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What's new in psychiatry

What's new in psychiatry
Literature review current through: Jan 2024.
This topic last updated: Jan 17, 2024.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

BIPOLAR DISORDER

Duration of adjunctive antidepressant use for bipolar depression (August 2023)

For acute bipolar major depression that remits with adjunctive antidepressants, it is unclear how long to continue them. In a recent trial, 177 patients with bipolar I major depression who remitted with an antimanic drug plus an antidepressant were randomly assigned to continue the antidepressant for 8 or 52 weeks [1]. There was no statistically significant difference in relapse with any mood episode (depressive or manic/hypomanic) between the two groups. Generally, we continue antidepressants for approximately two to four months after remission of the depressive syndrome. (See "Bipolar major depression in adults: Efficacy and adverse effects of antidepressants", section on 'Maintenance treatment'.)

CHILD AND ADOLESCENT PSYCHIATRY

Dialectical behavior therapy for adolescents with bipolar disorder (January 2024)

Several trials have demonstrated that dialectical behavior therapy can reduce suicide attempts in youth who are suicidal, but most excluded patients with bipolar disorder. A recent randomized trial in adolescents with bipolar disorder who all received pharmacotherapy found fewer suicide attempts over one year follow-up among those who received adjunctive dialectical behavior therapy rather than usual psychotherapy [2]. Although multiple psychotherapies are reasonable for youth with bipolar disorder, we suggest dialectical behavior therapy for those at increased risk of suicide (eg, lifetime history of suicide attempt). (See "Pediatric bipolar disorder: Efficacy and core elements of adjunctive psychotherapy", section on 'Dialectical behavior therapy'.)

NEUROCOGNITIVE DISORDERS

Adult-onset ADHD and dementia (December 2023)

Individuals with adult-onset attention deficit hyperactivity disorder (ADHD) may have difficulties compensating for deficits from neurodegenerative or cerebrovascular processes, but any association with dementia has been inconsistent. In a prospective study including over 100,000 adults without ADHD or dementia at baseline, those who were subsequently diagnosed with adult-onset ADHD were more likely to receive a diagnosis of dementia (adjusted relative risk 2.8) [3]. Whether symptoms that resulted in the ADHD diagnosis were early or prodromal dementia symptoms is uncertain; nevertheless, these findings suggest that caregivers be alert for signs of dementia in individuals with adult-onset ADHD. (See "Attention deficit hyperactivity disorder in adults: Epidemiology, clinical features, assessment, and diagnosis", section on 'Comorbidity'.)

DEPRESSIVE DISORDERS

Esketamine for treatment-resistant depression (December 2023)

Although esketamine has established efficacy for treatment-resistant depression, direct comparisons with other agents are limited. In a recent open label randomized trial in 676 adults with treatment-resistant major depression receiving baseline antidepressant therapy, addition of esketamine nasal spray for 32 weeks led to higher remission rates than addition of quetiapine extended release (XR, 49 versus 33 percent) [4]. Rates of discontinuation for adverse events were nearly three times lower with esketamine then quetiapine XR (4 versus 11 percent). Nevertheless, clinicians and patients considering esketamine need to weigh its benefits and disadvantages, including the need to administer it in a certified medical clinic. (See "Unipolar depression in adults: Choosing treatment for resistant depression", section on 'Initial approach'.)

Psilocybin for treatment-resistant depression (October 2023)

The psychedelic psilocybin is being evaluated for treatment-resistant unipolar major depression and may provide a relatively rapid and durable response. In a trial of 104 patients, a single dose of psilocybin resulted in greater improvements in depressive symptoms than a single dose of niacin (the active placebo control); this effect occurred as early as day 8 and persisted until the end of the trial, at day 43 [5]. In addition, anxiety, psychosocial functioning, and quality of life improved more with psilocybin. However, it resulted in more frequent adverse events. Additional trials are necessary to determine who is most likely to benefit from psychedelics, the optimal dose and number of psilocybin sessions, type of patient preparation, whether and what type of accompanying psychotherapy should be administered, and how long the benefit persists. (See "Unipolar depression in adults: Choosing treatment for resistant depression", section on 'Psilocybin'.)

