Leah Kuntz

Akili announced new data on its therapeutic EndeavorRx, an FDA-cleared digital treatment for children diagnosed with attention-deficit/hyperactivity disorder (ADHD). The data, which highlights real-world improvements and benefits, includes results from the STARS-Adjunct trial, a multi-site open-label study created to examine the impact of EndeavorRx on impairments in daily life scenarios for children with ADHD. The initial presentation of data occurred this week at the American Academy of Child and Adolescent Psychiatry (AACAP) 2020 Virtual Annual Meeting.

“The STARS-Adjunct study provides further evidence for physicians on the use of EndeavorRx in clinical practice, including duration of treatment and use alongside traditional ADHD medications,” said Anil Jina, MD, chief medical officer of Akili, to press. “Building on the improvements in objective measures of attention demonstrated in our prior clinical studies of EndeavorRx, these data help show the benefits of treatment seen by parents assessing their child’s ADHD-related impairments in everyday life.”

The study included 206 pediatric participants aged 8-14 years with a diagnosis of ADHD, across 2 cohorts: children who were taking ADHD stimulant medications and children who were not taking ADHD medications for the duration of the study. Children completed 1 month of treatment with EndeavorRx, followed by a 1 month pause and then another 1-month treatment with EndeavoRx.

Administered as a video game experience, EndeavorRx is shown to improve attention function as ascertained by computer-based testing in children aged 8-12 with primarily inattentive or combined-type ADHD. It is not intended to be used as a sole treatment and is not an adequate replacement for a child’s medication.

Several key results about EndeavorRx were revealed in the presentations. First, both children taking stimulants and those not taking any ADHD medication demonstrated similar and statistically significant improvements on the ADHD Impairment Rating Scale (IRS) compared to baseline.

Second, observations from parents showed half of children responded to the treatment following 1 month of usage. Improvements remained stable for 1 month following treatment.

Third, 34.5% of children no longer showed attention impairment on at least 1 aspect of objective attention post-treatment.

Lastly, early evidence suggests children who improved in attention functioning following treatment also improved their math and reading skills, as demonstrated by their performance on the Test of Silent Reading Efficiency and Comprehension (TOSREC) and the Mathematics Fluency and Calculation Tests (MFaCTS).

1. Researchers Present New Outcome Data for Akili Digital Therapeutic EndeavorRx™ in Pediatric ADHD. News release. 

https://www.businesswire.com/news/home/20201021005068/en/Researchers-Present-New-Outcome-Data-for-Akili-Digital-Therapeutic-EndeavorRx™-in-Pediatric-A DHD

Articles

Akili announces new data on treatment EndeavorRx that reports real-world improvement for children with ADHD. 

New Data Supports Use of Digital Treatment for ADHD 

Carlos M. Grilo, PhD, in his talk at the Annual Psychiatric Times® World CME Conference™, discussed the latest updates in diagnosing, understanding, and treatment options for patients with binge-eating disorder (BED).

“My biggest take home,” Grilo said, “is to avoid stigmatizing. Ask what language your patient would like used when discussing their weight.”

BED is a DSM-5 eating disorder, characterized by the consumption of large amounts of food while experiencing a loss of control. To classify as binge eating disorder, at least 3 of the 5 behavioral indicators must be met: 1) the patient must eat rapidly; 2) the patient must eat large amounts of food even when not hungry; 3) the patient must eat to the point of discomfort; 4) the patient will eat alone due to embarrassment; and 5) the patient will feel disgusted, depressed, or guilty about their eating.

Studies of adults with BED reveal that patients have both elevated psychiatric and medical comorbidity. The most common psychiatric comorbidities include mood disorders, anxiety, and substance use disorders. Medical comorbidities include obesity, chronic pain conditions, and cardiometabolic problems, like diabetes or hypertension.

When discussing pharmacotherapy treatment options for BED, Grilo noted that there is only 1 FDA-approved medication: lisdexamfetamine. Lisdexamfetamine is used for moderate to severe BED, taken once daily in the morning. Patients must be monitored carefully, as it has a black box warning that notes its high potential for abuse. 

Pharmacotherapy for treating BED is an emerging research topic. While several small clinical trials have found medications superior to placebos for reducing binge-eating, those studies only gauged the short-term, limited effects. Next to no data exists regarding long term effects.

