Telehealth Transdiagnostic Cognitive Behavioral Therapy for Depression in Parkinson's Disease: A Pilot Randomized Controlled Trial

Abstract

Background

Cognitive behavioral therapy (CBT) is an effective treatment for depression in persons with Parkinson′s disease (PwPD), but there are significant barriers preventing PwPD from receiving care in person. Telehealth CBT circumvents many of these barriers.

Objectives

We conducted a pilot randomized controlled trial evaluating the efficacy, feasibility, and acceptability of telehealth transdiagnostic CBT intervention for depression in PwPD.

Methods

Twelve PwPD with Major Depressive Disorder were enrolled, half randomly assigned to the treatment‐immediate condition (TI) and half to the waitlist control condition (WLC). TI and WLC participants received 12 CBT sessions and assessments before treatment, immediately after treatment, and at the 6‐week follow‐up.

Results

The intervention was efficacious for treating depression in PwPD, with secondary benefits to anxiety, apathy, learning, memory, and quality of life. Improvements were largely maintained at follow‐up. The intervention was highly feasible and acceptable.

Conclusions

Telehealth transdiagnostic CBT was an effective intervention for PwPD with depression.

Depression affects ~30% of persons with Parkinson's disease (PwPD) ¹ and is associated with physical and cognitive decline ² and poor quality of life. ³ Cognitive behavioral therapy (CBT) is an effective treatment for depression in PwPD, ⁴ , ⁵ , ⁶ , ⁷ , ⁸ , ⁹ but significant barriers prevent in‐person treatment, including motor disability, reliance on others for transportation, caregiver burden, ¹⁰ and perceived stigma causing reluctance to leave home. ¹¹ A potential solution is telehealth to deliver psychotherapy. PwPD express high interest in telehealth approaches to mental health treatment. ¹² Few studies have investigated the effectiveness of telehealth psychotherapy for mental health conditions in PD; a video‐to‐home CBT program effectively treated depression in veterans with PD ⁴ ; telephone‐based CBT resulted in improvements in depression and anxiety ⁵ , ⁹ ; CBT improved anxiety following in‐person/videoconference treatment. ¹³

We evaluated the efficacy, feasibility, acceptability, and secondary benefits of a video‐based telehealth CBT intervention for depression in PwPD. Our clinical trial differed from the above‐mentioned studies by (1) using a semi‐structured diagnostic interview with dimensional Clinical Severity Rating of DSM‐5 diagnoses as the primary outcome measure; (2) including secondary outcomes of anxiety, apathy, sleep, cognition, quality of life, and daily function; (3) examining underlying mechanisms of treatment; (4) assessing feasibility and acceptability; (5) delivering the intervention over videoconference; and (6) following an empirically‐supported transdiagnostic treatment, instead of an eclectic compilation of skills. ⁴ , ⁵ , ¹²

We hypothesized that the intervention would be superior to no intervention (waitlist control) on principal outcomes and secondary outcomes of anxiety, apathy, sleep, cognition, quality of life, and daily function and that treatment gains would be maintained after a 6‐week no‐contact period. We predicted that PwPD would regularly attend appointments, and find the intervention easy to use, engaging, and helpful.

Methods

Participants

Participants were recruited through Fox Trial Finder and American Parkinson Disease Association websites, the Parkinson's Disease and Movement Disorders Center at Boston University School of Medicine and Boston Medical Center, and community outreach. Inclusion criteria were medical record documentation of idiopathic PD (per Hughes et al.) ¹⁴ ; diagnosis of Major Depressive Disorder at baseline based on clinical interview; stability of psychotropic (antidepressant, anxiolytic) medication for ≥6 weeks and dopaminergic medication ≥2 weeks before intake; English‐fluent; able to attend all treatment sessions/assessments; access to a computer with videoconferencing capabilities, and reliable internet connection. Exclusion criteria were score ≤13 on Beck Depression Inventory‐II (BDI‐II) ¹⁵ ; neurological disorder besides PD; history of traumatic brain injury; current suicidal or homicidal ideation or intent (except passive suicidal ideation); dementia (diagnosis, or Telephone Interview for Cognitive Status ¹⁶ score ≤20 on screening); CBT within the past 5 years or currently receiving other psychotherapy.

