Insights and Highlights From the Annual Psychiatric Times World CME Conference

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CONFERENCE REPORTER

Held virtually this year, the 2023 Annual Psychiatric Times World CME Conference featured leading researchers and clinicians from around country sharing their expertise on issues in everyday practice. Chaired by John J. Miller, MD, Psychiatric Times’ Editor in Chief, the conference was curated to share short, pithy discussions on new research and evolving treatment options and strategies with practical take-away messages for the clinician. Anita Clayton, MD, and Sanjai Rao, MD, co-chaired the 3-day conference and, along with Miller, participated in

question-and-answer sessions, addressing comments from the audience. Complete coverage of this year’s meeting as well as previous meetings can be found at PsychiatricTimes.com.

How Can We Better Understand Alcohol Misuse in Women?

Erin O’Brien

“Alcohol misuse in women is becoming an increasingly important topic because it used to be thought of as recently as 50 years ago as a men’s disorder. But epidemiological surveys have shown that gender gaps [in] alcohol consumption and alcohol-related harms are narrowing for women and men—such that alcohol is growing women’s health issue.”

Barbara J. Mason, PhD, discussed alcohol misuse in women at the 2023 Annual Psychiatric Times World CME Conference. Mason is director of the Pearson Center for Alcohol and Addiction Research and director of the Scripps Research Institute’s P60 Alcohol Research Center of Excellence.

Mason began by emphasizing the similarities and differences between men and women when it comes to alcohol use and related harms. She noted that the gap between men and women has narrowed in terms of prevalence and frequency of drinking, binge drinking, total amount of alcohol consumed, early-onset drinking, drunk driving, alcohol-induced cirrhosis, related emergency department visits, related hospitalizations, related deaths, and prevalence of alcohol use disorder (AUD).

Mason also stated that women are less likely than men to receive treatment for AUD and are more likely than men to experience a variety of alcohol-related harms at comparable doses, including hangovers, blackouts, liver disease, brain atrophy, cognitive deficits, cardiomyopathy, faster progression of AUD, and certain cancers. One such cancer is breast cancer: One study Mason cited found that light drinkers have a 1.04-fold higher risk, moderate drinkers have a 1.23-fold higher risk, and heavy drinkers have a 1.6-fold higher risk of developing breast cancer.

Mason also explored some possible differences in motivation for drinking between men and women. She stated that, generally, women are more likely to drink for negative reinforcement (eg, to dampen stress and negative affect), whereas men are more likely to drink for positive reinforcement (eg, for stimulation, to enhance mood). Although this reflects sex differences in the neurobiological underpinnings of drinking behavior, Mason also noted that there is some overlap between these populations: Some women may drink largely for positive reinforcement, while some men may drink largely for negative reinforcement.

Mason also noted that the sex differences in neurobiology that drive the motivation(s) to drink alcohol may influence responses to AUD pharmacotherapy. She discussed some recent research on AUD treatment with 2 drugs approved for this indication by the US Food and Drug Administration: naltrexone and acamprosate. In several studies on naltrexone, the drug did not show efficacy in women, suggesting that further study of the drug’s efficacy in women is warranted. In recent research on acamprosate, however, the drug showed equivalent efficacy and safety in men and women.

Mason emphasized the importance of better understanding the differences between men and women when it comes to alcohol misuse. She posed 2 hypotheses currently under consideration:

1. Women may be more motivated to consume alcohol to relieve emotional discomfort and, therefore, may be more responsive to pharmacotherapies that restore homeostasis in brain stress systems (eg, acamprosate, gabapentin).

2. Alcohol appears to activate the reward system to a greater extent in men than it does in women, which leads to positive reinforcement. This suggests that men may be more responsive to pharmacotherapies that block the reward system (eg, naltrexone).

Mason concluded by posing the following questions that should be explored in future research:

• What is driving the escalation of alcohol use in women?
• What causes the differences in health effects in women compared with those in men?
• How and why do women and men differ in their relationships with alcohol?
• How can AUD prevention and treatment strategies be modified to address women’s issues with alcohol more effectively?

Exploring DORAs for Insomnia

Heidi Anne Duerr, MPH

The new class of medications for addressing insomnia—the dual orexin receptor antagonists (DORAs)—show promise in terms of efficacy and adverse effect profile, explained Paul P. Doghramji, MD. He told attendees they do not adversely affect sleep architecture and do not have rebound insomnia, tolerance issues, or withdrawal symptoms.

