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The goal of individualized medicine is to determine which therapy works best for each individual patient. Predicting optimal treatments for individuals involves collecting large data sets of potential predictive variables, each with small non-linear effects and complex interactions. Machine learning methods can generate predictions from these vast datasets more efficiently than humans can.

Computers can also calculate Personalized Advantage Indexes (PAIs), which compare the likelihood of a successful outcome from one treatment to that of an alternative treatment. PAIs can then be used to guide physicians to offer patients their optimal treatment. 

Meyers et al. [Behaviour Research and Therapy] developed and tested a treatment-matching algorithm for veterans at high risk for suicide, aiming to predict which veterans would benefit more from Mindfulness-Based Cognitive Therapy for Suicide Prevention (MBCT-S) or enhanced treatment-as-usual (TAU).

The researchers performed a secondary analysis of data from a 2021 study in which 140 veterans at high risk for suicide were randomly assigned to either MBCT-S or enhanced TAU within the Veterans Administration (VA) system. The primary outcome measured was the number of suicide attempts or hospitalizations and emergency room visits for severe suicidal ideation over the ensuing 12-month period. The study collected a vast array of data that could be used as potential outcome predictors.

The researchers aimed to: 1) develop machine learning models to predict outcomes within each study arm, 2) identify key variables that predicted suicidal behavior, and 3) generate PAIs for each patient and evaluate their utility. 

MBCT-S was delivered in eight group and two individual sessions. TAU consisted of usual VA care (including access to psychopharmacology, psychotherapy, and residential care as needed) and attention from suicide prevention coordinators, who helped patients develop safety plans, encouraged compliance, and monitored progress.

The researchers selected  55 potential predictor variables from the demographic, clinical, and neurocognitive study data and the electronic medical records. Data were processed using a machine learning “random forest” approach. Data from 80% of the patients were used to train the predictive models, while data from the remaining 20% were reserved for subsequent model validation.

The results showed that the suicide prediction model was 73% accurate in the training sample and 67% accurate in the validation sample for the MBCT-S group. The predictive model for the TAU group was 66% accurate in the training sample and 60% accurate in the validation sample. The MBCT-S predictive model met the researcher’s standards of acceptability, but the TAU predictive model did not.

Within the MBCT-S group, the variables that best predicted future suicidal behavior were a diagnosis of PTSD, history of parasuicidal behavior, residential care in the past year, number of acute psychiatric admissions in the past year, and poor performance on a sustained attention task. In the TAU group, the best predictors were the number of acute hospitalizations and outpatient visits in the past year, severity of suicidal ideation, and better attentional control.

PAIs indicated that 63% of MBCT-S patients were in their PAI-indicated optimal treatment group compared to 39% of the TAU patients. Patients in their PAI-indicated optimal treatment were significantly less likely to have a suicidal event in the next year. While the main effect of treatment assignment on suicidal events was not significant, the interaction between treatment assignment and PAI indication was significant.

The findings support the use of large dataset machine learning to generate predictions about which patients may benefit most from particular therapies. It serves as a demonstration of what may be possible in the future, though creating a truly predictive model requires larger patient datasets and cross-validation on independent samples. The study was also limited by the use of a TAU control, which did not offer a uniform treatment experience to all participants.

Reference:

Myers, C. E., Dave, C. V., Chesin, M. S., Marx, B. P., St. Hill, L. M., Reddy, V., Miller, R. B., King, A., & Interian, A. (2024). Initial evaluation of a personalized advantage index to determine which individuals may benefit from mindfulness-based cognitive therapy for suicide prevention. Behaviour Research and Therapy. 

Link to study

Some early studies suggest that combining meditation with a psychedelic substance may increase mindfulness, compassion, and well-being beyond meditation practice alone. Most of this research involves psilocybin, but little is known about whether other psychedelics might have a similar synergistic effect when combined with meditation. 

Meling et al. [Journal of Psychopharmacology] tested whether a combination of Dimethyltryptamine (DMT) and Harmine had psychologically beneficial effects when compared to a placebo. DMT is one of the psychoactive substances in ayahuasca, a plant that contains the monoamine oxidase inhibitor Harmine. The combination of DMT and Harmine is often considered an “ayahuasca analog” because Harmine slows the biodegradation of DMT, thereby prolonging its effects. 