We excluded 5 of 19 PwPD assessed for eligibility. Two PwPD scored ≤13 on the BDI‐II, one was not English‐fluent, one felt the study did not fit their treatment needs, and one was no longer interested after learning what the study entailed. Fourteen eligible participants consented and were randomized to the treatment‐immediate (TI) or waitlist control (WLC) condition by a research assistant using computerized simple randomization. Two of eight PwPD assigned to TI discontinued treatment because of unrelated medical reasons (eg, cancer diagnosis) and were excluded from analyses. Twelve participants (six TI, six WLC) completed all study components and were included in analyses.

Study Design

TI participants received three assessments: one before treatment (baseline 1), one immediately after (post‐treatment), and one 6 weeks after post‐treatment assessment (follow‐up). WLC participants had an additional assessment (baseline 2) 12 weeks after baseline 1 and before treatment. WLC design ensured that all participants would receive CBT and allowed for pre/post/follow‐up data to be pooled to examine individual differences in treatment response.

Treatment

Participants were treated in 12 weekly 50‐ to 60‐minute sessions via Cisco WebEx, a secure, confidential videoconferencing platform. CBT followed the Unified Protocol, 2nd edition, ¹⁷ a transdiagnostic treatment consisting of core modules that target clinical features that underlie all depressive and anxiety disorders, including emotion dysregulation.

Assessment

Primary Outcomes

Assessments were conducted as described previously. ¹⁸ Primary outcomes included clinical severity rating (CSR) of current DSM‐5 diagnoses using the Anxiety and Related Disorders Interview Schedule for DSM‐5 (ADIS‐5), ¹⁹ and the BDI‐II, which was administered at all assessments; clinical level of depression was indicated by a score >13. ¹⁵ The ADIS‐5 is a semi‐structured clinical interview focusing on DSM‐5 diagnoses of anxiety and mood disorders. Diagnoses are assigned a dimensional CSR scaled from 0 (none) to 8 (very severely disturbing/disabling), with ≥4 representing the clinical threshold for DSM‐5 criteria. Participants meeting criteria for two diagnoses with the same CSR were assigned co‐principal diagnosis. Participants meeting criteria for additional diagnoses at a lower CSR were assigned comorbid diagnosis. The full ADIS‐5 was administered at baseline (baseline 1 for TI and WLC, baseline 2 for WLC). At post‐treatment and follow‐up, participants were reassessed for only those diagnoses for which they met criteria at baseline.

Secondary Outcomes

We included measures of anxiety, ²⁰ apathy, ²¹ quality of life, ²² activities of daily living, ²³ sleep, ²⁴ sleepiness, ²⁵ examinations of mechanisms of treatment, ²⁶ , ²⁷ , ²⁸ and cognition including learning/memory, ²⁹ attention/working memory, ³⁰ processing speed, subjective cognition, ³¹ and executive function ³² (see Results).

Therapist and Treatment/Assessment Integrity

The therapist (R.J.P.) had 2 years′ experience using the Unified Protocol, trained and supervised by one of its developers (T.J.F.). A total of 20% of ADIS‐5 assessment recordings were independently scored by two blinded trained raters to determine assessment fidelity. Inter‐rater agreement was 100% for principal, co‐principal, and comorbid diagnoses (ie, within one CSR; see Brown et al). ³³

PD‐Specific Adaptations

Participants were instructed to not engage in such exercises as the interoceptive exposure “spinning in circles” because PwPD are prone to falls. ³⁴ As appropriate, other exposures were substituted (eg, spin in a chair).

Data Analysis

Linear regression assessed the effect of treatment on primary outcomes. For each, post‐treatment scores were regressed onto a dummy‐code variable representing treatment condition (WLC = 0, TI = 1), and pre‐treatment score (to evaluate change in outcome). Standardized regression coefficients represented the direct effect of the treatment condition. Effect size estimates (Hedges’ g) included correction for small samples. Hypotheses regarding the effect of treatment on diagnostic‐specific outcome variables and maintenance of treatment gains were evaluated using effect size estimates and paired‐samples t tests; likewise for secondary outcome variables. Analyses were conducted using SPSS version 24.0.

