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GME Research Review

GME Research Review is a monthly newsletter edited by Rajnish Mago, MD, Associate Professor of Psychiatry at Thomas Jefferson University, author of The Latest Antidepressants and Side Effects of Psychiatric Medications: Prevention, Assessment, and Management. Dr. Mago  selects, summarizes, and provides a clinical commentary on the latest published research in psychiatry.  


Issue 40, August 2015

Brexpiprazole as adjunctive therapy to antidepressants for the treatment of major depressive disorder

Thase et al. Efficacy and safety of adjunctive brexpiprazole (OPC-34712) in major depressive disorder: results of two pivotal clinical studies. Poster presented at the 53rd annual meeting of the American College of Neuropsychopharmacology (ACNP). December, 2014. Phoenix, AZ.


Why is this study important?


  • In July 2015, brexpiprazole (brand name Rexulti) was approved by the United States Food and Drug Administration.


  • One of the “indications” for which it was approved was “adjunctive therapy to antidepressants for the treatment of major depressive disorder.”


  • But what is the data supporting this indication?


  • FDA approval requires that the efficacy of the drug is supported by at least two separate controlled clinical trials. (There may or may not be other clinical trials that were positive, negative, or failed; doesn’t matter in terms of FDA approval.)


  • Data on the two “pivotal” clinical trials that led to the FDA approval have not been published as of August 1, 2015. However, these data from both the studies were presented together in a poster that is discussed here.





  • Brexpiprazole is a second-generation (“atypical”) antipsychotic that is a partial agonist at 5-HT1a, D2, and D3 receptors and an antagonist at 5-HT2A, 5-HT2B, 5-HT7, alpha-1A, alpha-1B, alpha-1D, and alpha-2C receptors.


  • There are a few differences in pharmacological activity between brexpiprazole and aripiprazole that were hypothesized to potentially offer some advantages in term of tolerability. Of course, these hypotheses would have to be verified in actual clinical trial data:

    1. Brexpiprazole has lower intrinsic activity for partial agonism at D2 receptors. It was hypothesized that this may lead to a lower potential to cause adverse effects that are mediated through agonism of D2 receptors, i.e., akathisia, insomnia, restlessness, and nausea.

    2. Brexpiprazole was also hypothesized to have a lower potential to adverse effects that re mediated through D2 antagonism, i.e., parkinsonism, hyperprolactinemia.

    3. Brexpiprazole has similar potency at D2, 5-HT1A, and 5-HT2A receptors. It was hypothesized that this may also contribute to lower incidences of activation adverse effects and D2 antagonism associated adverse effects.
  • The efficacy, safety, and tolerability of brexpiprazole for adjunctive use in addition to an antidepressant for patients with major depressive disorder were evaluated in two phase III clinical trials.





  • Patients with major depressive disorder who had already had an inadequate response to between one and three standard antidepressants even prior to entering the study were enrolled.


  • In the first part of the study, all patients received another antidepressant for eight weeks. This was done on a single- blind basis. The term “single-blind” means that the researchers knew that the patients were getting an antidepressant and a placebo, but the patients believed that they were getting an antidepressant and brexpiprazole. This is now a pretty standard strategy in clinical trials of augmentation strategies.


  • In the second part of the study, patients who even after these eight with an inadequate response after this prospective phase were randomized to addition of either brexpiprazole or placebo for six weeks.


  • In both studies, the dose of brexpiprazole that each patient received was fixed. In one study, the dose was fixed as 2 mg/day. In the other study, some patients got 1 mg/day and others got 3 mg/day. Please note that the recommended dose of brexpiprazole for adjunctive use in major depressive disorder is 2 mg/day with a maximum of 3 mg/day.


  • It is also important to note that the drug was titrated up to the target dose, which was probably wise and presumably improved its tolerability.


  • The severity of the depression was measured as the total score on the Montgomery- Åsberg Depression Rating Scale (MADRS).





  • Patients in whom either 2 mg/day or 3 mg/day of brexpiprazole was added to the antidepressant showed a statistically significantly greater reduction in severity of depression at the end of treatment (i.e., after six weeks of treatment or earlier if the patient discontinued treatment prematurely).


  • The difference between the 1 mg/day dose of brexpiprazole and placebo was not statistically significant, i.e., it cannot say with statistical confidence that it was not due to chance alone. However, the p values were 0.09 and 0.07 (depending on the criteria used); we sometimes say in such cases that “there was a trend towards statistical significance.”


