Real-world clinical outcomes and treatment patterns in patients with MDD treated with vortioxetine: a retrospective study.

BACKGROUND: This study included evaluation of the effectiveness of vortioxetine, a treatment for adults with major depressive disorder (MDD), using patient-reported outcome measures (PROMs) in a real-world setting. METHODS: This retrospective chart review analyzed the care experiences of adult patients with a diagnosis of MDD from Parkview Physicians Group - Mind-Body Medicine, Midwestern United States. Patients with a prescription for vortioxetine, an initial baseline visit, and ≥ 2 follow-up visits within 16 weeks from September 2014 to December 2018 were included. The primary outcome measure was effectiveness of vortioxetine on depression severity as assessed by change in Patient Health Questionnaire-9 (PHQ-9) scores ~ 12 weeks after initiation of vortioxetine. Secondary outcomes included changes in depression-related symptoms (i.e., sexual dysfunction, sleep disturbance, cognitive function, work/social function), clinical characteristics, response, remission, and medication persistence. Clinical narrative notes were also analyzed to examine sleep disturbance, sexual dysfunction, appetite, absenteeism, and presenteeism. All outcomes were examined at index (start of vortioxetine) and at ~ 12 weeks, and mean differences were analyzed using pairwise t tests. RESULTS: A total of 1242 patients with MDD met inclusion criteria, and 63.9% of these patients had ≥ 3 psychiatric diagnoses and 65.9% were taking ≥ 3 medications. PHQ-9 mean scores decreased significantly from baseline to week 12 (14.15 ± 5.8 to 9.62 ± 6.03, respectively; p < 0.001). At week 12, the response and remission rates in all patients were 31.0% and 23.1%, respectively, and 67% continued vortioxetine treatment. Overall, results also showed significant improvements by week 12 in anxiety (p < 0.001), sexual dysfunction (p < 0.01), sleep disturbance (p < 0.01), cognitive function (p < 0.001), work/social functioning (p = 0.021), and appetite (p < 0.001). A significant decrease in presenteeism was observed at week 12 (p < 0.001); however, no significant change was observed in absenteeism (p = 0.466). CONCLUSIONS: Using PROMs, our study results suggest that adults with MDD prescribed vortioxetine showed improvement in depressive symptoms in the context of a real-world clinical practice setting. These patients had multiple comorbid psychiatric and physical diagnoses and multiple previous antidepressant treatments had failed.

Impact of adherence to antidepressants on healthcare outcomes and costs among patients with type 2 diabetes and comorbid major depressive disorder.

OBJECTIVE: To evaluate the association between adherence to antidepressants and an effect on clinical outcomes and healthcare costs in patients with major depressive disorder (MDD) and comorbid type 2 diabetes (T2D). METHODS: This retrospective study used MarketScan claims data from January 2012 to March 2014. Study entry was the first claim for an antidepressant and a diagnosis code for MDD and T2D in the prior 6 months. Adherence and persistence with antidepressant therapy in the first 180 days were defined as medication possession ratio (MPR) ≥ 80% and length of therapy (LOT), with no treatment gap of >15 days, respectively. T2D control (HbA1c <7%), oral diabetes medication adherence, and healthcare costs were measured in the 12 month post-index period. The impact of antidepressant adherence and persistence on outcomes was assessed using multivariable analyses. RESULTS: Among the 1361 patients included, the mean age was 59 years and 55% were women. About one-third of the patients were adherent (35.9%, mean MPR = 40%), persistent (32.0%, average LOT = 100 days), and adherent/persistent (31.2%) on antidepressants. Being adherent, persistent, or adherent/persistent to antidepressants was associated with a two-fold improvement in adherence to oral diabetes medications. Of those with HbA1c data (n = 121), adherence or adherence/persistence to antidepressants was associated with patients being five times more likely to have T2D control (odds ratio [OR]: 4.95; 95% confidence interval [CI]: 1.39, 17.59, p = .0134). Comparison between antidepressant-persistent and non-persistent patients was not significant. Mean difference in adjusted all-cause annual costs showed lower costs among antidepressant-adherent and adherent/persistent patients (adherent: -$350, 95% CI: -$462, -$247; adherent/persistent: -$1165; 95% CI: -$1280, -$1060). CONCLUSIONS: Patients with better antidepressant adherence and adherence/persistence demonstrated better HbA1c control, with lower all-cause total and medical costs. Adherence, persistence, or adherence/persistence to antidepressants was associated with improved adherence to oral diabetes medications.

The role of glia in the hypothalamus: implications for gonadal steroid feedback and reproductive neuroendocrine output.

Neuron-to-glia, glia-to-neuron, and glia-to-glia communication are implicated in the modulation of neuronal activity and synaptic transmission relevant to reproduction. Glial cells play an important role in neuroendocrine regulation and participate in the sexual differentiation of neuronal connectivity of brain regions involved in the control of reproductive neuroendocrine output. During puberty, modifications in the morphology and chemistry of astrocytes and tanycytes in the hypothalamus and median eminence influence the maturation of the neuronal circuits controlling the secretion of GnRH. During adult reproductive life, the glial cells participate in the transient remodeling of neuronal connectivity in the preoptic area, the arcuate nucleus, the median eminence, and other brain regions involved in the control of reproduction. Gonadal hormones regulate glial plasticity by direct and indirect effects and regulate various other endocrine signals, local soluble factors and adhesion molecules that also affect glial function and glia-to-neuron communication. The glial cells, therefore, are central to the coordination of endocrine and local inputs that bring about neural plasticity and adapt reproductive capacity to homeostatic signals.

Pubertal hormones modulate the addition of new cells to sexually dimorphic brain regions.

New cells, including neurons, arise in several brain regions during puberty in rats. Sex differences in pubertal addition of cells coincide with adult sexual dimorphisms: for each region, the sex that gains more cells during puberty has a larger volume in adulthood. Removing gonadal hormones before puberty eliminates these sex differences, indicating that gonadal steroids direct the addition of new cells during puberty to maintain and accentuate sexual dimorphisms in the adult brain.

Cellular phenotype of androgen receptor-immunoreactive nuclei in the developing and adult rat brain.

Androgen exposure during development and adulthood promotes cell-to-cell communication, modulates the size of specific brain nuclei, and influences hormone-dependent behavioral and neuroendocrine functions. Androgen action involves the activation of androgen receptors (AR). To elucidate the mechanisms involved in AR-mediated effects on forebrain development, double-label fluorescent immunohistochemistry and confocal microscopy were employed to identify the cellular phenotype of AR-immunoreactive (AR(+)) cells in the developing (embryonic day 20, postnatal days 0, 4, 10) and adult male rat forebrain. Sections were doubly labeled with antibodies directed against AR and one of the following: neurons (immature, nestin; mature, NeuN) or astrocytes [immature, vimentin; mature, glial fibrillary acidic protein (GFAP)] or mature oligodendrocytes (mGalC). In all brain regions examined, by far the majority of AR(+) cells were neurons. In addition, small subsets of AR(+) cells were identified as mature astrocytes (GFAP(+)) but only in specific brain regions at specific ages. AR(+)/GFAP(+) cells were observed in the cerebral cortex but only in postnatal day 10 rats and in the arcuate nucleus of the hypothalamus but only in adult rats. Immature neurons, immature astrocytes, and oligodendrocytes were not AR(+) at any age, in any region. Thus, both neurons and astrocytes in the male rat forebrain contain ARs, suggesting that androgens, via ARs, may exert effects on both cell types in an age- and region-dependent manner.