Antidepressant Effects on Sleep

I am often asked about the effects that antidepressants have on overall sleep architecture. Here’s the breakdown:

Cyclic antidepressants. The cyclic antidepressants have long been associated with managing insomnia associated with depression. The majority of these agents are sedating and suppress REM sleep. The sedating cyclics typically block the actions of serotonin and histamine, examples include amitriptyline and doxepin. Doxepin is sold here in the U.S. under the brand name Silenor, in 3mg and 6mg strengths for primary insomnia. In recent years, treating clinicians have come to understand the importance of scaling back the dosages of these antidepressants to avoid daytime drowsiness and sleepiness.

Trazodone and its first cousin nefazodone do not suppress REM, although the latter has fallen out of favor due to liver toxicity, in some instances resulting in fatalities. Because trazodone doesn’t markedly affect REM, it remains a favorite on most formularies. Doses in the 50mg to 100mg range nightly are generally sufficient.

SSRIs. When it comes to sleep, the regulation of serotonin is complicated due to the quantity and quality of serotonin receptor activity. Prozac and Paxil have been studied the most, but as a class the SSRIs appear to slow the onset of sleep and increase the number of awakenings leading to an overall poor sleep cycle. Again as a class, the SSRIs suppress REM sleep and are linked to intense and vivid dreams.

SNRIs. Not surprisingly, this group, which includes the agents Effexor, Cymbalta and Pristiq is reported to have effects on sleep that are similar to the SSRIs. Sleep continuity and REM are compromised by these antidepressants and their norepinephrine activating effects are also not friendly to sleep initiation and continuation.

Atypicals. The atypical antidepressant Remeron possesses the three-fold action of norepinephrine, serotonin and histamine inhibition and blockade. The drug’s profile therefore provides a strong basis for helping users get to sleep quickly and stay asleep longer. In fact, some users sleep too much – up to 12 hours per day. Daytime somnolence can be a problem and Remeron produces the most weight gain among all of the contemporary antidepressants. A dosing range of 15mg to 30mg nightly is sufficient.

Wellbutrin differs from all of the other agents discussed in that it has no serotonin effects. Wellbutrin can be described as a DNRI – dopamine and norepinephrine reuptake inhibitor. Although Wellbutrin does not suppress REM sleep, increased activation of norepinephrine and dopamine often leads to complaints of insomnia, particularly difficulty getting to sleep.


Knowledge of how different antidepressants affect the sleep spectrum is an important determinant when it comes to selecting an agent that most suitably meets the needs of depressed patients.

Joseph Wegmann, R.Ph., LCSW is a licensed clinical pharmacist and a clinical social worker with more than thirty years of experience in the field of psychopharmacology. His diverse professional background in psychopharmacology and counseling affords him a unique perspective on medication management issues. In addition to consulting with numerous psychiatric facilities, he has presented psychopharmacology seminars to thousands of clinicians in 46 states.

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