Current and Emerging Technologies to Address the Placebo Response Challenge in CNS Clinical Trials: Promise, Pitfalls, and Pathways Forward.

Excessive placebo response rates have long been a major challenge for central nervous system (CNS) drug discovery. As CNS trials progressively shift toward digitalization, decentralization, and novel remote assessment approaches, questions are emerging about whether innovative technologies can help mitigate the placebo response. This article begins with a conceptual framework for understanding placebo response. We then critically evaluate the potential of a range of innovative technologies and associated research designs that might help mitigate the placebo response and enhance detection of treatment signals. These include technologies developed to directly address placebo response; technology-based approaches focused on recruitment, retention, and data collection with potential relevance to placebo response; and novel remote digital phenotyping technologies. Finally, we describe key scientific and regulatory considerations when evaluating and selecting innovative strategies to mitigate placebo response. While a range of technological innovations shows potential for helping to address the placebo response in CNS trials, much work remains to carefully evaluate their risks and benefits.

Impact and efficiency of treatment across two PTSD clinical trials comparing in-person and telehealth service delivery formats.

The intent of this study is to examine treatment impact and efficiency observed when cognitive behavioral treatments for posttraumatic stress disorder (PTSD) are delivered in-person or using telehealth. This study pooled data from 268 veterans enrolled in two PTSD clinical trials. In both trials, treatment was delivered using in-home telehealth (telehealth arm), in-home in-person (in-home arm), and in-office care, where patients traveled to the Department of Veterans Affairs for either office-based telehealth or office-based in-person care (office arm). Average age was 44 (SD = 12.57); 80.9% were males. The PTSD Checklist for DSM-5 (PCL-5) was used to assess symptom severity. Treatment impact was measured by (a) the proportion of participants who completed at least eight treatment sessions and (b) the proportion with a reliable change of ≥ 10 points on the PCL-5. Treatment efficiency was measured by the number of days required to reach the end point. The proportion of participants who attended at least eight sessions and achieved reliable change on the PCL-5 differed across treatment formats (ps < .05). Participants in the in-home (75.4%) format were most likely to attend at least eight treatment sessions, followed by those in the telehealth (58.3%) and office (44.0%) formats, the latter of which required patients to travel. Participants in the in-home (68.3%, p < .001) format were also more likely to achieve reliable change, followed by those in the telehealth (50.9%) and office (44.2%) formats. There were no significant differences in the amount of time to complete at least eight sessions. Delivery of therapy in-home results in a significantly greater likelihood of achieving both an adequate dose of therapy and a reliable decrease in PTSD symptoms compared to telehealth and office formats. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A Pilot Study Examining Feasibility and Initial Efficacy of Remotely Delivered Cognitive Adaptation Training.

Cognitive Adaptation Training (CAT) is an evidence-based treatment that uses environmental supports including signs, text messages, checklists, smart pill containers, and the organization of belongings to bypass cognitive and motivational impairments and to cue adaptive behavior in the home or work environment. We developed and tested a remote version of CAT to make the treatment available more broadly. Because CAT is focused on working with the individual in their home environment to establish supports, CAT may not be as easy to translate into an effective virtual treatment as talk-therapies. Fifty-six members of managed care were assigned to or given their treatment preference for CAT or Remote CAT (R-CAT) for 6 months. In-person or virtual pill counts were conducted monthly and assessments of habit-formation, symptoms, functioning, and satisfaction were administered every 2 months by independent raters. Analyses using mixed models with repeated measures focused on pre-planned evaluations of within-group change. Adherence improved significantly in R-CAT, functioning improved significantly in CAT and both groups improved significantly on measures of habit-formation and symptoms across 6 months. Higher functioning individuals appeared to choose R-CAT. Satisfaction with treatment was very high in both groups. R-CAT appears to be a potentially effective treatment, particularly for medication follow-though. However, in contrast to decades of previous research, fewer than 20% of eligible Medicaid recipients agreed to participate in the study. This may have been due to recruitment during and immediately post-pandemic.

Unmet needs with antipsychotic treatment in schizophrenia and bipolar I disorder: patient perspectives from qualitative focus groups.

