Treatment of chronic insomnia disorder in menopause: evaluation of literature

Objective: Insomnia both as a symptom and as part of chronic insomnia disorder is quite common in menopause. Comorbid conditions, such as restless legs syndrome and obstructive sleep apnea, occur with high prevalence among perimenopausal women with insomnia. Insomnia in this population group is associated with adverse health outcomes, and there are no clear standards on how to treat it.Methods: Based on extensive literature search, 76 articles were identified. Two authors independently graded evidence according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence.Results: Evaluation and treatment of other comorbid sleep disorders are recommended, as is cognitive-behavioral therapy for insomnia. Hormone therapy, eszopiclone, escitalopram, gabapentin, isoflavones, valerian, exercise, and hypnosis are suggested. Zolpidem, quiteiapine XL, citalopram, mirtazapine followed by long-acting melatonin, ramelteon, Pycnogenol, Phyto-Female Complex, yoga, and massage may be considered. Kampo formulas are not recommended. Acupuncture may not be suggested, and cognitive-behavioral therapy that is not tailored for insomnia probably should not be considered.Conclusions: Although a variety of interventions are shown to be helpful in improving sleep in menopause, there is a need for well-designed head-to-head trials with uniform outcome measures.Teva PharmaceuticalsNorthwestern Univ Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USAUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Gynecol, São Paulo, BrazilSUNY Buffalo, Sch Med, Dept Neurol, Buffalo, NY 14260 USAUniv Kentucky Coll Med, Dept Med, Lexington, KY USAUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Gynecol, São Paulo, BrazilWeb of Scienc

Lithium’s effects on therapeutic targets and MRI biomarkers in Parkinson’s disease: A pilot clinical trial

Background: Lithium has a wide range of neuroprotective actions, has been effective in Parkinson’s disease (PD) animal models and may account for the decreased risk of PD in smokers. Methods: This open-label pilot clinical trial randomized 16 PD patients to “high-dose” (n = 5, lithium carbonate titrated to achieve serum level of 0.4–0.5 mmol/L), “medium-dose” (n = 6, 45 mg/day lithium aspartate) or “low-dose” (n = 5, 15 mg/day lithium aspartate) lithium therapy for 24-weeks. Peripheral blood mononuclear cell (PBMC) mRNA expression of nuclear receptor-related-1 (Nurr1) and superoxide dismutase-1 (SOD1) were assessed by qPCR in addition to other PD therapeutic targets. Two patients from each group received multi-shell diffusion MRI scans to assess for free water (FW) changes in the dorsomedial nucleus of the thalamus and nucleus basalis of Meynert, which reflect cognitive decline in PD, and the posterior substantia nigra, which reflects motor decline in PD. Results: Two of the six patients receiving medium-dose lithium therapy withdrew due to side effects. Medium-dose lithium therapy was associated with the greatest numerical increases in PBMC Nurr1 and SOD1 expression (679% and 127%, respectively). Also, medium-dose lithium therapy was the only dosage associated with mean numerical decreases in brain FW in all three regions of interest, which is the opposite of the known longitudinal FW changes in PD. Conclusion: Medium-dose lithium aspartate therapy was associated with engagement of blood-based therapeutic targets and improvements in MRI disease-progression biomarkers but was poorly tolerated in 33% of patients. Further PD clinical research is merited examining lithium’s tolerability, effects on biomarkers and potential disease-modifying effects