Smartphone Cognitive Behavioral Therapy as an Adjunct to Pharmacotherapy for Refractory Depression: Randomized Controlled Trial

Mantani, Akio; Kato, Tadashi; Furukawa, Toshi A; Horikoshi, Masaru; Imai, Hissei; Hiroe, Takahiro; Chino, Bun; Funayama, Tadashi; Yonemoto, Naohiro; Zhou, Qi; Kawanishi, Nao

doi:10.2196/jmir.8602

Cited by 142 publications

(180 citation statements)

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“…Music and EE-based interventions may serve as preclinical surrogate for developing adjunct digital therapeutics for cancer patients (43,58,127), since music can lower cancer-treatment biomarker IL-6 (94,112,145) while EE and physical exercise can reduce tumor size and increase lifespan in cancer animal models (127,128,146). Other clinical opportunities to combine non-pharmacological modalities with pharmaceutical drugs and biologics include Parkinson's and Alzheimer's diseases (21), asthma (147), arthritis (148) and affective disorders (143,149).…”

Section: Translational Implications Of Studying Enriched Environmentmentioning

confidence: 99%

Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs

Metcalf

Huntsman

Garcia³

et al. 2019

Front. Neurol.

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Digital therapeutics (software as a medical device) and mobile health (mHealth) technologies offer a means to deliver behavioral, psychosocial, disease self-management and music-based interventions to improve therapy outcomes for chronic diseases, including pain and epilepsy. To explore new translational opportunities in developing digital therapeutics for neurological disorders, and their integration with pharmacotherapies, we examined analgesic and antiseizure effects of specific musical compositions in mouse models of pain and epilepsy. The music playlist was created based on the modular progression of Mozart compositions for which reduction of seizures and epileptiform discharges were previously reported in people with epilepsy. Our results indicated that music-treated mice exhibited significant analgesia and reduction of paw edema in the carrageenan model of inflammatory pain. Among analgesic drugs tested (ibuprofen, cannabidiol (CBD), levetiracetam, and the galanin analog NAX 5055), music intervention significantly decreased paw withdrawal latency difference in ibuprofen-treated mice and reduced paw edema in combination with CBD or NAX 5055. To the best of our knowledge, this is the first animal study on music-enhanced antinociceptive activity of analgesic drugs. In the plantar incision model of surgical pain, music-pretreated mice had significant reduction of mechanical allodynia. In the corneal kindling model of epilepsy, the cumulative seizure burden following kindling acquisition was lower in animals exposed to music. The music-treated group also exhibited significantly improved survival, warranting further research on music interventions for preventing Sudden Unexpected Death in Epilepsy (SUDEP). We propose a working Metcalf et al. Music-Enhanced Analgesic and Antiseizure Activities model of how musical elements such as rhythm, sequences, phrases and punctuation found in K.448 and K.545 may exert responses via parasympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. Based on our findings, we discuss: (1) how enriched environment (EE) can serve as a preclinical surrogate for testing combinations of non-pharmacological modalities and drugs for the treatment of pain and other chronic diseases, and (2) a new paradigm for preclinical and clinical development of therapies leading to drug-device combination products for neurological disorders, depression and cancer. In summary, our present results encourage translational research on integrating non-pharmacological and pharmacological interventions for pain and epilepsy using digital therapeutics.

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Section: Translational Implications Of Studying Enriched Environmentmentioning

confidence: 99%

Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs

Metcalf

Huntsman

Garcia³

et al. 2019

Front. Neurol.

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“…The effectiveness of the system was demonstrated in a randomized controlled trial (RCT) comparing antidepressant medication switch plus Kokoro-App against antidepressant medication switch alone among patients who had been unresponsive to one or more antidepressants: the effect size of the intervention was a standardized mean difference of 0.40 in depression severity as measured by masked assessors ( P <.001) [ 17 ]. This study aims to examine how the patients used the smartphone CBT app during the trial and to investigate what use characteristics differentiated the more successful users of the CBT app from the less successful ones.…”

Section: Introductionmentioning

confidence: 99%

Cognitive and Behavioral Skills Exercises Completed by Patients with Major Depression During Smartphone Cognitive Behavioral Therapy: Secondary Analysis of a Randomized Controlled Trial

