Leah Kuntz

 showed that treatment with a blended digital therapy targeting reasoning did not result in reduced self-reported paranoia at 24 weeks. However, it may improve paranoia in general.

SlowMo, a digitally supported reasoning intervention that consists of 8 face-to-face sessions lasting 60-90 minutes, takes an interventionist-causal approach to increasing cognitive behavioral therapy effectiveness by targeting casual reasoning processes in paranoia. The therapy was designed to build awareness of a tendency to jump to conclusions and develop increased belief flexibility.

“SlowMo also uses digital technology and inclusive, human-centered design to improve the user experience with the aim of enhancing engagement and adherence for the widest possible range of people,” wrote Philippa Garety, PhD, et al. “SlowMo builds on the encouraging findings for stand-alone and blended mobile phone apps for psychosis and, to our knowledge, is the first blended digital psychological intervention for paranoia (using digitally supported face-to-face therapy and a mobile app).”

A total of 361 participants with clinical paranoia from UK community health services were included in intention-to-treat analysis. Those with schizophrenia-spectrum psychosis and distressing paranoia lasting 3 months or longer were considered eligible. Of the 361, 332 participants provided primary outcome data, with 181 participants randomly assigned to the SlowMo group. Blind assessments were performed at clinics or in participant’s homes at 0 weeks for baseline, 12 weeks for postintervention, and 24 weeks for follow-up.

The primary outcome was paranoia, measured by the Green et al Paranoid Thoughts Scale (GPTS) total score at 24 weeks. While SlowMo therapy did not result in significant improvements in the primary outcome of total GPTS paranoia score at 24 weeks, secondary beneficial effects were found on this measure at 12 weeks.

“The results indicate that the treatment was effective, in part, through helping people to slow down their thinking and to worry less,” Garety et al concluded.

The study’s authors noted further work to optimize SlowMo’s effects is needed.

1. Garety P, Ward T, Emsley R, et al. Effects of SlowMo, a blended digital therapy targeting reasoning, on paranoia among people with psychosis: A randomized clinical trial. 

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2778159

Articles

While this digital therapy failed to meet its primary endpoint in a recent clinical trial, results suggest it may improve paranoia in general. 

Digital Therapeutics Improves Paranoia

Photos provided by Harold J. Bursztajn, MD

Today on Yom Hashoah, or Holocaust Remembrance Day, the International March of the Living commemorates the 6 million Jews who were killed in the Holocaust. For 2021, they give special thanks to the health care community community in the special online symposium “

Medicine and Morality: Lessons from the Holocaust and COVID-19

.” The event was also supported by the Maimonides Institute for Ethics and the Holocaust, the Miller Center at Rutgers University, the USC Shoah Foundation, and Teva Pharmaceuticals.

“This year, the International March of the Living proudly dedicates the 2021 Virtual March in honor of the very amazing medical community, as together we proclaim, ‘never means never,’” said Phyllis Greenberg Heideman, President of the International March of the Living said at the 

Anthony Fauci, MD, Director of the US National Institute of Allergy and Infectious Diseases and Chief Medical Advisor to the US President, also received special recognition. For his work fighting COVID-19 and dedication to the wellbeing of humankind, Fauci received the Moral Courage in Medicine.

Fauci had this to say during his acceptance: “During this past year, we have witnessed unspeakable suffering caused by a terrible pandemic. However, we have also seen thousands of men and women of great moral courage caring for the sick and the dying with compassion and love, risking their own health. We recognize them as heroes and we all remain in gratitude for their sacrifices. At this time of Holocaust remembrance, we also remember the millions taken by unspeakable evil, whose voices nonetheless speak to us across time. It is important we never forget, not just because evil has not been vanquished, but because virtue and goodness must always remain strong in us.”

In anticipation of the event, psychiatrist Eran Harary, MD, vice president of Global Therapeutic Area Head, Neurology & Psychiatry, Specialty Clinical Development, at Teva shared: “The Nazis and their collaborators worked systematically to exterminate our people, conducting monstrous experiments. We are now a world leader when it comes to science and medicine, developing drugs and bringing improved health to the lives of patients across the world. From a nation that was condemned to death and destruction during the Holocaust, we are a people engaged in preserving life.”

