The Challenges of Developing Novel Psychiatric Therapies

Authored by: Shreya Bhardwaj

Art by: Amber Briscoe

In recent years, medication has become critical to the way that the healthcare industry approaches the treatment of mental health conditions. In 2020, over 18% of the overall U.S. population had taken medication for their mental health in the past 12 months, amounting to over 59 million people! [1] Following the boom of mental health awareness in the late 2010s, demand for using medication to manage mental health has only continued to soar. Unfortunately, drug development of novel psychiatric therapies has been significantly curtailed, making up only 4.8% of all FDA drug approvals from 2018 to 2022 [2]. Though the general process remains the same, psychiatric drug development faces unique obstacles, such as difficulties in measuring treatment efficacy, ethical concerns, and especially high failure rates in clinical trials.

One of the biggest challenges in psychiatric drug development is the difficulty of measuring treatment efficacy, as the majority of mental health conditions lack objective biomarkers which makes it difficult to determine whether a treatment is working based solely on patient self-reports [3]. The placebo effect further complicates this issue, as many psychiatric conditions including depression and anxiety, tend to have more subjective symptoms. In their article “Considerations in Designing Randomized Clinical Trials in Psychiatry”, authors Rabinowitz and Davidson highlight how placebo responses can reach up to 50% in psychiatric trials, making it challenging to distinguish between genuine therapeutic effects and patient perception [3]. To address this, researchers are exploring alternative approaches such as neuroimaging, digital tracking tools, and active comparator trials where new treatments are measured against existing therapies rather than a placebo [4].

Another major barrier is the high failure rate of clinical trials for drugs of these kinds. Many potential treatments show promise in early studies but fail in later-stage trials due to a lack of efficacy or unforeseen side effects. As per Dr. Leslie Citrome’s Q&A with WCG Clinical, psychiatric trials tend to take longer and cost more than trials for other medical conditions due to high dropout rates, difficulty recruiting participants, and the need for extended follow-up periods [5]. This has led to a decline in industry investment in psychiatric drug development, as pharmaceutical companies are often reluctant to fund research with a high risk of failure. Pharmacologists P. J. Conn and B. L. Roth suggest that a lack of innovation in trial design is partially to blame, as traditional methodologies may not be well-suited for evaluating psychiatric treatments [6]. To improve outcomes, researchers are advocating for adaptive trial designs that allow for real-time adjustments based on interim data, potentially reducing costs and improving efficiency.

Beyond methodological challenges, there are also significant ethical concerns within this kind of drug development. For example, several mental health conditions affect one’s ability and mindset to make decisions, which raises questions about whether certain participants can fully understand the risks and benefits of experimental treatments. As noted in an academic article by Tong Zhu, a drug developer at Astellas Pharma, these ethical concerns contribute to lengthy regulatory approval processes as additional safeguards are required to ensure patient safety, and while these measures are necessary, they often slow the development of new drugs, making it harder for innovative treatments to quickly reach the market [7].

Psychiatric conditions continue to have huge unmet medical needs. Overall, striking a balance between ethical responsibility and the urgent need for new and effective therapies remains a central challenge in psychiatric research.

References:

1. Centers for Disease Control and Prevention. (2021, October). Symptoms of anxiety or depressive disorder and use of mental health care among adults — United States, August 2020–February 2021 (Data Brief No. 419). National Center for Health Statistics. https://www.cdc.gov/nchs/products/databriefs/db419.htm

2. Giliberto, S., Shishodia, R., Nastruz, M., Brar, C., Bulathsinhala, S., Terry, J., Pemminati, S., & Shenoy, S. K. (2024). A Comprehensive Review of Novel FDA-Approved Psychiatric Medications (2018-2022). Cureus, 16(3), e56561. https://doi.org/10.7759/cureus.56561

3. Rabinowitz, J., & Davidson, M. (2009). Considerations in designing randomized clinical trials in psychiatry: Challenges and methodology. International Journal of Neuropsychopharmacology, 12(5), 575–589. https://doi.org/10.1017/S146114570900992

4. Lenze, E. J., Nicol, G. E., Barbour, D. L., Kannampallil, T., Wong, A. W. K., Piccirillo, J., Drysdale, A. T., Sylvester, C. M., Haddad, R., Miller, J. P., Low, C. A., Lenze, S. N., Freedland, K. E., & Rodebaugh, T. L. (2021). Precision clinical trials: a framework for getting to precision medicine for neurobehavioural disorders. Journal of psychiatry & neuroscience : JPN, 46(1), E97–E110. https://doi.org/10.1503/jpn.200042

5. WCG Clinical. (2022). Q&A with CNS Expert Dr. Leslie Citrome. https://www.wcgclinical.com/wp-content/uploads/2022/03/q-a-with-cns-expert-dr-leslie-citrome.pdf

6. Conn, P. J., & Roth, B. L. (2008). Opportunities and challenges of psychiatric drug discovery: roles for scientists in academic, industry, and government settings. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology, 33(9), 2048–2060. https://doi.org/10.1038/sj.npp.1301638

7. Zhu, T. (2021). Challenges of Psychiatry Drug Development and the Role of Human Pharmacology Models in Early Development-A Drug Developer's Perspective. Frontiers in Psychiatry, 11, 562660. https://doi.org/10.3389/fpsyt.2020.562660