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Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, use requirements, and place in therapy of esketamine for treatment-resistant depression (TRD). Data Sources: A comprehensive PubMed search (1966 to October 2019) was conducted using the search terms depression, treatment-resistant, suicide, intranasal, esketamine , and JNJ-54135419 . Additional data were obtained from references of identified articles, governmental sources, manufacturer product labeling, and Clinicaltrials.gov . Study Selection and Data Extraction: All English-language trials evaluating intranasal esketamine for TRD were included and discussed. Data Synthesis: Intranasal esketamine was approved by the US Food and Drug Administration, in conjunction with an oral antidepressant, for treating TRD in adults. Two short-term trials (TRANSFORM-1 and -2) found statistically significant reduction in the Montgomery-Asberg Depression Rating Scale score at day 28 for the fixed 56-mg dose (-4.1; 95% CI = -7.69 to -0.49; P = 0.027 [exploratory]) and flexible-dosed arms (-4.0; 95% CI = -7.31 to -0.64; P = 0.02), though the fixed-dose 84-mg arm (-3.2; 95% CI = -6.88 to 0.45; P = 0.088) of TRANSFORM-1 and TRANSFORM-3 did not (-3.6; 95% CI = -7.2 to 0.07; P = 0.059). Two long-term trials (SUSTAIN-1 and -2) suggested maintenance of response with continued use. Esketamine's adverse effects include dizziness, dysgeusia, somnolence, dissociation, suicidal thoughts and behaviors, and increased heart rate and blood pressure. Relevance to Patient Care and Clinical Practice: Although providing a novel antidepressant mechanism and formulation for TRD, esketamine's role in treatment will likely be limited by cost, administration, and diversion concerns. Conclusion: Intranasal esketamine significantly reduced depression symptoms in TRD, though with tolerability issues.

Background: Atypical antipsychotic use among children and adolescents is a cause for concern secondary to metabolic adverse effects. There have been reports of weight gain, metabolic syndrome, dyslipidemia, glucose abnormalities, and decreased insulin sensitivity in children aged 4 to 19 years using atypical antipsychotics., Objective: To determine the prevalence of antidiabetic and antilipidemic medication use among children and adolescents receiving atypical antipsychotics and to evaluate whether the odds of receiving antidiabetic and antilipidemic medication differs among atypical antipsychotic agents., Methods: This retrospective cross-sectional study included Virginia Medicaid beneficiaries (2-17 years) continuously enrolled from August 1, 2010, to July 31, 2011. The participants were categorized into atypical antipsychotic exposed and unexposed. The prevalence of antidiabetic and antilipidemic medication use within the groups was computed. Logistic regression was used to calculate the odds of receiving antidiabetic or antilipidemic medication after controlling for age, sex, and race., Results: A total of 299593 and 4922 beneficiaries were identified in unexposed and exposed groups, respectively. The prevalence of antidiabetic medication use was 0.32% in the unexposed and 1.40% in the exposed group (P < 0.0001). Prevalence of antilipidemic medication use was 0.09% in the unexposed and 0.35% in the exposed group (P < 0.0001). Risperidone and quetiapine users had lower odds than olanzapine users of receiving antidiabetic medication. No differences between the odds of receiving antilipidemic medication among the different antipsychotics (P = 0.1653) were observed., Conclusions: Prevalence of antidiabetic and antilipidemic medication use was significantly higher among children and adolescent atypical antipsychotic users in a Virginia Medicaid population., (© The Author(s) 2016.)

Objective: To review the pharmacology, pharmacokinetics, efficacy data, and adverse effects of eszopiclone in the treatment of transient and chronic insomnia in adult and geriatric patients., Data Sources: A MEDLINE literature search (1966-May 2005) was conducted to retrieve articles and abstracts involving eszopiclone. The manufacturer of the drug provided a general summary of clinical data and abstracts of unpublished Phase III clinical trials., Study Selection and Data Extraction: All articles identified from the data sources were reviewed, and information deemed relevant was included for this review., Data Synthesis: Food and Drug Administration approval of eszopiclone was based on 6 double-blind, placebo-controlled trials. Five trials published in abstract or study form were reviewed. The sixth trial was not available for evaluation. An open-label continuation trial was also reviewed. All studies showed statistically significant improvements in sleep parameters in adult and elderly patients treated for insomnia with eszopiclone., Conclusions: The results of the 5 available double-blind, placebo-controlled studies (and 1 open-label, 6-month extension) showed that eszopiclone was safe and effective in the treatment of transient and chronic insomnia in adult and geriatric patients. Tolerance with long-term exposure (6 mo) and rebound insomnia were not observed. The results of the 6-month, open-label extension trial demonstrated that improvements in sleep parameters were sustained. Future studies comparing eszopiclone with other non benzodiazepine sedative-hypnotics (eg, zolpidem, zaleplon) are needed with cost data to clearly define the role of eszopiclone in the pharmacotherapy of chronic insomnia.

Objective: To review the clinical presentation and management of cognitive impairment associated with central nervous system HIV type 1 (HIV-1) infection., Data Sources: A MEDLINE search pertaining to HIV-related dementia (HIV-D) and pharmacologic management was performed. Additional literature was obtained from reference lists of the identified articles., Study Selection and Data Extraction: All clinical trials and case reports evaluating pharmacologic efficacy in terms of clinical response, cerebrospinal fluid (CSF) changes, and neuropathology were considered for inclusion. Selection was not restricted by study design because most information consists of open uncontrolled trials and case reports., Data Synthesis: HIV-D is characterized by a triad of disturbances in cognition, motor performance, and behavior in adults. Children present with developmental delay, cognitive impairment, poor brain growth, and other neurologic symptoms. The exact pathophysiologic mechanisms of HIV-D are not known. Numerous pharmacologic agents (e.g., nucleoside reverse transcriptase inhibitors, pentoxifylline, nitroglycerin, memantine, nimodipine, peptide T) are under investigation for management of HIV-D. Zidovudine is the most thoroughly investigated medication, with patients developing HIV-D less frequently and showing improvement on neuropsychological, CSF, and neuropathologic evaluations. Sustained response to zidovudine lasts 6 months to 1 year and optimal response is achieved at higher, but less tolerated, dosages. HIV-D patients frequently have comorbid psychiatric disorders requiring psychopharmacologic agents and are sensitive to the adverse effects of these medications., Conclusions: HIV-D is a devastating complication of HIV-1 infection. Zidovudine is the therapy of choice for prevention and management of cognitive impairment in symptomatic HIV-infected patients and patients with AIDS. Recommendations for other medications cannot be made secondary to lack of data. The management of HIV-D may include multiple agents as more data become available regarding combination therapy. Well-designed controlled trials are needed to evaluate the efficacy of established treatments and investigational medications in the management of HIV-D.