The researchers randomly assigned 40 experienced meditators with an interest in DMT research (average age = 44 years; average meditative experience = 2,400 hours; 55% male; 83% with postgraduate degrees, 95% White) to either a DMT-Harmine group or a placebo group. All participants attended a 3-day meditation retreat at a Swiss Zen Meditation Center focused on mindfulness, compassion, and walking meditations. On the second day of the retreat, participants received four sublingual doses of DMT-Harmine or placebo over a 2-hour period. Each active dose contained 30mg of DMT and 30mg of Harmine. 

Participants completed self-report measures one day before the retreat, on each of the three retreat days, one day after the retreat, and at 1- week and 1-month follow-up.  Measures included state and trait mindfulness, compassion,  insight, emotional breakthrough, and mystical and non-dual experience.

Insight was a measure of how much participants thought they learned new information about their personalities and lives, while emotional breakthrough was a measure of how much participants experienced a cathartic emotional release, explored their emotions, or resolved an emotional issue.

At 1-month follow-up, participants were asked whether they could guess whether they had received the substance or placebo (83% correctly identified their group) and how meaningful, spiritually significant, and beneficial the retreat had been.

The results showed that DMT-Harmine did not offer advantages over the placebo in terms of enhanced mindfulness or compassion scores. However, DMT-Harmine significantly enhanced psychological insight (ηp2 = 013), emotional breakthrough (ηp2=0.21), and mystical (ηp2=0.30) and non-dual (ηp2=0.13) experience on the day it was administered.

At 1-month follow-up, the group receiving DMT-Harmine rated their experience as significantly more personally meaningful, spiritually significant, and more positively impactful in terms of well-being and life-satisfaction. 

The study shows that while DMT-Harmine did not offer improved mindfulness or compassion scores in experienced meditators beyond the meditation retreat, it does boost psychological insight, emotional breakthrough, and transcendent experience. Forty-five percent of the DMT-Harmine group rated their experience as one of the top five spiritual experiences of their lives.

The study’s limitations include the absence of a non-meditation control group and the fact that participants detected their study group. It remains unclear how divided doses of DMT-Harmine compare to a single dose, or how the low dose of Harmine in this study compares to studies that employ ayahuasca which has higher naturally occurring amounts of Harmine.

Reference:

Meling, D., Egger, K., Aicher, H. D., Jareño Redondo, J., Mueller, J., Dornbierer, J., Temperli, E., Vasella, E. A., Caflisch, L., Pfeiffer, D. J., Schlomberg, J. T., Smallridge, J. W., Dornbierer, D. A., & Scheidegger, M. (2024). Meditating on psychedelics. A randomized placebo-controlled study of DMT and harmine in a mindfulness retreat. Journal of Psychopharmacology.

Link to study

Mindfulness-based interventions (MBIs) are often recommended as first-line or ancillary treatments for chronic pain. However, several barriers prevent widespread access to these programs. including cost, the availability of nearby programs, and the challenge of coordinating patients’ schedules with group session times . 

Newer programs using smartphone and telehealth technologies allow chronic pain patients to learn mindfulness at home, often on their own schedule and at a lower cost. Burgess et al. [JAMA Internal Medicine] conducted a randomized controlled trial to compare the effect of a group-based and a self-paced telehealth MBIs in treating veterans with chronic pain, compared to a treatment-as-usual (TAU) control group.

The researchers randomly assigned 811 American veterans with moderate-to-severe chronic pain (average age = 55; 52% male; 66% White), recruited from three Veterans Affairs (VA) facilities, into one of three groups: a group-based telehealth MBI with treatment as usual, a self-paced telehealth MBI with treatment as usual, or a treatment-as-usual only group. Both MBIs were 8-week programs modeled the after Mindfulness-Based Stress Reduction program.  

The group-based MBI included an orientation session and eight 90-minute synchronous group telehealth sessions, featuring pre-recorded mindfulness education and exercises, followed by facilitated discussions. Participants were encouraged to practice at home using a workbook, smartphone app, and website with guided meditations. 

