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Cited by 23Circadian rhythm and melatoninTreatment of Major DepressionSleep and related disorders

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Effects of trazodone and imipramine on the biological rhythm: An analysis of sleep EEG and body core temperature

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Suzuki, Hideaki, Yamadera, Hiroshi, Nakamura, Shuichi, Endo, Shunkichi·2002·Journal of Nippon Medical School
DOI 10.1272/jnms.69.333
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Abstract

Depression commonly involves abnormalities of the sleep-wake rhythm, the temperature rhythm, and other biological rhythms. The changes of these biological rhythms are caused in remission by medications. However, it has yet to be clarified whether the biological rhythms are changed as a result of recovery from depression or from the direct pharmacological effects of the antidepressants. Therefore, we have undertaken a study on the direct effects of the antidepressants trazodone and imipramine on the biological rhythms of healthy volunteers. The study involved 12 healthy male volunteers (ages 21 approximately 28 years, mean age 23.9+/-1.7 years) who had given written informed consent. Placebo, trazodone, and imipramine were each administered in a single blind manner four times a day, during the three-day study period. The total daily dosage of trazodone was 100 mg (50 mg in one subject), and of imipramine 40 mg (20 mg in one subject). Subjects were submitted to polysomnography (PSG) and body core temperature (rectal temperature) measurements during the study period. We compared the data concerning the antidepressants to those of the placebo. The results show that, with regard to the sleep rhythm, trazodone significantly increased slow wave sleep (SWS), but no changes were observed in REM (rapid eye movement) sleep. Imipramine significantly decreased REM sleep and prolonged the REM cycle. With regard to the temperature rhythm, trazodone showed a tendency to advance the appearance time of the minimal temperature. Imipramine significantly lowered the maximal temperature and decreased the difference between the maximal and the minimal temperature, but no changes in the phases were observed. Neither antidepressant had any effect on the temperature cycle. Trazodone and imipramine showed different effects on PSG. Furthermore, they had different effects on the temperature rhythm. The changes of the sleep-wake rhythm were greater than those of the temperature rhythm. Although the two antidepressants had different mechanisms of action, it is worthy of note that both directly influenced the biological rhythms of healthy volunteers.

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  • The findings support consideration of trazodone for clinical use as an intervention against cognitive decline.

    “Overall, the above findings support for the first time the consideration of trazodone for clinical use, not only toward improving quality of life in older adults by increasing sleep duration [10], but also as an intervention against cognitive decline”

    From Long-Term Trazodone Use and Cognition: A Potential Therapeutic Role for Slow-Wave Sleep Enhancers (2019) · cites this paper as [10]

    The citation is attached to the claim that trazodone increases sleep duration in older adults; the subsequent proposal concerning cognitive decline is the citing authors’ own conclusion. The Discussion reports no change in sleep period time or other sleep-continuity measures and says the study involved healthy volunteers, not older adults. It therefore does not support the cited sleep-duration claim. (LLM, conf=0.82)

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  • Trazodone has been shown to enhance SWS by 50-56% on polysomnography in younger and older adults.

    “While melatonin, ramelteon, or mirtazapine use did not produce significant improvement on sleep measures, trazodone, previously shown to enhance SWS by 50-56% on polysomnography in younger and older adults [10, 11], increased total sleep time by 42.5 minutes on actigraphy in patients with AD [12, 13].”

    From Long-Term Trazodone Use and Cognition: A Potential Therapeutic Role for Slow-Wave Sleep Enhancers (2019) · cites this paper as [10]

    The PSG results (Table 1) show SWS rising from 14.88% with placebo to 22.29% with trazodone—approximately a 50% relative increase. But Subjects and Methods identifies all 12 participants as men aged 21–28; this paper does not establish the claimed 56% increase or a result in older adults. (LLM, conf=0.90)

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Citations

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Metadata

Authors
Suzuki, H., Yamadera, H., Nakamura, S., & Endo, S.
Affiliations
Nippon Medical School (JP)
ORCID
Suzuki, Hideaki
Venue
Journal of Nippon Medical School
Publisher
Medical Association of Nippon Medical School
Published
2002
Volume
69
Issue
4
Pages
333-341
ISSN
  • 0048-0444 (ISSN-L)
  • 1345-4676
  • 1347-3409
DOI
10.1272/jnms.69.333
OpenAlex
W2031099229
Cited by
23
References
1
Citations by year
2026: 1 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 2 · 2014: 3 · 2013: 1 · 2012: 1
FWCI
0.10
Type
journal article
Language
en
Open access
Locations
  • Journal of Nippon Medical School (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
Keywords
trazodone, imipramine, antidepressants, biological rhythms, sleep-wake cycle, core body temperature, circadian rhythm, slow-wave sleep, REM sleep, polysomnography, healthy volunteers
MeSH terms
Adult, Antidepressive Agents, Tricyclic, Body Temperature, Electroencephalography, Humans, Imipramine, Male, Periodicity, Sleep, Trazodone, Antidepressive Agents, Second-Generation

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