Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
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.
Lithium may decrease self-harm in patients with bipolar disorder (August 2016)
Self-harm causes substantial morbidity in bipolar disorder, and patients who self-harm have an increased risk of suicide. Lithium may reduce the risk of self-harm. A recent study used electronic health records from a nationally representative sample from the United Kingdom to identify over 6000 patients with bipolar disorder who received maintenance monotherapy with lithium, valproate, olanzapine, or quetiapine . Self-harm included any nonfatal act of self-injury, regardless of suicidal intent. Patients were matched on observed potential confounders such as history of prior self-harm, sex, and comorbid disorders. Self-harm rates were lower with lithium, compared with valproate, olanzapine, or quetiapine. There was no difference in the rate of self-harm among valproate, olanzapine, or quetiapine. Lithium is one of our preferred options for maintenance therapy for patients with bipolar disorder. (See "Bipolar disorder in adults: Choosing maintenance treatment", section on 'Reduced risk of suicide'.)
CHILD AND ADOLESCENT PSYCHIATRY
Effectiveness of antidepressants for pediatric unipolar major depression (August 2016)
Antidepressant medications are often used to treat moderately to severely ill children with unipolar major depression. For children and adolescents with acute depressive disorders, first-line pharmacotherapy is typically fluoxetine. There are several randomized trials comparing antidepressant medications with placebo, but there are few head-to-head comparison trials. In a recent meta-analysis of 34 trials comparing one antidepressant with placebo or another active drug for the acute treatment of major depressive disorder in children and adolescents, fluoxetine, sertraline, and escitalopram were statistically more efficacious than placebo . In addition, paroxetine was superior to clomipramine and fluoxetine was superior to nortriptyline. In a network meta-analysis subsequently performed to compare and rank antidepressants for the acute treatment of major depressive disorder, only fluoxetine was better than placebo. In comparison with other antidepressants, fluoxetine was significantly more effective than nortriptyline. Important limitations of the network meta-analysis include risk of bias within individual studies, lack of power and generalizability, and potential selective reporting. (See "Pediatric unipolar depression and pharmacotherapy: Choosing a medication", section on 'All antidepressants'.)
Continuation treatment with electroconvulsive therapy plus pharmacotherapy for remitted late-life depression (August 2016)
Electroconvulsive therapy (ECT) is often more effective for unipolar major depression than pharmacotherapy and psychotherapy, particularly for late-life depression. Although continuation treatment for patients who remit with ECT typically consists of pharmacotherapy, ECT plus pharmacotherapy is superior to pharmacotherapy alone. In one study, older adults with unipolar major depression were acutely treated with ECT plus venlafaxine; those who remitted (n = 120) were randomly assigned to six months of open-label continuation treatment with ECT plus pharmacotherapy (continuation venlafaxine plus lithium) or pharmacotherapy alone . Continuation ECT consisted of four weekly treatments following randomization and subsequent treatments as warranted by symptoms. Depression rating scale scores were lower with ECT plus pharmacotherapy than pharmacotherapy alone. There was no difference between the two groups in global cognitive functioning at baseline and post-ECT. Continuation ECT plus pharmacotherapy can benefit patients with late-life depression who initially respond to acute treatment with ECT plus pharmacotherapy. (See "Overview of electroconvulsive therapy (ECT) for adults", section on 'Efficacy'.)
FEEDING AND EATING DISORDERS
Treatment of binge eating disorder (July 2016)
Several psychotherapies and medications have been studied for treating binge eating disorder. In a recent systematic review and meta-analysis of trials evaluating the efficacy of different treatment options compared with no treatment or placebo, there was strong evidence supporting the use of therapist-led cognitive-behavior therapy (CBT), lisdexamfetamine, or second-generation antidepressants (eg, selective serotonin reuptake inhibitors) . In addition, less compelling evidence indicated that patients can achieve abstinence with self-help CBT or topiramate. We regard CBT as first-line treatment; however, no head-to-head trials have compared the efficacy of different active treatments. (See "Binge eating disorder in adults: Overview of treatment", section on 'Cognitive-behavior therapy'.)
MEDICAL CONSEQUENCES OF PSYCHIATRIC TREATMENTS
Olanzapine linked to drug reaction with eosinophilia and systemic symptoms (DRESS) (May 2016)
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, potentially life-threatening, drug-induced hypersensitivity reaction that includes skin eruption, fever, hematologic abnormalities, lymphadenopathy, and internal organ involvement. Antiepileptic agents and allopurinol are the most frequently reported causes. In May 2016 the US Food and Drug Administration issued a warning that the antipsychotic drug olanzapine may cause DRESS, with 23 cases reported worldwide since 1996 . A prolonged latency time (two to eight weeks) between drug exposure and development of symptoms is characteristic of DRESS. Prompt withdrawal of the offending drug and supportive measures are the mainstay of treatment. (See "Drug reaction with eosinophilia and systemic symptoms (DRESS)", section on 'Etiology and risk factors'.)