The self-paced MBI group consisted of eight 30- to 60-minute asynchronous sessions using the same pre-recorded materials as the group-based MBI but without facilitated discussion. Instead, participants received three phone calls from facilitators to address problems, monitor progress, and discuss strategies.

TAU included the availability of acupuncture, massage, exercise, yoga, tai chi, meditation, medication, spinal injections, and counseling and psychotherapy. All groups  used the non-meditation TAU modalities to a similar extent, and 42% of the TAU group also accessed some form of meditation or mindfulness training on their own. 

Patients were assessed at 10 weeks, 6 months, and 12 months on primary and secondary outcomes. The primary outcome was improvement in pain-related impairment of daily activities. Secondary outcomes included anxiety, depression, fatigue, sleep disturbance, PTSD, and social role functioning. Sixty-nine percent of the group-based MBI participants completed 6 or more of the group sessions, while 76% of the self-paced group participated in at least two facilitator calls. 

Averaged over the three assessment periods, the group-based MBI (effect size = -0.20) and the self-paced MBI (effect size= -0.40) had significantly lower pain interference scores with their daily lives compared to the TAU controls. There was no significant difference in effect between the two MBI groups.

The group-based MBI had significantly lower pain-related interference scores at 10 weeks and 6 months, while the self-paced MBI outperformed the TAU group at all time points. 

A greater percentage of patients in both MBI groups attained 30% and 50% pain improvement over baseline compared to controls. MBI groups showed significantly better improvement on almost all the secondary measures compared to the TAU group. There were no differences between the MBI groups on these secondary measures. No adverse events were reported in any of the study groups

Reference:

Burgess, D. J., Calvert, C., Hagel Campbell, E. M., … Taylor, B. C. (2024). Telehealth Mindfulness-Based Interventions for Chronic Pain: The LAMP Randomized Clinical Trial. JAMA Internal Medicine.

Link to study

Mindfulness-based interventions (MBIs) are often recommended as first-line or ancillary treatments for chronic pain. However, several barriers prevent widespread access to these programs. including cost, the availability of nearby programs, and the challenge of coordinating patients’ schedules with group session times. 

Newer programs using smartphone and telehealth technologies allow chronic pain patients to learn mindfulness at home, often on their own schedule and at a lower cost. Burgess et al. [JAMA Internal Medicine] conducted a randomized controlled trial to compare the effect of a group-based and a self-paced telehealth MBIs in treating veterans with chronic pain, compared to a treatment-as-usual (TAU) control group.

The researchers randomly assigned 811 American veterans with moderate-to-severe chronic pain (average age = 55; 52% male; 66% White), recruited from three Veterans Affairs (VA) facilities, into one of three groups: a group-based telehealth MBI with treatment as usual, a self-paced telehealth MBI with treatment as usual, or a treatment-as-usual only group. Both MBIs were 8-week programs modeled the after Mindfulness-Based Stress Reduction program.  

The group-based MBI included an orientation session and eight 90-minute synchronous group telehealth sessions, featuring pre-recorded mindfulness education and exercises, followed by facilitated discussions. Participants were encouraged to practice at home using a workbook, smartphone app, and website with guided meditations. 

The self-paced MBI group consisted of eight 30- to 60-minute asynchronous sessions using the same pre-recorded materials as the group-based MBI but without facilitated discussion. Instead, participants received three phone calls from facilitators to address problems, monitor progress, and discuss strategies. TAU included the availability of acupuncture, massage, exercise, yoga, tai chi, meditation, medication, spinal injections, and counseling and psychotherapy. All groups  used the non-meditation TAU modalities to a similar extent, and 42% of the TAU group also accessed some form of meditation or mindfulness training on their own. 

Patients were assessed at 10 weeks, 6 months, and 12 months on primary and secondary outcomes. The primary outcome was improvement in pain-related impairment of daily activities. Secondary outcomes included anxiety, depression, fatigue, sleep disturbance, PTSD, and social role functioning. Sixty-nine percent of the group-based MBI participants completed 6 or more of the group sessions, while 76% of the self-paced group participated in at least two facilitator calls. 