A larger variety of psychological and behavioral treatments exist to treat BED. Specific focal psychological treatments, like cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT), are well-established, significantly reduce binge eating, and have approximately 50% remission rates. Behavioral weight loss (BWL), a generalist treatment, achieves comparable binge-eating reductions and produces some weight loss.

Grilo concluded his talk with a number of suggestions. First and foremost, be prepared to recognize BED. Once you have assessed the psychiatric and medical comorbidities, consider pharmacological, psychological, and combined therapy options. Let your patient know that treatments exist that may help, often quickly. Discuss options and alternatives, and above all, avoid stigmatizing.

The Annual Psychiatric Times® World CME Conference™ was held October 15 – 17. More information can be found 

. Next year’s conference is scheduled for September 30 – October 2, 2021, in San Diego.

Carlos M. Grilo, PhD, explained symptoms, causes, and treatment for binge-eating disorder in his talk at The Annual Psychiatric Times® World CME Conference™. 

Remove the Stigma Around Binge Eating Disorder 

David N. Osser, MD, in his talk at the Annual Psychiatric Times® World CME Conference™, gave 10 examples of evidence from the Psychopharmacology Algorithm Project at the Harvard South Shore Psychiatry Residency Training Program that might change how you practice.

“We’re offering you realistic, evidence-based medicine,” Osser said.

The published and peer-reviewed algorithms, available 

, help practitioners determine treatments with the best efficacy, tolerability, and cost. They intend to lighten the load for clinicians who cannot keep up with the volume of new research by providing decision-making tools that are practical for everyday usage.

1. Selection of first antidepressant for major depression

If the patient has not had an adequate trial of sertraline, escitalopram, or bupropion, the algorithm suggests two selective serotonin reuptake inhibitors as the first line of treatment for depression. Meta-analyses indicate that sertraline and escitalopram are among the most effective, best tolerated, and least costly. Bupropion should be considered if the patient wishes to avoid the risk of sexual side effects.

Serotonin and norepinephrine reuptake inhibitors, mirtazapine, vortioxetine, and tricyclic antidepressants are not recommended as first line treatment due to various side effects, health risks, or cost.

2. Selection of a second treatment for major depression

If the patient has no response after an adequate trial with any of the agents previously suggested, it is time to switch or augment. No evidence suggests preferring either switching or augmenting; it is mostly the patient’s choice.

3. Duloxetine as an alternative to an SSRI and a first line treatment for general anxiety disorder (GAD)

Duloxetine may be a good first choice when treating GAD because its efficacy is similar to that of an SSRI, it has lower rates of sexual side effects, and its US Food and Drug Administration- -approved. Concerns with duloxetine are infrequent urinary retention, perspiration, and risky for those with liver abnormalities. 

Hydroxyzine as an alternative to an SSRI and a first line treatment for GAD

Hydroxyzine, an antihistamine with 5-HT2 receptor blocking effects, has low abuse potential, sedating properties, and a lack of sexual side effects. However, clinicians are skeptical of it because it has no known benefit for comorbid disorders like depression or other anxiety disorders.

5. Pregabalin as an alternative to an SSRI and a first line treatment for GAD

Approved for GAD in Europe, pregabalin was found to be comparably effective to other medications for both somatic and psychic symptoms of GAD; however, it was not approved by the FDA for an undisclosed reason. It has a rapid onset, helps with sleep, but may have dangerous side-effects for the elderly, such as somnolence, dizziness, and increased risk for fractures via fall.

6. Bupropion as an alternative to an SSRI and a first line treatment for GAD

While bupropion is not usually considered for treating anxiety, a double-blind controlled trial with 24 outpatients aged 18-64 years with DSM-IV GAD found endpoint scores favored bupropion over escitalopram.

Benzodiazepine should not be a first line option

Despite the advantages of benzodiazepine, the side effects (eg, sedation, memory impairment, and psychomotor dysfunction like falls and car accidents) are dissuading. Additionally, up to 40% of patients develop tolerance or dependence. It could be fatal when combined with opiates and should not be used in patients with substance use disorders.

8. For nightmares or disturbed awakenings in patients with posttraumatic stress disorder try prazosin

Prazosin is a non-sedating alpha-1 antagonist that crosses the blood-brain barrier. It has 5 out of 8 positive placebo-controlled studies, whereas sertraline has 4 randomized controlled negative placebo-controlled trials in Veterans and no positive trials. 

