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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.
Antenatal exposure to lithium and congenital cardiac defects (June 2017)
Fetal lithium exposure may increase the risk of cardiac malformations, although the data are conflicting. In a retrospective study examining cardiac defects in infants exposed to lithium or lamotrigine during the first trimester, cardiac malformations occurred more frequently in infants exposed to lithium (2.4 versus 1.4 percent) . There was a dose-response relationship between the lithium dose and the risk of cardiac malformations. These results support using lamotrigine for euthymic patients with bipolar disorder who are pregnant or planning a pregnancy and are receiving maintenance pharmacotherapy. (See "Teratogenicity, pregnancy complications, and postnatal risks of antipsychotics, benzodiazepines, lithium, and electroconvulsive therapy", section on 'Cardiac'.)
CHILD AND ADOLESCENT PSYCHIATRY
Childhood adversity and risk of adolescent and young adult suicide (May 2017)
Although suicide rates generally appear to be declining, the rate in adolescents and young adults is increasing, and suicide is one of the leading causes of death in this group. In a cohort study of nearly 550,000 adolescents and young adults (431 of whom committed suicide), which examined the relationship between childhood adversity and risk of suicide, childhood adversity increased the risk of suicide in a dose-dependent manner; exposure to multiple childhood adversities was associated with a greater risk of suicide than exposure to one adversity . Thus, adolescents with a history of multiple childhood adversities may constitute a high-risk group that is readily identifiable for targeted preventive interventions. (See "Suicidal behavior in children and adolescents: Epidemiology and risk factors", section on 'Childhood adversity'.)
Methylphenidate for apathy in patients with Alzheimer disease (October 2017)
Apathy is a common and understudied symptom of dementia that can emerge early in the disease course and contribute to functional impairment and caregiver burden. In a randomized trial of 77 patients with mild Alzheimer disease (AD), methylphenidate improved apathy scores compared with placebo over a 12-week treatment period . Adverse effects were similar between groups. These results add support to low-dose methylphenidate as an option in patients with persistent and distressing apathy despite a cholinesterase inhibitor and treatment of depression. (See "Management of neuropsychiatric symptoms of dementia", section on 'Apathy'.)
Management of treatment resistant depression in adults (August 2017)
For patients with treatment resistant depression, there has been little comparative evidence to guide the choice between add-on therapy (augmentation) and switching to a different antidepressant drug. In an open label trial, more than 1500 patients with treatment resistant depression were randomly assigned to one of three treatment strategies: augment the current antidepressant with aripiprazole, augment with bupropion sustained release, or switch to bupropion . At 12 weeks, remission was more likely in the augment-aripiprazole group than the switch group, but the clinical difference was small (29 versus 22 percent). Akathisia, somnolence, weight gain, and laboratory abnormalities were more common with aripiprazole, and anxiety occurred more often in the other groups. Based on these results, we now favor augmentation for managing treatment resistant depression; however, switching remains a reasonable alternative, especially for patients who want to avoid medication side effects. (See "Unipolar depression in adults: Treatment of resistant depression", section on 'Efficacy of augmentation compared with switching'.)
Transcranial direct current stimulation for major depression (July 2017)
Transcranial direct current stimulation (tDCS) is an investigational nonpharmacologic therapy for major depression. In a 10-week trial, 245 patients with unipolar depression were randomly assigned to active tDCS (22 sessions) plus oral placebo, sham tDCS plus escitalopram (20 mg/day), or sham tDCS plus oral placebo . Improvement of depression was greater with escitalopram than active tDCS, and both were superior to placebo. Pharmacotherapy and/or psychotherapy remain the treatment of choice for depression. (See "Depression in adults: Overview of neuromodulation procedures", section on 'Efficacy'.)