Averaged over the three assessment periods, the group-based MBI (effect size = -0.20) and the self-paced MBI (effect size= -0.40) had significantly lower pain interference scores with their daily lives compared to the TAU controls. There was no significant difference in effect between the two MBI groups. The group-based MBI had significantly lower pain-related interference scores at 10 weeks and 6 months, while the self-paced MBI outperformed the TAU group at all time points. 

A greater percentage of patients in both MBI groups attained 30% and 50% pain improvement over baseline compared to controls. MBI groups showed significantly better improvement on almost all the secondary measures compared to the TAU group. There were no differences between the MBI groups on these secondary measures. No adverse events were reported in any of the study groups

The study reveals that telehealth-delivered MBIs can reduce veteran pain interference with daily life scores compared to TAU. Although the effect sizes were small, they persisted throughout the follow-up period. Notably, the group-based MBI conferred no additional benefit over a self-paced MBI. The study is limited by the lack of comparison between telehealth and in-person treatment, as well as MBIs and other evidenced-based treatments like cognitive-behavioral therapy.

Reference:

Burgess, D. J., Calvert, C., Hagel Campbell, E. M.,… Taylor, B. C. (2024). Telehealth Mindfulness-Based Interventions for Chronic Pain: The LAMP Randomized Clinical Trial. JAMA Internal Medicine.

Link to study

The demand for psychiatric services far exceeds availability, and there are barriers such as cost and time to accessing services, even when they are available. Recently, various digital mental health interventions (DMHI) have been developed to help address the gap between mental health care need and publicly available services. These interventions are accessible by smartphone, available at any time, and have lower costs than personnel-delivered mental health services. 

While studies show that specific cognitive-behavioral DMHIs and Mindfulness-Based DMHIs are more effective than no-treatment controls, there is little research comparing their relative effectiveness. Horwitz et al. [JAMA Network Open] compared the relative effectiveness of five different DMHIs in reducing depressive symptoms within an adult  general outpatient psychiatric population.

The researchers recruited 2,079 adults (average age =  37 years; 68% female; 77% white) who had sought mental health services within the University of Michigan Health System and had scheduled an appointment or recently had their first appointment. Participants were paid $20 for completing the initial assessment and an additional $20 for completing the 6-week follow-up assessment. They agreed to pair their smartphones with a smartphone app, sync their smartphones with a wrist-worn activity monitor, and use the smartphone app for 6 weeks. The primary study outcome was improvement in depressive symptoms, with secondary outcomes including improvements in anxiety, substance use, and suicidal ideation.

Five digital treatment interventions were randomly  assigned to participants: 1) enhanced personal feedback (EPF), 2) cognitive-behavioral therapy, 3) mindfulness meditation, 4) cognitive-behavioral therapy + EPT, and 5) mindfulness meditation + EPT.  EPF consisted of sending pop-up notifications to smartphones twice daily. For example, if the activity monitor showed relative inactivity, a message might be sent to encourage more walking. Other notifications suggested participants be kind to others or engage more with the cognitive-behavioral and mindfulness meditation apps. 

Cognitive-behavioral therapy was delivered via the Silvercloud app, which helped participants monitor mood, activity schedule, and engage in cognitive restructuring through text, video, and journaling.  Mindfulness meditation involved access to the library of guided meditations on the Headspace app.  

The results showed that depressive symptom scores significantly decreased in all five digital intervention groups, but without between-group differences reaching significance. Depressive symptoms initially averaged 12.7 on a 27-point scale at baseline and decreased by a range of  2.1 to 2.9 points below baseline across the various interventions. 

There were similar improvements for secondary outcomes. The Headspace app interventions showed a significantly greater (but probably not clinically meaningful) decrease in suicidal ideation compared to the other intervention groups. The degree of improvement in these groups was the same regardless of whether participants attended 0, 1, 2, or more treatment meetings with therapists during the 6-week trial suggesting that clinic visits did not contribute to symptom changes across study groups.