Harold J. Bursztajn, MD, who attended the symposium, associate professor of Psychiatry (part-time) at Harvard Medical School and a clinical forensic psychiatrist in Cambridge, Massachusetts, feels especially strongly about Yom Hashoah.

“This pandemic year we have experienced both our individual health, our collective health, our body public, our democracy, under siege. With COVID-19 virulent, there has been a rise of anti-Semitism, racism, and social injustice. For many Shoah survivors, their families, and those of us who care, the medical community has been the supply line to reason, empowerment, and hope,” Bursztajn told 

Bursztajn has a personal connection to the topic—

“They were members of the Lodz ghetto fekalist (sanitation workers) resistance whose average life span was 6 months. Together with the medical community, they defeated the Typhoid epidemic that threated to destroy the ghetto. Then, in the summer of 1944, they resisted the German efforts to liquidate the ghetto survivors when the Russian advance stalled.”

Bursztajn’s parents can be seen here, within months of liberation in the spring of 1945.

To watch the ceremonies and participate in the virtual march, visit 

1. International Match of the Living. The 2021 International March of the Living Commemoration and Ceremony​. April 8, 2021. 

2. International March of the Living pays tribute to medical resistance and heroes of the Holocaust in symposium dedicated to “Medicine and Morality.” Press release. International March of the Living. April 1, 2021. Accessed April 8, 2021. 

https://www.prnewswire.com/il/news-releases/international-march-of-the-living-pays-tribute-to-medical-resistance-and-heroes-of-the-holocaust-in-symposium-dedicated-to-medicine-and-morality--849381995.html

This year, the March of the Living honors of Holocaust victims and survivors, the medical community, and Dr Anthony Fauci.

Never Means Never: International March of the Living Honors the Medical Community

The US Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Acadia Pharmaceuticals regarding their supplemental New Drug Application (sNDA) for pimavanserin for the treatment of hallucinations and delusions in patients with dementia-related psychosis (DRP). The FDA indicated the application cannot be approved in its current state.

The CRL cited the lack of substantial evidence of effectiveness needed for approval—specifically, lack of statistical significance in some of the subgroups of dementia and insufficient numbers of patients with less common forms of dementia.

“Acadia stands behind the robustly positive results from the pivotal Phase 3 HARMONY study and the prospectively agreed trial design and criteria for establishing efficacy in DRP. Over the entire course of the review, the Division did not raise any concerns regarding the agreed upon study design, including the issues raised in the CRL,” said Steve Davis, Chief Executive Officer of Acadia. “We will immediately request a Type A meeting to work with the FDA to address the CRL and determine an expeditious path forward for the approval of pimavanserin in DRP.”

Type A meetings are considered “immediately necessary for an otherwise stalled drug development program to proceed,” according to the 

Prior agreements with the FDA Division of Psychiatry regarding the pivotal phase 3 HARMONY study design concluded the intent was to target a broad DRP patient population analyzed as a single group. Prespecified requirements did not include statistical separation by dementia subgroups and minimum numbers of patients with specific subtypes.

The CRL also stated that the phase 2 Alzheimer disease psychosis study -019, a supportive study included in the sNDA filing, was inadequate and not well controlled.

 Reasoning for this belief included that it was a single center study, and there was no type I error control of secondary endpoints in which protocol deviations took place. Despite this, Acadia believes there is no impact on the positive results, nor on the study’s overall efficacy.

1. Acadia Pharmaceuticals. Acadia Pharmaceuticals receives Complete Response Letter from US FDA for supplemental New Drug Application for pimavanserin for the treatment of hallucinations and delusions associated with dementia-related psychosis. News release. April 5, 2021. 

https://www.businesswire.com/news/home/20210405005229/en/Acadia-Pharmaceuticals-Receives-Complete-Response-Letter-from-U.S.-FDA-for-Supplemental-New-Drug-Application-for-Pimavanserin-for-the-Treatment-of-Hallucinations-and-Delusions-Associated-with-Dementia-Related-Psychosis

2. US Food and Drug Administration. Type A Meetings. Accessed April 7, 2021. 

https://www.accessdata.fda.gov/cder/sb-navigate/topic3/topic3/da_01_03_0090.htm

3. Park B. FDA rejects pimavanserin sNDA for dementia-related psychosis. 

https://www.empr.com/home/news/drugs-in-the-pipeline/fda-rejects-pimavanserin-snda-for-dementia-related-psychosis/

CRL cites lack of substantial evidence of efficacy needed for approval. 

