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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'.)
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 DISORDERS
Amygdalar activity and cardiovascular events (March 2017)
In a retrospective study of patients who underwent positron emission tomography/computerized tomography and were followed for a median of four years, increased resting metabolic activity in the amygdala was associated with an increased risk of cardiovascular events such as myocardial infarction, stroke, and unstable angina . A separate cross-sectional study showed that perceived stress was positively associated with amygdalar activity and arterial inflammation. These studies further add to the evidence that chronic emotional stress is associated with an increased risk of cardiovascular disease, and the mechanism that underlies this association may involve neural circuits that include the amygdala. (See "Psychosocial factors in acute myocardial infarction", section on 'Central nervous system dysfunction'.)
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'.)
PSYCHIATRIC CONSEQUENCES OF MEDICAL CONDITIONS
Psychiatric comorbidities in patients with narcolepsy (March 2017)
Small studies have found an increased rate of depression in patients with narcolepsy, but the risk of other psychiatric comorbidities has not been well established. In a population-based case-control study that included 9312 adults with narcolepsy and more than 45,000 age- and gender-matched controls, a broad range of psychiatric disorders were more common in patients with narcolepsy; the most prevalent were depressive disorders and anxiety, which were three to four times more common than in controls . Thus, recognition and treatment of psychiatric disorders is an important component of the care of patients with narcolepsy. (See "Clinical features and diagnosis of narcolepsy in adults", section on 'Other features'.)
Antipsychotics for delirium in terminally ill patients (January 2017)
The benefit of antipsychotics for management of delirium in terminally ill patients has been called into question by a randomized trial in which 247 inpatients of a hospice or palliative care service with mild to moderately severe delirium were assigned to oral risperidone, haloperidol, or placebo every 12 hours for 72 hours . All patients received individualized supportive care. Patients who received antipsychotics had more severe delirium, worse delirium-associated distress scores, more use of midazolam, more extrapyramidal effects, and worse short-term survival. In our view, this study does not justify abandoning the use of antipsychotics for severely agitated delirious patients but points to the importance of reversing precipitating causes, providing best supportive care for symptomatic distress associated with delirium, and the need for additional research on the use of antipsychotics. (See "Overview of managing common non-pain symptoms in palliative care", section on 'Treatment'.)
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'.)
Antipsychotic drugs and risk of falls and fracture (March 2017)
In a large, population-based sample of Finnish people with Alzheimer disease, new users of antipsychotic medication had an increased risk of hip fractures from the first days of use . Subsequent to multiple similar reports in patients with varied disorders, the US Food and Drug Administration (FDA) issued a warning that antipsychotic drugs may cause falls and fractures as a result of somnolence, postural hypotension, and/or motor and sensory instability, and recommended that a fall risk assessment be completed when initiating antipsychotic treatment and recurrently for patients continuing on long-term antipsychotics. (See "Second-generation antipsychotic medications: Pharmacology, administration, and side effects", section on 'Falls'.)
Abnormal glucose homeostasis in unmedicated schizophrenia (February 2017)
Hyperglycemia in patients with schizophrenia is principally thought of as a side effect of antipsychotic medications. However, in a meta-analysis of case-control studies comparing glucose homeostasis in antipsychotic-naïve individuals with first-episode schizophrenia versus healthy controls, patients with schizophrenia had higher fasting plasma glucose and insulin levels, lower glucose tolerance, and greater insulin resistance compared with controls, indicating altered glucose homeostasis from illness onset . Glycosylated hemoglobin did not differ between groups. Prospective studies are needed to determine whether the alterations are intrinsic to schizophrenia versus a result of factors associated with the disorder, such as a more sedentary lifestyle. (See "Schizophrenia in adults: Clinical manifestations, course, assessment, and diagnosis", section on 'Metabolic disturbances'.)
SUBSTANCE USE DISORDERS
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'.)
Concurrent benzodiazepines in opioid-using patients and overdose risk (April 2017)
Benzodiazepines can potentiate the respiratory depressant effects of opioid medication, and concurrent use may be a factor in the rising rate of opioid overdose. In an analysis of a large sample of patients prescribed an opioid, the proportion who concurrently received a benzodiazepine nearly doubled over 12 years . Concurrent use of both medications was associated with an increased risk of opioid overdose compared with patients receiving only the opioid. Avoiding this medication combination may prevent some overdoses. (See "Prevention of lethal opioid overdose in the community", section on 'Risk factors'.)
Heroin and fentanyl may drive rise in opioid overdose deaths (February 2017)
Mortality rates from drug overdoses involving methadone declined in 2015 in the United States, while drug overdoses involving heroin and synthetic opioids other than methadone increased sharply . The rise in overdoses from synthetic opioids was likely driven by illicitly manufactured fentanyl, a highly potent opioid used to "cut" heroin. (See "Prevention of lethal opioid overdose in the community", section on 'Epidemiology of overdose'.)
TRAUMA - AND STRESSOR-RELATED DISORDERS
Posttraumatic stress disorder after stroke (April 2017)
Recognition that experiencing a stroke or transient ischemic attack (TIA) can lead to posttraumatic stress disorder (PTSD) has emerged gradually over the past two decades. In a recent review of the literature, epidemiologic studies suggest that up to one in four cases of stroke or TIA may be associated with significant PTSD symptoms . (See "Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical manifestations, course, assessment, and diagnosis", section on 'Stroke'.)
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'.)
AASM guideline on pharmacotherapy for chronic insomnia in adults (March 2017)
The American Academy of Sleep Medicine (AASM) has released a new clinical practice guideline on the pharmacologic treatment of chronic insomnia in adults . The guideline reviews evidence of effectiveness for a variety of medications (including benzodiazepines, nonbenzodiazepine hypnotics, ramelteon, doxepin, and suvorexant) and notes limitations and potential biases to the evidence, leading to low confidence in the overall estimation of risk-to-benefit ratio. The potential short-term benefits of pharmacologic therapy need to be balanced with the risk of side effects and dependence with long-term use. We continue to prefer behavioral therapy, rather than pharmacotherapy, as an initial treatment approach in most patients. (See "Treatment of insomnia in adults", section on 'Choice of an agent'.)
Interactive web-based CBT for chronic insomnia (January 2017)
Cognitive behavioral therapy (CBT) is an effective treatment of chronic insomnia, but access to trained practitioners can be limited. In a randomized trial of 303 adults recruited via the internet, a six-week interactive web-based CBT program resulted in greater improvement in subjective sleep measures than internet patient education alone, and benefits were sustained at one year . Thus, internet-based CBT programs may be an alternative to in-person delivery for motivated, technology-savvy individuals. (See "Treatment of insomnia in adults", section on 'Cognitive behavioral therapy'.)
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