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Background: The management of late-life depression is challenged by high rates of treatment-resistance and adverse effects, along with medical comorbidities and polypharmacy. Together with the limited data on managing treatment-resistant depression in older adults, there is a need for investigating the efficacy of nonpharmacological treatment strategies. Repetitive transcranial magnetic stimulation (rTMS) is one modality that may better serve this patient population.Methods: The present study examines data from two previous clinical trials (NCT00305045 and NCT01515215) to explore the efficacy of bilateral and unilateral high-frequency left-sided (HFL) rTMS in older adults suffering from treatment-resistant depression. A total of 43 adults aged 60 or older with a current major depressive episode were randomized to bilateral sequential, unilateral HFL, or sham. Bilateral sequential stimulation involved low-frequency (1 Hz) right dorsolateral prefrontal cortex (DLPFC) stimulation followed immediately by high-frequency (10 Hz) left DLPFC. The unilateral condition was HFL stimulation alone, and the placebo condition was either HFL or sequential bilateral form of sham. The primary outcome was remission of depression.Results: Participants receiving bilateral rTMS experienced greater remission rates (40%) compared with unilateral (0%) or sham (0%) groups. Response to rTMS in the Hamilton Depression Rating Scale scores similarly favored the efficacy of bilateral rTMS.Conclusion: This study suggests that sequential bilateral treatment may be an optimal form of rTMS when used for treatment-resistant depression in older adults. Further large-scale comparative effectiveness trials of bilateral rTMS in this population are warranted. [ABSTRACT FROM AUTHOR]

Background: Zinc is an essential micronutrient with diverse biological roles in cell growth, apoptosis and metabolism, and in the regulation of endocrine, immune, and neuronal functions implicated in the pathophysiology of depression. This study sought to quantitatively summarize the clinical data comparing peripheral blood zinc concentrations between depressed and nondepressed subjects. Methods: PubMed, Cumulated Index to Nursing and Allied Health Literature, and PsycINFO were searched for original peer-reviewed studies (to June 2012) measuring zinc concentrations in serum or plasma from depressed subjects (identified by either screening or clinical criteria) and nondepressed control subjects. Mean (±SD) zinc concentrations were extracted, combined quantitatively in random-effects meta-analysis, and summarized as a weighted mean difference (WMD). Results: Seventeen studies, measuring peripheral blood zinc concentrations in 1643 depressed and 804 control subjects, were included. Zinc concentrations were approximately −1.85 µmol/L lower in depressed subjects than control subjects (95% confidence interval: [CI]: −2.51 to −1.19 µmol/L, Z 17 = 5.45, p < .00001). Heterogeneity was detected (χ2 17 = 142.81, p < .00001, I2 = 88%) and explored; in studies that quantified depressive symptoms, greater depression severity was associated with greater relative zinc deficiency (B = −1.503, t 9 = −2.82, p = .026). Effect sizes were numerically larger in studies of inpatients (WMD −2.543, 95% CI: −3.522 to −1.564, Z 9 = 5.09, p < .0001) versus community samples (WMD −.943, 95% CI: −1.563 to −.323, Z 7 = 2.98, p = .003) and in studies of higher methodological quality (WMD −2.354, 95% CI: −2.901 to −1.807, Z 7 = 8.43, p < .0001). Conclusions: Depression is associated with a lower concentration of zinc in peripheral blood. The pathophysiological relationships between zinc status and depression, and the potential benefits of zinc supplementation in depressed patients, warrant further investigation. [ABSTRACT FROM AUTHOR]

Highlights: [•] Plasma zinc concentrations are lower in major depression. [•] Zinc deficiency induces depression-like behaviors in animals. [•] Zinc interacts with multiple endocrine and immune functions. [•] Synaptic zinc modulates neural networks that regulate mood and cognition. [Copyright &y& Elsevier]