Furukawa¹,

Horikoshi²,

Fujita³

et al. 2018

JMIR Ment Health

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BackgroundA strong and growing body of evidence has demonstrated the effectiveness of cognitive behavioral therapy (CBT), either face-to-face, in person, or as self-help via the Internet, for depression. However, CBT is a complex intervention consisting of several putatively effective components, and how each component may or may not contribute to the overall effectiveness of CBT is poorly understood.ObjectiveThe aim of this study was to investigate how the users of smartphone CBT use and benefit from various components of the program.MethodsThis is a secondary analysis from a 9-week, single-blind, randomized controlled trial that has demonstrated the effectiveness of adjunctive use of smartphone CBT (Kokoro-App) over antidepressant pharmacotherapy alone among patients with drug-resistant major depressive disorder (total n=164, standardized mean difference in depression severity at week 9=0.40, J Med Internet Res). Kokoro-App consists of three cognitive behavioral skills of self-monitoring, behavioral activation, and cognitive restructuring, with corresponding worksheets to fill in. All activities of the participants learning each session of the program and completing each worksheet were uploaded onto Kokoro-Web, which each patient could use for self-check. We examined what use characteristics differentiated the more successful users of the CBT app from the less successful ones, split at the median of change in depression severity.ResultsA total of 81 patients with major depression were allocated to the smartphone CBT. On average, they completed 7.0 (standard deviation [SD] 1.4) out of 8 sessions of the program; it took them 10.8 (SD 4.2) days to complete one session, during which they spent 62 min (SD 96) on the app. There were no statistically significant differences in the number of sessions completed, time spent for the program, or the number of completed self-monitoring worksheets between the beneficiaries and the nonbeneficiaries. However, the former completed more behavioral activation tasks, engaged in different types of activities, and also filled in more cognitive restructuring worksheets than the latter. Activities such as “test-drive a new car,” “go to a coffee shop after lunch,” or “call up an old friend” were found to be particularly rewarding. All cognitive restructuring strategies were found to significantly decrease the distress level, with “What would be your advice to a friend who has a similar problem?” found more helpful than some other strategies.ConclusionsThe CBT program offered via smartphone and connected to the remote server is not only effective in alleviating depression but also opens a new avenue in gathering information of what and how each participant may utilize the program. The activities and strategies found useful in this analysis will provide valuable information in brush-ups of the program itself and of mobile health (mHealth) in general.Trial RegistrationJapanese Clinical Trials Registry UMIN CTR 000013693; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ ctr_view.cgi?recptno=R...

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“…may provide a useful aid and incentive for real-life perception and social cognition in the depressed, a potential demonstration of compensatory mechanism at work to enhance the impoverished emotional and social stimulation in depression. In Japan, a randomized controlled trial which assigned an intervention group of depressed participants to both antidepressants and a smartphone application based cognitive-behavioral therapy sessions utilizing animated cartoon characters' interactions had a better outcome on the Beck Depression Inventory scores, though the inclusion of cartoon characters was not considered an independent variable [17].…”

Section: Resultsmentioning

confidence: 99%

The Potential Benefit of Cartoon Stimuli for Depression

Kong¹

2019

J Dep Anxiety

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The possible significance of compromised exposure to positive stimuli during an individual's early childhood could contribute to impoverished positive memory development and subsequently dysregulated emotional responses to such valence of stimuli in adulthood. This could potentially explain dampened positive emotional responses of depressed individuals as reported in imaging studies of the brain's mesolimbic reward pathways. This paper provides emphasis and suggestions for a preliminary exploration of positive cartoon stimuli as a new tool in therapeutic targets for depression treatment and research that cater to a subgroup of depressive individuals who had experienced childhood trauma and stressful episodes as their primary causes of the disorder. Cartoon stimuli as a form of visual and interactive therapy may provide a compensatory and restorative component for the emotional losses and insults on an otherwise healthy childhood positivity required for normal and balanced neuropsychological development and growth. Unfortunately, such readily available resources for therapy have hardly been considered and utilized. The potential benefit of exposure to cartoon stimuli may extend beyond the method of positive mood induction and further addresses the need for both implicit and explicit comfort, understanding, emotional and situational relatedness that compensate for the lack of such stimulation during an early stressful life. Through evoking childlike positive associations, it is hypothesized that depression could reduce in severity and the threshold for activation of response to positive stimuli and themes lowered, thereby restoring negative and positive mood imbalances.

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Smartphone Cognitive Behavioral Therapy as an Adjunct to Pharmacotherapy for Refractory Depression: Randomized Controlled Trial

Cited by 142 publications

References 50 publications

Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs

Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs

Cognitive and Behavioral Skills Exercises Completed by Patients with Major Depression During Smartphone Cognitive Behavioral Therapy: Secondary Analysis of a Randomized Controlled Trial

The Potential Benefit of Cartoon Stimuli for Depression

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