Paul Gleason, PhD

found that a combinational pharmacogenetic test was a better predictor of medication blood level and patient outcomes than single-gene testing alone.

Common psychiatric medications for depression and anxiety can react with patients’ genes in ways that inhibit the drugs’ effectiveness. It is possible to test single genes for potential interactions, but Myriad Genetics has developed a test that 

 The study found that testing variations in multiple genes led to better, more predictive results.

The study’s lead author was Anthony J. Rothschild, MD, Irving S. and Betty Brudnick Endowed Chair and Professor of Psychiatry at the University of Massachusetts Medical School. In the article, he and his coauthors explained the importance of the findings as follows: “This evaluation of clinical validity shows that only the combinational pharmacogenomic test was significantly associated with improved patient outcomes. In addition, the combinatorial pharmacogenomic test was a superior predictor of medication blood levels across a larger group of medications relative to guidelines focused on only CYP2C19 and CYP2D6.”

The study was based on data from the Genomics Used to Improve DEpression Decisions (GUIDED) randomized-controlled trial.

 Between 2014 and 2017, the GUIDED trial drew participants from 60 psychiatry and primary care centers around the United States. In order to be eligible, participants needed a major depression disorder diagnosis and a score of 11 or more on the 16-item Quick Inventory of Depressive Symptomatology Scale at screening. They also needed at least 1 failed trial of psychotropic medication during their current depressive episodes.

 Participants were placed blindly into the pharmacogenomic-guided care or conventional treatment arms of the trial for 8 weeks. The researchers then measured and analyzed their outcomes.

The GUIDED trial did have some limitations. It was not a controlled pharmacokinetics study, meaning “blood levels were not controlled for time of intake or medication adherence.”

 As blood levels were only collected at screening, they could not be directly linked to adverse events or other outcomes. Still, the results were promising.

“This analysis demonstrates that the combinatorial approach of the GeneSight test more accurately predicts blood drug levels and identifies more patients with significant gene-drug interactions who would be missed by single-gene testing,” Mark Pollack, MD, chief medical officer of Myriad Neuroscience, said in a statement to the press. “Combinatorial pharmacogenomics like the GeneSight test should become the standard-of-care to help physicians understand gene-drug interactions that could improve care for people with depression, anxiety and other conditions.”

1. Rothschild AJ, Parikh SV, Hain D, et al. Clinical validation of combinatorial pharmacogenomic testing and single-gene guidelines in predicting psychotropic medication blood levels and clinical outcomes in patients with depression. 

2. GeneSight psychotropic test’s combinational approach proves better than single-gene testing at predicting patient outcomes and medication blood levels. 

February 8, 2021. Accessed March 4, 2021. 

https://www.globenewswire.com/news-release/2021/02/08/2171246/0/en/GeneSight-Psychotropic-Test-s-Combinatorial-Approach-Proves-Better-than-Single-Gene-Testing-at-Predicting-Patient-Outcomes-and-Medication-Blood-Levels.html

Articles

A study finds that testing genetic variations can predict outcomes and medication blood levels in patients with depression. 

How Will Patients React to Medications? The Answer May Be in Their Genes

A phase 2 trial of an adjunctive treatment for schizophrenia has stopped after failing to meet its primary and secondary endpoints. The treatment, CTP-692, developed by Concert Pharmaceuticals Inc, was a deuterated form of D-serine.

“The body of evidence in the field supporting D-serine as an adjunctive treatment for schizophrenia was compelling and led us to advance CTP-692 into a Phase 2 proof of concept study,” Roger Tung, PhD, president and chief executive officer of Concert Pharmaceuticals 

. “Unfortunately, we didn’t see the results we hoped for to support continuation of this program.”

CTP-692 was designed to improve on the efficacy and safety profile of existing schizophrenia treatments. Current research suggests that D-serine can improve outcomes for patients with schizophrenia, but it is accompanied by significant 

 Patients with schizophrenia also experience from cognitive impairments, and it was hoped that D-serine, which has shown positive effects on cognition in other contexts, would improve patient cognition without the renal risks.