Transcranial direct current stimulation for unipolar major depression (August 2023)

Transcranial direct current stimulation (tDCS) is an investigational noninvasive treatment that uses two scalp electrodes to deliver a constant low-amplitude (weak) direct current to specific superficial cortical regions. Although tDCS has been effective for unipolar major depression in multiple randomized trials, a relatively large six-week trial in patients who had not responded to an antidepressant found comparable rates of remission with the addition of active versus sham tDCS [6]. Additional study is necessary to clarify whether tDCS has a role in the treatment of depression and which patients are most likely to benefit. (See "Unipolar depression in adults: Overview of neuromodulation procedures", section on 'Efficacy'.)

Zuranolone for severe postpartum depression (August 2023)

For patients with severe postpartum depression who prioritize rapid improvement, we suggest initial therapy with brexanolone; however, the agent requires continuous intravenous infusion for 60 hours in an inpatient facility. Recently, the US Food and Drug Administration approved zuranolone for postpartum depression; clinical availability is anticipated by the end of 2023 [7,8]. Zuranolone is an oral agent that is administered over 14 days, has a similar mechanism of action to brexanolone, and can also result in rapid remission of symptoms. We expect that some patients will prefer zuranolone over the infusion required for brexanolone. (See "Severe postpartum unipolar major depression: Choosing treatment", section on 'Treatment that is approved but not yet available'.)

OBSESSIVE-COMPULSIVE AND RELATED DISORDERS

Memantine for trichotillomania and skin picking disorder (July 2023)

Skin picking (excoriation) disorder (SPD) and related conditions, such as trichotillomania, are separate diagnoses in the group of obsessive-compulsive and related disorders; successful treatment is challenging. Pharmacologic therapy (primarily selective serotonin reuptake inhibitor antidepressants or, for patients with features of delusional disorder, atypical antipsychotics) is suggested for patients who don’t accept or are not responsive to behavioral therapy but efficacy is unclear. Memantine, an oral glutamate modulator, was evaluated in a randomized trial that included 100 adults with trichotillomania, skin picking disorder, or both [9]. At eight weeks, memantine, compared with placebo, was associated with greater improvement from baseline in the modified National Institute of Mental Health Trichotillomania Symptom Severity Scale and in the Clinical Global Impressions severity scale. Treatment was generally well tolerated with adverse effects occurring with similar frequency in both groups. While encouraging, the efficacy and safety of memantine needs confirmation in larger and longer duration trials. (See "Skin picking (excoriation) disorder and related disorders", section on 'Memantine'.)

PSYCHIATRIC CONSEQUENCES OF MEDICAL CONDITIONS

COVID-19 and mental health (September 2023)

Cross-sectional studies have suggested that mental health in the general public deteriorated during the COVID-19 pandemic. However, recent meta-analyses of higher-quality studies that assessed the same individuals before and during the pandemic indicate that overall mental health and anxiety symptoms did not worsen in the general population, and depressive symptoms worsened only slightly [10]. Nevertheless, the pandemic was associated with increased mental health symptoms in several subgroups, including females, older adults, parents, sexual minority groups, and university students. Surveillance of overall mental health, anxiety, and/or depression within these subgroups is warranted. (See "COVID-19: Psychiatric illness", section on 'General population'.)

SUBSTANCE USE DISORDERS

Mortality risk in alcohol-associated liver disease (January 2024)

Few studies have reported the long-term outcomes of patients with alcohol-associated liver disease (ALD). In a national registry study including over 23,000 patients with ALD diagnosed at median age 58 years, 67 percent died during >100,000 person-years of follow-up and liver disease was the primary cause of death in 45 percent [11]. The 5- and 10-year mortality rates due to liver disease were 26 and 31 percent, respectively. These data emphasize the importance of treating patients with alcohol use disorder and may inform strategies to prevent liver-related mortality in those with ALD. (See "Management of alcohol-associated steatosis and alcohol-associated cirrhosis", section on 'Mortality'.)

Cannabinoids and mental health in adolescents (December 2023)

Cannabis use is associated with an increased risk of mental health disorders. However, little is known about the effects of cannabidiol (CBD), a nonpsychoactive component of cannabis used for anorexia and childhood epilepsy, or of recreational synthetic cannabinoids. In a school-based survey from the United Kingdom that included over 6500 adolescents ages 13 to 14 years, reported use of cannabis, CBD, or synthetic cannabinoids were each associated with probable depression, anxiety disorder, or conduct disorder, as well as with auditory hallucinations [12]. For each disorder, the risk appeared greatest with synthetic cannabinoids. This study highlights the need for further investigation into the association between mental health effects in youth and the different types of cannabinoids. We advise adolescents (and younger children) to avoid cannabis consumption, including CBD. (See "Substance use disorder in adolescents: Epidemiology, clinical features, assessment, and diagnosis", section on 'Cannabis, cannabidiol, and synthetic cannabinoids'.)