Investigational treatment for postpartum depression (July 2017)
Although several options are available to treat postpartum depression, many patients do not readily respond to standard treatments. In a trial comparing the investigational drug brexanolone (a neuroactive steroid, administered as a single, continuous intravenous infusion for 60 hours) with placebo in 21 inpatients with severe postpartum unipolar major depression, improvement in depression score at 60 hours was greater with brexanolone . A larger trial is in progress. (See "Severe postpartum unipolar major depression: Treatment", section on 'Investigational treatments'.)
FEEDING AND EATING DISORDERS
Genetics of anorexia nervosa (June 2017)
Although aggregation of anorexia nervosa in families suggests that genetic factors (and/or environmental factors) may be involved, multiple genome-wide association studies have not identified single nucleotide polymorphisms that are associated with the illness. However, a recent meta-analysis of genome-wide association studies, which included nearly 3500 cases and 11,000 controls, identified a significant locus on chromosome 12 (rs4622308) that was correlated with anorexia nervosa . In addition, the study found positive genetic correlations between anorexia nervosa and neuroticism, schizophrenia, and educational attainment, suggesting that the same genes are involved across these phenotypes. (See "Eating disorders: Overview of epidemiology, clinical features, and diagnosis", section on 'Pathogenesis and neurobiology'.)
MEDICAL CONSEQUENCES OF PSYCHIATRIC TREATMENTS
Valbenazine for tardive dyskinesia (May 2017)
Tetrabenazine and valbenazine are vesicular monoamine transporter 2 inhibitors that deplete presynaptic dopamine and may be useful therapeutic agents for tardive dyskinesia (TD). Data from old, small studies supported the utility of tetrabenazine for this indication. Now there is evidence from the placebo-controlled KINECT 3 trial that valbenazine 40 mg once daily reduces dyskinesia in patients with TD . For patients who have disturbing and intrusive tardive dyskinesia or tardive dystonia not amenable to treatment with botulinum toxin, we suggest treatment with tetrabenazine or valbenazine. (See "Tardive dyskinesia: Prevention and treatment", section on 'Valbenazine'.)
Medication for ADHD and motor vehicle collision risk (May 2017)
Previous studies have found that individuals with attention deficit hyperactivity disorder (ADHD) are more likely to experience a motor vehicle collision compared with individuals without the disorder. A cohort study of more than two million people treated for ADHD in the United States found a reduction in the risk of a motor vehicle collision during months when they were receiving ADHD medication compared with months when they were not . Future research might examine the consistency of the risk reduction across ADHD medications and dosing strategies. (See "Pharmacotherapy for adult attention deficit hyperactivity disorder", section on 'Effect on ADHD consequences'.)
Long-acting injectable antipsychotics and rehospitalization (June 2017)
Compared with daily oral antipsychotic drugs, long-acting injectable (LAI) antipsychotics are thought to benefit schizophrenia patients with medication nonadherence and multiple relapses. Although clinical trials and observational studies have not detected this advantage, they are limited due to the difficulty of enrolling unstable patients in trials and by selection bias between observed groups. In a population-based study of Swedish patients with schizophrenia, which included patients without regard to adherence or relapse, and in which each patient served as his/her own control, use of LAI antipsychotics compared with equivalent oral formulations was associated with a reduction in the risk of rehospitalization . These results support our suggestion to use LAI antipsychotics for patients with schizophrenia who relapse due to medication nonadherence. (See "Pharmacotherapy for schizophrenia: Long-acting injectable antipsychotic drugs", section on 'Efficacy'.)
Cariprazine for negative symptoms in schizophrenia (May 2017)
Multiple classes of psychotropic medications, including second-generation antipsychotics (SGA), have failed to reduce negative symptoms of schizophrenia (eg, decreased expressiveness, apathy, and flat affect) to a clinically meaningful degree. In a well-designed trial comparing a new SGA, cariprazine, to risperidone in schizophrenia patients with predominantly negative symptoms, cariprazine was more effective in reducing negative symptoms . The findings, which were accompanied by an improvement in patient social functioning, require replication in an additional trial. (See "Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment", section on 'Drug efficacy'.)