The phase 2 trial was a double-blind, placebo-controlled study. It included 325 patients on antipsychotic medication. These participants were randomly selected to receive 1, 2, or 4-gram doses of CTP-692 once-daily, or a placebo. The trial took place over a 12-week period.

At the end of the 12-week period, the patients showed no improvement on the Positive and Negative Syndrome Scale (PANSS) compared to baseline scores, and the trial was discontinued. The company has also decided to discontinue study of this compound.

1. Concert Pharmaceuticals announces results from CTP-692 phase 2 trail in patients with schizophrenia. News release. Concert Pharmaceuticals Inc. February 1, 2021. Accessed February 17, 2021. 

https://ir.concertpharma.com/news-releases/news-release-details/concert-pharmaceuticals-announces-results-ctp-692-phase-2-trial

2. Concert Pharmaceuticals discontinues schizophrenia drug after trial failure. GlobalData Healthcare. February 3, 2021. February 17, 2021. 

https://www.clinicaltrialsarena.com/comment/concert-pharmaceuticals-schizophrenia-failure/

Is this phase 2 trial the end of the road for a potential new treatment?

A Potential Schizophrenia Treatment Trial Falls Short 

In the United States, there are currently no Federal Drug Administration (FDA) approved medications for the treatment of psychosis in Alzheimer disease (AD). This is a problem because approximately 25% to 50% of individuals with AD develop psychosis during their illness, and 

But a recent trial found that pimavanserin reduced psychosis symptoms in patients with AD. According to Rajesh Tampi, MD, MS, DFAPA, 

 neuropsychiatry section editor, this research could be ground-breaking because “pimavanserin will be the first drug, if approved, for this indication in the US with an indication for psychosis in AD.”

Pimavanserin could improve patient outcomes significantly. Existing antipsychotic drugs may be effective for treating delusions and hallucinations, but antipsychotics are also associated with increased risk for death, cerebrovascular adverse events, sedation, falls, and pneumonia. Given these concerns, effective and safe pharmacological treatment of psychosis in AD remains a pressing need.

A literature review of clinical studies on pimavanserin as a treatment for psychosis concluded that “pimavanserin may be a pharmacologic consideration for the treatment of psychosis in AD.”

 In 2 publications, pimavanserin improved psychotic symptoms in individuals with AD when compared with a placebo after 6 weeks. The authors of the literature review warned that further randomized controlled trials were needed before pimavanserin could be considered a standard treatment.

 to the FDA, asking it to approve pimavanserin for dementia-related psychosis.

 A serotonergic agent and selective serotonin (5-HT) 2A receptor inverse agonist, pimavanserin may be able to treat hallucinations and delusions.

Acadia’s study is a Phrase 3 trial that began in 2019. It included 117 study locations, scattered across the US, Europe, and Chile, and enrolled 392 participants with dementia who had suffered from symptoms of psychosis for at least the last 2 months.

 Following a 12-week open-label period, participants who responded were broken into 2 groups for the following 26 weeks, in which 1 received a placebo and the other pimavanserin. The study then followed the patients until they had a relapse, defined by hospitalization as a result of dementia-related psychosis, deterioration of dementia symptoms, withdrawal from the study due to lack of efficacy, or use of another antipsychotic medication. 

Acadia reported that pimavanserin significantly reduced the risk of a relapse. Those on the placebo were 2.8 times more likely to relapse during the study period. Given promising results, they filed a supplemental New Drug Application (sNDA) with the FDA.

Pimavanserin is already FDA approved for the treatment of hallucinations and delusions in individuals with Parkinson disease psychosis (PDS), but the same symptoms have no standard drug treatment for individuals with dementia-related psychosis. The FDA will likely not render a verdict before April 2021, but clinicians may want to keep this research in mind, as it could be an indication for using pimavanserin in the near future.