BACKGROUND: Schizophrenia (SZ) and bipolar I disorder (BD-I) are chronic mental health disorders often treated with antipsychotic medications. This qualitative study sought to better understand disease burden and treatment experiences with oral antipsychotic medications in participants living with SZ or BD-I. METHODS: Six 90-min focus groups were conducted with participants diagnosed with SZ or BD-I. Trained moderators facilitated discussions using a semistructured guide. Participants described symptoms, impacts of disease, and experiences with oral antipsychotic medications, whether favourable or unfavourable. RESULTS: Among participants with SZ (n = 15; 3 groups, 5 per group), 53% were male and 33% were white, with a mean of 18.6 years since diagnosis. Of participants with BD-I (n = 24; 3 groups, 8 per group), 33% were male and 42% were white, with a mean of 13.0 years since diagnosis. Participants described numerous symptoms of their illnesses that impacted relationships and daily life, including effects on emotional health, the ability to work, and encounters with law enforcement. Previous antipsychotic medications were deemed effective by 14/15 (93%) participants with SZ and 12/16 (75%) participants with BD-I. Most participants with SZ (13/15; 87%) or with BD-I (16/24; 67%) reported discontinuing their antipsychotic medication at some point. Side effects were a common reason for discontinuing or switching medications for participants with SZ (8/15; 53%) and for those with BD-I (11/24; 46%). The most common side effects reported in both cohorts were weight gain, drowsiness, sexual problems, and neurologic symptoms. Side effects negatively affected quality of life, leading to serious health problems and issues with self-esteem. CONCLUSIONS: People living with SZ or BD-I cited a range of favourable and unfavourable experiences with oral antipsychotic medications. Most participants reported that their antipsychotics were effective at controlling their symptoms, but multiple side effects impacted their quality of life, caused additional serious health problems, and often led to discontinuation of or switching antipsychotics. Findings from this study contribute to a better understanding of patients' experiences with antipsychotics and highlight a need for new medications with favourable benefit/risk profiles.

Changes in Clinical Management of Patients with Schizophrenia Treated with Long-Acting Injectable Antipsychotics (LAIs), Including Telepsychiatry Use, During the COVID-19 Pandemic.

Purpose: The COVID-19 pandemic substantially impacted care of patients with schizophrenia treated with long-acting injectable antipsychotics (LAIs). This study (OASIS-MAPS) examined how clinical sites adapted operations and used telepsychiatry to maintain standard of care for these patients during the pandemic. Methods: Two online surveys (initial: October-November 2020, N = 35; follow-up: July-September 2021, N = 21) were completed by a principal investigator (PI) or PI-appointed designee at sites participating in the OASIS study (NCT03919994). Survey responses were analyzed descriptively. Results: At the time of the initial survey, all 35 participating sites were using variants of telepsychiatry, with 20 sites adopting it after the pandemic started. Most sites reported no negative impacts of the pandemic on medication adherence, although approximately 20% of sites reported decreased adherence for LAIs. Twelve sites (34%) reported switching patients with schizophrenia from LAIs to oral antipsychotic medications, while 11 sites (31%) reported switching patients from shorter to longer injection interval LAIs during the pandemic. Most sites did not experience difficulties in implementing or expanding telepsychiatry services, although lower reimbursement rate for telepsychiatry and patients' lack of access to and training on relevant technologies were the most frequently reported barriers. Conclusion: Changes made by sites after the pandemic onset were viewed by almost all participants as satisfactory for maintaining standard of care. Almost all participants thought that the use of telepsychiatry services would continue after the pandemic in a hybrid manner combining telepsychiatry and office visits. Ensuring that patients have equitable access to telepsychiatry will be important in the post-pandemic future.

Development and validation of a fidelity instrument for Cognitive Adaptation Training.

