Electrophysiological and Neuropsychological Indices of Cognitive Dysfunction in Patients with Chronic Insomnia and Severe Benzodiazepine Use Disorder.

Benzodiazepine (BDZ) misuse is a growing health problem, with 1-2% of patients under BDZ treatment meeting the criteria for use disorder or dependence. Although BDZ addiction potential has been known for decades, much remains unknown its effects on brain functions. The aim of this study was to assess the neuropsychological and neurophysiological profile of a group of chronic insomniacs taking long-term high doses of benzodiazepine. We recruited 17 consecutive patients admitted to our third-level Sleep Medicine Unit for drug discontinuation (7 males, mean age 49.2 ± 11.2 years, mean education 13.7 ± 3.9 years, mean daily diazepam-equivalent BDZ: 238.1 ± 84.5 mg) and 17 gender/age-matched healthy controls (7 males, mean age 46.8 ± 14.1 years, mean education 13.5 ± 4.5 years). We performed a full neuropsychological evaluation of all subjects and recorded their scalp event-related potentials (Mismatch-Passive Oddball-Paradigm and Active Oddball P300 Paradigm). Patients with chronic insomnia and BDZ use disorder showed a profound frontal lobe executive dysfunction with significant impairment in the cognitive flexibility domain, in face of a preserved working, short and long-term memory. In patients, P300 amplitude tended to be smaller, mainly over the frontal regions, compared to controls. BDZ use disorder has a severe cognitive impact on chronic insomnia patients. Long-term high-dose BDZ intake should be carefully evaluated and managed by clinicians in this specific patient population, especially in relation to risky activities.

Sleep architecture in insomniacs with severe benzodiazepine abuse.

OBJECTIVE: Benzodiazepines (BZDs) are the most commonly prescribed compounds in insomnia. A long-term of BZDs use may cause dependence and abuse. The aim of this study was to evaluate sleep architecture and microstructure (in terms of cyclic alternating pattern - CAP - analysis and of sleep EEG power spectral analysis) in a group of long-term users of high doses of BZDs for their primary chronic insomnia. METHODS: Twenty patients consecutively admitted at the Sleep Centre for drug discontinuation and 13 matched healthy controls underwent a full nocturnal video-polysomnographic recording, after one adaptation night. RESULTS: Significant differences were found in time in bed, REM sleep latency and sleep stage 1% which were increased in patients compared to controls, while CAP rate was dramatically decreased. During NREM sleep, patients showed a clear decrease in the relative power of delta band. CONCLUSIONS: Our data demonstrate that in adults with chronic insomnia, long-term use of high doses of BZDs induces a severe disruption of sleep microstructure, while sleep architecture seems to be much less affected. SIGNIFICANCE: The long term use of high doses of BZDs for chronic insomnia induces a marked depression of slow wave activity and of its physiological instability.

Pramipexole versus ropinirole: polysomnographic acute effects in restless legs syndrome.

BACKGROUND: Pramipexole and ropinirole have become the first-line treatment for restless legs syndrome. The aim of this study was to perform the first direct comparison between these two molecules in restless legs syndrome. METHODS: A double-blind, placebo-controlled, double-night and prospective investigation was carried out in 45 consecutive naïve patients with idiopathic restless legs syndrome. Each patient underwent two consecutive full-night polysomnographies: the first baseline recording was performed without premedication and, before the second recording, first group received a single oral dose of 0.25 mg pramipexole, second group a single oral dose of 0.5 mg ropinirole, and the remaining patients received placebo. RESULTS AND DISCUSSION: Both dopamine agonists improved restless legs syndrome symptoms and markedly suppressed periodic leg movements during sleep compared to placebo, without significant differences between pramipexole and ropinirole. No significant side effects, except for mild morning nausea (2 patients treated with ropinirole, 3 with pramipexole, and 1 with placebo), were reported.