Dementia-Related Psychosis Treatment Receives Complete Response Letter

The US Food and Drug Administration (FDA) has approved Qelbree, viloxazine extended-release capsules created by Supernus Pharmaceuticals, for the treatment of attention-deficit/hyperactivity disorder (ADHD) in pediatric patients aged 6 to 17.

“Based on the efficacy demonstrated in the clinical program, we believe Qelbree offers a unique new alternative for the treatment of ADHD,” said Jack A. Khattar, President and Chief Executive Officer of Supernus Pharmaceuticals. “Qelbree provides prescribing physicians and patients living with ADHD a therapy that is not a controlled substance with proven efficacy and a tolerable safety profile. We are grateful to the patients, families and their care givers who participated in and supported our research.”

Qelbree is a once-daily, rapid and extended release, sprinkleable capsule. The approval of the medication is supported by data from 4 phase 3 clinical trials that studied more than 1000 pediatric patients whose ages ranged from 6 to 17 years.

“ADHD is one of the most common mental health issues in the US,” said Andrew J. Cutler, MD, clinical associate professor of psychiatry at SUNY Upstate Medical University, and Chief Medical Officer at the Neuroscience Education Institute. “The right treatment is key for children and adolescents, as they grow and navigate school and social relationships. This approval offers a novel once a day sprinkleable non-stimulant that can be a great option for children and adolescents with ADHD.”

Qelbree does carry the boxed warning of higher rates of suicidal thoughts and behaviors, which were observed in pediatric patients with ADHD during clinical trials. Qelbree-treated patients should be monitored for worsening or emergence of suicidal thoughts.

Supernus also announced positive results from a phase III trial in adult patients with ADHD in December 2020. They plan to submit a supplemental New Drug Application to the FDA for Qelbree in adults in the second half of 2021.

1. Supernus Pharmaceuticals. Supernus announces FDA approval of Qelbree™ (SPN-812) for the treatment of ADHD. News release. April 2, 2021. 

https://www.globenewswire.com/news-release/2021/04/02/2204030/0/en/Supernus-Announces-FDA-Approval-of-Qelbree-SPN-812-for-the-Treatment-of-ADHD.html

2. Supernus Pharmaceuticals. Highlights of prescribing information for Qelbree. 

https://www.supernus.com/sites/default/files/Qelbree-Prescribing-Info.pdf

This once-daily sprinkleable capsule may help patients aged 6 to 17 years with attention-deficit/hyperactivity disorder.

Pediatric ADHD Medication Gets FDA Green Light

Patients with heart disease who take lamotrigine may be at increased risk for arrhythmias, according to a US Food and Drug Administration (FDA) review. The FDA promised further information once other medicines in the same drug class are evaluated for similar effects.

“Laboratory testing performed at therapeutically relevant concentrations has shown that lamotrigine can increase the risk of serious arrhythmias, which can be life-threatening in patients with clinically important structural or functional heart disorders,” the FDA warned.

Lamotrigine is a seizure treatment for patients aged 2 years and older as well as a maintenance treatment for patients with bipolar disorder. It has been approved and on the market for more than 25 years.

Reports of abnormal electrocardiographic (ECG) findings and other serious issues raised the alarm. The FDA then required the in vitro studies to further examine lamotrigine’s effect on the heart. Reported problems included chest pain, loss of consciousness, and cardiac arrest.

The challenge now is to determine whether the potential benefits of lamotrigine outweigh the risk of arrhythmias in each individual patient.

The FDA encourages medical professionals and patients alike to report adverse events and side effects associated with lamotrigine to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program through the 

 or by calling 1-800-332-1088 to request a form.

1. US Food and Drug Administration. Studies show increased risk of heart rhythm problems with seizure and mental health medicine lamotrigine (Lamictal) in patients with heart disease. News release. March 31, 2021. 

https://www.fda.gov/drugs/studies-show-increased-risk-heart-rhythm-problems-seizure-and-mental-health-medicine-lamotrigine

Is this treatment for bipolar disorder risking patients’ heart health? 

FDA Warning: Bipolar Medication May Increase Risk for Arrhythmias

The Biden Administration revealed its first-year plan to address the nation’s addiction crisis, with 7 priorities highlighted and a focus on the inequality of treatment access. 

