Building more resilient psychiatric trials through better recruitment and retention

The growing urgency of mental health research 

The need for psychiatric solutions is becoming more important in the drug development industry. The global mental health burden has been increasing, with one in every eight people living with a mental disorder. Post-COVID depression and anxiety rates have surged, and a youth mental health crisis is unfolding. Psychiatric R&D is responding with more drugs in development and scientific momentum. However, psychiatric clinical trials are often difficult to navigate successfully, with recruitment and retention of trial participants being one of the most difficult aspects for drug developers to manage.  

These challenges raise an important question: why are psychiatric studies so difficult to enroll and sustain, and what can be done to change that? The answer lies in the unique characteristics of psychiatric research, including complex comorbidities, subjective clinical measures, high placebo responses, and the daily realities faced by patients and caregivers. Understanding these factors and developing strategies that address them from both a scientific and human perspective is essential to designing trials that advance the data and support the people behind it. 

Why depression highlights the core challenges of psychiatric trials  

Among psychiatric conditions, depression clearly shows how scientifically and operationally difficult these studies can be. While it is one of the most common and well-studied mental health disorders, the process of designing and running a depression trial reveals the core challenges that sponsors face across psychiatry. 

One of the biggest hurdles lies in how depression is measured. Unlike many therapeutic areas that rely on objective biomarkers, depression depends on subjective rating scales such as the Hamilton Depression Rating Scale or the Montgomery–Åsberg Depression Rating Scale. These tools depend on patient self-reporting and rater interpretation, which introduces variability across sites. 

Another major issue is eligibility complexity. In most real-world settings, patients experience overlapping symptoms or comorbidities. Conditions like anxiety, attention-deficit disorders, and substance use often occur alongside depression, making it difficult to determine which diagnosis best explains a participant’s symptoms. 

Protocol design can also limit recruitment. Some of the more common challenges include: 

• Narrow inclusion and exclusion criteria, which can unintentionally reduce generalizability and exclude large segments of the patient population. 
• Washout requirements, where patients must discontinue current medications before joining the trial, leading to patient hesitancy. 
• Medication overlaps, because many people use low-dose adjunct antidepressants or combination therapies that make them ineligible. 
• High study visit frequency and lengthy rating assessments, involving frequent in-person visits, extensive baseline or screening assessments, and repeated specialized procedures can deter patients.  

Together, these factors lead to: 

• Smaller eligible patient pools 
• Slower site start-up and enrollment 
• Data and a study population that may not represent the diversity of real-world depression 

Understanding these challenges is the first step in building depression trials that are both scientifically sound and patient centered. 

The participant experience: Burden, stigma and attrition risk  

Even after eligible participants are identified, keeping them engaged throughout a psychiatric trial can be one of the most common difficulties for researchers. Depression studies, in particular, place significant demands on participants’ time, energy, and emotional resilience. 

Time and logistics

Early in a study, participants often visit sites once a week. Each visit can last four to five hours and may include multiple assessments, interviews, and blood draws. Balancing these appointments with work, school and family responsibilities can quickly become overwhelming. 

Emotional weight 

For participants who are assigned placebo, the lack of symptom relief can feel discouraging. Many begin the trial with optimism but lose motivation when progress is slow or uncertain. 

Stigma and trust

Some patients still view clinical trials as experimental or risky, particularly when it involves mental health. Building trust through education and communication is essential to helping participants feel safe and supported. 

Caregiver load

In adult depression studies, caregiver involvement is usually minimal. In adolescent trials, however, parents or guardians must manage transportation, scheduling, and communication with study staff. Sponsors that accommodate adjustments to study calendars or offer extended visit hours can ease this burden. Flexible visit windows, weekend hours, or transportation assistance can significantly reduce this participant barrier. 

Impact on data

Every participant lost to withdrawal or nonadherence weakens a study’s statistical power. High dropout rates increase attrition bias, which can distort results and make it more difficult to determine whether a treatment is truly effective. 

Managing these burdens with empathy and foresight is essential for maintaining participant engagement and ensuring data reliability in psychiatric research. 

Reducing placebo and bias in psychiatric studies  

Sponsors working within psychiatric clinical trials must also be adept in managing the impact of placebo and bias on study outcomes. Placebo and nocebo responses are especially common in psychiatric studies. Participants often experience changes in mood or symptoms based on expectations alone. While this can occur in any therapeutic area, it is amplified in psychiatry, where emotional and psychological factors play a direct role in perceived improvement. 

Common contributors

Several factors can increase variability in results: 

• Participant expectations or disappointment about receiving placebo 
• Investigator tone, body language or unintentional encouragement 
• Inconsistent administration of rating scales or assessments 

Strategies that work

Reducing placebo effects and measurement bias requires consistency and awareness across every site. Effective approaches include: 

• Providing placebo-response training for all site staff to reinforce neutral interactions 
• Using standardized scripts and neutral language when engaging with participants 
• Offering clear reminders about randomization and the importance of honest symptom reporting 
• Conducting regular inter-rater reliability checks and scientific surveillance to detect rating drift early 
• Leveraging centralized rating or remote independent raters to add an additional layer of consistency 

The goal is to preserve empathy while maintaining objectivity. With consistent training, communication, and oversight, study teams can minimize bias without compromising the compassionate care participants need. 

