Circadian rhythms and the pharmacology of affective illness

The chronic effects of antidepressant drugs (ADs) on circadian rhythms of behavior, physiology and endocrinology are reviewed. The timekeeping properties of several classes of ADs, including tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, serotonin agonists and antagonists, benzodiazepines, and melatonin are reviewed. Pharmacological effects on the circadian amplitude and phase, as well as effects on day-night measurements of motor activity, sleep-wake, body temperature (Tb), 3-methoxy-4-hydroxyphenylglycol, cortisol, thyroid hormone, prolactin, growth hormone and melatonin are examined. ADs often lower nocturnal Tb and affect the homeostatic regulation of sleep. ADs often advance the timing and decrease the amount of slow wave sleep, reduce rapid eye movement sleep and increase or decrease arousal. Together, AD effects on nocturnal Tb and sleep may be related to their therapeutic properties. ADs sometimes delay nocturnal cortisol timing and increase nocturnal melatonin, thyroid hormone and prolactin levels; these effects often vary with diagnosis, and clinical state. The effects of ADs on the coupling of the central circadian pacemaker to photic and nonphotic zeitgebers are discussed.