision to engage in research and increases the likelihood of long-term retention.
Advancing Mental Health Research Through Smarter, Human-Centered Recruitment
The world cannot respond effectively to the mental health crisis without more inclusive, robust, and timely clinical trials. We must improve recruitment strategies to be both scientific and empathetic so we can attract more untreated and undiagnosed populations and speed approval of therapies for those that need them most.
By understanding how human and operational burdens shape participation, embracing diagnosis-specific engagement approaches, and leveraging scientific tools that reveal where challenges lie, sponsors can make mental health research more predictable, equitable, and effective.
Mental disorders present a global public health crisis that demands we rise to the occasion with a model that respects the lived experience of participants, supports the realities of site operations, and strengthens the integrity of clinical evidence. This is how progress is made—one trial, one participant, and one insight at a time.
Suzanne Harris is Senior Vice President of Marketing and Communications at SubjectWell.
Footnotes
- World Health Organization, Mental Health Disorders Fact Sheet
- World Health Organization, Mental Health of Adolescents Fact Sheet
- World Health Organization, Alcohol Fact Sheet
- World Health Organization, Special Initiative for Mental Health
- McKinsey Health Institute, Investing in the future: How better mental health benefits everyone