Over-the-counter opioid antagonist for opioid overdose (September 2023)

Drug overdose is a major public health problem; opioids were reported to be involved in nearly 80 percent of the 600,000 overdose deaths worldwide in 2019. The increasing rate of fatal overdose is driven by the presence of the synthetic opioid fentanyl. Naloxone 4 mg nasal spray rapidly reverses the effects of opioid overdose and is now the first opioid antagonist agent available for over-the-counter purchase in the United States [13]. The increased availability is part of an ongoing effort by the US Food and Drug Administration Overdose Prevention Framework to encourage harm reduction through developing and expanding access to novel overdose reversal products. (See "Prevention of lethal opioid overdose in the community", section on 'Community-based naloxone'.)

New buprenorphine formulation for opioid use disorder (August 2023)

Buprenorphine, an opioid agonist used in the treatment of opioid use disorder, suppresses withdrawal symptoms and craving and blocks the effects of other opioids, thereby reducing opioid use. In 2023, the US Food and Drug Administration approved a new long-acting subcutaneous formulation of buprenorphine-XR (Brixadi) that is available in weekly or monthly formulations and does not require stabilization on sublingual buprenorphine [14]. Prior studies had demonstrated similar response rates and urine toxicology outcomes with this formulation compared with sublingual formulations. This option provides a long-acting alternative that may improve adherence while limiting misuse or diversion. (See "Opioid use disorder: Pharmacologic management", section on 'Injectable buprenorphine'.)

TRAUMA - AND STRESSOR-RELATED DISORDERS

Written exposure therapy for posttraumatic stress disorder (November 2023)

Many effective psychotherapies for posttraumatic stress disorder (PTSD), such as prolonged exposure therapy, are time- and resource-intensive; written exposure therapy (WET) is emerging as an alternative brief intervention. In a randomized trial, WET resulted in largely similar improvements in PTSD symptoms compared with prolonged exposure therapy and had a lower dropout rate (13 versus 36 percent) [15]. In addition to an earlier study in which WET compared favorably with cognitive processing therapy, these findings suggest that WET may be a viable psychotherapeutic option for individuals with PTSD who cannot participate in more intensive options. (See "Posttraumatic stress disorder in adults: Psychotherapy and psychosocial interventions", section on 'Efficacy of exposure therapy'.)

MDMA-assisted therapy for posttraumatic stress disorder (October 2023)

Posttraumatic stress disorder (PTSD) is a chronic, disabling disorder that is often resistant to treatment despite combined medication and psychotherapeutic management. The synthetic stimulant 3,4 methylenedioxymethamphetamine (MDMA, or "ecstasy") appears effective for moderate or severe PTSD when combined with a specific psychotherapy. In a trial of 104 subjects with PTSD undergoing three months of psychotherapy, those randomly assigned to also receive MDMA had a greater reduction in PTSD symptoms overall and a higher likelihood of no longer meeting criteria for PTSD by the end of the study (71 versus 48 percent) compared with those who received placebo [16]. While research using MDMA-assisted therapy is promising, MDMA is a restricted substance in most locations worldwide and such therapy thus has limited availability. (See "Posttraumatic stress disorder in adults: Treatment overview", section on 'Medications with limited supporting evidence'.)

OTHER PSYCHIATRY

Solriamfetol for ADHD in adults (January 2024)

Stimulants are typically first-line pharmacotherapy for attention deficit hypersensitivity disorder (ADHD) in adults but may be poorly tolerated and suboptimally effective in some patients. Solriamfetol, a selective dopamine/norepinephrine reuptake inhibitor used to treat narcolepsy, may be an effective alternative. In a trial of adults with ADHD, six weeks of solriamfetol resulted in higher rates of being "much improved" or "very much improved" (45 versus 6 percent) and higher rates of remission (24 versus 3 percent) compared with placebo [17]. While the treatment group had more adverse effects overall (ie, decreased appetite, insomnia, cardiovascular), all side effects related to treatment medication were mild or moderate in severity. Further trials are needed to determine the role of solriamfetol in adult ADHD treatment. (See "Attention deficit hyperactivity disorder in adults: Treatment overview", section on 'Treatments with limited supporting data in adult ADHD'.)

