Psychopharmacology [antikvár]

SATELLITESYMPOSIUMSA.01Depression, Sleep Disorders and TRIMIPRAMINEOrganized by Rhőne-Poulenc SantéSA 01.02DEPRESSION, CIRCADIAN RIYTHMS AND TRIMIPRAMINE E. RÜTHERDepressive syndromes with disturbances of circadianand ultradian sleep rhythms are reviewed in relation-to hormonal secretions and temperature.The many different states of depressions cannot besimply explained in terms of endogenous-rhvthms phaseshifts.Circadian variations in hormone levels during endogen ous depression are normalized by successful treatment. The mechanism of action of anti-depressants are partly due to their influence on both circadian rhythms and REM deprivation.However other mechanisms are responsible for drugac-tivity on sleep regulation and mood disturbances in non-endogenous depressions treated with trimipramine and other non REM suppressive drugs. Psychiatrische Klinik, Der Universität Göttingen Von-Siebold, Strasse n" 5, D-3400 Göttingen FRGSA 01.01SLEEP, DEPRESSION AND ANTIDEPRESSANTS A.N. NicholsonChanges in sleep occur with depression, including difficulty in falling asleep, intermittent nocturnal wakefulness, reduced slow wave sleep and early morning awakening. The interval from sleep onset to REM sleep may be reduced and so the duration of REM sleep during the early part of the night increased. At least one of these abnormalities may be present in patients with a major depressive disorder. Sleep variables are sometimes used to help the diagnosis. All antidepressants bring about immediate and often pronounced changes in sleep. Some reduce, while others increase, nocturnal wakefulness, but most suppress REM sleep, though it is uncertain whether elevation of mood is directly related to the changes in REM sleep.Changes in wakefulness during nocturnal sleep are related to the individual pharmacological profile of the drug. Drugs which selectively inhibit the uptake of noradrenaline lead to sedation, while others which inhibit 5-HT uptake lead to disturbed sleep. Changes in sleep continuity also arise with pharmacologically less selective antidepressants, and, in some cases, through the interaction of various properties which alone may not lead to marked effects on sleep.The appearance of REM sleep is now believed to be controlled by both cholinergic and monoaminergic influences, and it is the modulation of these activities which disturbs the balance essential to its optimal appearance. Reduced REM sleep is seen with drugs which selectively modulate noradrenaline or 5-HT activity and those altering cholinergic or monoaminergic transmission as part of a complex pharmacological profile. The introductory paper to this symposium will discuss these various issues as they relate to the activity of antidepressants and the complex relations which exist between sleep and depression on one hand and antidepressants on the other. Royal Air Force Institute of Aviation Medicine Farnborough, Hampshire, United Kingdom.SA 01.03TRIMIPRAMINE, MODULATION OF SIEEP IN MAN A.N. NICHOLSON and P.A. PASCOESleep abnormalities occur in depressive illness. Drugs used as antidepressants lead to sleep changes and supress REM slepp. This does not appear related to a single transmitter, whereas changes in wakefulness during sleep are linked to specific activity. The effects of trimipramine on sleep are of interest as it is a tricyclic antidepressant with an atypical profile. 6 healthy male volunteers {20-22 years) each ingested 25, 50 and 75 mg trimipramine, 60 mg fluoxetine and 10 mg diazepam as active controls which suppress REM sleep and reduce wakefulness, respectively, and 2 placebos. Overnight sleep was recorded by EEG and staged according to conventionally. Fluoxetine (60 mg) reduced total sleep time and sleep efficiency ; increased awake activity and stage 1 sleep. The REM/non REM ratio was reduced and so was REM sleep. Diazepam (10 mg) reduced the number of awakenings, the duration cf awake activity and stage 1 sleep, latency to REM sleep was increased, but the duration of REM sleep was unchanged. With trimipramine there were fewer awakenings. Awake activity was decreased by 50 and 75 mg and there was less stage 1 sleep after 25 and 75 mg. REM sleep and the REM/non REM ratio were reduced with 50 and 75 mg. Trimipramine, unlike other tricyclic antidepressants, is a weak inhibitor of monoamine uptake. It is also an antagonist of W. 1 adrenergic and dopamine receptors, with antihistaminic (HI) and anticholinergic properties. Although individually antagonism of HI,1 and dopamine receptors may have limited effects on wakefulness during nocturnal sleep, these activities could explain the sedative profile of trimipramine. Suppression of REM sleep could be due to blockade of acetylcholine ando(i adrenergic receptors, upset time the balance of the influences normally controlling the appearance of this stage.Royal Air Force Institute of Aviation Medicine Farnborough, Hants, GU1A4 6SZ United Kingdom