1. Srinivasan S, Tampi RR, Balaram K, Kapoor A. Pimavanserin for the treatment of psychosis in Alzheimer's disease: A literature review. 

2. Pimavanserin – dementia-related psychosis. News release. Acadia Pharmaceuticals, Inc. Accessed November 9, 2020. https://www.acadia-pharm.com/pipeline/pimavanserin-drp/

3. Pimavanserin. Alzforum: networking for a cure. Updated July 24, 2020. Accessed November 9, 2020. 

https://www.alzforum.org/therapeutics/pimavanserin

A new treatment for hallucinations and delusions in individuals with Alzheimer disease may be on the horizon. 

Hope for Dementia-Related Psychosis 

The United States Food and Drug Administration (FDA) has announced a nationwide recall of 2 drugs: sildenafil and trazodone. Sildenafil is the active ingredient in popular erectile dysfunction treatments, while trazodone hydrochloride is indicated for the treatment of major depressive disorders.

According to the FDA, various lots of these drugs were wrongly packaged together at a third-party facility. The drugs were distributed to wholesalers, and then distributed nationwide. This is dangerous because both drugs carry significant health risks.

Sildenafil could be particularly dangerous for individuals with diabetes, high blood pressure, or heart disease. Prescription drugs for these conditions often contain nitrates. When sildenafil interacts with nitrates, it can lower blood pressure to dangerous levels.

Trazodone carries significant risks as well. It can cause constipation, blurred vision, dizziness, and somnolence and sedation. These side effects may put elderly individuals at risk for falls, or cause impairment while driving.

The FDA recommended that consumers contact their physicians if they experience any problems or symptoms consistent with inadvertently taking these drugs.

1. AvKARE issues voluntary nationwide recall of sildenafil 100mg tablets and trazodone 100 mg tables due to product mix-up. News release. U.S. Food and Drug Administration; December 9, 2020. Accessed December 10, 2020. 

AvKARE Issues Voluntary Nationwide Recall of Sildenafil 100mg Tablets and Trazodone 100mg Tablets Due to Product Mix-Up | FDA

Sildenafil and trazodone were inadvertently bottled together, posing serious health risks to consumers. 

FDA Recalls A Pair of Drugs Due to a Packaging Mix-Up

Researchers at Yale University have found that prazosin, a drug developed to treat high blood pressure, can also reduce alcohol use in patients with 

“There has been no treatment readily available for people who experience severe withdrawal symptoms,” 

, an author on the study and director of the Yale Stress Center. “These are the people at the highest risk of relapse and are most likely to end up in hospital emergency rooms.”

Alcohol withdrawal symptoms include shakes, heightened cravings, anxiety, and difficulty sleeping, which can easily lead to poor treatment outcomes.

In order to study the possible effects of prazosin on alcohol use, Sinha and her co-authors designed a 12-week, double-blind trial, recruiting 100 patients with alcohol dependence. The researchers collected information on the participants’ self-reported drinking habits (including average drinks per day) and their moods, levels of anxiety, alcohol cravings, and sleep quality ratings.

At the end of the 12-week study, researchers found that participants with high alcohol withdrawal symptoms who received prazosin reported fewer “drinking” and “heavy drinking” days than patients who received a placebo.

 Patients with high withdrawal symptoms also reported decreased anxiety, depression, and alcohol cravings. Patients with no or low withdrawal symptoms did not receive a similar benefit from prazosin.

Originally developed to treat high blood pressure, prazosin has also been shown to affect stress centers in the brain, improving memory while reducing anxiety and cravings.

 Sinha’s lab has previously found that the recovery process disrupts stress centers in the brain, especially in patients with severe withdrawal symptoms.

Fortunately, these disruptions decrease over time. The hope, Sinha said, is that prazosin could bridge the gap between patients’ initial withdrawal symptoms and long-term recovery.