Nurse-delivered brief behavioral treatment for insomnia (October 2023)

A growing body of evidence supports the use of brief, behaviorally-focused treatments for insomnia, which involve fewer sessions than traditional cognitive behavioral therapy and can be delivered by clinicians with varied levels of expertise. In an open-label randomized trial in England involving nearly 650 adults with insomnia disorder recruited from 35 general practices, four sessions of nurse-delivered sleep restriction therapy (table 1) improved patient-reported insomnia severity scores and six-month response rates compared with a sleep hygiene booklet alone (table 2) [18]. Training nurses or advanced practice providers to deliver brief behavioral treatments may be a feasible and cost-effective way to improve outcomes for insomnia. (See "Cognitive behavioral therapy for insomnia in adults", section on 'Brief behavioral treatment approaches'.)

  1. Yatham LN, Arumugham SS, Kesavan M, et al. Duration of Adjunctive Antidepressant Maintenance in Bipolar I Depression. N Engl J Med 2023; 389:430.
  2. Goldstein TR, Merranko J, Rode N, et al. Dialectical Behavior Therapy for Adolescents With Bipolar Disorder: A Randomized Clinical Trial. JAMA Psychiatry 2024; 81:15.
  3. Levine SZ, Rotstein A, Kodesh A, et al. Adult Attention-Deficit/Hyperactivity Disorder and the Risk of Dementia. JAMA Netw Open 2023; 6:e2338088.
  4. Reif A, Bitter I, Buyze J, et al. Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression. N Engl J Med 2023; 389:1298.
  5. Raison CL, Sanacora G, Woolley J, et al. Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. JAMA 2023; 330:843.
  6. Burkhardt G, Kumpf U, Crispin A, et al. Transcranial direct current stimulation as an additional treatment to selective serotonin reuptake inhibitors in adults with major depressive disorder in Germany (DepressionDC): a triple-blind, randomised, sham-controlled, multicentre trial. Lancet 2023; 402:545.
  7. US FDA Approves First Oral Treatment for Postpartum Depression. August 4, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-postpartum-depression (Accessed on August 04, 2023).
  8. Prescribing Information (Label) for Zuranolone. August 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217369s000lbl.pdf (Accessed on August 14, 2023).
  9. Grant JE, Chesivoir E, Valle S, et al. Double-Blind Placebo-Controlled Study of Memantine in Trichotillomania and Skin-Picking Disorder. Am J Psychiatry 2023; 180:348.
  10. Sun Y, Wu Y, Fan S, et al. Comparison of mental health symptoms before and during the covid-19 pandemic: evidence from a systematic review and meta-analysis of 134 cohorts. BMJ 2023; 380:e074224.
  11. Kann AE, Jepsen P, Madsen LG, et al. Cause-specific mortality in patients with alcohol-related liver disease in Denmark: a population-based study. Lancet Gastroenterol Hepatol 2023; 8:1028.
  12. Hotham J, Cannings-John R, Moore L, et al. Association of cannabis, cannabidiol and synthetic cannabinoid use with mental health in UK adolescents. Br J Psychiatry 2023; 223:478.
  13. Naloxone Nasal Spray prescribing information. US Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208411lbl.pdf.
  14. Brixadi prescribing information. US Food and Drug Administration. https://www.brixadi.com/pdfs/brixadi-prescribing-information.pdf (Accessed on August 18, 2023).
  15. Sloan DM, Marx BP, Acierno R, et al. Written Exposure Therapy vs Prolonged Exposure Therapy in the Treatment of Posttraumatic Stress Disorder: A Randomized Clinical Trial. JAMA Psychiatry 2023; 80:1093.
  16. Mitchell JM, Ot'alora G M, van der Kolk B, et al. MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nat Med 2023; 29:2473.
  17. Surman CBH, Walsh DM, Horick N, et al. Solriamfetol for Attention-Deficit/Hyperactivity Disorder in Adults: A Double-Blind Placebo-Controlled Pilot Study. J Clin Psychiatry 2023; 84.
  18. Kyle SD, Siriwardena AN, Espie CA, et al. Clinical and cost-effectiveness of nurse-delivered sleep restriction therapy for insomnia in primary care (HABIT): a pragmatic, superiority, open-label, randomised controlled trial. Lancet 2023; 402:975.
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