Version August 2025
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.
CHILD AND ADOLESCENT PSYCHIATRY
Neuropsychiatric events with initiation of montelukast versus long-acting beta-agonist for asthma (April 2025)
Whether leukotriene antagonist administration results in increased neuropsychiatric events (NPEs) in children and adolescents is controversial. Large observational studies often demonstrate an association with increased risk; however, this may be related to worsening asthma control in those who required leukotriene antagonist initiation. In a new national database study from Sweden, investigators compared new montelukast users with new long-acting beta-agonist (LABA) users to help avoid this confounding. Incident neuropsychiatric adverse events were uncommon and nearly identical in those with new montelukast use compared with those with LABA use (2.39 versus 2.41 per 100 patient-years; hazard ratio 0.99) [1]. These data should offer reassurance to clinicians and caregivers of those who require these medications. (See "Antileukotriene agents in the management of asthma", section on 'Leukotriene receptor antagonists'.)
Suicide in preteens (February 2025)
Although suicide deaths in preteens are rare, they remain a leading cause of death and the incidence appears to be increasing over time. A recent study in children ages 8 to 12 years found that the rate of suicide between the periods 2009 to 2015 and 2016 to 2023 increased by 40 percent [2]. Among preteens with risk factors for suicide, such as psychiatric disorders, we suggest monitoring for suicidal ideation and behavior. Patients with suicidality should be treated for any underlying disorder and provided with a safety plan. (See "Suicidal behavior in children and adolescents: Epidemiology and risk factors", section on 'Age'.)
DEPRESSIVE DISORDERS
Bright light therapy in nonseasonal major depression (February 2025)
Although bright light therapy is a standard treatment for seasonal affective disorder, its efficacy for nonseasonal major depression has been less certain. In a recent meta-analysis of eight randomized trials involving 547 participants with nonseasonal depression, bright light therapy (eg, 10,000 lux for 30 minutes for four weeks) resulted in a greater remission rate than control interventions (typically dim red light; 41 versus 24 percent) [3]. Inclusion of individuals with both unipolar and bipolar depression limited the certainty of these findings. In individuals with nonseasonal major depression, we suggest bright light therapy as an adjunct to pharmacotherapy and/or psychotherapy. (See "Major depressive disorder in adults: Treatment with supplemental interventions", section on 'Bright light therapy'.)
Treatment of postpartum depression by nonspecialists (January 2025)
Although cognitive-behavioral therapy (CBT) is an established treatment for postpartum depression, access may be limited due to the restricted availability of specialists to administer it. A recent trial of over 700 individuals with postpartum depression found that recovery was two times more likely with CBT provided by nonspecialist health workers than with usual care [4]. These results support our recommendation of standard psychotherapies such as CBT, administered by specialists or nonspecialists, for all patients with mild to moderate postpartum depression to improve outcomes for patients and their offspring. (See "Mild to moderate postpartum unipolar major depression: Treatment", section on 'Evidence of efficacy'.)
FEEDING AND EATING DISORDERS
Anorexia nervosa and cardiovascular conditions (March 2025)
Weight loss and malnutrition in anorexia nervosa can lead to comorbidities, including cardiovascular conditions such as cardiomyopathy and conduction disorders. A recent study found that the incidence of any cardiac condition at the five-year follow-up was nearly two times greater in those with anorexia nervosa compared with controls without any eating disorder [5]. Patients with anorexia nervosa should be monitored for comorbidities, including structural and functional cardiovascular conditions, that may warrant specific management along with nutritional replenishment. (See "Anorexia nervosa in adults and adolescents: Medical complications and their management", section on 'Any cardiovascular condition'.)
NEURODEVELOPMENTAL DISORDERS
Methylphenidate safety during pregnancy (January 2025)
Stimulants are the preferred drug class for pharmacologic therapy of ADHD in adults; however, their safety during pregnancy has not been firmly established. In a meta-analysis that evaluated fetal outcomes in over 30,000 pregnant adults with ADHD, exposure to methylphenidate during pregnancy was not associated with an increased risk of congenital abnormality or miscarriage [6]. These data add to the growing literature on the safety of methylphenidate during pregnancy, and we discuss them with pregnant patients (or patients planning pregnancy) when using shared decision-making regarding use of stimulants for ADHD. (See "Attention deficit hyperactivity disorder in adults: Treatment overview", section on 'Pregnancy'.)
PSYCHIATRIC CONSEQUENCES OF MEDICAL CONDITIONS
Screening for anxiety and depression in children and adolescents with epilepsy (November 2024)
New consensus-based recommendations on the diagnosis and treatment of anxiety and depression in children and adolescents with epilepsy are available from the International League Against Epilepsy (ILAE) [7]. These recommendations include screening for anxiety and depression in all children and adolescents with epilepsy at age 7 years and annually thereafter, use of a formal screening questionnaire to assess symptoms of anxiety and depression, and closer surveillance for groups at higher risk (eg, those with suicidal behavior). Screening interviews should include the child with epilepsy and their parents or other caregivers, and they should be informed about the potential adverse behavioral effects of antiseizure medications. We agree with the ILAE recommendations, including referral of patients with moderate to severe depression or anxiety to a mental health care clinician. (See "Epilepsy in children and adolescents: Comorbidities, complications, and outcomes", section on 'Anxiety and depression'.)