Purpose: Cognitive Adaptation Training (CAT) is a psychosocial intervention with demonstrated effectiveness. However, no validated fidelity instrument is available. In this study, a CAT Fidelity Scale was developed and its psychometric properties, including interrater reliability and internal consistency, were evaluated. Methods: The fidelity scale was developed in a multidisciplinary collaboration between international research groups using the Delphi method. Four Delphi rounds were organized to reach consensus for the items included in the scale. To examine the psychometric properties of the scale, data from a large cluster randomized controlled trial evaluating the implementation of CAT in clinical practice was used. Fidelity assessors conducted 73 fidelity reviews at four mental health institutions in the Netherlands. Results: After three Delphi rounds, consensus was reached on a 44-item CAT Fidelity Scale. After administration of the scale, 24 items were removed in round four resulting in a 20-item fidelity scale. Psychometric properties of the 20-item CAT Fidelity Scale shows a fair interrater reliability and an excellent internal consistency. Conclusions: The CAT fidelity scale in its current form is useful for both research purposes as well as for individual health professionals to monitor their own adherence to the protocol. Future research needs to focus on improvement of items and formulating qualitative anchor point to the items to increase generalizability and psychometric properties of the scale. The described suggestions for improvement provide a good starting point for further development.

The Acceptability of Remotely Delivered Cognitive Adaptation Training.

Cognitive Adaptation Training (CAT) is a psychosocial treatment using environmental supports such as signs, checklists, technology, and the organization of belongings to bypass cognitive and motivational impairments for those with serious behavioral health problems. We conducted a survey of 204 members of managed Medicaid in Texas to examine the acceptability of, opinions about and preferences for CAT delivered in-person (CAT) or remotely (R-CAT) where supplies would be mailed and visits would occur via videoconferencing. The telephone survey presented descriptions of CAT and R-CAT in counterbalanced order eliciting general opinions about the treatments, such as (1) whether they would accept the treatments if they were offered the day of the survey at no cost, (2) which treatment was preferred, and (3) the extent to which they agreed or disagreed with a number of statements about components of the treatments. Results indicated that both R-CAT and CAT were acceptable to respondents with overall acceptance rates significantly higher for R-CAT 87% than for CAT (78%). With respect to preferences, 27% and 28% of respondents preferred CAT and R-CAT, respectively, and 41% of respondents preferred both equally. Black respondents more often preferred in-person CAT to other alternatives. Respondents agreed that they needed help, that they were comfortable with technology, and that they believed the programs would help them. The vast majority of qualitative comments about the treatments were positive. Results suggest that it will be important to assess the efficacy and effectiveness of CAT delivered remotely in randomized trials.

Mental Health Care Provider's Perspectives Toward Adopting a Novel Technology to Improve Medication Adherence.

Objective: To understand perspectives of mental health care providers regarding barriers and drivers of adopting a medication ingestible event monitoring (IEM) system in clinical practice. Methods: Between April and October 2019, a cross-sectional, online survey was conducted among 131 prescribing clinicians and 119 non-prescribing clinicians providing care to patients with major depressive disorder, bipolar disorder, and schizophrenia. Results: Most prescribing clinicians were physicians (79.4%) while most non-prescribing clinicians (52.9%) were licensed clinical social workers, followed by counselors (30.8%), clinical psychologists (13.4%), and case managers (2.5%). Most respondents (93.2%) reported that clinicians can influence adherence, that the IEM technology was in their patients' best interest (63.6%), and a willingness to beta test the technology (54.8%). Support was positively associated with prescribing clinicians (OR: 2.2; 95% CI: 1.1, 4.5), belief that antipsychotics reduce the health, social, or financial consequences of the condition (OR: 3.8; 95% CI: 1.3, 11.0), concern for patients' well-being without monitoring (OR: 3.3; 95% CI: 1.2, 8.7), and belief the technology will enhance clinical alliance (OR: 3.1; 95% CI: 1.5, 6.3) or improve patient engagement (OR: 3.0; 95% CI: 1.5, 6.2). Support was inversely related to concerns about appropriate follow-up actions (OR: 0.4; 95% CI: 0.2, 0.9) and responsibilities (OR: 0.3; 95% CI: 0.1, 0.8) when using the technology. Conclusions: Our results suggest that IEM sensor technology adoption will depend upon additional evidence that patients will actively engage in the use of the technology, will benefit from the technology through improved outcomes, and that the additional burden placed upon providers is minimal compared to the potential benefit.

Patient and Provider Perspectives on Medication Non-adherence Among Patients with Depression and/or Diabetes in Diverse Community Settings - A Qualitative Analysis.

Background: Diabetes and depression affect a significant percentage of the world's total population, and the management of these conditions is critical for reducing the global burden of disease. Medication adherence is crucial for improving diabetes and depression outcomes, and research is needed to elucidate barriers to medication adherence, including the intentionality of non-adherence, to intervene effectively. The purpose of this study was to explore the perspectives of patients and health care providers on intentional and unintentional medication adherence among patients with depression and diabetes through a series of focus groups conducted across clinical settings in a large urban area. Methods: This qualitative study utilized a grounded theory approach to thematically analyze qualitative data using the framework method. Four focus groups in total were conducted, two with patients and two with providers, over a one-year period using a semi-structured facilitation instrument containing open-ended questions about experiences, perceptions and beliefs about medication adherence. Results: Across the focus groups, communication difficulties between patients and providers resulting in medication non-adherence was a primary theme that emerged. Concerns about medication side effects and beliefs about medication effectiveness were identified as perceptual barriers related to intentional medication non-adherence. Practical barriers to medication adherence, including medication costs, forgetting to take medications and polypharmacy, emerged as themes related to unintentional medication non-adherence. Conclusion: The study findings contribute to a growing body of research suggesting health system changes are needed to improve provider education and implement multicomponent interventions to improve medication adherence among patients with depression and/or diabetes, both chronic illnesses accounting for significant disease burden globally.

Addressing chronic pain with Focused Acceptance and Commitment Therapy in integrated primary care: findings from a mixed methods pilot randomized controlled trial.

BACKGROUND: Over 100 million Americans have chronic pain and most obtain their treatment in primary care clinics. However, evidence-based behavioral treatments targeting pain-related disability are not typically provided in these settings. Therefore, this study sought to: 1) evaluate implementation of a brief evidence-based treatment, Focused Acceptance and Commitment Therapy (FACT-CP), delivered by an integrated behavioral health consultant (BHC) in primary care; and 2) preliminarily explore primary (self-reported physical disability) and secondary treatment outcomes (chronic pain acceptance and engagement in valued activities). METHODS: This mixed-methods pilot randomized controlled trial included twenty-six participants with non-cancer chronic pain being treated in primary care (54% women; 46% Hispanic/Latino). Active participants completed a 30-min individual FACT-CP visit followed by 3 weekly 60-min group visits and a booster visit 2 months later. An enhanced treatment as usual (ETAU) control group received 4 handouts about pain management based in cognitive-behavioral science. Follow-up research visits occurred during and after treatment, at 12 weeks (booster visit), and at 6 months. Semi-structured interviews were conducted to collect qualitative data after the last research visit. General linear mixed regression models with repeated measures explored primary and secondary outcomes. RESULTS: The study design and FACT-CP intervention were feasible and acceptable. Quantitative analyses indicate at 6-month follow-up, self-reported physical disability significantly improved pre-post within the FACT-CP arm (d = 0.64); engagement in valued activities significantly improved within both the FACT-CP (d = 0.70) and ETAU arms (d = 0.51); and chronic pain acceptance was the only outcome significantly different between arms (d = 1.04), increased in the FACT-CP arm and decreased in the ETAU arm. Qualitative data analyses reflected that FACT-CP participants reported acquiring skills for learning to live with pain, consistent with increased chronic pain acceptance. CONCLUSION: Findings support that FACT-CP was acceptable for patients with chronic pain and feasible for delivery in a primary care setting by a BHC. Results provide preliminary evidence for improved physical functioning after FACT-CP treatment. A larger pragmatic trial is warranted, with a design based on data gathered in this pilot. TRIAL REGISTRATION: clinicaltrials.gov, NCT04978961 (27/07/2021).

In-office, in-home, and telehealth cognitive processing therapy for posttraumatic stress disorder in veterans: a randomized clinical trial.

