Changes during weeks in effects of tricyclic drugs on the human sleeping brain.
The time-courses of two effects of tricyclic drugs on the human brain are contrasted. Imipramine, desipramine, chlorimipramine and doxepin 75 mg. reduced paradoxical (REM) sleep duration, chlorimipramine being most powerful and doxepin least. The effect lessened significantly during a month of regular administration and a rebound followed which lasted up to a month. Imipramine, desipramine and chlorimipramine increased intra-sleep restlessness and this effect did not diminish with time nor show a rebound. Doxepin reduced intrasleep restlessness. Neither iprindole 75 mg. nor trimipramine 75 or 150 mg. caused these effects on sleep.

It is concluded that some tricyclic drugs can have both of two types of effects on the human brain. One type is independent of duration of administration. The other is a time-changing effect brought about through the slow modification of unknown cerebral components that can be deduced to have a life span of 3-4 weeks.