Results

Sample characteristics did not differ for TI and WLC (all P > 0.20) (Table 1). All 12 participants met criteria for Major Depressive Disorder. Four also met criteria for Generalized Anxiety Disorder. Two met criteria for co‐principal diagnosis of Generalized Anxiety Disorder and one for comorbid Generalized Anxiety Disorder; one for principal diagnosis of Generalized Anxiety Disorder with comorbid Major Depressive Disorder. Seven reported current antidepressant use (three TI, four WLC) and five antianxiety medication use (three TI, two WLC).

TABLE 1.

Study sample characteristics. No significant differences between TI and WLC groups

	TI (n = 6)	WLC (n = 6)	Total sample (n = 12)
Age, y, mean (SD)	58.5 (8.1)	64.1 (5.9)	61.3 (7.4)
Age range, y	45–67	56–70	45–70
Women:men, n (%)	4:2 (66.7:33.3)	4:2 (66.7:33.3)	8:4 (66.7:33.3)
Education, y, mean (SD)	16.0 (2.7)	16.3 (1.9)	16.1 (2.2)
Age at PD onset, y, mean (SD)	50.5 (8.8)	55.2 (5.3)	52.8 (7.3)
PD duration, y, mean (SD)	7.9 (2.8)	8.8 (5.1)	8.4 (4.0)
Telephone Interview for Cognitive Status, mean (SD)	34.6 (3.0)	35.3 (1.3)	35.0 (2.2)
Telephone Interview for Cognitive Status, n (%)
Nonimpaired range	5 (83.3)	6 (100)	11 (91.7)
Ambiguous range	1 (16.7)	0 (0)	1 (8.3)
Mildly impaired range	0 (0)	0 (0)	0 (0)
Moderately to severely impaired range	0 (0)	0 (0)	0 (0)
Diagnoses, n (%)
Major Depressive Disorder	6 (100)	6 (100)	12 (100)
Principal	3 (50)	6 (100)	9 (75)
Co‐principal	2 (33.3)	0 (0)	2 (16.7)
Comorbid	1 (16.7)	0 (0)	1 (8.3)
Generalized Anxiety Disorder	4 (66.7)	0 (0)	4 (33.3)
Principal	1 (16.7)	0 (0)	1 (8.3)
Co‐principal	2 (33.3)	0 (0)	2 (16.7)
Comorbid	1 (16.7)	0 (0)	1 (8.3)
Medication use, n (%)
Antidepressant	3 (50.0)	4 (66.7)	7 (58.3)
Antianxiety	3 (50.0)	2 (33.3)	5 (41.7)
Race (%)
White	100	100	100
Asian	0	0	0
Black or African	0	0	0
American Indian/ Alaskan Native	0	0	0
More than one race	0	0	0
Unknown or not reported	0	0	0
Ethnicity (%)
Not Hispanic	100	100	100
Hispanic	0	0	0
Other	0	0	0
Unknown or not reported	0	0	0

One participant scored in the “ambiguous” range on the Telephone Interview for Cognitive Status (ie, cognitive impairment may be present).

Abbreviations: TI, treatment‐immediate; WLC, waitlist control.

For primary outcome variables (Table 2), regarding diagnostic severity, the treatment produced strong reductions in TI (treatment) compared to WLC (no treatment) on ADIS‐5 CSRs for Major Depressive Disorder, and on ADIS‐5 CSRs for (co‐) principal diagnosis and self‐reported depression (BDI‐II). At post‐treatment and follow‐up compared to pre‐treatment, the intervention produced strong reductions on ADIS‐5 CSRs for Major Depressive Disorder, for (co‐) principal diagnosis, and for BDI‐II. No differences were observed between post‐treatment and follow‐up scores, indicating maintenance of treatment gains. For secondary outcomes (Table 2), at post‐treatment and follow‐up compared to pre‐treatment, the intervention produced significant positive effects on apathy, quality of life, experiential avoidance, and verbal learning, and treatment gains were maintained at follow‐up. The intervention also produced significant positive effects on anxiety and verbal memory recall at post‐treatment and on beliefs about negative emotions at follow‐up. Treatment did not affect daily function, sleep quality, daytime sleepiness, use of cognitive reappraisal or expressive suppression to regulate emotions, attention/working memory, processing speed, subjective cognition, or executive function.

