Sleep Initiation and Maintenance Disorders: Becker PM

Singh H, Becker PM. · The University of Texas, Southwestern Department of Psychiatry, Sleep Medicine Fellowship Program, Dallas, TX 75390, USA. · Expert Opin Investig Drugs. · Pubmed #17685877 No free full text.

Abstract: Low-dose doxepin hydrochloride (1, 3 and 6 mg) is a tricyclic antidepressant currently being investigated for the treatment of primary insomnia in adult and geriatric patients. Although it has been used at much higher doses to treat depression effectively for a number of decades, it offers a unique potency and selectivity for antagonizing the H1 (histamine) receptor at low doses. This mechanism of action may prove to be advantageous compared with other medications currently approved for the treatment of insomnia. This article reviews previous clinical studies using doxepin for insomnia and the recent clinical trial data, and briefly discusses other potential roles of this compound in clinical practice.

Becker PM. · Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA. · Psychiatr Clin North Am. · Pubmed #17118272 No free full text.

Abstract: When patients report problems sleeping, a psychiatrist must determine their significance based on frequency, duration, and daytime impairment. Because up to 50% of adults report sleep problems in any year, it is necessary to define when insomnia becomes long-standing, severe, and a complication to daytime function. Psychiatrists must determine if a sleep disturbance reduces mood, motor performance, or cognitive function. If insomnia syndrome is present, major depression, dysthymia, and anxiety disorders commonly are comorbid. To assist in evaluating insomnia, psychiatrists are urged to use the 6 Ps + M of insomnia model to conceptualize the characteristics of the insomnia and coordinate therapeutic intervention.

Becker PM. · Sleep Medicine Associates of Texas, Dallas, TX, USA. · Neurol Clin. · Pubmed #16243620 No free full text.

Abstract: Insomnia in its chronic form is present in high numbers of patients presenting to physicians. As older women who have medical problems have the highest rates of chronic insomnia, physicians must have a high index of suspicion and be prepared to explore various etiologic factors that might be operative. Treatment should focus on setting specific goals, with patients using strategies that combine lifestyle changes, behavioral interventions, and appropriate medications. OTC agents, sedating antidepressants at low dosages (trazodone, doxepin, amitriptyline, and others), and nonhypnotic benzodiazepines are insufficiently studied to provide evidence-based support for their use to treat chronic insomnia. Particularly in the elderly, close monitoring is needed to prevent falls, accidents, and cognitive impairment from these agents. FDA-labeled hypnotic agents are efficacious, but long-term studies have not been available until the recent release of eszopiclone in the United States. Recent work encourages the use of CBT even in patients who have used sleeping pills for several years, although the success of CBT has been less encouraging when applied to chronic insomnia sufferers who have concurrent psychiatric disorders and who have taken hypnotics for years.

Kushida CA, Becker PM, Ellenbogen AL, Canafax DM, Barrett RW, Anonymous00077. · Stanford University Center of Excellence for Sleep Disorders, Stanford, CA 94305-5730, USA. · Neurology. · Pubmed #19188575 No free full text.

Abstract: OBJECTIVE: To assess the efficacy and tolerability of the nondopaminergic agent XP13512/GSK1838262 in adults with moderate to severe primary restless legs syndrome (RLS). METHODS: Patient Improvements in Vital Outcomes following Treatment in Restless Legs Syndrome I was a 12-week, multicenter, randomized, double-blind, placebo-controlled trial of XP13512 1,200 mg or placebo taken once daily at 5:00 pm with food. Coprimary endpoints were mean change from baseline International Restless Legs Scale (IRLS) total score and proportion of investigator-rated responders (very much improved or much improved on the Clinical Global Impression-Improvement scale) at week 12 (last observation carried forward). Tolerability was assessed using adverse events, vital signs, and clinical laboratory parameters. RESULTS: A total of 222 patients were randomized (XP13512 = 114, placebo = 108) and 192 patients (XP13512 = 100, placebo = 92) completed the study. At week 12, the mean change from baseline IRLS total score was greater with XP13512 (-13.2) compared with placebo (-8.8). Analysis of covariance, adjusted for baseline score and pooled site, demonstrated a mean treatment difference of -4.0 (95% confidence interval [CI], -6.2 to -1.9; p = 0.0003). More patients treated with XP13512 (76.1%) were responders compared with placebo (38.9%; adjusted OR 5.1; 95% CI, 2.8 to 9.2; p < 0.0001). Significant treatment effects for both coprimary measures were identified at week 1, the earliest time point measured. The most commonly reported adverse events were somnolence (XP13512 27%, placebo 7%) and dizziness (XP13512 20%, placebo 5%), which were mild to moderate in intensity and generally remitted. CONCLUSIONS: XP13512 1,200 mg, taken once daily, significantly improved restless legs syndrome (RLS) symptoms compared with placebo and was generally well tolerated in adults with moderate to severe primary RLS.