“The overdose and addiction crisis has taken a heartbreaking toll on far too many Americans and their families. Since 2015, overdose death numbers have risen 35 percent, reaching a historic high of 70,630 deaths in 2019. This is a greater rate of increase than for any other type of injury death in the United States. Though illicitly manufactured fentanyl and synthetic opioids other than methadone (SOOTM) have been the primary driver behind the increase, overdose deaths involving cocaine and other psychostimulants, like methamphetamine, have also risen in recent years, particularly in combination with SOOTM,” the Biden Administration statement read.

 “New data suggest that COVID-19 has exacerbated the epidemic, and increases in overdose mortality have underscored systemic inequities in our nation’s approach to criminal justice and prevention, treatment, and recovery.”

1) Expanding access to evidence-based treatment 

2) Advancing racial equity in our approach to drug policy 

3) Enhancing evidence-based harm reduction efforts 

4) Supporting evidence-based prevention efforts to reduce youth substance use 

5) Reducing the supply of illicit substances 

6) Advancing recovery-ready workplaces and expanding the addiction workforce; and 

7) Expand access to recovery support services.

Susan R. Bailey, MD, American Medical Association President, had this to say: “The agenda outlined today by the Biden Administration tackles overdoses and substance use disorder head-on in ways that will reduce stigma and remove barriers to treatment. The AMA strongly supports the approaches outlined, including: increasing access to evidence-based treatment for patients with substance use disorders—with particular emphasis on removing unnecessary barriers to prescribing buprenorphine—enforcing mental health and substance use parity, advancing racial equity, and enhancing harm-reduction efforts.”

The Substance Abuse and Mental Health Services Administration (SAMHSA) will direct $1.65 billion in Substance Abuse Prevention and Treatment Block Grant funding and $825 million in Community Mental Health Services Block Grant funding to states and territories.

“Focusing on both mental and substance use disorders—challenges that pre-date the COVID-19 pandemic but that have worsened over the past year—will be a crucial part of SAMHSA’s approach to helping the nation move forward,” said Acting Assistant Secretary for Mental Health and Substance Use Tom Coderre.

The Substance Abuse Prevention and Treatment Block Grant program will allow states to focus and evaluate measures to prevent and treat substance use disorder. Specifically, funding will allow recipients to maximize the efficiency of current treatments and address local needs to ensure substance use disorder prevention.

The Community Mental Health Services Block Grant program will allow states to provide comprehensive community mental health services and address gaps in treatment services for those with severe mental illnesses.

1. Executive Office of the President, Office of National Drug Control Policy. The Biden-Harris Administration’s statement of drug policy priorities for year one. Accessed April 1, 2021. 

https://www.whitehouse.gov/wp-content/uploads/2021/03/BidenHarris-Statement-of-Drug-Policy-Priorities-April-1.pdf

2. American Medical Association. AMA applauds Biden Administration’s first-year drug policy priorities. News release. April 1, 2021. 

https://www.ama-assn.org/press-center/ama-statements/ama-applauds-biden-administration-s-first-year-drug-policy-priorities

3. The Substance Abuse and Mental Health Services Administration. With pandemic worsening the mental illness and addiction crisis, Biden Administration to provide nearly $2.5 billion to states, territories for treatment, prevention aid. News release. March 11, 2021. 

https://www.samhsa.gov/newsroom/press-announcements/202103110230

Government funding for the drug addiction crisis is on the way. 

Biden Administration Plan Tackles Drug Addiction Crisis

The first study to use social media listening (SML) analysis of unsolicited patient and caregiver insights might give a better look into the perspective of patients with tardive dyskinesia (TD).

TD, a difficult movement disorder, is commonly associated with prolonged exposure to dopamine receptor blocking agents such as antipsychotics. Based on gathered data, it also has a number of patients left feeling unheard.

“Because the emotions and sentiments of patients (and sometimes caregivers) on social media platforms are unsolicited and unfiltered, SML methods… offer a more comprehensive context for understanding how patients experience TD and the unmet needs in this therapeutic space,” Farrar et al. wrote in their discussion. “As indicated in the recent FDA guidance on patient engagement for drug development,

 social media can allow access to difficult-to-reach populations, provide accurate and automatic capture of data, and possibly result in greater self-disclosure by patients.”

For this pilot study, researchers collected patient insights from 261 social media posts made by patients and caregivers, mainly on blog forums and Twitter, using predefined search terms. Of the 261 posts, 107 were used for analysis. Overall, the sentiments leaned negative, with 64% responses being negative, 33% neutral, and only 3% positive.

Three themes emerged: anger, insecurity, and symptoms. Common sentiments showed patients were angry about developing TD from a medication used to treat another of their conditions, insecure about feeling unaccepted by society, and afraid of being judged.

All posts were gathered from publicly available, nonpassword protected sites. In order to protect the identity of users, all personal information was excluded prior to any manual review of the content and verbatim quotes were not included in the final report.

While researchers admitted that the study might be limited by a small sample size and reliance on self-reporting, they concluded social media may help convey unmet patient needs that do not get addressed in clinical discussions.

1. Farrar M, Lundt L, Franey E, Yonan C. Patient perspective of tardive dyskinesia: results from a social media listening study. 

2. US Food and Drug Administration. Patient-focused drug development: collecting comprehensive and representative input guidance for industry, Food and Drug Administration staff, and other stakeholders. Center for Drug Evaluation and Research; 2020.

The first study to gather unsolicited patient responses via social media finds 3 negative themes. 

Patients With Tardive Dyskinesia Feel Unheard, Social Media Listens

Approximately 20 veterans per day die by suicide.

 Standard therapy and medications may not be enough to manage the symptoms of posttraumatic stress disorder (PTSD), but service dogs may help alleviate them.

 K9s for Warriors, the nation’s largest veteran service organization providing highly skilled service dogs to disabled veterans, has already rescued 653 veterans and 1278 dogs as of February 2021.

The PAWS Act, introduced by Florida Congressman John Rutherford, seeks to establish a competitive grant program for organizations like K9s for Warriors to pair service dogs with veterans.

Rory Diamond, the Chief Exectutive Officer of K9s for Warriors, and Maggie O’Haire, PhD, leader of the 

Organization for Human-Animal Interaction Research and Education (OHAIRE)

 research group, shared more on the effort to pair more veterans with dogs with 

: This February, the US House of Representatives reintroduced the Puppies Assisting Wounded Servicemembers (PAWS) Act, H.R. 1022, which would allocate federal funds for the training of service dogs for veterans. What kind of impact do you think this will have on the treatment of PTSD?

: Passing the PAWS Act would pave the way for allocating vital resources needed to properly train and pair more service dogs with the veterans who need them most. This type of legislation would ultimately make service dogs more accessible to more veterans as an alternative to traditional medication, while helping to restore their confidence and independence.

: Trademark symptoms of PTSD include heightened reactions, anxiety, and nightmares. Can you explain how the service dog might help alleviate these?

: PTSD service dogs are trained to perform a variety of tasks intended to alleviate PTSD symptoms. Many of these tasks are related to detecting signs of anxiety or distress and intervening. For example, a service dog can sense changes in an individualprior to a panic attack and nudge or lean against the individual to encourage them to refocus on the dog and the present space, thereby minimizing or preventing the panic attack. The service dog can also wake up a veteran from a disturbing nightmare to provide comfort. In our recent study of 134 veterans with PTSD service dogs, we found that veterans reported the most important trained service dog task was to calm/comfort from anxiety. They used this task on average 5 times every day and it was reported to help with 12 of 20 PTSD symptoms.

: In 2019, the VA reported that the suicide rate for veterans was 1.5 times the rate of non-veterans. Do you think the implementation of the PAWS Act could affect that statistic?

: Nearly 20 veterans commit suicide every day. These heroes return home feeling disconnected, unsafe, and unstable, tragically feeling like they have no other way forward. Implementing the PAWS Act would allow more of these American heroes to choose a trained service dog to help heal their invisible wounds, a proven method that’s backed by research from the US Department of Veterans Affairs (VA).

: Training these service animals can be expensive—costing almost $30,000. Do you think this price will decrease the number of trained dogs and therefore inhibit patients with PTSD from getting access?

: Despite acknowledging a national crisis exists with the alarming rate of veteran suicide, the VA has refused to take action by covering the cost of service dogs (a proven treatment method for PTSD) under the insurance benefits that veterans have earned through their military service. Upon introducing a service dog, veterans, along with their families/caregiver(s) experience a transformational improvement in quality of life, and the VA needs to take responsibility and remove the financial barrier that precludes more veterans from receiving this benefit.