  • If you have read prior issues of GME Research Review, you know what I am going to do next: ask, what were the percentage of patients who responded in each group and was the difference between the percentage of responders on the drug and on placebo of a magnitude that indicates a clinically useful effect?


  • In the first study, the percentages of responders (i.e., patients who had a 50% or greater reduction in the severity of depression) were 16% on placebo and 23% on brexpiprazole 2 mg/day. In the second study, the percentages were 14% on placebo, 23% on brexpiprazole 1 mg/day, and 23% on brexpiprazole 3 mg/day. In each case, the drug-placebo differences were statistically significant.


  • However, the magnitude of the differences — 8%, 9%, and 9% — are just below the usual minimum of a 10% drug-placebo difference for a clinically useful effect.


  • To give a bit of context, let’s look at the difference in the percentages of responders based on reduction in severity of depression between aripiprazole and placebo when used for the same purpose (albeit in flexible dose studies). This difference was 10% (Berman et al., 2007), 15% (Marcus et al., 2008).


  • In view of this, let’s also look at the differences in the percentages of responders on the Clinical Global Impressions – Improvement scale. This scale is simply the clinician noting overall whether the patient is minimally, much, or very much improved/worse, or whether there is no change (see On this scale, the percentages of responders (either much or very much improved) in one study were 26% on placebo and 43% on brexpiprazole 2 mg/day. In the other study, the percentages of responders were 34% on placebo, 41% on brexpiprazole 1 mg/day (not statistically significantly different from placebo), and 48% on brexpiprazole 3 mg/day. Thus, on the Clinical Global Impressions – Improvement scale, the drug-placebo differences of 17% (brexpiprazole 2 mg/day) and 14% (brexpiprazole 3 mg/day) were clinically substantial.


  • Adverse events that occurred in at least 5% of patients on any dose of brexpiprazole and at least twice as often as on placebo were as follows:

Adverse Event

Antidepressant + Placebo

Antidepressant + Brexpiprazole 1 mg/day

Antidepressant + Brexpiprazole 2 mg/day

Antidepressant + Brexpiprazole 3 mg/day






Weight increase





Significant weight increase*





















* Significant weight increase refers to an increase in weight of 7% or greater of the baseline weight. This is now widely used as a criterion for significant weight gain.


  • For comparison, the rates of akathisia with aripiprazole were 23% versus 5% on placebo (Berman et al., 2007), or 26% versus 4% on placebo (Marcus et al., 2008).


  • Other adverse events that occurred at least twice as on placebo (on at least one of the doses of brexiprazole) were:

Adverse Event

Antidepressant + Placebo

Antidepressant + Brexpiprazole 1 mg/day

Antidepressant + Brexpiprazole 2 mg/day

Antidepressant + Brexpiprazole 3 mg/day












  • Based on several different ways of looking at the issue, brexpiprazole was not associated with an increase in serum glucose.


  • A specific questionnaire was used to assess sexual functioning. Brexpiprazole was not found to be associated with sexual dysfunction.


  • The poster provides limited data on changes in serum lipids, vital signs, or electrocardiogram, but no problems in these areas are noted. When the data is published, more details should be become available. 





  • Brexpiprazole is efficacious for the adjunctive treatment of major depressive disorder in patients who have had with an inadequate response to antidepressants alone.



Clinical Commentary


  • These two studies convincingly show that brexpiprazole is more efficacious than placebo for this purpose. Thus, brexpiprazole becomes one more item in our “menu of reasonable options” (a term used by a respected colleague and one that I love) for this purpose.


  • The differences in the percentages of responders on brexiprazole versus placebo as evaluated by MADRS were below 10%, though on the Clinical Global Impressions – Improvement scale they were more substantial. Thus, it should be realized that these two studies do not suggest that the efficacy of brexpiprazole is of a magnitude greater than that of currently available second-generation antipsychotics.


  • Where brexpiprazole may show an advantage is in terms of adverse effects. The drug-placebo difference for the incidence of akathisia for 2 mg/day of brexpiprazole (the recommended dose) is only 5%. In contrast, the incidence of akathisia with aripiprazole was 18% to 24% more than placebo. 