Share comments with your colleagues by emailing 

. Comments may be shared online pending review and editing for style.

1. Sinha R, Wemm S, Fogelman N, et al. Moderation of prazosin’s efficacy by alcohol withdrawal symptoms. 

2. Drug eases recover for those with severe alcohol withdrawal. 

. November 19, 2020. Accessed November 25, 2020. 

https://www.sciencedaily.com/releases/2020/11/201119124716.htm

A drug developed to treat high blood pressure has unexpected benefits for patients with severe withdrawal symptoms.

Blood Pressure Drug Benefits Patients Recovering From Alcohol Addiction

Spare a thought for anyone spending Thanksgiving all alone. 

 suggests that isolated individuals may long for company in the same way that hungry children long for that apple pie in the oven.

“People who are forced to be isolated crave social interactions similarly to the way a hungry person craves food,” Rebecca Saxe, a senior author of the study, 

. “Our finding fits the intuitive idea that positive social interactions are a basic human need, and acute loneliness is an aversive state that motivates people to repair what is lacking, similar to hunger.”

For the study, Saxe and her co-authors collected 40 participants, individuals aged 18 to 40. The participants underwent a pair of 10-hour test periods. One required a 10-hr fast, and the other required 10 hours of strict social isolation, alone in a windowless room on the campus of the Massachusetts Institute of Technology. After the test periods, the participants were scanned by a magnetic resonance imaging (MRI) scanner and shown pictures of either food or individuals interacting.

“We wanted to see if we could experimentally induce a certain kind of social stress,” Saxe explained to the press. “It’s a stronger intervention of social isolation than anyone had tried before.”

The researchers focused on the substantia nigra, a structure located in the midbrain and associated with hunger pangs. Sure enough, both fasting and isolated participants showed “craving signals.” The strength of the signal also correlated with the participants reports of how hungry or lonely they felt.

Additionally, participants who reported high levels of satisfaction with their social lives outside of the study experienced higher levels of social hunger. “For people who reported that their lives were really full of satisfying social interaction, this intervention had a bigger effect on their brains and on their self-reports,” Saxe said.

At the end of the published study, the authors raised the issue of how much “positive social interaction is sufficient to fulfill our social needs and thus eliminate the neural craving response.”

Whether digital communication alone can satisfy social hunger is an open question, they noted, and an important one.

“In early 2020 millions of humans experienced a sudden, externally mandated period of relative or complete physical isolation from others,” the authors concluded. “This unprecedented upheaval in people’s social routines emphasized the need for a better understanding of human social needs and the neural mechanisms underlying social motivation.”

What do you think? Are you craving company? 

1. Tomova L, Wang KL, Thompson T, et al. Acute social isolation evokes midbrain craving responses similar to hunger. 

Trafton A. Neuroscientists find that isolation provokes brain activity similar to that seen during hunger cravings. Medical Press. November 23, 2020. Accessed November 25, 2020. 

A new study finds that isolation makes us want company on a neural level, in much the same way that hunger makes us want food. 

Craving Company  

Pear Therapeutics has announced the availability of Somryst, the only US Food and Drug Administration-authorized digital therapeutic for chronic insomnia to date. (Read 

, MD, chief medical officer at Pear Therapeutics.)

“We’re excited to offer patients who have been struggling to find a long-term solution for chronic insomnia with a meaningful, first-line treatment,” Corey McCann, president and chief executive officer of Pear Therapeutics, said in a statement.

A prescription digital therapeutic (PDT), Somryst offers 6 to 9 weeks of cognitive behavioral therapy (CBT) via a tablet or smartphone. Clinical studies on the efficacy of this therapeutic have appeared in 

The prescription reduced the time needed to fall asleep by 45%, time spent awake during the night by 52%, and the severity of insomnia symptoms by 45%. Improvement continued 6 and 12 months after treatment.