: K9s For Warriors pairs dogs with those having posttraumatic stress, traumatic injury, and/or military sexual trauma. Is there an ideal patient/candidate for this service? When would this be contraindicated?

: K9s For Warriors and other service dog providers typically have an extensive application and screening process to ensure that a service dog pairing would be feasible and appropriate for both the veteran and the dog. It is important for veterans to be willing and open to bringing a new partner into their lives, including dog care, maintenance, and ongoing training. We do not yet know if there is an ideal patient/candidate for this service, but it is an ongoing area of our research. Not all veterans will be interested in having a service dog, particularly if there are allergies in the home.

: Can you share an example of a success story?

: We have more than 650 veteran graduates who can attest to the positive impact service dogs can have on both their emotional and physical state of mind. Each of these Warriors has their own success story, thanks to an unwavering bond they’ve built with their service dog battle buddy.

: Have there been any studies looking at the impact of this program? If so, could you share the results?

: Our research group at Purdue University has conducted a series of research studies in collaboration with K9s For Warriors (see publications 

). In a study of 141 veterans with PTSD, we found that those paired with service dogs showed clinically significant reductions in PTSD symptoms. The service dogs were not a cure for the disorder, but they helped make the symptoms more manageable on a daily basis.

The service dogs were also associated with broader improvements in quality of life. For example, veterans with service dogs who were employed missed work less often and reported less anxiety, depression, and greater satisfaction with their lives and social relationships. On a biological level, we also studied the stress hormone cortisol and found that veterans with service dogs had a cortisol level closer to that of healthy adults without PTSD. The evidence suggests that service dogs should not replace other services, but instead that they can provide a valuable addition to current evidence-based care. Some veterans tend to overestimate benefits and underestimate challenges, so it is also important for clinicians to work together with veterans to manage realistic expectations, thereby creating a maximally positive and productive experience for both veterans and dogs.

: Do you partner with psychiatrists/clinicians? And, if so, how?

: K9s For Warriors works in partnership with Purdue University’s College of Veterinary Medicine, and specifically Dr Maggie O’Haire (Center for the Human-Animal Bond). This partnership allows Dr O’Haire to conduct several research studies which have resulted in scientific proof of service dogs’ ability to help mitigate veteran’s symptoms of PTSD.

: How should practitioners get in contact with service dog programs?

: Practitioners can advise their (post 9/11) veteran patients to fill out an application with K9s For Warriors to be considered for our program: 

https://www.k9sforwarriors.org/warrior-application-survey

To see more on this topic, see Dr O’Haire’s video, 

1. K9s for Veterans. Updated February 2021. Accessed March 30, 2021. 

2. Purdue University. Study shows physiological and behavioral benefits may be experienced by veterans with PTSD who have service dogs. News release. June 12, 2018. Accessed March 30, 2021. 

https://www.k9sforwarriors.org/sites/default/files/180612%20OHairePTSD_final_06_08.pdf

3. Rutherford, Pappas, Waltz, Lawson, Stivers Reintroduce PAWS Act. News release. March 3, 2021. Accessed March 30, 2021. 

https://rutherford.house.gov/media/press-releases/rutherford-pappas-waltz-lawson-stivers-reintroduce-paws-act

Service animals can help save veterans’ lives.

Rx Dog Therapy: How Man’s Best Friend Helps Veterans With PTSD

The US Food and Drug Administration (FDA) recently accepted the new drug application (NDA) for Idorsia’s investigational dual orexin receptor antagonist, daridorexant, designed for the treatment of 

“I’m very happy that this first regulatory hurdle is behind us,” said Jean-Paul Clozel, MD, Chief Executive Officer of Idorsia. “This was a huge NDA and the team has done an excellent job in preparing the dossier, on which the FDA can judge the properties and merits of daridorexant. We now stand-by to work with the FDA to answer any questions that might arise concerning the effect of daridorexant on sleep, daytime functioning, and its safety profile.”

Daridorexant targets overactive wakefulness associated with insomnia by blocking the activity of orexin, has a rapid onset, and lasts long enough to cover the night without any next-morning residual sleepiness. According to data from the phase 3 registration program, daridorexant is the first insomnia treatment to show statistically significant and clinically meaningful improvements in daytime functioning, sustained over time, as well as sleep during the night.