TABLE 2.

Descriptive statistics, between‐treatment type effect sizes for primary outcome variables, and within‐treatment effect sizes for primary and secondary outcome variables

Measure	TI (treatment; n = 12)		WLC (no treatment; n = 6)		B	t	Hedges’ g
	Pre mean (SD)	Post mean (SD)	Pre mean (SD)	Post mean (SD)
Between‐treatment type effect sizes and descriptive statistics for primary outcome variable
MDD Dx CSR	4.3 (.6)	1.9 (.9)	5.0 (1.0)	4.3 (.8)	−0.7	−4.3***	2.3
(Co‐) Principal Dx CSR	4.4 (.6)	2.2 (.8)	5.0 (1.0)	4.3 (.8)	−0.7	−4.0**	2.2
BDI‐II	19.8 (4.2)	9.9 (4.6)	21.6 (9.0)	17.6 (4.2)	−0.6	−3.2**	1.5

Measure	Pre mean (SD)	Post mean (SD)	Follow‐up mean (SD)	Pre‐post		Pre‐follow‐up		Post‐follow‐up
				t	Hedges’ g	t	Hedges’ g	t	Hedges’ g
Within‐treatment effect sizes and descriptive statistics for primary and secondary outcome variables (n = 12)
MDD Dx CSR	4.3 (.6)	1.9 (.9)	1.9 (.9)	−6.7***	2.4	−6.7***	2.5	0	0
(Co‐) Principal Dx CSR	4.4 (.6)	2.2 (.8)	2.1 (.9)	−6.3***	2.3	−6.3***	2.4	−0.3	<0.1
BDI‐II	19.8 (4.2)	9.9 (4.6)	9.0 (3.5)	−4.7***	1.8	−5.5***	2.3	−0.6	0.1
Beck Anxiety Inventory	13.9 (8.8)	8.0 (7.8)	9.5 (8.5)	−3.0*	0.5	−1.7	0.4	0.9	−0.1
Apathy Scale (apathy symptoms)	24.0 (4.0)	27.6 (5.2)	27.1 (5.5)	2.4*	−0.6	2.3*	−0.5	−0.7	<0.1
PD Quality of Life Questionnaire (overall quality of life)	50.7 (23.8)	40.9 (24.2)	39.5 (22.2)	−2.7*	0.3	−2.9*	0.4	−0.4	<0.1
Movement Disorder Society‐Unified Parkinson Disease Rating Scale‐Activities of Daily Living (daily function)	18.5 (10.9)	18.1 (11.1)	16.5 (8.7)	−0.2	<0.1	−1.0	0.1	−1.0	0.1
PD Sleep Scale‐2 (sleep quality)	20.0 (11.8)	20.2 (10.0)	19.7 (7.5)	0.1	<−0.1	−0.1	<0.1	−0.2	<0.1
Epworth Sleepiness Scale (daytime sleepiness)	9.4 (5.1)	11.2 (5.9)	10.2 (5.1)	1.7	−0.2	0.8	−0.1	−1.0	0.1
Emotion Regulation Questionnaire
Cognitive reappraisal	27.2 (9.1)	29.0 (10.3)	30.2 (8.6)	0.6	−0.1	1.3	−0.2	0.7	−0.1
Expressive suppression	15.1 (5.9)	13.1 (6.3)	13.6 (5.6)	−1.3	0.2	−1.0	0.2	0.4	<−0.1
Beliefs About Emotions Scale	36.5 (16.6)	29.5 (12.7)	30.0 (12.7)	−1.4	0.3	−2.3*	0.3	0.1	<−0.1
Brief Experiential Avoidance Questionnaire	53.9 (10.0)	43.7 (10.3)	45.6 (14.2)	−3.6**	0.8	−2.7*	0.5	1.1	−0.1
Rey Auditory Verbal Learning Test
Immediate recall (total no. words recalled trial 1–trial 5)	43.2 (8.8)	49.6 (7.8)	47.8 (11.2)	3.1**	−0.6	2.2*	−0.3	−1.1	0.1
Delayed recall (no. words recalled)	7.6 (2.9)	9.8 (3.9)	8.5 (3.3)	2.5*	−0.5	2.0	−0.2	−1.8	0.2
Digit Span	27.4 (4.1)	29.0 (4.6)	28.3 (4.6)	1.3	−0.2	0.9	−0.1	−0.5	0.1
Serial 3s
Total time to completion	160.0 (109.3)	162.4 (152.0)	144.0 (105.6)	0.1	<−0.1	−1.6	0.1	−0.8	0.1
Quality of Life in Neurological Disorders: Cognitive Function	96.0 (22.1)	99.7 (25.7)	100.0 (24.8)	1.1	−0.1	0.9	−0.1	0.1	<−0.1
Verbal Fluency
Letters	42.6 (9.0)	—	43.7 (11.8)	—	—	0.5	<−0.1	—	—
Categories	41.6 (10.2)	—	42.0 (10.1)	—	—	0.1	<−0.1	—	—
Category switching	15.1 (2.3)	—	13.8 (2.7)	—	—	−1.7	0.4	—	—