The algorithm notes a regimen of dosage that best works for men, and a separate, lower dose regimen for women based on a 2013 study by Raskind and colleagues.

10. The pharmacotherapy of obsessive-compulsive disorder (OCD)

Meta-analysis of the dose-response relationship shows only a 9% or 7% greater decline in OCD symptoms for those on a high dose SSRI compared to a low- or medium-dose SSRI treatment. 

So, a good trial on a low dose should occur first.

The above list is only a demonstration of how the algorithms might assist a clinician’s decision-making process. Osser hopes these algorithms can help avoid ineffective, inefficient, or harmful medical practices. 

. Next year’s conference is scheduled for September 30 

Can algorithms improve how you practice? Dr Osser explained more in his speech at the Annual Psychiatric Times® World CME Conference™.

Algorithms for Improved Practice

Scientific research has—and is—exploring psychedelic substances as medical treatment. Shannon Carlin, MA, AMFT, discussed the role of psychedelic substances in treating mental conditions and what clinicals trials are currently underway in her presentation at the Annual Psychiatric Times® World CME Conference™.

The Multidisciplinary Association for Psychedelic Studies (MAPS), founded in 2014, is a nonprofit that sponsors MDMA-assisted psychotherapy clinical trials. Carlin, an employee of the MAPS Public Benefit Corporation (MAPS PBC), explained how psychedelic drug development could benefit patients with posttraumatic stress disorder.

Carlin shared the effects MDMA had on mice: it promoted fear extinction, potentially allowed for some memory reconsolidation, and made the mice’s brains respond more like their adolescent brains, with greater rewards for socialization.

In human brains, she explained that MDMA reduced cerebral blood to the amygdala and hippocampus, decreased resting state connectivity between the medial prefrontal cortex and hippocampus, decreased activity in the insular cortex, and increased cerebral blood flow in the ventromedial prefrontal cortex. What does this mean? A total of 3 MDMA therapy sessions, followed by talk therapy integration sessions, both 90 minutes each, may assist patients with PTSD in overcoming their fear response, or fight-or-flight instincts.

In MAPS’s current therapy sessions, 2 clinicians work as co-therapists at every session, as the co-therapy model is designed to ensure consistent and through psychological care, although Carlin stated she was curious as to what might happen in a one-on-one session with a therapist. Further research might explore the safety and efficacy of 1 clinician rather than 2.

Carlin suggested she was hopeful that novel treatments of psychedelic therapies could bring new cures for mood and anxiety disorders.

The Annual Psychiatric Times® World CME Conference™ is being held October 15 – 17. More information can be found 

. Next year’s conference is scheduled for September 30 - October 2, 2021 in San Diego. 

New research is being conducted on how psychedelic substances may change the future of mental health care. Dr Carlin explained more in her speech at the Annual Psychiatric Times® World CME Conference™.

The New Frontier: Psychedelics as Treatment 

“Just because it’s natural, doesn’t mean there aren’t side effects,” said David A. Gorelick, MD, PhD, DLFAPA, at the Annual Psychiatric Times® World CME Conference™ in his presentation on the clinical, legal, and ethical issues surrounding cannabis.

Cannabis, the third most widely used psychoactive drug, is a hot button issue in the United States. As Gorelick noted, the country is divided on state and federal levels about the legality of cannabis and all cannabis-related products. Federally, cannabis is illegal, classified as a Schedule I drug by the Controlled Substances Act (CSA). Several states, however, have expanded and adopted laws for the legalization of cannabis, with 33 approved for legal medical cannabis use. The 2018 Farm Act legally approved hemp, or the Cannabis sativa where the delta-9 tetrahydrocannabinol concentration (or THCs) is below 0.3%. 

Very few other cannabis-derived products have been approved, he explained. Those that have are used to treat childhood seizures, nausea in cancer or chemotherapy patients, and spasticity in multiple sclerosis.

There a few controlled clinical trials on cannabis and cannabis-derived compounds, which are the gold standard for regulatory approval, Gorelick reported. The scattered case studies do not establish efficacy, and therefore cannot prove the safety and effectiveness of these substances for treatment of any disease or condition. Until more observance is done clinically, the likelihood of federal approval of cannabis is low.

Gorelick also spoke on cannabis use disorder. To treat patients with cannabis use disorder, he suggested the use of psychosocial modalities, which have proven efficacy in controlled clinical trials, such as cognitive-behavioral therapy (CBT) and motivational enhancement therapy (MET). He stated that while contingency management was effective when combined with either CBT or MET, it was minimally effective when used as the singular method of treatment.