Age of symptom onset and diagnosis of adult ADHD (September 2016)
Attention deficit hyperactivity disorder (ADHD) is conceptualized as a disorder with childhood onset that persists in adulthood. DSM-5 diagnostic criteria for adult ADHD require the presence of several symptoms prior to age 12 years. Multiple recent studies, however, have challenged this understanding of the disorder. One of them, a longitudinal cohort study, followed all children born in Pelotas, Brazil in 1993 up to the ages of 18 or 19 years . Three hundred ninety-three of the 5249 children were diagnosed with ADHD at age 11 and 492 were diagnosed with ADHD at age 18 or 19 years. Only 60 children with ADHD continued to have ADHD as young adults (17.2 percent) and only 60 young adults with ADHD had the disorder in childhood (12.6 percent). The requirement of childhood onset for the diagnosis of adult ADHD is controversial and may be reexamined as further data become available. (See "Attention deficit hyperactivity disorder in adults: Epidemiology, pathogenesis, clinical features, course, assessment, and diagnosis", section on 'Course'.)
Adjunctive antidepressant treatment in patients with schizophrenia (September 2016)
Approximately one in four patients with schizophrenia will experience a major depressive episode in their lifetime. Identification and management of depression requires exclusion of other clinical entities with overlapping presentations, such as negative symptoms of schizophrenia or antipsychotic drug-induced extrapyramidal symptoms. Previous systematic reviews have reported mixed effects of adjunctive antidepressants in schizophrenia patients; the clinical trials have multiple methodological limitations. A recent systematic review and meta-analysis, the largest to date, found that adjunctive antidepressant treatment compared with placebo or no adjunctive treatment in antipsychotic-treated schizophrenia patients led to reductions in depressive, negative, and overall symptoms without increasing psychotic symptoms . Beyond the typical antidepressant side effects, no differences in adverse events were seen between groups. The findings support antidepressant treatment of apparent depression in schizophrenia, particularly after optimization of antipsychotic medication management. (See "Depression in schizophrenia", section on 'Pharmacotherapy for major depressive disorder'.)
SUBSTANCE USE DISORDERS
Clinical manifestations of severe synthetic cannabinoid toxicity (July 2016)
Synthetic cannabinoids consist of a heterogeneous group of chemical compounds that act as agonists at cannabinoid receptors with 2 to 800 times the potency of delta-9 tetrahydrocannabinol (THC), the active component of cannabis (marijuana). They have emerged as a popular recreational drug in the United States and Europe. In an observational study of a multicenter, hospital-based registry of medical toxicology consultations, over two-thirds of 277 patients with single-agent exposure to synthetic cannabinoids had altered mental status including severe agitation, toxic psychosis, hallucinations, seizures, and coma . Rhabdomyolysis and acute kidney injury were present in approximately 5 percent of these patients. There were three deaths, including a 17-year-old adolescent with sudden death after first-time inhalational use. Thus, unlike cannabis, synthetic cannabinoids have significant potential to cause serious and life-threatening toxicity among recreational users. (See "Synthetic cannabinoids: Acute intoxication", section on 'Clinical manifestations'.)
Efficacy of long-acting buprenorphine implant in opioid use disorder (July 2016)
Sublingual buprenorphine reduces opioid use and improves abstinence in patients with opioid use disorder. Inconsistent adherence, misuse, and diversion, however, limit the drug's effectiveness. Prior trials have found that a long-acting buprenorphine implant is more effective than a placebo implant, but the implanted and sublingual formulations of the drug had not been subject to blinded comparison. A recent, noninferiority trial compared sublingual buprenorphine with placebo implants versus buprenorphine implants with sublingual placebo in 177 opioid-dependent outpatients who had been abstinent on a stable dose of sublingual buprenorphine for at least three months . There was no difference between groups in the proportion of patients who responded to treatment over a six-month period (87.6 and 96.4 percent, respectively). Response rates were very high in this trial; further trials are still needed in the broader population of opioid-dependent patients. (See "Pharmacotherapy for opioid use disorder", section on 'Long-acting subdermal implant'.)
