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What's new in psychiatry

What's new in psychiatry
Authors:
David Solomon, MD
Michael Friedman, MD
Literature review current through: Feb 2022. | This topic last updated: Mar 01, 2022.

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

Lumateperone for bipolar depression (January 2022)

Drawbacks to antipsychotics currently used for treatment of bipolar disorder include poor efficacy for associated depression, which often accounts for a high proportion of morbidity in such patients, and frequent undesirable side effects. In a clinical trial of individuals with type I or II bipolar depression, lumateperone, an antipsychotic with a novel mechanism, led to greater rates of response (51 versus 37 percent) and remission (40 versus 34 percent) compared with placebo [1]. Treatment emergent side effects occurred at similar rates to placebo. While lumateperone may be a promising new option with minimal side effects for the treatment of bipolar disorder, further studies are needed in order to define its optimal role. (See "Bipolar major depression in adults: Efficacy and adverse effects of second-generation antipsychotics", section on 'Lumateperone'.)

Prenatal antipsychotics and psychopathology in the offspring (September 2021)

Maternal use of antipsychotics during pregnancy does not appear to increase the risk of psychopathology in offspring. A retrospective study of electronic medical records identified over 400,000 mother-child pairs in which 706 had gestational exposure to antipsychotics [2]. After adjusting for potential confounding factors, the risks of attention-deficit hyperactivity disorder and autism spectrum disorder in the exposed and nonexposed children were comparable. These results are reassuring for pregnant patients with bipolar disorder who require antipsychotics. (See "Teratogenicity, pregnancy complications, and postnatal risks of antipsychotics, benzodiazepines, lithium, and electroconvulsive therapy", section on 'Developmental effects'.)

CHILD AND ADOLESCENT PSYCHIATRY

Rise in functional tics in adolescents and young adults (January 2022)

An increase in functional tics has been observed during the COVID-19 pandemic. Cases have been referred to as "TikTok tics," as affected individuals have commonly viewed online videos depicting tic-like behaviors [3]. Most patients are females between 15 and 25 years of age. Symptom onset is usually acute, with complex vocal and motor tics involving large-amplitude arm movements, self-injury, and a wide range of odd words or phrases, often with obscenities. The stresses of the pandemic are believed to be contributing, and comorbid depression and anxiety disorders are common. (See "Functional movement disorders", section on 'Functional tics'.)

NEUROCOGNITIVE DISORDERS

Clinical use of pimavanserin in patients with neurodegenerative dementias (September 2021)

Pimavanserin is a newer antipsychotic agent that has been approved in the United States (US) since 2016 for treatment of psychosis in patients with Parkinson disease (PD). Two new reports expand information on both efficacy and potential risks in patients with neurodegenerative diseases:

In a randomized discontinuation trial of pimavanserin in 351 patients with dementia-related psychosis, among those who responded initially to treatment, relapses were approximately half as common in patients assigned to continued pimavanserin compared with placebo [4].

In a retrospective cohort study of >20,000 older adults with PD living in long-term care facilities in the US, pimavanserin use, compared with nonuse, was associated with an increased adjusted risk of 30-day hospitalization and mortality at multiple time points [5]. Residual confounding is possible, although other studies have raised similar safety concerns for antipsychotic agents as a class.

Like other antipsychotic agents, pimavanserin should be used selectively in patients with dementia and/or PD after discussing potential risks and benefits of treatment, alternative therapies for psychosis (algorithm 1 and algorithm 2), and risks related to ongoing symptoms. (See "Management of nonmotor symptoms in Parkinson disease", section on 'Refractory psychotic symptoms' and "Management of neuropsychiatric symptoms of dementia", section on 'Antipsychotic drugs'.)

DEPRESSIVE DISORDERS

Omega-3 fatty acids and depression (March 2022)

Marine omega-3 fatty acids may have a limited adjunctive role in treatment of selected patients with acute major depression; however, recent evidence indicates that they do not prevent depression. A five-year randomized trial compared omega-3 fatty acids with placebo in more than 18,000 patients (mean age 68 years) without depression [6]. Active treatment consisted of eicosapentaenoic acid 465 mg/day and docosahexaenoic acid 375 mg/day. Onset of depressive symptoms was comparable in the two groups. Thus, we recommend not prescribing omega-3 fatty acids to prevent depression. (See "Diagnosis and management of late-life unipolar depression", section on 'Prevention'.)