In reviewing the available DORAs, Doghramji said suvorexant was first on the market; it was approved in 2014 for difficulties with sleep onset and/or maintenance. Available in 5-, 10-, 15-, and 20-mg doses, Doghramji finds most patients do best at the 20-mg dose but suggested starting with the 10-mg dose. He noted that it has a half-life of 15 hours and a Tmax of 2 hours. The most common adverse effects in trials were somnolence, headache, abnormal dreams, dry mouth, cough, and upper respiratory infection. The female:male adverse events rate was 2:1. There were no differences in psychomotor or morning driving performance compared with placebo. Doghramji shared highlights of an interesting study in which there were significant improvements in both total sleep time and wake after sleep for patients with insomnia and mild to moderate Alzheimer in the suvorexant group compared with the placebo group.¹

Next was lemborexant, which was approved for difficulties with sleep onset and/or maintenance. It is available in 5- and 10-mg doses; Doghramji noted it is better to start with the 5-mg dose, and if the desired effect is not realized, move to the higher dose. Lemborexant has more effect on orexin 2 than orexin 1 with a Tmax of 1 to 3 hours and a half-life of 17 to 19 hours. Doghramji added that because it induces CYP2B6, which impacts the area under the curve for bupropion, patients on both drugs will need a higher dose of bupropion. The most common adverse effects in trials were somnolence/fatigue. Research indicates it is safe in mild obstructive sleep apnea, and there was no difference in middle-of-the-night auditory awakening threshold or morning cognitive performance, body sway, and driving performance compared with placebo. Lemborexant also showed an improvement in sleep latency to persistent sleep almost as good as if not better than zolpidem.² In addition to sustained efficacy, patients reported improved fatigue during the day, an indicator of treatment success.^3,4

Approved in 2022, daridorexant is the most recent DORA approved for difficulties with sleep onset and/or maintenance. Daridorexant is available in 25- and 50-mg doses. It has a Tmax of 1 to 2 hours and a half-life of 8 hours, which he noted is about half that of the other DORAs. Compared with placebo, after 4 days of treatment there was no morning driving impairment, and he said safety has been demonstrated in mild obstructive sleep apnea and moderate chronic obstructive pulmonary disease. Interestingly, the most common adverse effects were nasopharyngitis and headache; somnolence and fatigue were also reported.

In addition to improving latency to persistent sleep and wake after sleep onset, daridorexant was found to improve daytime function. Doghramji explained that the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) was created and validated according to FDA guidelines to evaluate daytime functioning in individuals with insomnia. At the 50-mg dose, daridorexant improved the IDSIQ sleepiness domain at months 1 and 3, with clinically meaningful improvement at month 3.⁵

There are 2 emerging DORAs: seltorexant and vornorexant. Seltorexant is a selective orexin-2 receptor antagonist and is currently in phase 3 trials as an adjunctive therapy to antidepressants for patients with major depressive disorder and insomnia symptoms. Vornorexant is a balanced dual orexin antagonist that showed significant improvement in sleep latency to persistent sleep and wake after sleep onset.

References

1. Herring WJ, Ceesay P, Snyder E, et al. Polysomnographic assessment of suvorexant in patients with probable Alzheimer’s disease dementia and insomnia: a randomized trial. Alzheimers Dement. 2020;16(3):541-551.

2. Rosenberg R, Murphy P, Zammit G, et al. Comparison of lemborexant with placebo and zolpidem tartrate extended release for the treatment of older adults with insomnia disorder: a phase 3 randomized clinical trial. JAMA Netw Open. 2019;2(12):e1918254.

3. Kärppä M, Yardley J, Pinner K, et al. Long-term efficacy and tolerability of lemborexant compared with placebo in adults with insomnia disorder: results from the phase 3 randomized clinical trial SUNRISE 2. Sleep. 2020;43(9):zsaa123.

4. Chepke C, Jain R, Rosenberg R, et al. Improvement in fatigue and sleep measures with the dual orexin receptor antagonist lemborexant in adults with insomnia disorder. Postgrad Med. 2022;134(3):316-325.

5. Mignot E, Mayleben D, Fietze I, et al. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. Lancet Neurol. 2022;21(2):125-139. 