The study shows that psychiatric outpatients experience a small but significant degree of improvement in psychiatric symptoms after being assigned digital mental health interventions regardless of intervention content.

The authors suggest that digital mental health interventions may be helpful for patients awaiting assignment for first visits to therapists. However, the study is limited by the absence of a no-treatment group to eliminate the claim that simple engagement in a research study as a participant also improves depressive symptoms. It also did not measure the extent to which participants actually used their assigned apps.

Reference:

Horwitz, A. G., Mills, E. D., Sen, S., & Bohnert, A. S. B. (2024). Comparative Effectiveness of Three Digital Interventions for Adults Seeking Psychiatric Services: A Randomized Clinical Trial. JAMA Network Open, 7(7), e2422115. 

Link to study

Very low birthweight is associated with physical, psychological, and social difficulties during early childhood development. In studies previously reported in our September and November 2023 issues, newborns from a large cohort of women at high risk for very low-birthweight delivery benefited from both the Mediterranean Diet and from Mindfulness-Based Stress Reduction (MBSR). Both interventions resulted in fewer very low-birthweight deliveries, better early childhood developmental scores, and measurable differences in fetal brain development. 

Very low birthweight is usually due to placental dysfunction, but those earlier analyses did not assess whether the treatments affected placental health. In a secondary analysis, Nakaki et al. [Acta Obstetricia et Gynecologica Scandinavica] used Magnetic Resonance Imaging (MRI) to assess placental volume and blood perfusion in a subset of the women from the original study.

The original study recruited 1,221 pregnant Spanish women who were at risk for delivering very low birthweight infants based on clinical guidelines. MBSR, the Mediterranean Diet, or treatment-as-usual conditions were randomly assigned to women. MBSR included 2.5-hour weekly group sessions, a full-day retreat, and home meditation practice.

The Mediterranean diet intervention involved monthly group assessment and education sessions along with the provision of extra virgin olive oil and walnuts for consumption. The usual care group received pregnancy care following current obstetrical protocols. 

The authors invited a randomly selected subset of 350 of these women to undergo magnetic resonance imaging (MRI) of the placenta to assess placental volume and perfusion during the 36th week of pregnancy, and 165 women(average age = 38 years; 79% white) agreed to participate in this additional protocol. 

The results show that while there was no significant between-group difference in average placental volume, there were significant differences in the likelihood of having a placental volume below the 10th percentile. Only 3.9% of the Mediterranean Diet group had volumes below the 10thpercentile, compared to 5% of the MBSR group and 17% of the treatment-as-usual group. Very small placental volumes were associated with significantly increased odds of giving birth to a very low birthweight infant.

No significant differences in blood perfusion were detected. Blood perfusion is a measure of the blood flow between the placenta and the fetus which is in turn related to the amount of nutrition and oxygen the fetus receives.

The study shows that the Mediterranean Diet and MBSR both lower the odds of having a very small placenta, which is in turn associated with the odds of giving birth to a very low weight infant. The authors discuss how the anti-inflammatory effects of the Mediterranean diet can beneficially affect placental development, and how lower levels of stress-related glucocorticoids can beneficially impact placental growth and nutrient transport. 

The study’s method of measuring blood perfusion may not have been sensitive enough to detect meaningful differences. This relatively highly educated sample of pregnant women had low rates of obesity and gestational diabetes and may not be typical of the general obstetric population. 

Reference:

Nakaki, A., Denaro, E., Crimella, M., Castellani, R., Vellvé, K., Izquierdo, N., Basso, A., Paules, C., Casas, R., Benitez, L., Casas, I., Larroya, M., Genero, M., Castro-Barquero, S., Gomez-Gomez, A., Pozo, Ó. J., Vieta, E., Estruch, R., Nadal, A., … Youssef, L. (2024). Effect of Mediterranean diet or mindfulness-based stress reduction during pregnancy on placental volume and perfusion: A subanalysis of the IMPACT BCN randomized clinical trial. Acta Obstetricia et Gynecologica Scandinavica.

Link to study

Most cigarette smokers want to quit, but only 7% succeed in any given year. While smoking cessation interventions can be helpful for some, most people attempt to quit without professional assistance. The widespread use of smartphones and the growing popularity of wearable smart bands and watches suggests new mediums for supporting targeted smoking cessation efforts.

