Effects on Sleep: A Double-Blind Study Comparing Trimipramine to Imipramine in Depressed Insomniac Patients

Abstract

Trimipramine, a sedating tricyclic antidepressant, and imipramine were compared on polysomnographic parameters during a 4-week double-blind trial in depressed patients with insomnia and anxiety. Trimipramine eliminated objective evidence of sleep disturbance. This was not the case with imipramine, although depression improved similarly in both groups. Subjects' sleep appeared unchanged or more disturbed at the end of the treatment with imipramine. For trimipramine, the major changes in sleep parameters occurred during the first week of drug administration and did not parallel the gradual changes seen in the measures of depression. Additionally, trimipramine did not suppress REM sleep even in a subgroup of six trimipramine patients who had short rapid-eye-movement (REM) sleep latencies during the placebo baseline period, even though their depression was alleviated. The data demonstrate that (a) antidepressants may vary in their effects on sleep, even though they have similar effects on depression; (b) REM sleep suppression does not necessarily accompany improvement in depression; and (c) reports of improved sleep by patients undergoing antidepressant therapy may not reflect improvement on objective measures of sleep. The different sleep effects suggest the possibility of different antidepressant pathways.

The Effects of Nefazodone on Sleep Architecture in Depression

“…Vogel and colleagues have proposed that drug-induced suppression of REM sleep is, in fact, the mechanism of action of most antidepres sant medications. Antidepressant-induced REM suppres sion may occur in both endogenous and nonendogenous depressed patients (Ware et al 1989). Furthermore, some antidepressant drugs, such as trirnipramine and nefazodone, do not suppress REM sleep, although they clearly alleviate depression.…”

“…In support of this, Kupfer et al (1981) have shown that a drug-in duced increase in REM latency predicted antidepressant response, and under some circumstances, drug-induced REM suppression predicted symptom improvement (Kupfer et al 1981). With the exception of trimipramine, a sedating tricyclic (Ware et al 1989), most antidepres sant drugs of this class, and also monoamine oxidase inhibitors (Kay et al 1976), inhibit REM sleep (Vogel et al 1990). Nefazodone, a phenylpiperazine agent, is a serotonin-2 (5-HT2) receptor antagonist and a selec tive 5-HT reuptake inhibitor (Eison et al 1990).…”

The Effects of Antidepressants on Sleep in Patients with Depression

“…As mentioned above, response to trimipramine is not related to a decrease in the amount ofREM sleep (22)(23)(24).…”

“…With the exception of iprindole and trimipramine, tricyclic antidepressants (TCAs) are potent REM sleep suppressors, prolonging REM latency and decreasing the total amount of REM sleep time (17,(21)(22)(23)(24). Clomipramine and desipramine are 2 ofthe most potent REM-suppressing TCAs, followed by imipramine and nortriptyline (25)(26)(27)(28)(29).…”

Is the nonREM–REM sleep cycle reset by forced awakenings from REM sleep?

“…For ethical concerns, subjects had to be offered an antidepressant. Trimipramine was chosen for its property not to suppress REM sleep [27,28]. The dosage was kept as low as possible and adapted to clinical requirements like agitation, insomnia and side effects.…”