There’s a paradox with antidepressants. Even as they improve mood they can worsen sleep, and poor sleep is both a symptom and a cause of depression. It’s a common problem, but one that can be avoided by selecting the right antidepressant. At the American Psychiatric Association’s Annual Meeting, Nikhil Rao, MD, identified antidepressants that work well with specific sleep disorders, including insomnia, restless legs syndrome (RLS), and obstructive sleep apnea.
Antidepressants and insomnia
A sedating antidepressant makes sense for patients with insomnia and depression, but just as important is how that antidepressant affects sleep quality. Mirtazapine and trazodone are two antidepressants that help patients fall asleep and improve their sleep architecture. However, mirtazapine’s sedative effects are greater in the lower dose range (15 mg and below), which may not treat depression. Trazodone also has limitations. Its sedative effects tend to wear off over time, and it comes with risks including daytime fatigue, reduced recovery rates in depression (a paradoxical phenomenon seen in adolescents),1 and dry mouth─which itself may interfere with sleep.
Some atypical antipsychotics have sedative effects, particularly quetiapine (Seroquel). Quetiapine carries too many risks to recommend it for primary insomnia, but it is appropriate for antidepressant augmentation (150 to 300 mg qhs). Quetiapine is not just sedating. It also improves the deep, restorative phase of sleep.2
The SSRIs can cause insomnia and worsen sleep quality, but bupropion is surprisingly more favorable for sleep. Although it is activating in the daytime, bupropion causes no more insomnia than the SSRIs and has neutral or positive effects on sleep architecture. Most of the tricyclics have similar problems as the SSRIs. Two exceptions are amitriptyline and doxepin. These sedating tricyclics can help with sleep initiation, but they do not improve sleep architecture.
One hypnotic that Dr Rao warned against is diphenhydramine, the sedative ingredient in many over-the-counter sleep aids from Benadryl to Tylenol PM. The problem is that diphenhydramine worsens cognition in the short term and raises the risk of dementia with chronic use.3,4 Its anticholinergic and histaminergic mechanism is the likely culprit here. Hydroxyzine (Vistaril) has similar effects and probably carries similar risks. Dr Rao pointed out another limitation of diphenhydramine: its sedative effects tend to wear off after 3 weeks.
Antidepressants in restless legs syndrome
RLS is common in two conditions that often co-occur with depression: ADHD and PTSD. Although serotonergic antidepressants can cause RLS, bupropion appears to treat it, according to a randomized controlled trial.5 Another medication to watch for in patients with RLS is mirtazapine. Although it is often used for insomnia, in some studies the risk of RLS is greater with mirtazapine than with other antidepressants.6
Finally, there is an FDA-approved treatment for RLS that can treat depression as well: pramipexole. In small, positive controlled trials in both bipolar and unipolar depression, this dopaminergic agonist worked as monotherapy and as augmentation. The dose for depression (1 to 2 mg qhs) is higher than the typical RLS dose (0.125 to 1 mg qhs).7
Dr Aiken does not accept honoraria from pharmaceutical companies but receives honoraria from W.W. Norton & Co. for Bipolar, Not So Much, which he coauthored with Jim Phelps, MD.
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