Olanzapine acute administration in schizophrenic patients increases delta sleep and sleep efficiency.

BACKGROUND: A delta sleep deficit has been observed in schizophrenic patients. Olanzapine is a novel atypical antipsychotic agent with affinity at dopaminergic, serotonergic, muscarinic, adrenergic and histaminergic binding sites. The present study was designed to analyze a sleep promoting effect reported for olanzapine. METHODS: Twenty schizophrenic patients (DSM-IV) were studied, who were drug free and inpatients. Patients slept for 5 consecutive nights in the sleep unit as follows: one acclimatization night; two baseline nights (the first for sleep disorder screenings); and two olanzapine nights (10 mg olanzapine, one hour before sleep onset). RESULTS: Sleep continuity variables and total sleep time showed an overall improvement with olanzapine. Waking time was reduced since the first night of olanzapine administration. The main sleep architecture changes were: reduction in sleep stage 1, while sleep stage 2 and delta were significantly enhanced. Rapid eye movement density was also increased by the second olanzapine night. CONCLUSIONS: Total sleep improvement was due to the increase in sleep stages 2 and delta sleep. This may be related to serotonergic antagonistic properties of olanzapine. Olanzapine seems to have a sleep promoting effect in schizophrenic patients.

Sleep changes after 4 consecutive days of venlafaxine administration in normal volunteers.

BACKGROUND: The purpose was to examine the effect of the antidepressant drug venlafaxine on sleep architecture and periodic leg movements of sleep (PLMS) in normal volunteers. METHOD: Eight normal volunteers were studied under laboratory sleep conditions as follows: 1 acclimatization night, 1 baseline night, and 4 consecutive nights of venlafaxine p.o. administration (75 mg during the first 2 nights and 150 mg the last 2 nights). RESULTS: Venlafaxine increased both wake time and sleep stage I. Sleep stages II and III were reduced. REM sleep time was reduced after the first venlafaxine dose, and, by the fourth night, REM sleep was completely suppressed in all volunteers. Six of the eight volunteers showed PLMS at a frequency above 25 per hour. CONCLUSION: Venlafaxine produces several sleep disturbances, which include abnormal leg movements.

Effects of transderman nicotine on mood and sleep in nonsmoking major depressed patients.

The role of nicotine as an indirect cholinergic agent in sleep has been studied in normal subjects. There are no studies of its effects on sleep in depressed patients. Nicotine transdermal patches (17.5 mg), were studied in eight depressed patients (DSM-III-R) and eight normal volunteers. Subjects wore placebo and nicotine patches for 24 h. Depressed patients showed increased REM sleep without changes in other sleep variables. They also showed a short term improvement of mood. Normal volunteers had sleep fragmentation, and reduction of REM sleep time. No major side effects were reported in either group.

Development of tolerance after repeated administration of a selective muscarinic M1 antagonist biperiden in healthy human volunteers.

The muscarinic antagonist biperiden produces a dose-dependent inhibition of (REM) sleep on acute administration. The present study addressed the possibility of pharmacological tolerance after repeated biperiden administration. Six healthy volunteers were studied under sleep laboratory conditions in the following situations: one acclimatization, night, two baseline (that were averaged), 4 nights of biperiden administration, and 4 nights of placebo recovery administration. Six milligrams of biperiden and placebo were administered in identical capsules. Volunteers and technicians were blind to the order of the administration of the capsules. REM sleep time was reduced during the first and the second night, but was not significantly different in comparison with baseline by the third night. During placebo recovery nights, REM sleep time was not different from baseline. REM sleep latency was increased during the first and second nights of biperiden administration, but tolerance to this effect was observed by the third night. On placebo nights a dramatic shortening of REM latency was observed. The present findings support the hypothesis that anticholinergic drugs, even a selective M1 antagonist such as biperiden, induce tolerance soon after administration. A similar effect has been reported with scopolamine, a nonselective muscarinic antagonist, but the main difference is that biperiden withdrawal was not followed by an REM sleep rebound. The observed effect on REM sleep latency during placebo administration may be related to a supersensitivity to muscarinic M-1 receptors that trigger the first REM sleep period. Because short REM latency has been the main finding in the sleep of depressed patients, some implications of the present findings are discussed.

Biperiden administration during REM sleep deprivation diminished the frequency of REM sleep attempts.

Sixteen subjects were assigned to a group using either placebo or biperiden, with eight subjects in each group. Both groups were studied for one acclimatization night, one baseline night, four nights of rapid eye movement (REM) sleep deprivation and two recovery nights. All the subjects received either placebo or 4 mg biperiden 1 hour before sleep during the four nights of REM sleep deprivation. During the baseline and the recovery nights both groups received placebo capsules. The results showed that REM sleep time during the REM sleep deprivation was reduced by 70-75% below the baseline night in both groups. The number of attempts to enter REM sleep was significantly reduced by biperiden as compared to placebo for each of the four REM sleep deprivation nights. Because the total sleep time in the biperiden group was reduced, the number of REM sleep attempts was corrected by the total sleep time. The adjusted number of REM sleep attempts was also significantly reduced in the biperiden group. REM sleep latency showed a reduction in the placebo group, whereas in the biperiden group REM sleep latency was unchanged throughout the deprivation nights. In the recovery night REM sleep time was increased in both groups, with no differences between the groups. The REM sleep latency showed a reduction in the first recovery night in both groups that persisted through the second recovery night. The above findings support the role of biperiden as a REM sleep suppressive drug.

Rapid eye movement (REM) sleep increases by auditory stimulation reverted with biperiden administration in normal volunteers.

Auditory stimulation during REM sleep increases REM sleep time. The purpose of the present work was to determine if the selective muscarinic M-1 antagonist biperiden could modify the effect of the auditory stimulation on REM sleep. Twelve healthy volunteers were divided into placebo and biperiden groups. All the volunteers were studied under sleep laboratory conditions as follows: one acclimatization night, one baseline night, four nights with auditory stimulation either with placebo or biperiden, and two follow-up nights. Biperiden (4 mg) or placebo in identical capsules was administered 1 hour before beginning the sleep recordings. REM sleep time and REM density in the placebo group were increased relative to baseline by auditory stimulation. Biperiden blocked the REM time increase over the three treatment nights and suppressed the REM density increase over all four treatment nights. Biperiden also increased the latency compared to the placebo group. The present findings suggest that M-1 mechanisms are related to REM sleep regulation.

Biperiden administration in normal sleep and after rapid eye movement sleep deprivation in healthy volunteers.

Twenty-six healthy volunteers were randomly assigned to one of four groups. Groups Bip-4 and Bip-6, each with six subjects, received 4 and 6 mg of biperiden, respectively, and were studied on acclimatization, baseline, biperiden, and follow-up nights. Group REM-P (n = 7) and Group REM-Bip (n = 7) were studied on acclimatization, baseline, six nights of REM sleep deprivation, and one recovery (treatment) night with either placebo (group REM-P) or biperiden (group REM-Bip), and one follow-up night. Biperiden 4 and 6 mg increased REM sleep latency and biperiden 6 mg reduced REM sleep time. On the recovery night following REM sleep deprivation Group REM-P and REM-Bip showed an increase in sleep continuity. REM sleep time in the REM-P group was increased during the recovery (treatment) night (REM sleep recovery), while the REM-Bip group did not show a significant REM sleep increase during recovery (treatment) night. It was not until the follow-up night that REM sleep increased in the REM-Bip group.