The Evolution and Expansion of Emergency Psychiatry

Leah Kuntz

“In my time working in the world of emergency psychiatry, I have been very, very impressed by how it has evolved and expanded to really help with a great deal of patient care, outpatient, inpatient, and every single thing that kind of happens in between,” said Tony Thrasher, DO, DFAPA, who gave an overview of the initial approach to emergency psychiatry, including psychiatric ethics, skills needed, and legal considerations. “I always remind people, it is a great honor and a great stressor to be working with people on their worst days.”

“One of my favorite things about emergency psychiatry is that we sit at the intersection with our colleagues and emergency medicine. And there’s a lot of crossover and synergy between those particular scopes, including that of our more community colleagues in emergency medical services,” said Thrasher, who is immediate past president of the American Association for Emergency Psychiatry and medical director of crisis services of Milwaukee County.

In terms of ethics, Thrasher reviewed what he called to the “big 4”: beneficence, autonomy, nonmaleficence, and justice. “When you’re working in the world of emergency psychiatry, these do not always run in parallel to each other; in fact, they tend to bump into each other a lot,” said Thrasher.

Nonmaleficence and justice in particular have the potential to cause conflicts and they are what Thrasher said he finds clinicians in the world of emergency psychiatry struggle with the most, as the unfortunate reality is that it is sometimes easier for patients to access certain services when they are hospitalized involuntarily rather than voluntarily. When dealing with issues of nonmaleficence and justice, Thrasher encouraged clinicians to ask themselves: How are patients placed in the involuntary/emergency pathway? Are we using the involuntary/emergency pathway to ensure access and mitigate risk? How does this affect parity?

As to skill sets, Thrasher listed engagement, approach, de-escalation, and motivation as valuable skills for the emergency clinician to possess. Engagement, while useful in all fields, requires emergency clinicians to respect patients and find a fluid approach to meeting needs. As to approach, clinicians should be nonjudgmental and use trauma-informed techniques rooted in psychological first aid. Practicing de-escalation before needing it is also essential. Lastly, using motivation, or finding the immediate need of the patient in order to determine acute and chronic approaches to stress, is a valuable skill set for clinicians.

“If you see a skill set here in which you or your team feels they could use more instruction, bring in your emergency psychiatry colleagues. They are often very skilled at education and going over some of these concepts,” said Thrasher.

Identifying and Assessing Suicide Risk Amid Record High of Suicide Deaths

Leah Kuntz

According to 2022 CDC provisional data, the past year saw a record high of 49,369 suicide deaths after modest declines in 2019 and 2020.¹ Michael F. Myers, MD, spoke to attendees of the 2023 Psychiatric Times World CME Conference about identifying suicide risk and effective treatments to reduce it.

“Our job is to assess and do what we can to save this individual from self-harm. It is an awesome task, right? But it can be exciting and very gratifying to have this opportunity to save a life,” said Myers.

Myers stressed the importance of the initial data gathering, in which he suggested following 8 steps (Table 1).²

TABLE 1. The 8 Steps to Follow When Gathering Initial Data

Any clinician dealing with a patient who is contemplating suicide should document as many details as possible, including active suicidal intent, rehearsal behaviors, psychological stressors, access to means such as firearms, interpersonal factors, and protective factors.²

Myers also shared a short list of what he considers prudent clinician behaviors when dealing with a patient potentially considering suicide (Table 2).

TABLE 2. Prudent Clinician Behaviors When a Patient Is Contemplating Suicide

Myers then provided examples of how to discuss suicidal ideation with patients. The first is more up front: “I want you to look me in the eye and answer my question, ‘Are you having thoughts of suicide?’”³ The second is an analogy meant to destigmatize suicide: “Your pneumonia (depression) has worsened, you have spiked a fever (developed suicidal thinking), and that is why we need to treat you more aggressively (continue observation, medicate, admit).”

In summary, Myers shared these thoughts: “Screening tools are helpful, but never a substitute. Collateral information is absolutely key. Working collaboratively when we can with the patient makes it just so much easier.”

References

1. Saunders H, Panchal N. A look at the latest suicide data and change over the last decade. KFF. August 4, 2023. Accessed October 24, 2023. https://www.kff.org/mental-health/issue-brief/a-look-at-the-latest-suicide-data-and-change-over-the-last-decade/

2. Gold LH, Frierson RL, eds. The American Psychiatric Association Publishing Textbook of Suicide Risk Assessment and Management. APA Publishing; 2020.