PSYCHOTIC DISORDERS
Monitoring neutrophil count during clozapine treatment (March 2025)
Clozapine is effective for treatment of resistant schizophrenia or schizophrenia accompanied by persistent suicidality. However, the need for frequent neutrophil count monitoring through the Clozapine Risk Evaluation and Mitigation Strategy (REMS) program has been a barrier resulting in its underutilization. The US Food and Drug Administration has voted to abolish the REMS program after determining that it did not measurably mitigate the risk of neutropenia beyond what the labeling alone could accomplish [8]. Clinicians are encouraged to monitor neutrophil counts as detailed in the prescribing information until new evidence-based guidelines for clozapine initiation and monitoring are suggested. (See "Schizophrenia in adults: Guidelines for prescribing clozapine".)
SUBSTANCE USE DISORDERS
Treatment retention in opioid use disorder (February 2025)
Data from randomized trials suggest that in individuals with opioid use disorder (OUD), treatment retention is higher with methadone than buprenorphine-naloxone. However, many of these trials were conducted in selected populations before the widespread use of potent synthetic opioids, such as fentanyl. In a recent population-based cohort study including nearly 31,000 individuals initiating treatment for OUD, rates of treatment discontinuation were higher among recipients of buprenorphine-naloxone than methadone (89 versus 82 percent) [9]. Among participants who reached optimal medication doses, discontinuation rates continued to favor methadone (42 versus 31 percent), and these results were consistent after the introduction of fentanyl. This study reinforces prior evidence supporting greater treatment retention with methadone than buprenorphine-naloxone, even in populations using fentanyl. (See "Opioid use disorder: Treatment overview", section on 'Use of buprenorphine or methadone'.)
Semaglutide for alcohol use disorder (February 2025)
Preliminary findings from cohort studies suggest that semaglutide, a glucagon-like peptide-1 receptor agonist, may reduce alcohol cravings and alcohol use. In a randomized trial including 48 participants with alcohol use disorder, nine weeks of subcutaneous semaglutide (doses from 0.25 mg to 1 mg weekly) reduced weekly alcohol cravings and the number of heavy drinking days (by approximately one day per week) compared with placebo [10]. These results suggest a potential role for semaglutide in the management of alcohol use disorder and justify the need for larger trials. (See "Alcohol use disorder: Pharmacologic management", section on 'Therapies with unclear efficacy'.)
Masked taper for discontinuing benzodiazepines (December 2024)
For individuals who need to discontinue chronic benzodiazepines, the optimal tapering strategy to minimize withdrawal symptoms is unclear. In a recent randomized trial of 188 older adults with insomnia, a masked taper over nine weeks (ie, benzodiazepine pills with progressively increasing inert filler) plus augmented cognitive-behavioral therapy for insomnia (CBT-I, with exercises targeting expectations about the taper and placebo effects) increased the rate of benzodiazepine discontinuation at six months compared with an unmasked taper plus standard CBT-I (73 versus 59 percent) [11]. Although the results suggest that blinding patients to the taper rate may help improve benzodiazepine discontinuation, participants took relatively low doses at baseline (4 mg diazepam equivalents); thus, the efficacy of this strategy in other populations using higher doses, as in benzodiazepine use disorder, is uncertain. (See "Benzodiazepine use disorder", section on 'Taper rate'.)
TRAUMA - AND STRESSOR-RELATED DISORDERS
Combination pharmacotherapy for posttraumatic stress disorder (February 2025)
Novel treatment options are needed for posttraumatic stress disorder (PTSD), which is often only partially responsive to treatment and frequently leads to persistent psychosocial dysfunction. In a randomized trial of 416 participants with PTSD, the combination of brexpiprazole, a second-generation antipsychotic agent, plus sertraline, a selective serotonin reuptake inhibitor, reduced measures of symptoms severity after ten weeks compared with sertraline plus placebo [12]. Measures of anxiety, depression, and psychosocial functioning, and discontinuation due to adverse effects also favored treatment with brexpiprazole plus sertraline. Further studies investigating the utility of this combination in the treatment of PTSD are warranted. (See "Posttraumatic stress disorder in adults: Treatment overview", section on 'Treatments with limited supporting evidence'.)
OTHER PSYCHIATRY
Concurrent administration of parenteral olanzapine and a benzodiazepine not associated with increased risk of tracheal intubation (November 2024)
Concurrent use of intravenous or intramuscular olanzapine with a parenteral benzodiazepine has been discouraged based on a post-marketing report of excess sedation and respiratory depression, including 29 fatalities. In a retrospective study of nearly 700 patients treated for agitation in the emergency department, the 144 patients receiving parenteral olanzapine and a benzodiazepine within 60 minutes of each other had similar rates of tracheal intubation compared with those receiving two doses of parenteral olanzapine only (549 patients, 3.8 versus 3.5 percent, respectively) [13]. Other studies (most retrospective) have also found similar rates of complications. Combining parenteral olanzapine with a benzodiazepine is likely not associated with an increased risk of complications compared with olanzapine alone or other sedative agents; potential complications can be mitigated with proper monitoring and avoidance of this coadministration in patients with alcohol intoxication or compromised respiratory function. (See "The acutely agitated or violent adult: Pharmacologic management", section on 'Second-generation (atypical) antipsychotics'.)