“While we designed daridorexant to have the optimal profile for a sleep medicine, I am none-the-less stunned by the results. Once approved, by providing daridorexant to the millions of patients with insomnia, Idorsia will have a major impact on this medical, social, and economic problem,” Clozel said. “It has struck me particularly in these times of confinement that we are living through, that sleep problems are a major issue and require an extremely safe and effective drug that can be used by the many. With these results Idorsia is entering into a new era; less than 3 years since its creation, Idorsia is taking a huge step forward in delivering on the vision to become a fully-fledged biopharmaceutical company.”

Adverse events included headache, somnolence, fatigue, dizziness, and nausea, although the incidence of somnolence was low and did not increase with daridorexant 50 mg when compared with placebo.

Idorsia submitted the NDA on January 8, 2021 and anticipates a US launch in the first half of 2022, should approval be received.

1. Idorsia Pharmaceuticals. FDA accepts the new drug application for review of Idorsia’s daridorexant for the treatment of adult patients with insomnia. 

https://www.globenewswire.com/news-release/2021/03/10/2190042/0/de/FDA-accepts-the-new-drug-application-for-review-of-Idorsia-s-daridorexant-for-the-treatment-of-adult-patients-with-insomnia.html

2. Idorsia Pharmaceuticals. Idorsia announces positive results in the first Phase 3 study of daridorexant with improved overall sleep and daytime performance of patients with insomnia. News release. April 20, 2020. 

https://www.idorsia.com/media/news-details?newsId=2284972

This investigational dual orexin receptor antagonist improved sleep overnight and daytime functioning. 

Insomnia Treatment Without Daytime Sleepiness

Two companies received warning letters from the US Food and Drug Administration (FDA) for selling products labeled as cannabidiol (CBD) in ways that violate the Federal Food, Drug, and Cosmetic Act (FD&C Act). Unapproved drugs labeled as containing CBD are using illegal marketing, as the FDA has not approved any over-the-counter drugs with CBD.

“The FDA continues to alert the public to potential safety and efficacy concerns with unapproved CBD products sold online and in stores across the country,” FDA Principal Deputy Commissioner Amy Abernethy, MD, PhD, said to the press. “It’s important that consumers understand that the FDA has only approved 1 drug containing CBD as an ingredient. These other, unapproved, CBD products may have dangerous health impacts and side effects. We remain focused on exploring potential pathways for CBD products to be lawfully marketed while also educating the public about these outstanding questions of CBD’s safety. Meanwhile, we will continue to monitor and take action, as needed, against companies that unlawfully market their products — prioritizing those that pose a risk to public health.”

None of the CBD products in question from Honest Globe Inc and Biolyte Laboratories LLC meet the requirements to be legally marketed without an approved new drug application, nor have they gone through the FDA drug approval process. No FDA evaluation has been conducted to determine whether these products are effective for the claimed uses, what appropriate dosages would be, how they interact with other drugs, or what side effects they may have.

Additionally, the letters cited the 2 companies for substandard manufacturing practices, specifically failure to comply with current good manufacturing practices. The FDA requested written responses from the companies, to be provided within 15 workdays. These responses must detail how the companies intend to address the violations, or provide reasoning and supporting evidence as to why these products are not illegal. Should the companies fail to timely and appropriately address the violations, they may face legal action, such as product seizure and injunction.

This is not the first time the FDA has issued warnings to companies whose products violated the FD&C Act.

Selling CBD products that claim to prevent, diagnose, mitigate, treat or cure various diseases is illegal, and the FDA warns consumers to be wary of such products.

For more information on CBD and its impact on patients with mental illness, please see the 

1. US Food and Drug Administration. FDA warns companies illegally selling over-the-counter CBD products for pain relief. News release. March 22, 2021. 

https://www.fda.gov/news-events/press-announcements/fda-warns-companies-illegally-selling-over-counter-cbd-products-pain-relief?utm_medium=email&utm_source=govdelivery

2. US Food and Drug Administration. Warning letters and test results for cannabidiol-related products. Updated March 22, 2021. 

https://www.fda.gov/news-events/public-health-focus/warning-letters-and-test-results-cannabidiol-related-products

As patients flock to CBD as a “natural alternative” to medications, the FDA continues to crack down on false claims.