Emerging innovations improving recruitment and retention 

Psychiatric research is evolving quickly, and new technologies are enabling sponsors and sites to address long-standing barriers to patient recruitment and retention. These tools are designed to make participation easier for patients while giving study teams better visibility into progress and potential challenges. Some of the areas to watch include: 

Hybrid and decentralized models

While already common, virtual visits and digital assessments are expected to continue to grow in popularity, as they reduce the need for frequent travel. The ability to have some visits to take place remotely keeps participants engaged, especially in long or symptom-sensitive trials. 

Pre-screening and referral visibility

Modern tracking systems now give teams insight into where referrals originate and where patients may be dropping off during screening. This visibility allows sponsors and site teams to identify gaps and adjust outreach or follow-up quickly. 

Predictive analytics

Machine learning tools can forecast enrollment trends and identify potential slowdowns before they happen. With this insight, sponsors can allocate resources more effectively and make proactive decisions that keep studies on schedule. 

Digital engagement

Reminder apps, tele-check-ins, and other digital touchpoints have been increasing in popularity, as they have been effective in enabling participants to stay on track between visits. These tools support participant adherence and reduce missed appointments. 

Inclusive design

Diversity review teams are playing a larger role in protocol and materials development. Their input ensures eligibility criteria, recruitment language, and imagery that reflect populations most affected by the condition, so sponsors can create therapies that adequately serve the real-world patient populations. 

Centralized physician referral pathway  

Referrals from PCPs, mental health providers and other physician specialties will continue to play a significant role in patient identification because these clinicians have established relationships, access to medical histories, and trusted communication channels with their patients. However, referrals generated solely at the clinic level are limited by geographic reach and by how familiar each practice is with the local research site. A centralized physician referral pathway expands this reach by enabling a broader network of HCPs to connect their practices with nearby research sites. This model not only increases referral volume but also raises awareness of clinical research among community providers. In some cases, it may even encourage interested physicians to explore opportunities to collaborate more directly—such as becoming a principal investigator in the study. 

Together, these innovations are making psychiatric trials more accessible and patient-friendly while maintaining the data quality that sponsors depend on. 

Looking ahead: What’s next for psychiatric studies  

Psychiatric research continues to evolve as new therapies, technologies, and patient needs shape how studies are designed and delivered. Many of the challenges seen across conditions—such as anxiety, PTSD, and substance-use disorders—share common roots in how symptoms are measured, how patients experience treatment, and how sites support participation. When you look again at depression as an example, it is clear why its lessons are so influential. The operational and scientific complexities seen in depression studies closely mirror the realities of psychiatric research as a whole, which is why many of the strategies refined in this area are now guiding the future of the field. 

At the same time, the field is expanding in new directions. The resurgence of psychedelic-based therapies has introduced fresh operational considerations, including licensed sites, highly controlled settings and specialized training for facilitators. In parallel, advances in precision psychiatry are paving the way for treatments tailored to individual neurobiological and genetic profiles, moving the field closer to truly personalized medicine. 

Across every area of research, one principle remains clear: psychiatric trial success depends on designing around the lived experience of both patients and sites. As new therapies and technologies emerge, sponsors will need access to the tools, data, and expertise that allow them to stay at the forefront of this rapidly evolving landscape. 

How we enable sponsors to navigate the complex in psychiatric trials 

When recruiting and retaining patients in psychiatric research, success depends as much on patient-centricity and thoughtful design as it does on science. When sponsors understand patient realities such as time commitments, treatment transitions, and stigma, and work closely with well-trained, well-supported sites, trials are more likely to stay on track and deliver meaningful outcomes. 

Our experts at the PPD™ clinical research business of Thermo Fisher Scientific have the depth and breadth of experience needed to apply the necessary capabilities across psychiatric programs through: 

• Our select sites: highly engaged locations with psychiatric expertise, early feasibility input, and faster start-up. 
• Site Coach program: modular training that strengthens rating consistency, diversity awareness and digital readiness. 
• Patient recruitment and engagement leads: specialists who analyze data trends, guide recruitment planning and maintain sustained site relationships. Each study works with a single dedicated lead, creating consistency and stronger collaboration throughout the trial. 
• Centralized recruitment initiatives: Centralized recruitment capabilities allow sponsors to provide a unified recruitment hub that supports sites globally. By leveraging internal resources and strategic partnerships with external organizations, a coordinated patient-to-site pathway can be established. This centralized model enhances study advertising, drives qualified patient referrals, increases physician awareness and strengthens overall study advocacy throughout the duration of the trial. 
• Digital enablement: integrated pre-screen tracking and predictive forecasting that anticipate and address enrollment challenges before they slow progress. 

With these capabilities, we are at the forefront of psychiatric research, ready to support sponsors as new therapeutic frontiers continue to evolve. Together, sponsors, sites, and patients can build a future of psychiatric research that centers both scientific rigor and the patient experience.