Negative impact of antidepressant drugs on sleep: a narrative review

Introduction

Antidepressants are among the most widely used medications in Psychiatry and, consequently, their use in patients with sleep disorders is highly prevalent. As the relationship between sleep disorders and depression is bidirectional, the use of these drugs has many potential benefits. However, the sleep-related adverse effects are often overlooked and are one of the primary reasons for non-adherence to antidepressant treatment. Therefore, it is essential that clinicians be aware of these effects and the available strategies to mitigate them.

Methods

A narrative review was conducted using the PUBMED database. Articles published from 2020 onwards were searched using the following MeSH major topics: Antidepressive Agents, Sleep Wake Disorders, Sleep Initiation and Maintenance Disorders, Sleep Stages, Sleep Architecture, REM Sleep, Drug-Related Side Effects and Adverse Reactions, Somnolence, Disorders of Excessive Somnolence, and Sleep Deprivation.

Results

Most antidepressants exert adverse effects on sleep, including insomnia, excessive somnolence, REM sleep suppression, restless legs syndrome, nightmares, parasomnias, and bruxism. SSRIs and SNRIs may induce insomnia during the early phase of treatment (6 to 12 weeks), with bupropion, desvenlafaxine and reboxetine being the major culprits. The relationship between antidepressant use and insomnia is dose-dependent: some drugs display an initial plateau profile followed by an increased risk at higher doses, while others exhibit a modest initial increase followed by a plateau at higher doses. Amitriptyline, agomelatine, mirtazapine, and trazodone are the ones with the lowest risk. Sedating antidepressants may be associated with excessive somnolence, with fluvoxamine and mirtazapine carrying the highest risk. Sleep architecture is also impaired, with the majority increasing REM sleep latency and reducing REM sleep duration. Vilazodone and mirtazapine are the agents most frequently associated with specific sleep disorders.

Discussion

A thorough understanding of the pharmacological profile of antidepressants enables the appropriate clinical management of these adverse effects. Management strategies include dose adjustments and modification of administration timing, selection of antidepressants with a more favorable sleep profile, drug switching, cognitive-behavioral therapy for insomnia (CBT-I), and augmentation therapy with hypnotic agents. Knowledge of dose-effect relationship curves may guide clinicians in making dose adjustment decisions, as therapeutic benefits can often be achieved at very low doses. Agents with sedative properties should not be administered during the daytime but may be prescribed at night to promote sleep. Conversely, activating agents should be administered in the morning. Should these strategies prove insufficient in controlling adverse effects, drug switching, combination with hypnotics, or combined treatment with CBT-I may be considered. When an antidepressant induces or exacerbates restless legs syndrome (RLS) or REM sleep behavior disorder (RBD), the first-line step is drug switching. If switching is not clinically feasible, second-line strategies include the addition of low-dose dopaminergic agonists for RLS, or high-dose melatonin or clonazepam for RBD.

Conclusions

A comprehensive knowledge of the pharmacological profile of each agent is essential for the clinical management of sleep-related adverse effects, through strategies such as dose adjustment, judicious antidepressant selection, and combined therapeutic approaches.

References

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