The results of the study highlight variables (long-distance driving, youth, sleep restriction) that are frequently associated with sleep-related accidents.

Study ObjectivesTo asses the long-term safety and efficacy of pitolisant, an histamine H3-receptor antagonist, on narcolepsy.MethodsThis open-label, single-arm, pragmatic study, recruited adult patients with narcolepsy and Epworth Sleepiness Scale (ESS) score ≥12. After a titration period, patients were treated for up to 1 year with oral pitolisant once-a-day at up to 40 mg. Concomitant stimulants and anti-cataplectic agents were allowed. The primary endpoint was safety; secondary endpoints included ESS, cataplexy, and other diary parameters.ResultsPatients (n = 102, 75 with cataplexy) received pitolisant, for the first time in 73 of them. Sixty-eight patients (51 with cataplexy) completed the 12-month treatment. Common treatment-emergent adverse events were headache (11.8% of patients), insomnia (8.8%), weight gain (7.8%), anxiety (6.9%), depressive symptoms (4.9%), and nausea (4.9%). Seven patients had a serious adverse effect, unrelated to pitolisant except for a possibly related miscarriage. One-third of patients stopped pitolisant, mostly (19.6%) for insufficient benefit. ESS score decreased by 4.6 ± 0.6. Two-thirds of patients completing the treatment were responders (ESS ≤ 10 or ESS decrease ≥ 3), and one third had normalized ESS (≤10). Complete and partial cataplexy, hallucinations, sleep paralysis, and sleep attacks were reduced by 76%, 65%, 54%, 63%, and 27%, respectively. Pitolisant as monotherapy (43% of patients) was better tolerated and more efficacious on ESS than on add-on, but efficacy was maintained in this last case.ConclusionsLong-term safety and efficacy of pitolisant on daytime sleepiness, cataplexy, hallucinations, and sleep paralysis is confirmed.

The master biological clock situated in the suprachiasmatic nuclei of the anterior hypothalamus plays a vital role in orchestrating the circadian rhythms of multiple biological processes. Increasing evidence points to a role of the biological clock in the development of depression. In seasonal depression and in bipolar disorders it seems likely that the circadian system plays a vital role in the genesis of the disorder. For major unipolar depressive disorder (MDD) available data suggest a primary involvement of the circadian system but further and larger studies are necessary to conclude. Melatonin and melatonin agonists have chronobiotic effects, which mean that they can readjust the circadian system. Seasonal affective disorders and mood disturbances caused by circadian malfunction are theoretically treatable by manipulating the circadian system using chronobiotic drugs, chronotherapy or bright light therapy. In MDD, melatonin alone has no antidepressant action but novel melatoninergic compounds demonstrate antidepressant properties. Of these, the most advanced is the novel melatonin agonist agomelatine, which combines joint MT1 and MT2 agonism with 5-HT(2C) receptor antagonism. Adding a chronobiotic effect to the inhibition of 5-HT(2C) receptors may explain the rapid impact of agomelatine on depression, since studies showed that agomelatine had an early impact on sleep quality and alertness at awakening. Further studies are necessary in order to better characterize the effect of agomelatine and other novel melatoninergic drugs on the circadian system of MDD patients. In summary, antidepressants with intrinsic chronobiotic properties offer a novel approach to treatment of depression.

Compared with oral baclofen, intrathecal baclofen infusion did not affect respiratory function and improved sleep continuity. Intrathecal baclofen infusion in therapeutic doses may act at the spinal level rather than at the supraspinal level.