Positive effect sizes denote a decrease in scores, negative effect sizes denote an increase. Hedges’ g effect sizes contrast the post scores for the TI and WLC conditions.

Abbreviations: PD, Parkinson's disease; TI, treatment‐immediate; WLC, waitlist control; MDD, Major Depressive Disorder; Dx, diagnosis; CSR, Clinical Severity Rating; BDI‐II, Beck Depression Inventory‐II. Follow‐up = at 6 weeks. Rey Auditory Verbal Learning Test Immediate Recall = verbal learning; Rey Auditory Verbal Learning Test Delayed Recall = verbal memory recall; Digit Span = attention/working memory; Serial 3s = processing speed; Quality of Life in Neurological Disorders: Cognitive Function = subjective cognition; Verbal Fluency = executive function. For Apathy Scale, higher score indicates fewer symptoms. For PD Quality of Life Questionnaire, lower score indicates improvement.

^* P < 0.05.

^** P < 0.01.

^*** P < 0.001.

The intervention was highly feasible and acceptable. Participants regularly attended appointments and appeared engaged. Treatment fidelity was rated high. Eight of 12 participants provided feedback following the 6‐week follow‐up and it was very positive.

Discussion

The results indicate the efficacy, feasibility, and acceptability of telehealth transdiagnostic CBT for depression in PwPD. The intervention also resulted in secondary benefits to anxiety, apathy, learning, memory, and quality of life. To our knowledge, this is the first study to show that CBT for depression in PwPD has significant effects on non‐motor symptoms besides mood, anxiety, and quality of life, including reductions in apathy and improvements in learning and memory. This is significant, because ~40% of PwPD struggle with apathy ³⁵ and PwPD exhibit memory deficits. ³⁶ We found two potential mechanisms of treatment: reduction in experiential avoidance and in beliefs about the unacceptability of experiencing or expressing negative emotions.

This telehealth intervention may help address disparities in access to mental health resources for PwPD. Significant barriers prevent PwPD from receiving face‐to‐face psychotherapy, including motor disability, reliance on others for transportation, care partner burden, and perceived stigma associated with motor dysfunction or seeking treatment for mental illness. Telehealth circumvents these barriers because individuals can attend treatment sessions at home. Telehealth also makes specialized mental health treatment more accessible to individuals with geographic constraints (eg, rural areas with few therapy providers). Although larger, randomized trials with more diverse samples are needed, telehealth CBT appears to be well‐positioned to become a treatment of choice for depression in PwPD, especially because the coronavirus disease 2019 (COVID‐19) pandemic has increased demand for telehealth mental health treatment. ³⁷

