Written by Hana Lam Do, Intern
Clinical trials are the backbone of psychotherapy practice.
They provide evidence for what treatments are effective in combating what mental health problems. Professional helpers need research to employ scientifically-based and safe practices for their patients.
But here’s the issue: Are clinical research trials really generalizable to real-life patients?
⚠️ The Problem with Exclusion
In most randomized clinical trials, researchers exclude patients with complex comorbid conditions.
Example: Suicide risk trials often exclude patients with co-existing psychosis or substance use problems (Lawrence et al., 2025).
This improves research precision — but sacrifices generalizability.
🌀 Real-Life Patients Are Messy
In reality, patients often present with multiple conditions at once:
- People with PTSD are more likely to misuse drugs
- Depression often co-exists with anxiety, insomnia, or substance use problems
(Cuijpers et al., 2022; Leeman et al., 2017; Zimmerman et al., 2019)
👉 A lack of research on comorbid patients limits treatment options for both clients and physicians.
🌍 External Validity Matters
Real-life patients are “messy.” They might not be ideal clinical trial participants — but that’s exactly why they need help.
So, what can be done?
🔬 For Researchers
✔️ Conduct research trials on patients with comorbid conditions
✔️ Develop tailored or integrative treatments for complex mental health problems
🩺 For Therapists
✔️ Acknowledge the complexity of patients’ problems
✔️ Embrace the non-linear progress of treatment
✔️ Incorporate different approaches to tackle multiple facets of distress
📚 References
Cuijpers, P., Miguel, C., Ciharova, M., Quero, S., Plessen, C. Y., Ebert, D., … & Karyotaki, E. (2023). Psychological treatment of depression with other comorbid mental disorders: systematic review and meta-analysis. Cognitive Behaviour Therapy, 52(3), 246-268.
Zimmerman, M., Balling, C., Chelminski, I., & Dalrymple, K. (2019). Have treatment studies of depression become even less generalizable? Psychotherapy and Psychosomatics, 88(3), 165-170.
Lawrence, R. E., Jaffe, C., Zhao, Y., Wang, Y., & Goldberg, T. E. (2025). Clinical trials studying suicide risk reduction: who is excluded from participation. Archives of Suicide Research, 29(1), 77-90.
Leeman, R. F., Hefner, K., Frohe, T., Murray, A., Rosenheck, R. A., Watts, B. V., & Sofuoglu, M. (2017). Exclusion of participants based on substance use status: Findings from randomized controlled trials of treatments for PTSD. Behaviour Research and Therapy, 89, 33-40.