Insomnia in Generalized Anxiety Disorder: Polysomnographic, Psychometric and Clinical Investigations before, during and after Therapy with a Long- versus a Short-Half-Life Benzodiazepine (Quazepam versus Triazolam)

Abstract

Within a double-blind, comparative study on the effects of the long-half-life benzodiazepine (BDZ), quazepam, and the short-half-life BDZ, triazolam, on clinical symptomatology, sleep and anxiety of 45 patients with insomnia based on a mild to moderate generalized anxiety disorder (GAD) (ICD-9 code: 307.42-1, 300,0; ASDC-APSS-Code: A.2.a), we compared, in a first step at baseline, drug-free polysomnographic and psychometric data of 22 patients recorded in the laboratory (L-group) and 21 patients recorded by the Oxford Medilog 9000 system at home (H-group) with those of normal controls. Sleep efficiency, total sleep time, wake within total sleep period (middle insomnia) and wake before buzzer (late insomnia) were significantly deteriorated in both patient groups as compared with controls, while sleep induction time only differed significantly in home recordings. Regarding sleep architecture, stage (S)2 was reduced, S3 and S4 increased in the H-group only, while no intergroup differences were seen in SI, SREM and REM latency. Subjective sleep quality was reduced in both patient groups, but not awakening quality. Psychometric tests in the morning demonstrated for the noopsyche, only a significantly deteriorated psychomotor activity in both patient groups. In the thymopsyche, evening well-being and mood in the morning were reduced in both the L·and H-group, affectivity and morning well-being only in the H-group. The psycho-pharmacological part of the study was completed by 40 patients (there were 4 drop-outs in the triazolam, 1 in the quazepam group). They were treated after 1 week placebo with either 15–30 mg (median 15 mg) quazepam or 0.25–0.5 mg (median 0.25 mg) triazolam for 4 weeks, and thereafter for 2 weeks with placebo. Anxiety (rated by HAMA and SAS) improved significantly with both drugs and remained improved throughout 2 weeks post-drug placebo, with quazepam being slightly superior to triazolam. Polysomnography demonstrated a shortened sleep onset only after quazepam. Sleep efficiency improved after acute administration of both drugs, but the improvement was maintained by quazepam only (tolerance development with triazolam). Rebound insomnia was observed only in the 1 st post-triazolam placebo night (significant intergroup difference based on confirmatory testing). S2 increased, S3 + S4 decreased under and after quazepam, which represents a normalization in home-recorded GAD patients. SI decreased with both drugs, SREM only under quazepam. Subjective sleep quality behaved very similarly to objective sleep efficiency. Awakening quality improved after acute therapy with both drugs, somatic complaints only with quazepam. Psychometry in the morning showed increased attention with both drugs, while in concentration triazolam was superior to quazepam. The triazolam group was also better in memory and reaction time during the post-drug placebo period. Both drugs were well tolerated.

Placebo-Controlled Sleep Laboratory Studies on the Acute Effects of Zolpidem on Objective and Subjective Sleep and Awakening Quality in Nonorganic Insomnia Related to Neurotic and Stress-Related Disorder

“…Moreover, the sleep patterns of these patients were compared with those of age-and sex-matched normal controls in order to assess the normalizing effect of zolpidem on sleep. As we demonstrated recently, benzodiazepines are able to produce changes in objective sleep measures, but also in the waking EEG, which are exactly opposite to the differences between insomniac GAD patients and normal controls [20,21,31].…”

“…The score was based on a previous sleep study, in which insomniac GAD patients had also been treated by only 1 evening dosage of a sleep-promoting benzodiazepine [20]. According to a polydiagnostic approach, the patients were also required to meet the diagnostic criteria of the DSM-IV-R diagnoses 307.42 (insomnia) related to 300.02 (GAD), 300.00 (anxiety disorder) and 309 (adjustment disorder) and the ICSD diagnosis of 'sleep disorder associated with anxiety disorder'.…”

<i>Manasamitra vataka</i> and <i>Shirodhara</i> Treatments Preserve Slow Wave Sleep and Promote Sleep Continuity in Patients with Generalized Anxiety Disorder and Co-Morbid Generalized Social Phobia

“…the sleep architecture 5 . Our study also demonstrated such non-restorative quality of sleep by clonazepam.…”

“…Additionally, conventional anxiolytic agents such as clonazepam have been reported to affect sleep quality. Shortterm use of benzodiazepines helps improve the sleep quality, sleep duration and efficiency, but alters the sleep architecture 5 . Long-term treatment has many deleterious effects on sleep 6 .…”

Advanced Analysis of Pharmaco-Sleep Data in Humans

“…The objectives of these studies are multifarious such as supporting registration of a new drug, providing evidence of efficacy, evaluating central nervous system side effects or providing basic pharmacodynamic data at an early stage in drug development [13,14,15]. Generally, pharmacosleep studies have an important role in characterizing the effect of central nervous system-active drugs since an influence on sleep initiation, continuity and architecture may have a significant impact on the clinical use of the drug [16,17]. …”