  • Since the dosing strategies in the brexpiprazole and aripiprazole studies were different, future head-to-head studies would be very helpful to further assess differences in tolerability between brexpiprazole and aripiprazole. However, for a variety of reasons, such studies are very difficult to conduct.


  • In the September issue of GME Research Review, I will review the studies of brexpiprazole in schizophrenia.




Is ziprasidone another option for adding to an antidepressant in patients with major depressive disorder?

 Papakostas et al. Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Efficacy Results From a Randomized, Double-Blind, Placebo-Controlled Study. Am J Psychiatry. 2015 Jun 18:appiajp201514101251. [Epub ahead of print] PubMed PMID: 26085041.



Why is this study important?


I think that the readers will agree with the following points:


  • Second-generation (so called “atypical”) antipsychotics have become widely accepted as one of the important options for adding to an antidepressant in patients with major depressive disorder who have not adequately to the antidepressant alone. This is based on multiple clinical trials as well as subsequent extensive clinical experience.


  • However, there are some potential problems associated with use of second-generation antipsychotics for this purpose, including weight gain, increased blood sugar, and increased serum lipids.


  • Some second-generation antipsychotics are known to have lower incidence of such metabolic adverse effects; ziprasidone is one of them.


  • However, perhaps surprisingly, randomized, controlled trials supporting the use of ziprasidone for this purpose have not been published.


  • This is the first randomized, controlled trial of ziprasidone for inadequate response to an antidepressant alone in patients with major depressive disorder.





  • This study aimed to evaluate the efficacy of adjunctive ziprasidone in adults with non-psychotic unipolar major depression.


  • Specifically, this was for patients with persistent symptoms after eight weeks of open-label treatment with escitalopram alone.





  • Randomized, double-blind, placebo-controlled trial conducted at three academic medical centers.


  • The main (randomized, double-blind) part of the study included 139 outpatients with persistent symptoms of major depression after an eight-week open-label trial of escitalopram.


  • It is important to note the study excluded patients who had failed to benefit after more than three antidepressant trials of adequate dose and duration during the current major depressive episode. That is, patients who had higher degrees of inadequate response to treatment with antidepressants were excluded. The findings of this study should not be generalized to those patients.


  • Escitalopram dose allowed was 10 to 30 mg/day as needed and/or tolerated. The mean dose actually received was about 20 mg/day.


  • “Persistent symptoms” was defined as at least moderate severity of depression on the patient-rated scale that was used (Quick Inventory of Depressive Symptomatology – Self Report or QIDS-SR).


  • The patients were randomized to addition of either ziprasidone (i.e., escitalopram plus ziprasidone) or placebo (i.e., escitalopram plus placebo) for eight weeks.


  • The ziprasidone dose was 20 to 80 mg twice daily, i.e., 40 to 160 mg/day.


  • The Hamilton Depression Rating Scale was the primary measure of severity of the depression.





  • After eight weeks of treatment with escitalopram only 3% of patients responded, i.e., had a 50% or greater reduction in the severity of depression.


  • There was a statistically significantly greater reduction in the severity of depression in patients in whom ziprasidone had been added to the escitalopram than in those in whom placebo had been added.


  • As discussed in previous issues of GME Research Review, we should then immediately ask, “What percentages of patients improved?” This is because even small differences can be “statistically significant.”


  • In this clinical trial, the percentage of responders (i.e., those with 50% or greater reduction in the severity of depression as measured by the Hamilton Depression Rating Scale total score) was 35% with addition of ziprasidone vs. 21% with addition of placebo.


  • Rule of thumb: a 10% drug-placebo difference is the usual minimum for being a clinically useful difference; a 20% drug-placebo difference indicates a more clearly clinically useful effect.


  • The percentage of responders when defined by an alternative method — 50% or greater reduction in the severity of depression as measured by the QIDS-SR total score — was 31% with addition of ziprasidone versu 13% with addition of placebo. An 18% difference that is substantial.


  • It is interesting to note that the percentage of patients who showed a 50% or greater reduction in the total score on the Hamilton Anxiety Rating Scale (which actually measures both anxiety and depression symptoms) was 35% with addition of ziprasidone and 10% with addition of placebo — a 25% difference! There may be an association between this finding and the finding that, somewhat to the surprise of the authors, high rates of somnolence/fatigue were found in this study. It should be noted that ziprasidone does have moderate affinity for the histamine-1 receptors. Blocking of histamine-1 receptors is known to be associated with sedation.


