, Volume 116, Issue 4, pp 389–395 | Cite as

Clinical and polysomnographic effects of trazodone CR in chronic insomnia associated with dysthymia

  • Liborio Parrino
  • Maria Cristin Spaggiari
  • Mirella Boselli
  • Guido Di Giovanni
  • Mario Giovanni Terzano


Six middle aged subjects complaining of chronic insomnia associated with dysthymia were investigated in a 2-month single blind study: a 7-day placebo treatment period, followed by a 6-week phase with increasing doses of trazodone controlled release (CR) formulation (50 mg through days 8–10; 75 mg through days 11–13; 150 mg through days 14–49) and then a final 7-day withdrawal period under placebo. Medication was always administered at bedtime. Five polysomnographic recordings were accomplished by each subject (sleep 1: under baseline placebo; sleep 2-3-4: under active treatment; sleep 5: after drug discontinuation). A “blind” EEG reader analysed the traditional polysomnographic variables (macrostructure of sleep) and the amount and percentage ratio (CAP rate) of cyclic alternating pattern (CAP), the microstructural parameter that measures the instability of arousal during sleep. Visual analogue scales (VAS) for the evaluation of subjective sleep quality and the Hamilton rating scale for depression (HAM-D) were regularly assessed across the study. Statistical analysis was based on an ANOVA test with repeated measures completed by means of Bonferroni adjusted probabilities. No significant differences emerged from the macrostructural parameters referred to sleep initiation and maintenance, while significant overall modifications emerged from stage 2 (P<0.0005), slow wave sleep (P<0.0001), total CAP time (P<0.0001) and CAP rate (P<0.0001). Compared to the placebo baseline night, a significant increase of slow wave sleep (+40 min) and significant reductions of stage 2 (−67 min), CAP time (−90 min) and CAP rate (−23%) were already found on day 4 of treatment (sleep 2). These changes maintained significance throughout the active treatment period (sleep 3 and sleep 4), while a return to the baseline values occurred after drug discontinuation (sleep 5). The course of polysomnographic modifications was consistently associated with significant improvement of VAS and HAM-D scores during the active treatment period and by poor scores of the baseline and withdrawal periods. Trazodone appears to have a high affinity for 5-HT2 receptors. The availability of an effective slow acting serotonin-related drug with both sedative and antidepressant properties may open new perspectives in the treatment of chronic insomnia.

Key words

Sleep Insomnia Depression Trazodone Cyclic alternating pattern 


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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Liborio Parrino
    • 1
  • Maria Cristin Spaggiari
    • 1
  • Mirella Boselli
    • 1
  • Guido Di Giovanni
    • 1
  • Mario Giovanni Terzano
    • 1
  1. 1.Sleep Disorders Centre, Department of NeurologyUniversity of ParmaItaly

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