TABLE 9 

Summary of studies assessing the effects of mirtazapine (MRT) on sleep

StudyAgeDiagnosisDesign + Number of ParticipantsResultsAdverse EventsConclusion
Aslan et al. (2002)18–30Young healthy volunteersRCT with acute injection of MRT (30 mg) vs. placebo. N = 20.MRT increased stage N3, sleep efficiency, did not alter REM sleep and decreased the number of awakenings and their duration during sleep.Not analyzed.MRT is effective in inducing NREM sleep without affecting REM sleep in healthy subjects.
Cankurtaran et al. (2008)18–65Cancer with major depressive disorder, anxiety disorders, or adjustment disorder6-wk open-label trial. MRT 5–30 mg/day vs. imipramine 5–100 mg/day vs. untreated control group that refused drug therapy. N = 53.Percent of patients reporting nightly difficulty falling asleep in MRT group decreased from 65 at baseline to 15 at endpoint vs. a decrease from 53.8 at baseline in imipramine group to 30.8 at endpoint vs. a decrease from 50 at baseline in control group to 30 at endpoint.Not analyzed.MRT is effective at reducing symptoms of insomnia in cancer patients, and more effective than imipramine.
Dolev (2011)45–52Perimenopausal women with insomnia who did not suffer from depression by HAM-DCase series. MRT 15 mg/day for 2-4 wk followed by treatment with 2 mg prolonged-release melatonin with tapering of MRT for 1–3 mo. N = 11.Combination treatment with MRT and melatonin during MRT tapering period reduced PSQI global scores from 14.45 ± 1 at baseline to 6.00 ± 0.7 at endpoint. SOL as measured by PSQI question 2 (minute) decreased from 52.73 ± 14.04 at baseline to 18.64 ± 2.87 at endpoint.No AEs were reported.MRT followed by prolonged-release melatonin add-on treatment followed by melatonin monotherapy is effective at reducing symptoms of insomnia in perimenopausal women.
Kim et al. (2008)22–79Cancer patients with depression4-wk open-label trial. MRT 15–45 mg/day. N = 42.Amount of sleep (hours) increased from 3.6 ± 1.9 at baseline to 6.8 ± 2.5 at endpoint, P < 0.001. Ease of getting to sleep subscale of the Chonnam National University Hospital-Leeds Sleep Evaluation Questionnaire decreased from 4.2 ± 1.0 at baseline to 2.4 ± 1.0 at endpoint, P < 0.001.Four patients discontinued MRT due to side effects (Two due to sedation and one each for general weakness or constipation).MRT is effective at reducing symptoms of insomnia in cancer patients.
Theobald et al. (2002)40–83Advanced cancer patients with pain and other distressing symptomsOpen-label crossover study of MRT 15/30 mg/day. N = 36.There were no significant differences on NRS scales measuring insomnia. However, there was a trend toward improved sleep.Only one patient withdrew due to MRT side effects.MRT may be effective at reducing symptoms of insomnia in cancer patients.
Winokur et al. (2000)18–65Major depressive disorder with poor sleep quality2-wk open-label study. MRT 15–30 mg/day. N = 6.SOL improved, P = 0.009. TST improved, P = 0.004. SE improved, P = 0.0003. MRT did not significantly affect REM sleep parameters.Four of six subjects reported daytime somnolence during week 1, though the complaints resolved by week 2.MRT is effective at reducing symptoms of insomnia.
Winokur et al. (2003)18–45Major depressive disorder with insomnia8-wk randomized trial. MRT 15–45 mg/day vs. fluoxetine 20–40 mg/day. N = 19.Mean SOL (minute) by polysomnography decreased from 34.3 ± 24.0 at baseline to 10.9 ± 9.6 at Week 9 in MRT group, P < 0.05 vs. 38.6 ± 32.2 at baseline to 43.3 ± 28.4 at Week 8 in fluoxetine group. Total sleep time (minute) increased from 327.9 ± 81.8 at baseline to 428.1 ± 73.6 at Week 8 in MRT group, P < 0.05 vs. 317.4 ± 68.8 at baseline to 325.1 ± 116.4 in fluoxetine group.Not analyzed.MRT is effective at reducing symptoms of insomnia, and superior to fluoxetine.