  • For adverse events, I will follow my favored approach: let’s look first at adverse events that occurred in at least 5% of patients on the drug and at least twice as often as on placebo. These were:

    Somnolence/fatigue (34% vs. 12%)

    Akathisia (15% vs. 7%)

    Irritability (10% vs. 1%)

    Poor concentration/memory (8% vs. 1%)

    Anxiety/agitation (6% vs. 0%)

    Muscle twitching (11% vs. 1%), and

    Gastrointestinal upset (11% vs. 4%).


  • Important: A lot of patients stopped taking the ziprasidone — nearly one-third. In 14%, the reason was specifically known to be adverse events. However, the percentage of patients in whom adverse events were part of the explanation for stopping the drug was presumably higher.


  • The adverse events that led to stopping the ziprasidone were not surprising: anxiety and agitation/akathisia, sedation, insomnia, and, in one patient, QTc interval of > 500 ms.  





  • Addition of ziprasidone to escitalopram was efficacious for reducing severity of depression in patients with major depressive disorder who had persistent symptoms after eight weeks of treatment with escitalopram.



Clinical Commentary


  • Ziprasidone can also be considered as one of the medications that may be added to a selective serotonin reuptake inhibitor (SSRI) after inadequate response to the SSRI alone.


  • However, potential adverse effects of ziprasidone remain a significant problem. Is it possible that slower titration, lower doses, or other strategies may improve tolerability of ziprasidone? If so, its clinical utility would be enhanced.




Which patients with social anxiety disorder are most likely to benefit from medication?

Cohen et al. Clinical presentation and pharmacotherapy response in social anxiety disorder: The effect of etiological beliefs. Psychiatry Res. 2015 Jul 30;228(1):65-71. PubMed PMID: 25920804.



Why is this study important?


  • It is a huge and pervasive problem in mental health, that we have limited ability to predict which patients may do better with which treatment, i.e., personalized medicine.


  • This is true for Social Anxiety Disorder as well. There has been very little research into predictors of response to medication treatment for social anxiety disorder.





  • This study looked at the relationship between what patients said their social anxiety was due to and a) clinical features of the social anxiety, and b) response to medication.





  • 137 patients with social anxiety disorder were recruited.


  • Patients’ views on the etiology of the social anxiety were assessed using a questionnaire created specifically for this study.


  • All patients were treated with open-label paroxetine for 12 weeks. Paroxetine was started at 10 mg/day and increased as needed or tolerated within the range of 20 to 60 mg/day.


  • Patients were encouraged to expose themselves to the feared situations. They were told that the role of paroxetine was to make such exposure easier.





  • Through statistical analysis, four categories of patients’ beliefs about the etiology of their social anxiety disorder were identified. These were:

1) Familial Factors
2) Need to be Liked
3) Bad Social Experiences
4) Diffuse Beliefs.


  • Patients in these four classes of etiological beliefs were not identified as differing on age, gender, race, ethnicity, employment status, marital status, or religion.


  • At baseline, the most severe social anxiety (and rating of depression) was found in patients who were in one of the more psychosocially-driven groups of beliefs about etiology, i.e., either the Need to be Liked group or the Bad Social Experiences group of beliefs.


  • Patients in the Familial Factors class (i.e., those who attributed their social anxiety disorder to genetic, biological, and early life experiences) had greater improvement with paroxetine at 4 weeks.


  • However, there was no statistically significant difference between patients in the four groups of beliefs with regard to outcome at eight or twelve weeks.





  • Patients’ beliefs that the social anxiety disorder was due to Familial Factors (genetics, biology, and early life experiences) predicted better response to medication in the first few weeks.


  • These findings could contribute to some extent to selection of treatment in particular patients.



Clinical Commentary


  • In personal communication, the corresponding author told me that, “To me, the primary message is that people differ in the reasons for their responsiveness to treatments and some of these reasons may be rooted in their personal beliefs.  It may be important to assess patients’ beliefs and try to understand whether they might influence response, maybe through patients’ degree of compliance with medical regimen or through their willingness to experiment with new behaviors with the aid of medication.”