Participants were non‐Hispanic White and highly educated, had mild–moderate PD severity and mainly moderate depression severity, and no significant cognitive impairment; hence, they were not representative of the diverse PD community. In light of the considerable symptom overlap and lifetime comorbidity of mood and anxiety disorders, ³⁸ , ³⁹ future research should examine whether the Unified Protocol outperforms other CBT interventions for depression in PwPD. ⁴ , ⁵ , ¹² The Unified Protocol is an empirically supported transdiagnostic treatment consisting of five core modules (mindful emotion awareness, cognitive flexibility, countering emotional behaviors, understanding and confronting physical sensations, and emotion exposures), whereas other CBT interventions comprise an eclectic compilation of skills (eg, behavioral activation, cognitive restructuring, relaxation training, and sleep hygiene). ⁴ , ⁵ , ¹² A comparison trial is needed to determine which treatment is more helpful.

In conclusion, we report promising evidence of the efficacy, feasibility, and acceptability of telehealth transdiagnostic CBT for depression in PwPD. An important and novel finding was that CBT using the Unified Protocol led to significant reductions in apathy and improvements in learning and memory for PwPD. This intervention provided participants with foundational coping skills to manage the emotional and behavioral challenges of living with PD.

Author Roles

(1) Research project: A. Conception, B. Organization, C. Execution. (2) Statistical analysis: A. Design, B. Execution, C. Review and Critique. (3) Manuscript preparation: A. Writing of the First Draft, B. Review and Critique.

R.J.P.: 1A, 1B, 1C, 2A, 2B, 3A.

T.J.F.: 1B, 1C, 2A, 2C, 3B.

B.W.: 1A, 1B, 2C, 3B.

A.J.R.: 2A, 2B, 2C, 3B.

A.C.G.: 1A, 1B, 2C, 3B.

Disclosures

Ethical Compliance Statement: The study was approved by the Institutional Review Board of Boston University (protocol 5222). We obtained consent from participants before they engaged in the study. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest: Funding Source is American Parkinson Disease Association. T.J.F. receives royalties from Oxford University Press for being an author and co‐creator of the treatment used in the research study.

Financial Disclosures for the Previous 12 Months: R.J.P was a clinical psychology intern at Northwestern University Feinberg School of Medicine, Chicago, IL, and doctoral candidate at Boston University, Boston, MA. He received grant support from the American Parkinson Disease Association for his work on this study. T.J.F. was employed at Boston University, Boston MA. T.J.F. received royalties from Oxford University Press and grant support from the National Institute of Alcohol and Alcohol Abuse, and the John Templeton Foundation. B.W. was employed at Massachusetts General Hospital, Boston MA. She received funding on grants from the American Parkinson's Disease Association, National Institutes of Health (NIH) 5U19AG063911–03 (PI Seeley); 5R01AG063975–03 (PI Kong); 1R01AG059089 (PI Manor); 5R01AG061968–04 (PI Dickerson); 5R01AG054081–05 (PI Purdon, Dickerson); 5R01AG056015–05 (PIs Purdon, Dickerson); 5R01MH113234–05 (PI Feldman‐Barrett). A.J.R. was employed at Boston University, Boston, MA. He received funding on grants from HSRD IIR 19–372 (PI Vogt), the Simons Foundation 655,054 (PI Tager‐Flusberg), and the NIH R21 MH119492 (PI Rosellini), R01 MH110453 (PI Gradus), R01 MH110453 (PIs Wagner/Waller), R01 HL160850 (PIs Gradus/Sumner), and R01 NS120986 (PIs Tager‐Flusberg/Nelson). A.C.G. was employed at Boston University, Boston MA. She received funding on grants from the American Parkinson's Disease Association, NIH U01 EB029856 (PIs Boas, Kiran), R01 AG063775 (PI Reinhart), NIH R01 AG050595 (PIs Lyons, Kremen), and the Boston University Alzheimer's Disease Center. She received compensation for editorial service for the journal Psychological Science.