![]() But then why didn’t the drug improve their sleep? These studies relied on subjective measures of sleep, and ramelteon has a poor track record on subjective outcomes. One explanation for these intriguing results is that the positive trials enrolled patients with active insomnia, while the negative trial did not, suggesting that ramelteon might have preferential effects in patients with disturbed circadian rhythms. 15 A larger study attempted to replicate that finding, but the results were negative across all outcomes. As in the first trial, ramelteon did little to improve sleep (there was only a nonsignificant trend), but it did lower the risk of depression, more than doubling the time to a new episode from 84 to 188 days (P =. For 6 months, they took either placebo or a nightly dose of ramelteon 8 mg. ![]() 14 Next, ramelteon was tested in 83 patients with BD who had active insomnia but stable mood. The first study tested ramelteon in 21 patients with acute mania and found a reduction in depressive symptoms but no benefit in mania or sleep. Although ramelteon failed to improve sleep or mania, it did prevent depression in patients who struggled with insomnia. Pure melatonin failed to improve sleep, mania, or rapid cycling in 2 small controlled trials, 13 but the melatonin agonist ramelteon has intriguing results from 3 industry-sponsored, randomized, placebo-controlled trials in BD. Melatonin agonists have captured the interest of investigators because of their potential to realign the circadian system, which is often disrupted in BD. ![]() In a retrospective study, patients with BD who used sedating antidepressants for sleep were significantly more likely to develop mania and episode acceleration than those who took traditional hypnotics. Most, including trazodone and mirtazapine, are associated with case reports of triggering mania. Sedating antidepressants are more problematic, particularly in bipolar I disorder, in which the risk of manic induction is high. Helping Patients With Attentional Difficulties and Maladaptive Use of Psychoactive Substances McFarland, DO Luigi Grassi, MD Michelle Riba, MD, MS, DFAPA, FAPM 11Ī Simple Concept With Complex Implicationsĭaniel C. ![]() 10 Lithium is rarely sedating, but it does have positive effects on the circadian system, such as dampening the phase-advance (“night owl”) tendency that is associated with poorer health and greater risk of depression. Many antipsychotics are sedating, but some have more meaningful benefits in sleep quality these include quetiapine in particular, and possibly lumateperone, olanzapine, risperidone, and ziprasidone. 8,9Īnother approach to insomnia in BD is to choose mood stabilizers with sedative effects. 7 However, over the long term, benzodiazepines carry risks of tolerance and dependence, and long-term use may worsen cognition and mood in BD, according to nonrandomized studies that attempted to control for the confounding tendency to prescribe benzodiazepines in more severe cases. In contrast, clonazepam and lorazepam appear safer, with small controlled trials suggesting that these agents do not worsen, and may improve, manic symptoms (the benzodiazepines were not used as hypnotics in these trials).
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