  • I agree 100%. In addition, I also think that a way to understand the findings at a deeper level is that patients who think that their social anxiety is due to circumstances beyond their control (i.e., is due to genetics, biology, or early life experiences) expect to do better with medication than those who attribute their social anxiety to other factors. Presumably that is the reason that they seem to do better, at least initially, on medication than patients with other sets of beliefs about the etiology of their social anxiety.


  • However, placebo effects tend to diminish after the first few weeks. It is possible that this may be why there was no statistically significant difference between the groups at eight or twelve weeks.


  • I hypothesize that these patients who attributed their social anxiety to Familial Factors would, in general, not do as well if psychotherapy alone is recommended.


  • Is it possible that a good approach would be to start this subgroup of patients on medication initially with the focus gradually shifting to psychotherapy later?





What’s another non-medication option for insomnia that is better than sleep hygiene training?

Black et al. Mindfulness meditation and improvement in sleep quality and daytime impairment among older adults with sleep disturbances: a randomized clinical trial. JAMA Intern Med. 2015. Apr;175(4):494-501. PubMed PMID: 25686304.



Why is this study important?


  • Sleep disturbances are quite common in older adults.


  • These sleep disturbances often go untreated.


  • There are many concerns about using hypnotics in older adults, especially long term.


  • There is a need for relatively simple, non-medication strategies that can be used widely. 





  • This study assessed the potential efficacy of mindfulness meditation for improving sleep quality in older adults with moderate sleep disturbances.





  • This was a randomized, controlled clinical trial conducted at a medical research center.


  • Subjects included in the study were 49 older adults (mean age 66 years).


  • The subjects had moderate sleep disturbances defined as a Pittsburgh Sleep Quality Index score of greater than five.


  • Subjects were randomized to receive either:

    1. A standardized mindful awareness practices (MAPs) intervention, or

    2. A highly structured sleep hygiene education (SHE) intervention (Control group).


  • Both interventions were delivered by sessions lasting two hours per week for six weeks. In addition, “homework” was assigned.


  • An excellent thing about the methodology of this study was that the two interventions were designed in such a manner that they were equivalent for time spent, attention received by the subjects, degree of group interaction, and subjects’ expectancy of benefit.


  • A certified teacher with more than 20 years of mindfulness practice delivered the mindfulness intervention. The sleep hygiene education was delivered by a trained health educator who held an MPH degree in health education. We are not told in the paper how skilled and experienced the health educator was in treating persons with sleep difficulties.





  • On the Pittsburgh Sleep Quality Index, subjects who received the mindfulness awareness practices intervention showed statistically significantly greater improvement than those who received the sleep hygiene education intervention.


  • Subjects who received the mindfulness awareness practices intervention also showed statistically significantly greater improvement compared to the sleep hygiene education group on secondary outcomes: insomnia symptoms, depression symptoms, fatigue severity, and fatigue interference in functioning.


  • The two groups did not show statistically significant differences in terms of reduction of anxiety, stress, or inflammatory signaling via nuclear factor (NF-κB, which decreased equally in both groups).





  • In older adults with moderate sleep difficulties, mindfulness awareness practice improved sleep quality more than sleep hygiene education did.


  • These improvements also translated into reduction in fatigue, effect of fatigue on functioning, and in depression symptoms.



Clinical Commentary


  • I am definitely in favor of using non-medication treatments for sleep difficulties of mild, moderate, or severe intensity.


  • However, we do need more guidance as to which interventions or combination of interventions is most suitable for which patients.


  • Mindfulness should be added to our list of options for the treatment of sleep difficulties, at least for mild or moderate problems of longer duration.


  • Next, I will discuss another recent study of the use of mindfulness — this time for more significant and chronic insomnia.




Can we use mindfulness meditation as a treatment for chronic insomnia?


Ong et al. A randomized controlled trial of mindfulness meditation for chronic insomnia. Sleep. 2014 Sep 1;37(9):1553-63. PubMed PMID: 25142566.



Why is this study important?


  • Chronic insomnia is a common problem and hard to treat, especially without also causing significant adverse effects.


  • Each year, 45% of adults with insomnia symptoms use a complimentary and alternative medicine approach to treat these symptoms.


  • In recent years, there has been growing interest in mindfulness meditation as a treatment for several different conditions.


  • If found to be efficacious, for patients willing to practice it this could be a valuable, long-term treatment without known significant adverse effects.