Inflammatory markers in patients with depression (December 2021)

There is emerging interest in use of biomarkers, including inflammatory markers, to identify specific subpopulations of individuals with depression who may benefit from targeted treatment. In an analysis of 15 prospective studies including over 56,000 individuals with depression, elevated levels of C-reactive protein and interleukin-6 were associated with physical symptoms including appetite changes, anergia, and sleep difficulty [7]. In contrast, an association with specific emotional symptoms, such as hopelessness or fearfulness, was not found. Further study is warranted to investigate the potential role of anti-inflammatory agents for specific symptoms associated with elevated inflammatory markers. (See "Unipolar depression: Neurobiology", section on 'Inflammation'.)

Maintenance therapy of unipolar depression (December 2021)

The effectiveness and choice of maintenance therapy after recovery from unipolar depression are unclear. A recent trial enrolled 478 primary care patients who recovered from their most recent depressive episode with second-generation antidepressant drug therapy, continued taking the drug for at least nine months, and felt well enough to discontinue treatment [8]. In this double-blind trial, patients were randomly assigned to antidepressant maintenance or taper-and-discontinuation (with placebo substitution) over two months. Maintenance resulted in a lower rate of recurrence (39 versus 56 percent) and fewer anxiety and withdrawal symptoms; side effects were similar in the two groups. For patients who recover from an acute episode of depression, we recommend maintenance treatment. (See "Unipolar depression in adults: Continuation and maintenance treatment", section on 'Compared with placebo'.)

Electroconvulsive therapy and risk of serious medical events (September 2021)

Electroconvulsive therapy (ECT) is underutilized due to stigma and concerns about medical complications. However, in a retrospective cohort study of over 10,000 patients hospitalized for depression, the rate of serious medical events was low and trended lower among those exposed to ECT compared with a propensity score-matched unexposed group (0.25 versus 0.33 events per person-year) [9]. Serious medical events were defined as a composite of hospitalization for nonpsychiatric reasons and non-suicide mortality within 30 days of the exposure date or corresponding index date. Clinicians can use these findings and previous data to reassure candidates for ECT that it is one of the safest procedures performed under general anesthesia. (See "Overview of electroconvulsive therapy (ECT) for adults", section on 'Adverse general medical effects'.)

Electroconvulsive therapy and suicide (September 2021)

Electroconvulsive therapy (ECT) is often beneficial for patients with severe, treatment-resistant depression and may reduce the risk of suicide. In a Swedish national registry study comparing >5500 patients hospitalized for depression who received ECT with a similar number who did not, fewer patients in the ECT group died of suicide during the 12 months following hospital admission (1.1 versus 1.6 percent, after adjusting for potential confounding factors) [10]. We suggest offering ECT to patients with treatment-resistant depression and suicidal behavior. (See "Unipolar major depression in adults: Indications for and efficacy of electroconvulsive therapy (ECT)", section on 'Suicidality'.)

MEDICAL CONSEQUENCES OF PSYCHIATRIC DISORDERS

Preexisting psychiatric disorders and COVID-19-related outcomes (September 2021)

Patients with preexisting psychiatric disorders who develop SARS-CoV-2 infection may be at increased risk for severe COVID-19. In a meta-analysis of observational studies including nearly 1.5 million COVID-19 patients, preexisting psychiatric disorders (>40,000 patients) were associated with increased risks of COVID-19-related hospitalization and death, which remained after adjustment for confounding factors [11]. Patients with psychotic or mood disorders were at highest risk. These findings underscore the importance of SARS-CoV-2 vaccination in this vulnerable population, which may be less informed or have reduced access to care. (See "COVID-19: Psychiatric illness", section on 'Patients with pre-existing psychiatric illness'.)

SUBSTANCE USE DISORDERS

Dental problems associated with oral dissolving buprenorphine (January 2022)

There are >300 reports of dental problems associated with use of buprenorphine formulations dissolved in the mouth, including the buccal formulation and sublingual tablets [12,13]. Reported problems include dental caries, abscesses, and damaged teeth, many of which have required tooth removal. The incidence of dental problems with buprenorphine is unknown. Patients who use orally dissolving buprenorphine should swish and swallow water after the drug has dissolved, see a dentist soon after starting the drug, and make sure the dentist knows they are taking the drug. The US Food and Drug Administration (FDA) has issued a related safety advisory and will mandate a label change. (See "Use of opioids in the management of chronic non-cancer pain", section on 'Buprenorphine for chronic pain'.)

Varenicline for cannabis use disorder (December 2021)

Cannabis use disorder (CUD) can cause substantial psychosocial disability; however, few medications are effective in its treatment. Varenicline, a selective nicotinic acetylcholine receptor agonist used for smoking cessation, is a candidate agent for CUD treatment. In a trial of 72 individuals with CUD, six weeks of varenicline resulted in higher abstinence rates at each study visit (17 versus 5 percent at week six) and greater decrease in cannabis use (42 versus 27 percent fewer days) compared with placebo [14]. Additional and larger trials are warranted to confirm this effect of varenicline in patients with CUD. (See "Cannabis use disorder in adults", section on 'Potentially beneficial medications'.)

Aggressive buprenorphine dosing in individuals with opioid use disorder (August 2021)

Aggressively treating opioid use disorder (OUD) at a first encounter is a potential way to mitigate delays in access to care, although the efficacy and safety of this approach are uncertain. In a retrospective review of 579 individuals with OUD who were seen in the emergency department, aggressive initial dosing of buprenorphine (12 to 32 mg, given as monoproduct without naloxone) was well tolerated with a low incidence of nausea or vomiting and without toxicity (ie, sedation or respiratory depression) [15]. Fewer than 1 percent had precipitated withdrawal. The extended opioid blockade provided by the high dose may lessen withdrawal sufficiently to facilitate acceptance of buprenorphine by the patient and thus improve transition to outpatient treatment. (See "Medication for opioid use disorder".)

OTHER PSYCHIATRY

Daridorexant for treatment of insomnia in adults (January 2022)

Daridorexant, a dual orexin receptor antagonist (DORA), has been approved by the US Food and Drug Administration (FDA) for treatment of insomnia in adults [16]. Like lemborexant and suvorexant, daridorexant improves both subjective and objective measures of sleep onset and sleep maintenance compared with placebo [17]. Among the three DORAs, daridorexant has the shortest half-life (approximately eight hours) (table 1). For adults who fail or do not have access to cognitive behavioral therapy, we consider DORAs to be an acceptable first-line option for sleep maintenance insomnia, along with benzodiazepine receptor agonists (BZRAs) and low-dose doxepin (algorithm 3); for sleep-onset insomnia, we prefer trying medications with shorter half-lives first. (See "Pharmacotherapy for insomnia in adults", section on 'Dual orexin receptor antagonists'.)

Suicide in nurses and physicians (September 2021)

Older studies reported increased risks of suicide among physicians. However, in a retrospective study of United States suicide data from 2017 to 2018 in over 600 nurses, 200 physicians, and 40,000 individuals in the general population, the incidence of suicide among nurses was significantly higher than that in the general population (relative risk [RR] 1.18), whereas physicians had a similar incidence (RR 1.01), after adjusting for sex differences [18]. Nurses also had a nonstatistically significant increased incidence of suicide compared with physicians. The elevated suicide risk in nurses may be due to job demands, avoiding use of psychiatric care due to stigma, or access to medications as a means of suicide. Thus, efforts to enhance well-being in physicians should be accompanied by similar initiatives for nurses. (See "Suicidal ideation and behavior in adults".)

REFERENCES

  1. Calabrese JR, Durgam S, Satlin A, et al. Efficacy and Safety of Lumateperone for Major Depressive Episodes Associated With Bipolar I or Bipolar II Disorder: A Phase 3 Randomized Placebo-Controlled Trial. Am J Psychiatry 2021; 178:1098.
  2. Wang Z, Chan AYL, Coghill D, et al. Association Between Prenatal Exposure to Antipsychotics and Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Preterm Birth, and Small for Gestational Age. JAMA Intern Med 2021; 181:1332.
  3. Pringsheim T, Ganos C, McGuire JF, et al. Rapid Onset Functional Tic-Like Behaviors in Young Females During the COVID-19 Pandemic. Mov Disord 2021; 36:2707.
  4. Tariot PN, Cummings JL, Soto-Martin ME, et al. Trial of Pimavanserin in Dementia-Related Psychosis. N Engl J Med 2021; 385:309.
  5. Hwang YJ, Alexander GC, An H, et al. Risk of Hospitalization and Death Associated With Pimavanserin Use in Older Adults With Parkinson Disease. Neurology 2021; 97:e1266.
  6. Okereke OI, Vyas CM, Mischoulon D, et al. Effect of Long-term Supplementation With Marine Omega-3 Fatty Acids vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial. JAMA 2021; 326:2385.
  7. Frank P, Jokela M, Batty GD, et al. Association Between Systemic Inflammation and Individual Symptoms of Depression: A Pooled Analysis of 15 Population-Based Cohort Studies. Am J Psychiatry 2021; 178:1107.
  8. Lewis G, Marston L, Duffy L, et al. Maintenance or Discontinuation of Antidepressants in Primary Care. N Engl J Med 2021; 385:1257.
  9. Kaster TS, Vigod SN, Gomes T, et al. Risk of serious medical events in patients with depression treated with electroconvulsive therapy: a propensity score-matched, retrospective cohort study. Lancet Psychiatry 2021; 8:686.
  10. Rönnqvist I, Nilsson FK, Nordenskjöld A. Electroconvulsive Therapy and the Risk of Suicide in Hospitalized Patients With Major Depressive Disorder. JAMA Netw Open 2021; 4:e2116589.
  11. Vai B, Mazza MG, Delli Colli C, et al. Mental disorders and risk of COVID-19-related mortality, hospitalisation, and intensive care unit admission: a systematic review and meta-analysis. Lancet Psychiatry 2021; 8:797.
  12. Suzuki J, Mittal L, Woo SB. Sublingual buprenorphine and dental problems: a case series. Prim Care Companion CNS Disord 2013; 15.
  13. https://www.fda.gov/media/155352/download.
  14. McRae-Clark AL, Gray KM, Baker NL, et al. Varenicline as a treatment for cannabis use disorder: A placebo-controlled pilot trial. Drug Alcohol Depend 2021; 229:109111.
  15. Herring AA, Vosooghi AA, Luftig J, et al. High-Dose Buprenorphine Induction in the Emergency Department for Treatment of Opioid Use Disorder. JAMA Netw Open 2021; 4:e2117128.
  16. Quviviq (daridorexant) prescribing information. https://www.idorsia.us/documents/us/label/Quviviq_PI.pdf.
  17. 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; 21:125.
  18. Davis MA, Cher BAY, Friese CR, Bynum JPW. Association of US Nurse and Physician Occupation With Risk of Suicide. JAMA Psychiatry 2021.
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References

1 : Efficacy and Safety of Lumateperone for Major Depressive Episodes Associated With Bipolar I or Bipolar II Disorder: A Phase 3 Randomized Placebo-Controlled Trial.

2 : Association Between Prenatal Exposure to Antipsychotics and Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Preterm Birth, and Small for Gestational Age.

3 : Rapid Onset Functional Tic-Like Behaviors in Young Females During the COVID-19 Pandemic.

4 : Trial of Pimavanserin in Dementia-Related Psychosis.

5 : Risk of Hospitalization and Death Associated With Pimavanserin Use in Older Adults With Parkinson Disease.

6 : Effect of Long-term Supplementation With Marine Omega-3 Fatty Acids vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial.

7 : Association Between Systemic Inflammation and Individual Symptoms of Depression: A Pooled Analysis of 15 Population-Based Cohort Studies.

8 : Maintenance or Discontinuation of Antidepressants in Primary Care.

9 : Risk of serious medical events in patients with depression treated with electroconvulsive therapy: a propensity score-matched, retrospective cohort study.

10 : Electroconvulsive Therapy and the Risk of Suicide in Hospitalized Patients With Major Depressive Disorder.

11 : Mental disorders and risk of COVID-19-related mortality, hospitalisation, and intensive care unit admission: a systematic review and meta-analysis.

12 : Sublingual buprenorphine and dental problems: a case series.

13 : Sublingual buprenorphine and dental problems: a case series.

14 : Varenicline as a treatment for cannabis use disorder: A placebo-controlled pilot trial.

15 : High-Dose Buprenorphine Induction in the Emergency Department for Treatment of Opioid Use Disorder.

16 : High-Dose Buprenorphine Induction in the Emergency Department for Treatment of Opioid Use Disorder.

17 : Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials.

18 : Association of US Nurse and Physician Occupation With Risk of Suicide.