Horvath et al. [Annals of Medicine] conducted an uncontrolled study to investigate the feasibility of a wearable smartband designed to  detect smoking episodes and subsequently deliver a brief mindfulness session. The aim of the technology was to improve the timeliness of the intervention content in relation to smoking occurrences. 

The researchers recruited a sample of 155 adult smokers who owned smartphones (average age = 46 years; 54% female; 76% white) and wanted to quit smoking in response to posted Facebook ads. Participants were given a wearable smartband that paired with their personal smartphones. The bands used accelerometer and gyroscopic sensors to identify hand-to-mouth movements correlated with cigarette smoking behavior. 

When smoking movement was detected, the band vibrated and sent a message via smartphone prompting participants to confirm or deny they were smoking. Participants were instructed to wear the band on the hand they used for smoking 12 hours a day for 60 consecutive days. Participants could smoke as much or as little as they liked but set the 30th day of smart band wear as their intended “quit day.” 

At 21 days, participants completed a survey and a brief online mindfulness training. From day 21 to 28, whenever their band detected smoking, they were sent a two-minute audio “mindful smoking” exercise. On the 28th day, participants completed another survey and viewed a brief online training on using RAIN (Recognize, Allow, Investigate, Non-identification) to manage cravings.

From day 28 onwards, the smartphone delivered a two-minute audio-guided RAIN exercise when the band detected smoking. The completion of mindfulness exercises was time-stamped, and real-time data was gathered on cravings, mood, and the exercises’ helpfulness. At 60 days, participants completed another online survey.

The primary outcomes measured were the smartband’s accuracy to detect smoking, protocol adherence, and protocol acceptability. The secondary outcomes related to smoking included cigarette dependence, withdrawal symptoms,  and abstinence.

The results showed that the band detected smoking with 90% accuracy. Twenty-six percent of the participants did not complete study enrollment, never succeeded in paring the band with their phones, or never tried wearing the bands. Among the 115 participants who wore the band at least once, bands were worn on 70% of the treatment days and for at least 12 hours a day on 41% of those days.

The part of the sample that wore the band at least once completed 40% of the mindful smoking exercises and 86% of the RAIN exercises. Eighty-two percent of the participants who wore the bands at least once completed their surveys at all data points.

While participants found the mindful smoking and RAIN exercises helpful (79% and 75%, respectively) only a small majority liked them (58% and 52%, respectively). On average, participants reduced their  smoking by 9 cigarettes per day, and 12% reported achieving one-week point prevalence abstinence. 

The study suggests that a smartband can reliably detect smoking episodes and deliver subsequent prompting for interventions. While study retention was good, adherence and acceptability were variable in the sample of smokers. Some participants reported difficulty keeping the band paired with their phones, and some felt they received an excessive number of daily intervention prompts.

Reference:

Horvath, M., Pittman, B., O’Malley, S. S., Grutman, A., Khan, N., Gueorguieva, R., Brewer, J. A., & Garrison, K. A. (2024). Smartband-based smoking detection and real-time brief mindfulness intervention: Findings from a feasibility clinical trial. Annals of Medicine. 

Link to study

Alcohol misuse is a significant contributor to poor mental and physical health in people under age 50 worldwide. Existing interventions for alcohol misuse suffer from high attrition and relapse, prompting the search for more effective treatments.

Esketamine, a novel glutamatergic drug with dissociative, anesthetic, hallucinogenic and psychedelic properties has demonstrated antidepressant effects. A few studies suggest it may work synergistically with behavioral treatments to reduce alcohol use. Some researchers propose that esketamine facilitates greater psychological engagement with treatment in terms of motivation, commitment, and belief in the treatment process.

Gent et al. [Journal of Psychopharmacology] tested whether combining esketamine with a mindfulness training enhances treatment psychological engagement among individuals with alcohol use disorder.

The researchers randomly assigned 28 British adults (mean age = 22 years; 57% male; 93% white) with moderate to severe alcohol use disorder to a mindfulness training combined with either a single dose of esketamine or a vitamin C placebo administered on the eighth day of the intervention phase.