SUBSTANCE USE DISORDERS
Misuse of prescribed opioids (September 2017)
Misuse of prescribed opioid drugs is a major source of escalating rates of opioid use disorder and opioid overdose in the United States. The 2015 National Survey on Drug Use and Health estimated that among the 92 million US adults prescribed opioid drugs in the prior year, almost 13 percent reported prescription opioid misuse, and 2 percent reported having a prescription opioid use disorder . Misuse reported by study subjects included taking higher or more frequent doses than prescribed and buying or using opioids prescribed to someone else. (See "Prescription drug misuse: Epidemiology, prevention, identification, and management", section on 'Misuse'.)
N-acetylcysteine in cannabis use disorder (July 2017)
The antioxidant N-acetylcysteine (NAC) has shown promise of efficacy in a prior clinical trial comparing NAC with placebo in young adults receiving counseling with contingency management for cannabis use disorder. A new larger trial, however, that also compared NAC with placebo in adults receiving counseling with contingency management for cannabis use disorder found no difference in abstinence rates (based on urine tests) over 12 weeks . It is not known whether factors related to the trial designs, study samples, or medication effectiveness led to the disparate results. (See "Treatment of cannabis use disorder", section on 'N-acetylcysteine'.)
Methamphetamine use and cardiomyopathy (June 2017)
Cardiovascular complications, particularly cardiomyopathy, are the leading causes of death among individuals using methamphetamine, yet there are few data on cardiomyopathy outcomes among methamphetamine users. In a study of 30 methamphetamine users with reduced left ventricular ejection fraction (LVEF) who were followed for a mean of nearly three years, cessation of use compared with continuing use was associated with better cardiac function and a trend toward reduced cardiac symptoms . The extent of myocardial fibrosis was associated with the duration of methamphetamine use and may serve as a marker of irreversible ventricular changes. (See "Methamphetamine use disorder: Epidemiology, clinical manifestations, course, assessment, and diagnosis", section on 'Cardiovascular disease'.)
Contingency management for alcohol use (June 2017)
Contingency management, which offers incentives to discourage substance use and encourage abstinence, has been found to be effective for several common types of substance use disorders, although efficacy data for alcohol use have been limited. In a small clinical trial evaluating daily contingency management or daily noncontingent reinforcement in adults with heavy drinking, patients assigned to contingency management had a higher proportion of days with no drinking detected using an early stage, transdermal alcohol sensor (54.3 versus 31.2 percent) . This trial adds to the growing body of evidence showing the intervention may be efficacious for alcohol use. (See "Psychosocial treatment of alcohol use disorder", section on 'Contingency management'.)
Medical use of prescription opioid medications and misuse in adolescents (May 2017)
Surveys of high school seniors in the United States over 40 years show that the use of prescription opioids is strongly correlated with misuse in adolescents and that misuse typically follows medical use by the patient . Thus, health care providers should follow safe prescribing guidance for prescription opioids, including use of alternatives (eg, acetaminophen or ibuprofen) to control pain whenever possible, using the lowest effective dose and minimum quantity of prescription opioid medications when they are needed, and utilizing prescription drug monitoring programs, where available, to identify patients or caregivers who might be misusing (ie, abusing or diverting) prescription opioid medications. (See "Opioid intoxication in children and adolescents", section on 'Safe prescribing'.)
Preventing suicide attempts (June 2017)
Interventions for suicidality that address social isolation and provide a bridge between an emergency department visit and outpatient care may help reduce suicide attempts. In a prospective observational study comparing usual care alone; universal screening for suicidality plus usual care; and universal screening, usual care, plus an adjunctive intervention (eg, safety plan, follow-up phone calls) in nearly 1400 suicidal patients who presented to an emergency department, there were fewer suicide attempts in patients who received the intervention than in those who received usual care alone . There was no difference between usual care and universal screening plus usual care. A relatively brief adjunctive intervention for high-risk patients may decrease suicidal behavior. (See "Suicidal ideation and behavior in adults", section on 'Adjunctive interventions'.)