BACKGROUND: Trauma-focused psychotherapies for combat-related posttraumatic stress disorder (PTSD) in military veterans are efficacious, but there are many barriers to receiving treatment. The objective of this study was to determine if cognitive processing therapy (CPT) for PTSD among active duty military personnel and veterans would result in increased acceptability, fewer dropouts, and better outcomes when delivered In-Home or by Telehealth as compared to In-Office treatment. METHODS: The trial used an equipoise-stratified randomization design in which participants (N = 120) could decline none or any 1 arm of the study and were then randomized equally to 1 of the remaining arms. Therapists delivered CPT in 12 sessions lasting 60-min each. Self-reported PTSD symptoms on the PTSD Checklist for DSM-5 (PCL-5) served as the primary outcome. RESULTS: Over half of the participants (57%) declined 1 treatment arm. Telehealth was the most acceptable and least often refused delivery format (17%), followed by In-Office (29%), and In-Home (54%); these differences were significant (p = 0.0008). Significant reductions in PTSD symptoms occurred with all treatment formats (p < .0001). Improvement on the PCL-5 was about twice as large in the In-Home (d = 2.1) and Telehealth (d = 2.0) formats than In-Office (d = 1.3); those differences were statistically large and significant (d = 0.8, 0.7 and p = 0.009, 0.014, respectively). There were no significant differences between In-Home and Telehealth outcomes (p = 0.77, d = -.08). Dropout from treatment was numerically lowest when therapy was delivered In-Home (25%) compared to Telehealth (34%) and In-Office (43%), but these differences were not statistically significant. CONCLUSIONS: CPT delivered by telehealth is an efficient and effective treatment modality for PTSD, especially considering in-person restrictions resulting from COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02290847 (Registered 13/08/2014; First Posted Date 14/11/2014).

Perspectives of Patients and Providers in Using Shared Decision Making in Psychiatry.

There is increased interest over the last decade in the use of Shared Decision Making with individuals with serious mental illness to improve engagement in treatment and clinical outcomes. We conducted semi-structured qualitative interviews with 15 individuals with serious mental illness treated in an outpatient transitional care clinic serving people immediately after discharge from a psychiatric hospitalization. Parallel interviews were conducted with a variety of clinical providers (n = 9). Using latent thematic analysis, six themes were identified including: (1) Differences in the Use of SDM, (2) Consideration of Past Experiences, (3) Decisional Power Preferences, (4) Use of SDM in Psychiatry Versus Other Areas of Medicine, (5) Dignity and Disengagement, and (6) External Forces Impacting SDM. Implications for clinical practice and research using a shared decision-making approach within this treatment setting are further discussed.

Prescriber Attitudes, Experiences, and Proclivities Toward Digital Medicine and How They Influence Adoption of Digital Medicine Platforms.

BACKGROUND: Psychiatric prescribers (prescribers) typically assess medication adherence by patient or caregiver self-report. Despite likely clinical benefit of a new digital medicine technology, the role of specific prescriber attitudes, behaviors, and experiences in the likelihood of adoption is unclear. OBJECTIVE: To identify prescriber characteristics that may affect adoption of the ingestible event marker (IEM) platform. DESIGN: A survey of prescribers treating seriously mentally ill patients was conducted. Factor analysis was performed on 11 items representing prescriber characteristics believed to be related to endorsement of the IEM platform. Four factors were extracted. Regression analysis was used to test the strength of the relationships between the factors and likelihood of adoption of the IEM platform. RESULTS: A total of 131 prescribers completed the survey. Most (84%) agreed that visits allow enough time to monitor adherence. Factor analysis revealed four underlying dimensions: 1) perspectives on the value of adherence; 2) concerns about measuring adherence; 3) views toward digital health technologies; and 4) views on payer role/reimbursement. Factors 1 and 3 were related to gender, the belief that computerization benefits prescribers, the presence of office support staff, and the belief that new digital medicine (DM) technology will be cost prohibitive. Willingness to adopt the IEM platform was related to gender (p < 0.05) and perspectives on the value of adherence (p < 0.05), with those scoring higher on that measure also being more likely to adopt. CONCLUSION: Psychiatric prescribers are concerned about medication adherence, perceive current monitoring tools to be problematic, and are open to using digital technologies to improve accuracy of adherence assessment. Relationships among prescriber characteristics, beliefs, and experiences should be considered when developing educational materials, particularly when the goal is to encourage adoption and use of the IEM platform.