Participants attended the study center on day one for a baseline assessment. They were shown three brief videos introducing mindfulness and outlining its benefits for relapse prevention. They were also given a set of 14 daily mindfulness exercises, each lasting 5 to 25 minutes, to complete on their own over the following 14 days. 

They returned to the study center on the eighth day of the study for a single dose of either esketamine or placebo. After dosing, participants wore an eye mask and listened to soothing music for 40 minutes. Following this, they completed a post-intervention assessment. Participants also completed a final online assessment on day 14.

The mindfulness exercises emphasized relaxation and accepting thoughts and sensations. Two of the exercises specifically addressed managing alcohol cravings through mindfulness. Assessments measured the primary outcomes of engagement with treatment and alcohol cravings and use. 

The results showed a significant difference in treatment psychological engagement between esketamine and placebo groups. Engagement scores did not differ by groups during day 1-7, but after drug administration, self-reported engagement increased and remained higher for the esketamine group but not the placebo group.

There was also a significant but transient post-drug decrease in alcohol cravings on day 8 for the esketamine group, but not the placebo group. The esketamine group showed significantly more dissociative and mystical experiences after drug administration than placebo. Both groups decreased alcohol use, without a significant difference between. The groups did not differ in terms of self-reports of how many days or how many times a day they performed the mindfulness exercises.

The study shows a single dose of esketamine increased psychological engagement with a daily brief   mindfulness training and transiently reduced alcohol cravings. However, it did not improve alcohol-related outcomes at the study’s 2-week endpoint.

The study’s limitations include its small sample size, the limited number of data points for assessing daily alcohol cravings, and the brevity of the mindfulness training. 

Reference:

Gent, E. M., Bryan, J. W., Cleary, M. A., Clarke, T. I., Holmwood, H. D., Nassereddine, R. O., Salway, C., Depla, S., Statton, S., Krecké, J., & Morgan, C. J. (2024). Esketamine combined with a mindfulness-based intervention for individuals with alcohol problems. Journal of Psychopharmacology, 38(6), 541–550. 

Link to study

Children born very prematurely, defined as under 32 weeks gestational age, are at a greater risk for developing a wide spectrum of disorders including ADHD, autistic spectrum, and anxiety disorders. Functional connectivity is a measure of the degree to which large-scale brain networks synchronize their activity.

From birth through adulthood, children born very prematurely often show atypical functional connectivity patterns, which are associated with problems in cognitive and emotional functioning. Since mindfulness-based interventions (MBIs) can improve executive cognitive function and emotional regulation in some samples, MBIs may benefit children born very prematurely. 

Siffredi et al. [Psychiatry and Clinical Neuroscience] studied the effects of a MBI on neurobehavioral and functional connectivity measures in young adolescents born very prematurely, comparing them to an independent cohort of adolescents born full term.

The researchers enrolled 63 young Swiss adolescents (average age=12 years; 56% female) born very prematurely in an 8-week mindfulness program modeled after Mindfulness-Based Stress Reduction (MBSR) but modified for younger adolescents. Weekly in-person group MBI sessions were 90 minutes long, and meditations were brief (2-10 minutes) and guided by trained mindfulness teachers. 

Participants completed neurobehavioral assessments before and after intervention, and 39 of the participants also underwent functional magnetic resonance imaging (fMRI) before and after the intervention. A comparison group of 24 young adolescents born full term (average age=12 years; 38% female) also underwent neurobehavioral assessments and fMRI scanning but did not participate in the MBI.

Neurobehavioral assessments included self-rated and parent-rated questionnaires and computerized tasks measuring executive and socio-emotional functioning. fMRIs assessed resting-state dynamic brain functional connectivity: the ways in which correlations and anticorrelations between large-scale brain networks changed over time.

The results found the prematurely born cohort had significantly greater scores for executive and behavioral difficulties on parent-report questionnaires than full-term adolescents at baseline. Parents in the MBI group reported significantly improved executive function, metacognition, and behavioral regulation scores over time. Score improvements were correlated with longer activations in the frontolimbic and amygdala-hippocampus self-regulation networks, dorsolateral prefrontal attentional control network, and visual networks related to attention to relevant stimuli.