3. Gabbard GO, Myers MF. Critical issues in the treatment of suicidal physicians: life-saving tips for the practicing clinician. HMP Global Learning Network. May 20, 2017. Accessed October 24, 2023. https://www.hmpgloballearningnetwork.com/site/pcn/blog/critical-issues-treatment-suicidal-physicians-life-saving-tips-practicing-clinician

The Benefits of Long-Acting Injectable Antipsychotics for Schizophrenia

Leah Kuntz

Medication discontinuation is very common in schizophrenia, leading to relapse, treatment resistance, and poor outcomes.^1-3 Long-acting injectable (LAI) antipsychotics offer a solution to poor adherence, explained Sanjai Rao, MD, at the 2023 Psychiatric Times World CME Conference.

“By some estimates, up to half our patients will discontinue medications within the first 6 months of treatment, and perhaps up to 75% will discontinue medications within a year and a half of treatment. When this happens, even if it is after just a single psychotic episode, this can lead to relapse. The more often this happens to your patient, the more often they relapse and the longer it is going to take to get them back to something resembling remission,” said Rao, who is clinical professor of psychiatry and associate residency training director at the University of California, San Diego and site director of residency training at the VA San Diego Healthcare System.

LAIs offer several benefits as follows^4-5:

1. Clinicians know exactly how much medication the patient is receiving.

2. LAIs ensure stable plasma levels with less peak-to-trough fluctuation, with equal or increased efficacy, and sometimes fewer side effects than oral counterparts.

3. Missing a dose is not immediately catastrophic for patients, as there is no immediate drop in drug levels.

“The earlier you can intervene and prevent relapse, the more likely you are to have a more favorable outcome,” Rao said.

Furthermore, compared with oral antipsychotics, LAIs reduced the rate of all-cause hospitalizations, reduced the number of all-cause emergency department visits, and improved treatment adherence, all while having similar overall costs.

Speaking to patients about LAIs is all about reframing, Rao explained. Rather than taking a negative tone (ie, “Because you aren’t taking your pills, you should get the shot.”), it is better to approach with positive communication (“Would it be nicer for you to take your medication once a month instead of every day?”). According to a study of communication patterns concerning LAI antipsychotics, only 9% of psychiatrist communication when presenting LAI antipsychotics to patients focused on positive aspects, and as such only 33% of patients accepted LAI antipsychotic treatment. Once positive communication was used, 96% of patients who initially declined an LAI changed their minds and tried LAI treatment.

References

1. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005;353(12):1209-1223.

2. Emsley R, Chiliza B, Asmal L, Harvey BH. The nature of relapse in schizophrenia. BMC Psychiatry. 2013;13:50.

3. Lieberman JA, Alvir JM, Koreen A, et al. Psychobiologic correlates of treatment response in schizophrenia. Neuropsychopharmacology. 1996;14(suppl 3):13S-21S.

4. Lin D, Thompson-Leduc P, Ghelerter I, et al. Real-world evidence of the clinical and economic impact of long-acting injectable versus oral antipsychotics among patients with schizophrenia in the United States: a systematic review and meta-analysis. CNS Drugs. 2021;35(5):469-481.

5. Weiden PJ, Roma RS, Velligan DI, et al. The challenge of offering long-acting antipsychotic therapies: a preliminary discourse analysis of psychiatrist recommendations for injectable therapy to patients with schizophrenia. J Clin Psychiatry. 2015;76(6):684-690.

A Practical Guide to Buprenorphine

Erin O’Brien

“For someone feeling like they might not need treatment, introducing them to an option that they might not have known existed or might not have had the correct information about may allow them to then consider needing treatment.”

Jeffrey DeVido, MD, MTS, discussed buprenorphine and how clinicians can get started with the treatment at the 2023 Annual Psychiatric Times World CME Conference. DeVido is chief of addiction services at Marin County Health and Human Services, Department of Behavioral Health and Recovery Services, California, and a volunteer assistant clinical professor in the University of California, San Francisco (UCSF) Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences.

DeVido began the presentation by sharing some background and a review of buprenorphine, noting that it is a mu receptor partial agonist that produces little euphoria and has a long half-life and a high binding affinity, enabling it to block or displace other opioids. Approved by the US Food and Drug Administration for the office-based treatment of opioid use disorder (OUD) and pain, buprenorphine is a good analgesic with few adverse effects that is relatively safe in overdose.