Dopamine-agonist treatment for treatment-refractory cocaine dependence (June 2016)
Analogous to treating opioid-dependent patients with methadone (a long-acting opioid-agonist), researchers have attempted to treat cocaine-dependent patients with long-acting dopamine agonists. Three earlier trials achieved mixed results and high dropout rates. In a recent clinical trial from the Netherlands, 73 patients with treatment-refractory heroin and cocaine dependence were randomly assigned to receive either 12 weeks of oral dexamphetamine-sustained release (SR) or placebo . All patients received methadone and diacetylmorphine (heroin-assisted treatment). Eighty-nine percent of participants completed the trial in which dexamphetamine-SR treatment resulted in fewer days of cocaine use compared with placebo treatment (44.9 versus 60.6 days). Similar results were seen for secondary cocaine use outcomes. No serious adverse events occurred in dexamphetamine-treated patients. Further study is need to replicate and extend these results to stimulant-dependent patients in more routine treatment settings. (See "Pharmacotherapy for stimulant use disorders in adults", section on 'Dopamine agonists'.)
Extended-release naltrexone for prevention of opioid relapse in adults who had been incarcerated (May 2016)
Extended-release naltrexone may help prevent opioid relapse. A randomized trial in 308 community dwelling adults who had been incarcerated and who had a history of opioid dependence compared usual treatment (brief counseling and referral to community treatment programs) with extended-release naltrexone therapy for 24 weeks . Those who received extended-release naltrexone therapy had a longer time to relapse and lower rate of relapse. One year after the treatment (at 78 weeks), there were no overdose events in the intervention group and seven in the control group. However, the rates of opioid-negative urine samples were equal between groups at 78 weeks. (See "Clinical care of incarcerated adults", section on 'Substance use disorders' and "Pharmacotherapy for opioid use disorder", section on 'Long-acting injectable naltrexone'.)
Safety of smoking cessation medications in patients with and without mental health disorders (May 2016)
Reports of newly emergent depression, suicidal ideation, and suicidal behavior among patients receiving bupropion or varenicline for smoking cessation raised questions about the safety of these drugs in smokers with mental health disorders. In a recent trial examining the safety of these medications, more than 8000 motivated adult smokers, approximately half with clinically stable mental disorders, were randomly assigned to varenicline, bupropion, transdermal nicotine, or placebo for 12 weeks . Compared with patients without mental health disorders, patients with such disorders were more likely to experience neuropsychiatric adverse events (including anxiety, depression, agitation, or hostility) during treatment (2.1 versus 5.8 percent). However, in both patients with and without mental health disorders, the rate of events did not differ for patients assigned to varenicline or bupropion compared with placebo. Rates of smoking abstinence were higher for each of the three drugs compared with placebo, and higher with varenicline compared with bupropion or transdermal nicotine. The findings are consistent with previous, smaller trials supporting carefully monitored use of smoking-cessation medications in smokers with stable mental health disorders. (See "Pharmacotherapy for co-occurring schizophrenia and substance use disorder", section on 'Safety' and "Pharmacotherapy for smoking cessation in adults", section on 'Neuropsychiatric effects'.)
TRAUMA - AND STRESSOR-RELATED DISORDERS
Quetiapine monotherapy reduces symptoms of PTSD (August 2016)
There are few evidence-based medication options for patients with posttraumatic stress disorder (PTSD) who do not respond fully to treatment with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). In trials to date, second-generation antipsychotic (SGA) drugs have been most promising, but they carry a significant side effect burden and have limited evidence of benefit. In a recent 12-week clinical trial comparing quetiapine monotherapy with placebo in 80 United States military veterans with chronic PTSD, patients assigned to receive quetiapine compared with placebo experienced reductions in PTSD symptoms overall and in symptoms specific to re-experiencing and hyperarousal . These results support a role for SGA medications in the treatment of PTSD resistant to SSRIs/SNRIs. Trauma-focused cognitive behavioral therapy (CBT) is favored over medication as first-line treatment for PTSD, but medication is an acceptable alternative if CBT is not available or the patient prefers medication. (See "Pharmacotherapy for posttraumatic stress disorder in adults", section on 'Monotherapy'.)
Use of adjunctive antidepressants for treating complicated grief with comorbid depression (August 2016)
Complicated grief is a distinct syndrome that often occurs in bereaved individuals and is characterized by maladaptive thoughts, dysfunctional behaviors, and poorly regulated emotions. The best treatment for complicated grief is psychotherapy that is specific for complicated grief (complicated grief therapy, CGT). Antidepressants are frequently prescribed as an adjunctive therapy. Although adjunctive antidepressants do not appear to mitigate symptoms of complicated grief, they can improve comorbid unipolar major depression, which is common. In a recent trial, 395 adults with complicated grief were randomly assigned to citalopram alone, placebo alone, CGT plus citalopram, or CGT plus placebo . As expected, more patients responded to CGT plus placebo than placebo alone. The addition of citalopram did not significantly improve complicated grief outcomes. However, improvement of depressive symptoms was greater with citalopram. Thus, in patients with complicated grief and depressive symptoms, the addition of citalopram may be helpful. (See "Complicated grief in adults: Treatment", section on 'Other options'.)
