Normalizing effects of modafinil on sleep in chronic cocaine users

Abstract

Objective: The purpose of the present study was to determine the effect of morning-dosed modafinil on sleep and daytime sleepiness in chronic cocaine users.

Method: Twenty cocaine-dependent participants were randomly assigned to receive modafinil, 400 mg (N=10), or placebo (N=10) every morning at 7:30 a.m. for 16 days in an inpatient, double-blind randomized trial. Participants underwent polysomnographic sleep recordings on days 1 to 3, 7 to 9, and 14 to 16 (first, second, and third weeks of abstinence). The Multiple Sleep Latency Test was performed at 11:30 a.m., 2:00 p.m., and 4:30 p.m. on days 2, 8, and 15. For comparison of sleep architecture variables, 12 healthy comparison participants underwent a single night of experimental polysomnography that followed 1 night of accommodation polysomnography.

Results: Progressive abstinence from cocaine was associated with worsening of all measured polysomnographic sleep outcomes. Compared with placebo, modafinil decreased nighttime sleep latency and increased slow-wave sleep time in cocaine-dependent participants. The effect of modafinil interacted with the abstinence week and was associated with longer total sleep time and shorter REM sleep latency in the third week of abstinence. Comparison of slow-wave sleep time, total sleep time, and sleep latency in cocaine-dependent and healthy participants revealed a normalizing effect of modafinil in cocaine-dependent participants. Modafinil was associated with increased daytime sleep latency, as measured by the Multiple Sleep Latency Test, and a nearly significant decrease in subjective daytime sleepiness.

Conclusions: Morning-dosed modafinil promotes nocturnal sleep, normalizes sleep architecture, and decreases daytime sleepiness in abstinent cocaine users. These effects may be relevant in the treatment of cocaine dependence.

Figure 1

Polysomnographic sleep variables at 1, 2, and 3 weeks of abstinence in chronic cocaine users. Main effects of abstinence week and drug condition were present as were interactions between abstinence week and drug condition (see text). Post-hoc differences between placebo (black) and modafinil (gray) at each time point are indicated (t, p < 0.1; *, p < 0.05; **, p < 0.01; ***, p < 0.005).

Figure 2

Subjective sleepiness in the morning, afternoon, and evening as measured by the Stanford Sleepiness Scale is shown. There were main effects of drug condition, abstinence week, and time of day as well as a drug by abstinence week by time of day interaction (see text). There were statistically significant post-hoc differences between modafinil (gray) and placebo (black) at morning testing (p < 0.005), and as shown at each timepoint (t, p < 0.1; *, p < 0.05; ***, p < 0.005).

Figure 3

Normalizing effects of modafinil on polysomnographic sleep variables at abstinence week 3 in chronic cocaine users compared to control participants. Statistically significant, independent samples ANOVA (see text) was followed by post-hoc Tukey HSD (*, p< 0.05; **, p < 0.01). (Upper left) Modafinil increased slow-wave sleep time in cocaine users to be indistinguishable from control participants. (Upper right) REM sleep time was significantly less in placebo treated (but not modafinil treated) cocaine users compared to controls. (Lower left) Modafinil increased total sleep time in cocaine users but was still less (nonsignificantly) than in control participants. (Lower right) Sleep onset latency was significantly longer in placebo treated (but not modafinil treated) cocaine users compared to controls, and there was a statistical trend toward improved sleep latency in modafinil treated cocaine users.