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). 3 On the other hand, reports document 30 cases of high doses of zolpidem and regular doses of alprazolam and triazolam inducing mania.

A chart review of 278 z-hypnotic trials in adolescents with BD concluded that the drugs improved sleep in 40% to 60% of patients and did not lead to abuse with long-term use. These GABAergic hypnotics lack controlled trials in BD, and the few observational studies paint a mixed picture. It seems intuitive that a benzodiazepine or z-hypnotic (eg, eszopiclone, zaleplon, zolpidem) could halt the progression of insomnia into mania, but the idea has never been adequately tested. Fortunately, there are also new therapies that improve mood and sleep by entraining the circadian rhythm ( Table 2). 2 Some clinicians are liberal with hypnotics, while others prefer the lower abuse potential of sedating antidepressants like trazodone. 1,2 Insomnia persists in 70% of patients even when their mood is stable, and these sleep problems put them at risk for more episodes of mania and depression ( Table 1). The average patient with bipolar disorder (BD) spends half their life struggling with mood symptoms and the other half struggling with sleep.

Bipolar insomnia help depression