Cynthia K. Kirkwood

Management of Insomnia

OBJECTIVE To review current issues in the pharmacologic and nonpharmacologic management of insomnia. DATA SOURCES Controlled trials and case studies identified via MEDLINE for 1990 through April 1999 under the search terms insomnia, hypnotics, flurazepam, quazepam, estazolam, temazepam, triazolam, zolpidem, zaleplon, L-846, CL-284,846, melatonin, and valerian. DATA SYNTHESIS Insomnia is a common, undertreated disorder. Nonpharmacologic management strategies (e.g., stimulus control, relaxation therapy, sleep hygiene) are therapeutic options that, compared with medication use, provide more sustained effects. The benzodiazepines and zolpidem are the most commonly prescribed hypnotic agents, but their use is associated with tolerance and central nervous system adverse effects. A new nonbenzodiazepine hypnotic agent, zaleplon, was very recently approved in the United States. Because of its short half-life, zaleplon will be useful in patients experiencing difficulty in falling asleep and in those who wake up at night and have trouble falling back to sleep. Antidepressants, antihistamines, and alternative medications are other treatment options. To avoid complications of therapy, hypnotic agents should be used at their lowest possible doses and for limited treatment durations. CONCLUSION Pharmacotherapy is currently the most common treatment modality for insomnia, but long-term use of hypnotic agents can become complicated by drug tolerance, dependence, or rebound insomnia. Nonpharmacologic options--including combinations of behavioral interventions, sleep-restriction therapy, and patient education--provide longer-lasting benefits.

Eszopiclone for Insomnia

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 The manufacturer of the drug provided a general summary of clinical data and abstracts of unpublished Phase III clinical trials.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.

Pharmacotherapy of HIV dementia

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.

Prevalence of Antidiabetic and Antilipidemic Medications in Children and Adolescents Treated With Atypical Antipsychotics in a Virginia Medicaid Population

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.

Management of insomnia in elderly patients using eszopiclone

Insomnia is a common sleep complaint in the elderly. The safety and efficacy of eszopiclone, a non-benzodiazepine hypnotic, in elderly patients with chronic insomnia has been established in two 2-week and one 12-week randomized, double-blind, placebo-controlled trials. Eszopiclone 1 mg was effective in reducing sleep latency. Eszopiclone 2 mg was effective in reducing latency to sleep and for increasing sleep maintenance. Eszopiclone doses of 1 mg and 2 mg reduced the number of daytime naps and decreased the duration of naps in elderly patients. Eszopiclone 2 mg improved the quality of life measures for mood, physical health, household activities, medication, leisure activities, and self-report of physical functioning and vitality in the 2-week trials, and vitality and general health in the 12-week trial. The most commonly reported side effects in the elderly included unpleasant taste, dry mouth, dizziness, and somnolence. The concurrent use of drugs that inhibit or induce the cytochrome P450 enzyme CYP3A4 can alter concentrations of eszopiclone and the dose may need to be adjusted. The recommended starting dose of eszopiclone for difficulty falling asleep is 1 mg at bedtime. For elders who complain of difficulty maintaining sleep, eszopiclone should be initiated at 2 mg at bedtime. Overall, eszopiclone is a safe and well-tolerated treatment option for elderly patients with insomnia.

Economic Outcomes of Risperidone in Comparison to Typical Neuroleptic Agents for Treatment-Resistant Psychosis: A Community-Based Study

Objective: To compare the costs of treatment for psychosis with risperidone and typical neuroleptics in severely ill outpatients treated in a community mental health setting. Methods: This was an open, retrospective, controlled cohort comparison of actual costs of psychiatric treatment in a group of 17 patients treated with risperidone for psychotic disorders and 15 typical neuroleptic-treated controls matched for severity of illness. Assignment to the two groups was nonrandomized, and outcome data were gathered for the duration of the study for each subject, with dropouts included. Results: Risperidone use did not lead to increased treatment expenses compared with typical neuroleptic use in a mean of approximately nine months follow-up. The median overall cost per patient per year was

An exploratory study of drug abuse and dependence information in package inserts.

2,703 in the risperidone group, compared with

Development of a Competency-Based Assessment Process for Advanced Pharmacy Practice Experiences

2,551 in the typical neuroleptic group (p = 0.64). Increased drug costs (mean expenses per patient per year:

Student and Preceptor Perception of Performance in Advanced Pharmacy Practice Experiences

1,631 for risperidone vs.

The effect of sleep medication use and poor sleep quality on risk of falls in community-dwelling older adults in the US: a prospective cohort study

357 for typical neuroleptics; p = 0.005) were offset by reduced expenses due to decreased hospitalization rates (mean expenses per patient per year: