Low doses of lithium carbonate reduce melatonin light sensitivity in healthy volunteers.
ABSTRACT Sensitivity of the pineal hormone melatonin to bright light at night has been posited as a putative marker of affective disorders. Research demonstrates melatonin supersensitivity to light in bipolar disorder, however the role that lithium carbonate plays in this response is unclear. This study assessed the effect of lithium on nocturnal melatonin secretion and sensitivity to light in healthy adults. Ten participants, tested on two nights, had blood samples drawn between 20:00 and 02:30 hours. On testing nights participants were exposed to 200 lux of light between 24:00 and 01:00 hours. Participants took 250 mg of lithium daily for 5 d between testing nights. The results indicated that lithium had a significant effect on sensitivity to light but not on overall melatonin synthesis. This finding has implications on the true magnitude of the melatonin light response in people with bipolar disorder and may elucidate possible mechanisms of action of lithium.
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ABSTRACT: The circadian rhythm hypothesis of bipolar disorder (BD) suggests a role for melatonin in regulating mood, thus extending the interest toward the melatonergic antidepressant agomelatine as well as type I (acute) or II cases of bipolar depression. Twenty-eight depressed BD-II patients received open label agomelatine (25 mg/bedtime) for 6 consecutive weeks as an adjunct to treatment with lithium or valproate, followed by an optional treatment extension of 30 weeks. Measures included the Hamilton depression scale, Pittsburgh Sleep Quality Index, the Clinical Global Impression Scale-Bipolar Version, Young Mania Rating Scale, and body mass index. Intent to treat analysis results demonstrated that 18 of the 28 subjects (64%) showed medication response after 6 weeks (primary study endpoint), while 24 of the 28 subjects (86%) responded by 36 weeks. When examining primary mood stabilizer treatment, 12 of the 17 (70.6%) valproate and six of the 11 (54.5%) lithium patients responded by the first endpoint. At 36 weeks, 14 valproate treated (82.4%) and 10 lithium treated (90.9%) subjects responded. At 36 weeks, there was a slight yet statistically significant (P = 0.001) reduction in body mass index and Pittsburgh Sleep Quality Index scores compared to respective baseline values, regardless of mood stabilizer/outcome. Treatment related drop-out cases included four patients (14.28%) at week 6 two valproate-treated subjects with pseudo-vertigo and drug-induced hypomania, respectively, and two lithium-treated subjects with insomnia and mania, respectively. Week 36 drop outs were two hypomanic cases, one per group. Agomelatine 25 mg/day was an effective and well-tolerated adjunct to valproate/lithium for acute depression in BD-II, suggesting the need for confirmation by future double blind, controlled clinical trials.Neuropsychiatric Disease and Treatment 01/2013; 9:243-51. · 2.00 Impact Factor
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ABSTRACT: Sleep is highly altered during affective episodes in patients with bipolar disorder. There is accumulating evidence that sleep is also altered in euthymic states. A deficit in sleep regulation may be a vulnerability factor with aetiological relevance in the development of the disease. This study aims to explore the objective, subjective and lifetime sleep characteristics of patients with manifest bipolar disorder and persons with an elevated risk of developing the disease. Twenty-two patients with bipolar I and II disorder, nine persons with an elevated risk of developing the disorder and 28 healthy controls were evaluated with a structured interview to characterize subjective and lifetime sleeping habits. In addition, participants wore an actimeter for six nights. Patients with bipolar disorder had longer sleep latency and duration compared with healthy controls as determined by actigraphy. The subjective and lifetime sleep characteristics of bipolar patients differed significantly from healthy controls. The results of participants with an elevated risk of developing the disorder had subjective and lifetime characteristics that were largely analogous to those of patients with manifest bipolar disorder. In particular, both groups described recurring insomnia and hypersomnia, sensitivity to shifts in circadian rhythm, difficulties awakening and prolonged sleep latency. This study provides further evidence that sleep and circadian timing are profoundly altered in patients with bipolar disorder. It may also tentatively suggest that sleep may be altered prior to the first manic episode in subjects at high risk.Journal of Neural Transmission 08/2012; 119(10):1173-84. · 3.05 Impact Factor
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ABSTRACT: Sleep disturbances and dysregulation of circadian rhythms are core elements of bipolar disorder that might be involved in its pathogenesis. It has been proposed that patients with bipolar disorder have an abnormally shifted or arrhythmic circadian system and that the disturbance of circadian rhythms may be caused by an alteration in the circadian clock machinery. Chronotherapeutic strategies based on controlled exposures to environmental stimuli that act on biological rhythms have shown good efficacy in the treatment of illness episodes, thus confirming ex juvantibus the clinical relevance of internal timing in this illness.Current Psychiatry Reports 12/2009; 11(6):488-93. · 3.23 Impact Factor