Effect of Trazodone on REM Sleep
Trazodone reduces REM sleep in patients with insomnia, as demonstrated by polysomnographic studies showing significant decreases in REM sleep time with a rebound above baseline levels after withdrawal. 1
Evidence on Trazodone's Effects on Sleep Architecture
- Trazodone significantly reduces REM sleep during the treatment period, with rebound effects observed after discontinuation 1
- Unlike some other antidepressants that suppress REM sleep (such as imipramine), trazodone has a different mechanism of action on sleep architecture 2
- Trazodone increases slow-wave sleep (stages 3+4) while simultaneously decreasing REM sleep, suggesting it alters normal sleep architecture 1
- In healthy subjects, trazodone significantly increases slow wave sleep while decreasing stages 1 and 2 sleep, in contrast to imipramine which prolongs REM latency and decreases REM percentage 2
Trazodone's Effects on Other Sleep Parameters
- Trazodone decreases fast-frequency EEG activity during non-REM sleep, suggesting it has a stronger impact on cortical and physiological hyperarousal compared to cognitive behavioral therapy for insomnia (CBT-I) 3
- Trazodone significantly increases total sleep time (TST) by approximately 40 minutes compared to control groups 4
- It reduces the number of awakenings and waking time after sleep onset (WASO) 4
- Trazodone increases non-REM stage 3 (N3) sleep while decreasing non-REM stage 1 (N1) sleep 4
Clinical Implications and Guidelines
- Despite its effects on sleep architecture, clinical guidelines do not recommend trazodone for the treatment of insomnia 5
- The American Academy of Sleep Medicine does not recommend trazodone as a treatment for sleep onset or sleep maintenance insomnia, as evidence shows only minimal benefits at 50 mg doses 6
- The U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guidelines advise against using trazodone for chronic insomnia disorder, noting that its low-quality evidence of efficacy is outweighed by its adverse effect profile 5
- In a small RCT, trazodone was found to increase arousals during sleep 5
Adverse Effects and Considerations
- Trazodone use is associated with significantly more side effects than placebo, including headache (30% vs 19%) and somnolence (23% vs 8%) 5
- Daytime drowsiness (OR = 2.53) and decreased appetite (OR = 2.81) occur with greater frequency in patients taking trazodone compared to control groups 4
- When used for insomnia, trazodone should be administered at low doses, as higher doses may worsen sleep disruption 7
- The timing of administration is critical, as too late administration can lead to failure of insomnia treatment 7
Alternative Treatment Options
- For patients seeking treatment primarily for insomnia, guidelines recommend considering other medications like eszopiclone, zolpidem, or zaleplon for sleep onset issues, or suvorexant or doxepin for sleep maintenance issues 6
- Cognitive behavioral therapy for insomnia (CBT-I) is considered first-line treatment for adults with chronic insomnia disorder 5
In conclusion, while trazodone does reduce REM sleep and alter sleep architecture, current clinical guidelines do not support its use as a first-line treatment for insomnia due to its adverse effect profile and limited evidence of efficacy compared to other available treatments.