Schizophrenia, which affects 24 million individuals, or about 1 in 300, worldwide,1 is often associated with distress and impairment in social, educational, occupational, and other areas of everyday life. It is among the top 15 causes of disability worldwide, with an increased risk of premature mortality and high financial costs.2
Social disability and social disconnection are common in individuals with schizophrenia.3 Yet, in spite of more than 50 years of drug discovery efforts, the antipsychotics that are currently available have limited efficacy against the negative and cognitive symptoms of schizophrenia.4
Digital therapeutics (DTx), defined by the Digital Therapeutics Alliance as “evidence-based therapeutic interventions that are driven by high-quality software programs to treat, manage, or prevent a disease or disorder,”5 are showing promise in many areas. The world market for DTx was estimated at $6.2 billion in 2023, with a forecast compound annual growth rate (CAGR) of 27.2% from 2024 to 2030.6
In psychiatry and neurology, digital technologies have potential for treatment and diagnosis. Technologies in development include wearable devices, virtual reality smartphone applications, smart home devices, telepsychiatry and messaging systems for patients in rural areas.7 Examples of DTx include self-care apps for mental health disorders and virtual behavioral programs designed to help with addictions.8
Sidebar 1. Example of a Potential DTx for Schizophrenia
Accessible on mobile devices, CT-155 is an investigational prescription digital therapeutic designed to treat negative symptoms of schizophrenia under development by Click Therapeutics and Boehringer Ingelheim.9,10 This is a potential first-in-class treatment for this indication.11
CT-155 is evidence based, using psychosocial intervention techniques with individuals experiencing negative symptoms of schizophrenia, which affect mood, motivation, and interactions with others. The app gathers data on symptom severity and sleep-wake cycles, leveraging sensors to monitor biometrics such as heart rate.
CT-155 may provide an accessible, clinically validated mobile intervention that digitizes behavioral therapy and accompanies the person day-to-day. This DTx recently received breakthrough device designation as a prescription digital therapeutic for schizophrenia from the FDA.10,12 CenExel has worked on clinical trials for this product.
Prescription DTx are an innovative subset of this market, requiring regulatory approval and being prescribed to patients in a similar way to traditional therapeutics. These are regulated under the US Food and Drug Administration (FDA) Software-as-a-Medical-Device framework.9 A variety of FDA-approved prescription DTx products are shown in the Table.9 A promising product in development is described in Sidebar 1.9,10
Given this potential, sponsors should consider entering this field to enhance their development efforts in mental health indications including schizophrenia. These developments can build on our understanding of the underlying illnesses and may build on efforts in other areas of medicine, with key features of digital therapeutic studies including:
Sidebar 2. Patient Feedback
There have been anecdotal reports of positive impacts of DTx on individual schizophrenia study participants. Digital therapeutics appear to help in practical aspects of everyday living, such as interacting with others, staying organized, and managing symptoms.
Examples include participants saying that the DTx “changed the way they socialize” and that they are “better able to navigate their schizophrenia symptoms to function in the real world.” One patient said he was able to “think better” after using the therapeutic. There has been interest among participants in keeping access to the app after the trial is complete.
- Low risks to study participants, yet considerable potential for patient benefits: Digital therapeutics have potential to offer significant help to patients with schizophrenia in areas of unmet need, including supporting efforts to interact and socialize with others in everyday life, while posing minimal risk. This potential risk to benefit ratio many make individuals more willing to enroll into clinical studies.
- Straightforward protocols minimize burden: DTx trials typically involve few site visits and no medical procedures such as blood draws. This minimizes the burden of participation for patients who may be socially isolated and reluctant to travel. Site burden is also reduced by the fact that most study management and patient oversight can be carried out remotely. In addition, less scheduling and study coordination are required, with automatic data capture by the digital technology minimizing data entry requirements at site level.
- Ease of recruitment: An important feature of DTx is that they are used in addition to standard of care, so there is no need for patients to change their medications. This opens up a wider pool of potential study participants, easing the process of recruitment.
- High retention rates: These types of studies typically have low drop-out rates due to low patient burden of participation.
- Faster and more cost-effective than clinical trials for medications: DTx studies are usually straightforward to run, often costing less and taking less time than traditional, site-based clinical trials.
Concluding Thoughts
Prescription DTx have potential to advance personalized mental health care from diagnosis to disease management and longer-term support. Based on anecdotal evidence, patients have responded positively in clinical studies to date (Sidebar 2).
Further work remains to be done to determine which indications will be most amenable to these approaches. However, it is clear that prescription DTx may lead to significant improvements in challenging indications including schizophrenia and depression.
Dr Goenjian is principal investigator and medical director at CenExel CNS. He joined CenExel CNS in 2016 as a sub-investigator. Since 2018, he has been a principal investigator for trials at the Garden Grove location as well as a sub-investigator for trials at the Los Alamitos h location. Dr Goenjian has provided feedback for sponsor protocols and has been involved in the CenExel CNS phase 1 early development team.
References
1. Schizophrenia. World Health Organization. January 10, 2022. Accessed June 5, 2024. https://www.who.int/news-room/fact-sheets/detail/schizophrenia
2. Schizophrenia. National Institute of Mental Health. Accessed June 5, 2024. https://www.nimh.nih.gov/health/statistics/schizophrenia#part_2544
3. Green MF, Horan WP, Lee J, et al. Social disconnection in schizophrenia and the general community. Schizophr Bull. 2018;44(2):242-249.
4. Spark DL, Fornito A, Langmead CJ, Stewart GD. Beyond antipsychotics: a twenty-first century update for preclinical development of schizophrenia therapeutics. Transl Psychiatry. 2022;12:147.
5. Understanding DTx: a new category of medicine. Digital Therapeutics Alliance. Accessed June 5, 2024. https://dtxalliance.org/understanding-dtx/
6. Digital therapeutics market size & trends. Grand View Research. Accessed June 5, 2024. https://www.grandviewresearch.com/industry-analysis/digital-therapeutics-market
7. Chivilgina O, Elger BS, Jotterand F. Digital technologies for schizophrenia management: a descriptive review. Sci Eng Ethics. 2021;27(2):25.
8. Phan P, Mitragotri S, Zhao Z. Digital therapeutics in the clinic. Bioeng Transl Med. 2023;8(4):e10536.
9. Salsabili M, Tesell M, Alcusky M, et al. Prescription digital therapeutics: Applying Medicaid experience to value assessment and formulary management. J Manag Care Spec Pharm. 2023;29(6):685-691.
10. Boehringer Ingelheim and Click Therapeutics receive FDA breakthrough device designation. Boehringer Ingelheim. News release. January 4, 2024. Accessed June 5, 2024. https://www.boehringer-ingelheim.com/human-health/mental-disorders/schizophrenia/fda-grants-breakthrough-status-schizophrenia-2
11. Study of two digital therapeutics for the treatment of experiential negative symptoms of schizophrenia (CONVOKE). ClinicalTrials.gov. Last updated May 13, 2024. Accessed June 5, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05838625
12. Click Therapeutics and Boehringer Ingelheim initiate pivotal clinical trial of prescription digital therapeutics for the treatment of negative symptoms in schizophrenia. Click Therapeutics. News release. May 4, 2023. Accessed June 5, 2024. https://www.clicktherapeutics.com/press/click-therapeutics-and-boehringer-ingelheim-initiate-pivotal-clinical-trial/