As to the suggestion of whether or not oral CBD can effectively treat social anxiety disorder, Gorelick warned against listening to rumors. There are no clinical trials or evidence to suggest its effectiveness, but if the patient truly believes it is helpful, he recommended working with them to monitor side effects and efficacy, and to register to obtain legal cannabis-derived products.

Cannabis and cannabis-derived products are widely debated. Dr Gorelick covered the issues surrounding this substance. Read more for highlights. 

Cannabis in Psychiatry: Prominent Issues and Developments 

Sage Therapeutics, Inc. recently released the clinical study results for zuranolone (SAGE-217) for the treatment of depression. The study tested the safety and tolerability of zuranolone 30 mg in patients aged 18 to 75 years with major depressive disorder (MDD). Almost half of all trial participants who positively responded to the initial 14-day course of zuranolone 30 mg did not require additional treatment to maintain wellness through a year of follow up.

“This data from the SHORELINE Study show that medically-oriented, as needed treatment for depression has the potential to be a compelling option for many patients diagnosed with MDD,” Jeff Jonas, MD, chief executive officer at Sage Therapeutics, said to press. “Approximately 70% of patients who participated in the study only needed one or two treatment courses, a total of two to four weeks of treatment with zuranolone 30 mg, which we believe will be the minimally effective dose, if our development efforts are successful.”

Data analyzation indicates zuranolone was well-tolerated in the 30 mg dose, and the reported adverse events were generally consistent with previous clinical trial results. The most common adverse events were somnolence (9.5%), headache (8.7%), and dizziness (5.4%). Those who needed retreated saw similar safety, tolerability, and efficacy results to those seen in the initial treatment course.

Out of the 494 patients continuing in the study, 220 (44.5%) patients received only a single initial zuranolone course. Around 132 patients (26.7%) used a total of 2 courses, while 66 (13.4%) used a total of 3 courses, and 51 (10.3%) used a total of 4 courses. Only 27 (5.5%) used a total of 5 courses.

A sample of patients were retreated with a 50 mg dose of zuranolone. Higher rates and levels of intensity of adverse events were reported, although most were of mild or moderate intensity. A new cohort of patients simultaneously began their treatment with zuranolone 50 mg. In this group, the adverse event profile was similar to that of the 30 mg patients. Events included somnolence, dizziness, sedation, headache, and tremor, but most were mild or moderate. 

Sage plans to release comprehensive data from the 30 mg dose in early 2021.

1. Sage Therapeutics Announces Positive Interim, Topline Zuranolone Safety and Tolerability Data from Open-Label SHORELINE Study in Patients with MDD. Press release. 

https://www.businesswire.com/news/home/20201015005330/en/Sage-Therapeutics-Announces-Positive-Interim-Topline-Zuranolone-Safety-and-Tolerability-Data-from-Open-Label-SHORELINE-Study-in-Patients-with-MDD

Read about the new results from Sage’s clinical study of depression treatment, zuranolone.  

Anticipated Phase 3 Interim Results for Sage’s Depression Treatment, Zuranalone

In a recent study, Pål Kristensen, PhD at the Centre for Crisis Psychology at the University of Bergen in Norway and colleagues examined the parents and siblings of the victims of the 2011 terrorism attacks in Norway as they went through the grieving process.

 They found nearly 80% of the study participants had a high level of grief and experienced a slow recovery, if any recovery at all.

“The terror attack in 2011 was a huge national tragedy that affected all of us deeply. Still,

we needed to learn about the long-term mental health effects and how we could help those who were affected the most—the bereaved,” Kristensen said to the press.

In the aforementioned attack, a far-right Norwegian-born terrorist used a car bomb explosion to kill 8 people in Oslo, then shot and killed 69 people on Utøya Island. Researchers reached out to the family members of these victims; of the 208 contacted, nearly 60% responded.

According to the study, families of terrorist victims are at high risk of developing Prolonged Grief Disorder (PGD). PGD is an ailment marked by an intense longing for the deceased, so consistent and severe that it negatively affects daily life.

