Effects of Trazodone on Sleep Quality and Cognitive Function in Arteriosclerotic Cerebral Small Vessel Disease Comorbid With Chronic Insomnia

Abstract

Background Chronic insomnia is common in patients with arteriosclerotic cerebral small vessel disease (CSVD) and aggravates the cognitive impairment caused by CSVD. Low-dose trazodone is effective in treating insomnia, but it is unclear whether it can also improve cognitive function in CSVD patients. This study was performed to explore the effects of trazodone on sleep quality and cognitive function in CSVD comorbid with chronic insomnia. Methods This was a randomized, double-blind, placebo-controlled pilot study. Forty patients suffering from arteriosclerotic CSVD and insomnia were recruited from an outpatient clinic. Participants were randomized individually to receive either trazodone (study group) or a placebo (control group) for 4 weeks. The primary outcome was the cognitive score on the Montreal Cognitive Assessment scale (MoCA). Secondary outcomes included sleep parameters measured with polysomnography (PSG) and the Pittsburgh Sleep Quality Index. Results Trazodone caused significantly better improvements in concentration and recall abilities, measured with MoCA, as well as in PSG parameters such as sleep efficiency, N3 sleep ratio, and sleep continuity than the placebo, with no significant differences in the occurrence of side effects. The improvement of sleep quality was correlated with increased concentration and recall abilities. Conclusions A low dose of trazodone seems acceptable and effective in reducing insomnia severity and improving concentration and recall abilities in this pilot study. The improvement of cognition could be achieved by alleviation of insomnia severity. Considering the high incidence of insomnia in CSVD patients, the results of this preliminary study support the use of low-dose trazodone to deal with insomnia and cognitive impairment in CSVD.

The effects of trazodone on human cognition: a systematic review

“…The rightmost columns of Tables 1 and 2 display the ultimate effect of trazodone on human cognition. Overall, from the 16 studies included, seven showed no effect of trazodone on human cognition [ 7 , 9 , 14 , 15 , 17 – 19 ], while five showed a positive effect by improving cognition or reducing cognitive decline [ 6 , 10 – 12 , 16 ], and four showed a negative effect by impairing cognitive function [ 8 , 13 , 20 , 21 ].…”

“…Most studies demonstrated the effects of trazodone in domains other than cognitive function. Wang et al, Alikhani et al, Camargos et al, and Roth et al all showed that trazodone improved sleep quality and sleep parameters including sleep efficiency, N3 sleep ratio, and sleep continuity [ 6 ], daytime functioning [ 12 ], and nighttime sleep percent [ 17 ], while not inducing [ 12 , 17 ] or decreasing daytime sleepiness [ 6 , 20 ], reducing nighttime awakening [ 20 ], minutes of stage 1 sleep, or self-reports of trouble sleeping [ 20 ].…”

“…Lebert et al, Lawlor et al, and Pirker-Kees et al also reported the beneficial role of trazodone in the treatment of behavioural disturbances in neurodegenerative diseases [ 9 , 18 , 19 ]. Teri et al showed a modest reduction in agitation in patients with AD [ 8 ], while five studies revealed a decline and relief in symptoms of depression [ 11 , 12 , 14 , 15 ] or anxiety [ 6 , 12 ].…”

“…Only five studies mentioned the adverse effects of drugs used [ 6 , 8 , 15 , 17 , 19 ]. Overall, all study participants tolerated trazodone well, and adverse events were mild and not a major cause of participant drop-out.…”

“…However, if trazodone has a role in preventing cognitive decline, it is important to consider whether that effect is mediated through its action in the UPR pathway, by increasing the synaptic concentration of 5-hydroxytryptamine [ 6 ], or as a result of the sleep improvement this drug offers. Establishing the effect of trazodone on cognition and neurodegeneration would have significant implications for clinical practice, given the increasing prevalence of neurodegenerative diseases and the extensive use of trazodone in this patient population.…”