  • The study aimed to evaluate the efficacy of Mindfulness-Based Therapy for Insomnia (MBTI), a modification of Mindfulness-Based Stress Reduction specifically for the treatment of chronic insomnia.





  • This was a randomized controlled trial done in 54 adults with chronic insomnia.


  • Patients were randomized to receive one of the following three interventions for eight weeks:

    1. Mindfulness-Based Therapy for Insomnia (MBTI)

    2. Mindfulness-Based Stress Reduction (MBSR)

    3. Self-Monitoring (SM) — as a Control group.


  • Mindfulness-Based Therapy for Insomnia (MBTI) is a meditation-based program being developed by the authors. In addition to meditation techniques, it also incorporates behavioral techniques for insomnia. It aims to improve sleep by reducing the hyperarousal that develops in patients with chronic insomnia.


  • Both the Mindfulness-Based Therapy for Insomnia (MBTI) and the Mindfulness-Based Stress Reduction (MBSR) consisted of eight group meetings held once a week with each meeting lasting for 2.5 hours. In addition, one six-hour meditation retreat was held later in the course of both of the interventions.


  • So, what was the difference between the two interventions? The difference was in what was provided in addition to the meditation practice. In Mindfulness-Based Stress Reduction (MBSR), there was general discussion about at-home meditation practice and education on the daily applications of meditation. In Mindfulness-Based Therapy for Insomnia (MBTI), instead of didactics on general health and education on meditation and stress, specific behavioral strategies for insomnia (sleep restriction therapy, stimulus control, and sleep hygiene) were provided within the context of mindfulness principles.


  • The self-monitoring group used daily sleep/wake diaries and completed the pre-sleep arousal scale (PSAS) once a week. Subjects were provided behavior therapy later, but only after the eight-week period of this study was over. During the period of this study, they were told that the diary data completed during the self-monitoring period would be used to help in planning the behavior therapy that would be provided later. The self-monitoring was managed by the research staff and there was no structured contact with participants. Thus, you can see this self-monitoring intervention was a control group that had a low chance of improving due to non-specific factors. I am not happy about that.





  • Both patient-reported and “objective” outcome measures were used. Objective sleep measures were derived from laboratory polysomnography and wrist actigraphy.


  • On several measures, those receiving either one of the meditation-based interventions (MBSR or MBTI) had statistically significantly greater improvement compared to the control group (self-monitoring). These measures included total wake time based on sleep diaries (an average reduction of 44 vs. 1 minutes), the pre-sleep arousal scale, and the Insomnia Severity Index.


  • What about the two meditation-based interventions (MBSR or MBTI) compared with each other? In several ways, there were no statistically significant differences between the two groups:

    1. In the short run (over eight weeks), there was no statistically significant difference between the two groups.

    2. At six month follow up, 42% of subjects who received Mindfulness-Based Stress Reduction were in remission from the insomnia (i.e., had minimal insomnia symptoms left). For Mindfulness-Based Therapy for Insomnia, it was 50%. The difference between the two groups was not statistically significant.


  • In some other ways, subjects who received Mindfulness-Based Therapy for Insomnia fared better than those who received Mindfulness-Based Stress Reduction:

    1. At six-month follow-up, patients who received Mindfulness-Based Therapy for Insomnia had greater reductions in Insomnia Severity Index scores than those who received Mindfulness-Based Stress Reduction.

    2. At six-month follow up, there was a “response” (some important improvement) in 79% of subjects who received Mindfulness-Based Therapy for Insomnia versus in 42% of subjects who received Mindfulness-Based Stress Reduction. However, this difference was not statistically significant, i.e., may have occurred simply due to chance.





  • Mindfulness meditation appears to be another efficacious treatment option for adults with chronic insomnia



Clinical Commentary


  • Overall, the data suggest both meditation-based interventions produced improvement in the insomnia. In addition, there may be some advantage of Mindfulness-Based Therapy for Insomnia over Mindfulness-Based Stress Reduction.


  • If confirmed in the future, this would make sense intuitively — that combining a meditation approach with behavioral interventions might be more efficacious than meditation alone.


  • Clinicians will definitely need training, though, in how to deliver mindfulness-based interventions for insomnia.



Did you find these research summaries clear and easy to understand? Did you find them clinically useful? Your feedback is very important! Please send me your thoughts at [email protected].


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