Violence toward oneself and others (May 2017)
Deliberate self-harm in young adults may be associated with an increased risk of aggression toward others. In a national registry study of over 1.85 million individuals aged 15 to 32 years, including over 50,000 patients who were treated for deliberate self-harm, conviction of a violent crime occurred twice as often in patients treated for self-harm compared with the general population . The rate among males and females with self-harm was similar. Patients with intentional self-harm should be assessed for risk of violence toward others as well as themselves. (See "Suicidal ideation and behavior in adults", section on 'Association with violent criminality'.)
- Patorno E, Huybrechts KF, Bateman BT, et al. Lithium Use in Pregnancy and the Risk of Cardiac Malformations. N Engl J Med 2017; 376:2245.
- Björkenstam C, Kosidou K, Björkenstam E. Childhood adversity and risk of suicide: cohort study of 548 721 adolescents and young adults in Sweden. BMJ 2017; 357:j1334.
- Padala PR, Padala KP, Lensing SY, et al. Methylphenidate for Apathy in Community-Dwelling Older Veterans With Mild Alzheimer's Disease: A Double-Blind, Randomized, Placebo-Controlled Trial. Am J Psychiatry 2017; :appiajp201717030316.
- Mohamed S, Johnson GR, Chen P, et al. Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial. JAMA 2017; 318:132.
- Brunoni AR, Moffa AH, Sampaio-Junior B, et al. Trial of Electrical Direct-Current Therapy versus Escitalopram for Depression. N Engl J Med 2017; 376:2523.
- Kanes S, Colquhoun H, Gunduz-Bruce H, et al. Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial. Lancet 2017; 390:480.
- Duncan L, Yilmaz Z, Gaspar H, et al. Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa. Am J Psychiatry 2017; 174:850.
- Hauser RA, Factor SA, Marder SR, et al. KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia. Am J Psychiatry 2017; 174:476.
- Chang Z, Quinn PD, Hur K, et al. Association Between Medication Use for Attention-Deficit/Hyperactivity Disorder and Risk of Motor Vehicle Crashes. JAMA Psychiatry 2017; 74:597.
- Tiihonen J, Mittendorfer-Rutz E, Majak M, et al. Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia. JAMA Psychiatry 2017; 74:686.
- Németh G, Laszlovszky I, Czobor P, et al. Cariprazine versus risperidone monotherapy for treatment of predominant negative symptoms in patients with schizophrenia: a randomised, double-blind, controlled trial. Lancet 2017; 389:1103.
- Han B, Compton WM, Blanco C, et al. Prescription Opioid Use, Misuse, and Use Disorders in U.S. Adults: 2015 National Survey on Drug Use and Health. Ann Intern Med 2017; 167:293.
- Gray KM, Sonne SC, McClure EA, et al. A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults. Drug Alcohol Depend 2017; 177:249.
- Schürer S, Klingel K, Sandri M, et al. Clinical Characteristics, Histopathological Features, and Clinical Outcome of Methamphetamine-Associated Cardiomyopathy. JACC Heart Fail 2017; 5:435.
- Barnett NP, Celio MA, Tidey JW, et al. A preliminary randomized controlled trial of contingency management for alcohol use reduction using a transdermal alcohol sensor. Addiction 2017; 112:1025.
- McCabe SE, West BT, Veliz P, et al. Trends in Medical and Nonmedical Use of Prescription Opioids Among US Adolescents: 1976-2015. Pediatrics 2017.
- Miller IW, Camargo CA Jr, Arias SA, et al. Suicide Prevention in an Emergency Department Population: The ED-SAFE Study. JAMA Psychiatry 2017; 74:563.
- Sahlin H, Kuja-Halkola R, Bjureberg J, et al. Association Between Deliberate Self-harm and Violent Criminality. JAMA Psychiatry 2017.