Kristensen and colleagues examined participants at 18 months, 28 months, and 40 months after the attacks to gauge their grief levels. From these observations, they determined there were 3 potential trajectories: moderate grief that stabilized after 28 months; intense grief that slowly decreased after 28 to 40 months; extreme grief that persisted, becoming chronic. Of the participants, 13% felt no recovery, and 64% felt a slow recovery.

Other studies that examined grief typically found a track of resilience, where the participants could eventually recover post-tragedy. Kristensen et al. found no such trajectory among his participants. 

Kristensen stated he would like to see more longitudinal, qualitative studies to discover how to best support the needs of the grieving.

“We need to reach out to the terror-bereaved to offer help both early after an attack, but particularly across time when the social support is reduced,” Kristensen said.

Want more clinical tips for managing PTSD and grief in your patients? Join us at the Annual

World CME Conference October 15-17 to hear ideas and the latest clinical updates from Mark B. Hamner, MD. Register online https://www.gotoper.com/conferences/psychtimes/meetings/psychtimes20conference#registration

1. Kristensen P, Dyregrov K, Gjestad R. Different Trajectories of Prolonged Grief in Bereaved family members after Terror. 

. September 14, 2020. Accessed October 7, 2020. 

https://www.frontiersin.org/articles/10.3389/fpsyt.2020.545368/full

2. Recovery from grief is a slow, difficult process for families of victims of terrorist attacks. Frontiers Press Office. News release. October 14, 2020.

Terrorism is a crime from which the families of the victims may never recover. A recent study examines the grieving process in depth. 

Recent Study Examines Grief in Families of Victims of Terrorist Attacks 

Alkermes plc announced Friday, October 9, that the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted favorably for ALKS 3831 (olanzapine/samidorphan). ALKS 3831 is an investigational, oral antipsychotic drug candidate for the treatment of adults with schizophrenia or bipolar I disorder. The committees voted ALKS 3831 significantly diminishes olanzapine-associated weight gain (16 yes, 1 no) and that the safety profile of ALKS 3831 was correctly characterized (13 yes, 3 no, 1 abstention).

“The ALKS 3831 development program is part of our ongoing commitment to develop new therapeutic options for adults living with serious mental illness. Today's outcome marks an important step for this program and we look forward to working with the FDA as it completes its review of the ALKS 3831 New Drug Application,” said Craig Hopkinson, MD, Chief Medical Officers and Executive Vice President of Research & Development at Alkermes, in a release to press.

 He added, “The personal testimonies shared during today's open public hearing reinforced the need for treatment approaches that consider patients’ overall mental and physical health.”

The committees’ decisions will be taken into consideration by the FDA when completing the review of ALKS 3831 New Drug Application (NDA).

The NDA submission and clinical development program for ALKS 3831 are supported by data from 27 clinical studies. Of these 27 studies, 18 evaluated ALKS 3831, and 9 studies evaluated samidorphan alone.

Additionally, the committees voted that labeling is sufficient to mitigate the risks related to the opioid antagonist action of samidorphan (11 yes, 6 no); among the important queries posed for the FDA was the effects and outcomes of ALKS 3831 for patients who used opioids. Notes from reviewers included that ALKS 3831 could lead to withdrawal in patients who are opioid-dependent, could block the opioid pain-relief effects, or even lead to overdose if someone tried to overcome the effects of the antagonist.

Alkermes’ proposed solution to this problem is including a note indicated that it is contraindicated for those patients taking opioids. The FDA has not yet indicated whether this solution has resolved their concerns.

An FDA decision on this drug is due November 15, 2020.

1. FDA Advisory Committee Votes in Support of ALKS 3831 for the Treatment of Schizophrenia and Bipolar I Disorder. News release. Alkermes. October 9, 2020. Accessed October 12, 2020. 

https://investor.alkermes.com/news-releases/news-release-details/fda-advisory-committee-votes-support-alks-3831-treatment

Alkermes plc’s new drug, ALKS 3831, pending FDA approval, could be helpful in the treatment of patients with schizophrenia or bipolar I disorder.

FDA Advisory Committee Votes in Favor of ALKS 3831

Join Us for the Annual Psychiatric Times® World CME Conference™

Slideshows

The Annual Psychiatric Times® World CME Conference™ is going to be packed full of informative, must-see sessions. Check out this preview of the week's agenda. 

Supporting Mental Health Awareness Day 

World Mental Health Awareness Day is October 10. Here are some ideas for you to treat yourself while also supporting mental health. 

Author | Leah Kuntz