Cognitive-behavioral therapy and other psychotherapies for prevention of recurrent self-harm (August 2016)
Self-harm is defined as an intentional act of self-injury, regardless of suicidal intent, and is a growing problem that consumes considerable hospital resources. Psychotherapy is typically used to manage patients who self-harm, and a recent study establishes that specific psychotherapies can be beneficial. A meta-analysis of 10 randomized trials compared cognitive-behavioral therapy (CBT) or problem solving therapy with usual care in >2200 patients with an episode of self-harm who were followed for up to 12 months . Repetition of self-harm was less likely to occur with CBT/problem solving therapy than usual care (odds ratio 0.80). In addition, improvement of depression, including hopelessness and suicidal ideation, was greater with active treatment. The review also included a meta-analysis of three randomized trials that compared dialectical behavior therapy with usual care in patients with an episode of self-harm; the frequency of self-harm decreased more with dialectical behavior therapy. (See "Suicidal ideation and behavior in adults", section on 'Psychotherapy'.)
Clinical practice guideline for chronic insomnia in adults (May 2016)
The American College of Physicians has released a new clinical practice guideline for the management of chronic insomnia in adults . The guideline recommends that all patients receive cognitive behavioral therapy for insomnia (CBT-I) as the initial treatment for chronic insomnia disorder. The guideline suggests that clinicians use a shared decision-making approach, including discussion of benefits, harms, and costs of short-term use of medications, to decide whether to add medication to CBT-I in patients with persistent symptoms. This approach is consistent with our preference for behavioral therapy over medication in most patients with chronic insomnia, particularly in older adults and patients with organ dysfunction, who are at increased risk for side effects from sedative-hypnotic drugs. (See "Treatment of insomnia", section on 'General approach'.)
- Hayes JF, Pitman A, Marston L, et al. Self-harm, Unintentional Injury, and Suicide in Bipolar Disorder During Maintenance Mood Stabilizer Treatment: A UK Population-Based Electronic Health Records Study. JAMA Psychiatry 2016; 73:630.
- Cipriani A, Zhou X, Del Giovane C, et al. Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. Lancet 2016; 388:881.
- Kellner CH, Husain MM, Knapp RG, et al. A Novel Strategy for Continuation ECT in Geriatric Depression: Phase 2 of the PRIDE Study. Am J Psychiatry 2016; :appiajp201616010118.
- Brownley KA, Berkman ND, Peat CM, et al. Binge-Eating Disorder in Adults: A Systematic Review and Meta-analysis. Ann Intern Med 2016; 165:409.
- Caye A, Rocha TB, Anselmi L, et al. Attention-Deficit/Hyperactivity Disorder Trajectories From Childhood to Young Adulthood: Evidence From a Birth Cohort Supporting a Late-Onset Syndrome. JAMA Psychiatry 2016; 73:705.
- Helfer B, Samara MT, Huhn M, et al. Efficacy and Safety of Antidepressants Added to Antipsychotics for Schizophrenia: A Systematic Review and Meta-Analysis. Am J Psychiatry 2016; 173:876.
- Riederer AM, Campleman SL, Carlson RG, et al. Acute Poisonings from Synthetic Cannabinoids - 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010-2015. MMWR Morb Mortal Wkly Rep 2016; 65:692.
- Rosenthal RN, Lofwall MR, Kim S, et al. Effect of Buprenorphine Implants on Illicit Opioid Use Among Abstinent Adults With Opioid Dependence Treated With Sublingual Buprenorphine: A Randomized Clinical Trial. JAMA 2016; 316:282.
- Nuijten M, Blanken P, van de Wetering B, et al. Sustained-release dexamfetamine in the treatment of chronic cocaine-dependent patients on heroin-assisted treatment: a randomised, double-blind, placebo-controlled trial. Lancet 2016; 387:2226.
- Lee JD, Friedmann PD, Kinlock TW, et al. Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders. N Engl J Med 2016; 374:1232.
- Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet 2016; 387:2507.
- Villarreal G, Hamner MB, Cañive JM, et al. Efficacy of Quetiapine Monotherapy in Posttraumatic Stress Disorder: A Randomized, Placebo-Controlled Trial. Am J Psychiatry 2016; :appiajp201615070967.
- Shear MK, Reynolds CF 3rd, Simon NM, et al. Optimizing Treatment of Complicated Grief: A Randomized Clinical Trial. JAMA Psychiatry 2016; 73:685.
- Hawton K, Witt KG, Salisbury TL, et al. Psychosocial interventions following self-harm in adults: a systematic review and meta-analysis. Lancet Psychiatry 2016; 3:740.
- Qaseem A, Kansagara D, Forciea MA, et al. Management of Chronic Insomnia Disorder in Adults: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med 2016; 165:125.