There was no evidence that score improvements were associated with functional connectivity changes between large-scale brain systems.

This study reports that a MBI reduces parental ratings of behavioral problems in adolescents who were born very prematurely. These improvements in parental ratings are correlated with longer activation times in brain networks associated with attentional control and emotional regulation.

The study is limited by the absence of a comparator group that also underwent a MBI. All significant between-group differences and MBI-associated changes were at the level of self- and parent-report, and not on objective neuropsychological measures. Thus, some or all the improvement in parental-ratings may be due to expectancy bias.

Reference:

Siffredi, V., Liverani, M. C., Fernandez, N., Freitas, L. G. A., Borradori Tolsa, C., Van De Ville, D., Hüppi, P. S., & Ha-Vinh Leuchter, R. (2024). Impact of a mindfulness-based intervention on neurobehavioral functioning and its association with large-scale brain networks in preterm young adolescents. Psychiatry and Clinical Neurosciences.

Link to study

Patients discharged from intensive care units (ICUs) often report persistent psychological distress. This distress can result from a combination of factors: life-threatening illness, medical procedures, the financial burden of illness and treatment, and adjustment to residual disabilities and role changes. A previous pilot study showed that post-discharge use of a mindfulness meditation mobile app could reduce average levels of psychological distress in some participants.

Cox et al. [JAMA Internal Medicine]  investigated ways to optimize their previously piloted mindfulness app by varying the number of app-based meditations and phone contact with a human therapist.

Participants were 247 ICU patients (average age=50 years; 58% male; 73% white; average ICU stay length=7 days) with moderate or higher levels of psychological distress at discharge. All participants were discharged home with free access to a mindfulness meditation smartphone app. The app offered a month-long training program containing four week-long themes. The themes covered awareness of the breath, body, thoughts and emotions, and activities of daily living, as well as cultivating kindness and compassion. 

Participants were randomly assigned to one of eight meditation groups that comprised combinations of: 1) whether the themed units were introduced by an app video or a live therapist phone call; 2) whether reported increases in symptoms were responded to by the app or a live therapist phone call; 3) whether participants engaged in an 8-to-10-minute audio-guided meditation once or twice a day. 

Psychological symptoms were assessed at baseline and at 1- and 3-months post-randomization. The primary outcome was self-reported depressive symptoms, and self-reported anxiety and PTSD symptoms were secondary outcomes. The statistical test was not a between-groups analysis but rather assessed the degree to which each of the variables—meditation frequency, live therapist vs. app introductions, and live therapist vs. app response to symptoms—affected outcomes across groups.

The sample viewed on average 71% of the total app content, 89% of the sample were still actively viewing content by the fourth week, and 74% of the sample completed the 3-month follow-up assessment. All groups showed clinically meaningful improvement in depression and PTSD symptoms at 1- and 3-month follow-up.

The group meditating twice daily showed significantly more improved depression scores (from 10.4 to 5.6 points) than the group meditating once daily (from 10.4 to 7.0 points). Retention and outcomes weren’t improved in groups having live therapists introduce themes or respond to symptoms increases by telephone. 

The study shows discharged ICU patients with elevated distress using a mindfulness smartphone app report decreased distress scores over time, that meditating twice daily is associated with reducing such symptoms more than meditating once daily, and that talking by phone with live therapists neither improves study retention nor distress outcomes.

The study is limited by its lack of a non-mindfulness app comparator and low rate of ICU patients agreeing to participate (47%). Further, the number of patients reporting increased distress symptoms was too low (8%) to effectively test the value of having a therapist respond to symptoms.

Reference:

Cox, C. E., Gallis, J. A., Olsen, M. K., Porter, L. S., Gremore, T., Greeson, J. M., Morris, C., Moss, M., & Hough, C. L. (2024). Mobile Mindfulness Intervention for Psychological Distress Among Intensive Care Unit Survivors: A Randomized Clinical Trial. JAMA Internal Medicine. 

Link to study