DeVido also addressed some common concerns associated with buprenorphine, including initiation, precipitated withdrawal, diversion, length of treatment, and the drug’s potential effects on pregnancy and urine drug tests. Focusing on
initiation, DeVido shared 3 steps for clinicians to follow to start patients on buprenorphine:

1. Get the patient off opioids: The patient may enter withdrawal, but clinicians can incorporate some symptomatic medications such as clonidine, dicyclomine, loperamide, and lorazepam.
2. Initiate buprenorphine: Begin either in the office or at home, at 2 to 4 mg, then at 2 to 4 mg every 2 to 3 hours thereafter until cravings and withdrawal decrease. Clinicians should also watch for precipitated withdrawal.
3. Continue buprenorphine: The patient may be on the drug indefinitely (maintenance), or the drug may be tapered (withdrawal management).

DeVido continued with some updates, noting that the X waiver is gone, with all prescriptions for buprenorphine now only requiring a standard Drug Enforcement Administration registration number. There are also no patient limits, and clinicians who prescribe controlled substances (II to V) are now required to take 8 hours of training for new applications and renewals.

DeVido concluded by noting that although the patient must have a diagnosis of OUD in order to move forward with buprenorphine, clinicians do not need to be addiction specialists to make this diagnosis. He also advised clinicians to help patients avoid worrying about the long term and to offer patients with OUD the full range of medication-assisted treatment options available to them prior to deciding on a treatment plan. He also emphasized using a collaborative approach when working with patients, noting the potential of buprenorphine treatment to help facilitate this.

“Buprenorphine offers, in my opinion, a great opportunity for a collaborative approach to working with patients,” DeVido said. “And…it may offer an opportunity to be able to work with someone in such a way that they go from feeling like they don’t need treatment to saying, ‘Hey, maybe I’ll give this a try,’ which has a high likelihood of saving that person’s life.”

Motivational Interviewing for Eliciting Positive Change in Patients

Erin O’Brien

“In motivational interviewing, rather than confronting ambivalence, we explore it and help a patient resolve it, which means rather than saying, ‘This person is unmotivated,’ say, ‘Well, for what is this person motivated? What does this person want?’ ”

Brian Hurley, MD, MBA, FAPA, DFASAM, presented on motivational interviewing. Hurley is medical director of substance abuse prevention and control for the County of Los Angeles Department of Public Health as well as president of the American Society of Addiction Medicine, which runs a motivational interviewing course.

In his presentation, Hurley focused on the ways clinicians can apply the spirit of motivational interviewing when working with patients who are ambivalent about making changes in their lives. He also discussed the 4 metaprocesses of motivational interviewing; ways clinicians can identify and selectively reinforce the change talk that is elicited during clinical situations; and additional opportunities for training and practice of motivational interviewing skills.

Hurley discussed the nature of change, saying that it is natural, it occurs all the time, and it can be facilitated by treatment and interactions between clinicians and patients. Ambivalence, which clinicians often encounter when working with patients, is also normal, it needs to be explored rather than confronted, and resolving it can be the key to facilitating change. Hurley also emphasized the difference between change talk and sustain talk. He recommended that clinicians strengthen change talk because, as an individual argues on behalf of a position, the individual will become more committed to that position. He also recommended that clinicians soften sustain talk, as the more sustain talk is evoked during a counseling session, the more likely the patient will be to continue the status quo.

Hurley also described the “spirit” of motivational interviewing, which includes compassion, acceptance, partnership, and empowerment between clinicians and patients, and discussed the 4 processes involved in motivational interviewing, which include (1) planning, or how clinicians and patients will proceed; (2) evoking, or why clinicians and patients will proceed in this way; (3) focusing, or where clinicians and patients are planning to go; and (4) engaging, or clinicians and patients walking together throughout the journey; this is the most important step in motivational interviewing.

Finally, Hurley shared the core skills associated with effective motivational interviewing, which include asking open-ended questions, affirming, reflecting (in both simple and complex ways), summarizing, and informing and advising (with the patient’s permission). Hurley offered some practical tips for clinicians for eliciting change talk, including the following:

• Ask evocative questions.
• Explore decisional balance.
• Elaborate.
• Query extremes.
• Look both backward and forward.
• Explore goals and values.

Hurley ended the presentation by reminding listeners that engaging patients is the most important step in motivational interviewing. He also quoted 17th-century philosopher Blaise Pascal as a reminder for clinicians when trying to elicit positive change in their patients through motivational interviewing: “People are generally better persuaded by the reasons which they have themselves discovered than by those which have come into the mind of others.”

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