At present 30 million Americans suffer from chronic insomnia, but McCann noted that treatment options are especially “important now, more than ever, as we continue to navigate the COVID-19 pandemic.”

Indeed, sleep disorders have soared during the pandemic. Nearly half of respondents to a Pear Therapeutics survey reported pandemic-related sleep loss. The number reporting poor sleep almost doubled (from 15% to 27%), and younger generations have been especially affected, with nearly one-third of Gen Z and Millennials admitting to poor sleep quality.

Digital prescriptions may be good options for patients who cannot access a clinician. “Despite CBTi being the recommended first line treatment for chronic insomnia, there aren’t enough clinicians who are trained to deliver CBTi therapy,” Michelle Primeau, MD, medical director of the Palo Alto Medical Foundation Sleep Medicine Center in San Carlos, CA, told the press. “Somryst has been shown to address the underlying issues of chronic insomnia by training the brain and body to fall asleep faster and stay asleep longer.”

Are your patients experiencing increased insomnia? 

. Comments may be shared online pending review and may be edited for style.

Ritterband LM, Thorndike FP, Ingersoll KS, et al. Effect of a web-based cognitive behavior therapy for insomnia intervention with 1-year follow-up: a randomized clinical trial

Christensen H, Batterham PJ, Gosling JA, et al. Effectiveness of an online insomnia program (SHUTi) for prevention of depressive episodes (the GoodNight Study): a randomised controlled trial. 

Batterham P, Christensen H, Mackinnon A, et al. Trajectories of change and long-term outcomes in a randomized controlled trial of internet-based insomnia treatment to prevent depression. 

Potential relief for millions of Americans with pandemic-related sleep issues. 

A New Digital Therapeutic for Chronic Insomnia

The presidential election is not over. But around the nation, voters have made their voices heard on numerous down-ballot issues directly related to psychiatry and mental health. In this election round-up, 

 highlights a sampling of propositions, measures, and initiatives that may change mental health treatment for years to come. 

Voters in Colorado passed Proposition 118. One of the most progressive laws of its kind in the country, it requires that employers offer 12 weeks of paid time off for childbirth, emergencies, and other 

“I’m so proud that Colorado is the first state to do this on the ballot,” said Colorado State Senator 

. “We’ve always had stories of moms going back to work within two weeks of giving birth and cancer patients skipping chemotherapy to keep their jobs.” This law could reduce financial stressors for many patients, and eligible clinicians who can take advantage of family and medical leave may be 

The use of cannabis for mental health purposes 

 among psychiatrists, but 2 additional states have approved cannabis use for medical use. The state of Mississippi appears to have passed a medical marijuana measure by more than a 

. South Dakota voters passed a ballot measure that authorizes medical marijuana and, at the same time, an amendment that also allows 

The adoption of both at once is unprecedented, noted Erik Altieri, executive director of the National Organization for the Reform of Marijuana Laws (NORML). “No state has ever moved from marijuana prohibition to allowing both medical use and adult-use access, quite literally, overnight,” 

Oregon appears to be the first state that will allow the use of psilocybin (the active ingredient in so-called “magic mushrooms”) for 

. Ronan Levy of Field Trip Health, a Canadian company that uses psychedelics in psychotherapy, imagined that the new law could open doors to many new treatments. “There’s almost no mental health condition right now that’s not being looked at,” he said.

 on hallucinogenic psychedelics and their potential efficacy.

Former president of the American Psychiatric Association, Nada Stotland, MD, MS, has argued that abortion should be a real 

. “Access to this important aspect of women’s health care is vital not only to all women around the world,” she said, “but particularly to our patients.”

Colorado voters rejected Proposition 115, which would have outlawed abortions after 22 weeks. In Louisiana voters amended the state constitution, saying that the state neither protects abortion rights nor requires 

In addition to choosing a president and other political leaders, Americans cast their votes on a host of issues relevant to psychiatrists. 