HDAC Inhibitors as Epigenetic Regulators

Adapted with permission from Mencacci C, Di Sciascio G, Katz P, Ripellino C. of collaboration with an expert panel of Italian psychiatrists and health economists. The population comprised patients with a first diagnosis of major depressive disorder and Erythromycin Cyclocarbonate initiating one SSRI or SNRI drug for the first time. The time frame used was 12 months. Efficacy and power data for the model were retrieved from your literature and validated by the expert panel. Local data were utilized for resource utilization and for treatment costs based on the perspective of each regional health service. Scenario analyses and probabilistic sensitivity analyses were performed to test the robustness of the model. Results Base case analysis showed that escitalopram is usually associated with the largest health gain (in quality-adjusted life years) and a lower total cost at one year for Sardinia (except for sertraline, against which it was cost-effective) and for Veneto, and therefore dominates the other treatment strategies, given that more quality-adjusted life years are achieved at a lower total cost. Scenario analyses and probabilistic sensitivity analyses support the robustness of the model. Conclusion The results indicate that escitalopram is the most cost-effective pharmacologic treatment strategy for both regional health services compared with all SSRIs and all SNRIs used in the first-line treatment of major depressive disorder. strong class=”kwd-title” Keywords: antidepressants, major depressive disorder, cost-effectiveness quality of life, Italy Introduction Major depressive disorder (MDD) is usually a commonly occurring heterogeneous disorder with a highly variable course, an inconsistent response to treatment, and no established physiopathologic mechanism.1 The World Health Business ranked MDD as the principal cause of years lost due to disability and the third cause of disability worldwide, projecting that by 2030 it will be the first leading cause.2 Globally, MDD affects around 150 million adults, and in Italy the number of people with the disease is estimated to be about 5 million with a lifelong prevalence between 8% and 13%.3 MDD is considered an important burden in terms of direct costs,4 which represent 31% of the total costs, which are paid by patients, their families, and the health care services, and also in terms of indirect costs, which account for 62% of the overall costs of depression.5,6 In 2004, the worldwide economic burden of the disease was estimated at USD 83.1 billion.7 MDD is associated Erythromycin Cyclocarbonate with an increased risk of relapse after a first episode and a higher risk of suicidal behavior. Depressive disorders impact society mainly by increasing suicide risk; in a study of 102 fatal suicides, almost 70% of victims experienced experienced an affective disorder.8 Depressive disorders also have a major impact on quality of life. In a study of quality of life impairment in depressive disorders, 63% of respondents with MDD experienced severely impaired quality of life, while 56% of those with dysthymia and globally 85% of those with double depressive Erythromycin Cyclocarbonate disorder (MDD and dysthymia) have been reported to have quality of Erythromycin Cyclocarbonate life impairment in the severe range.9 The main therapeutic alternatives for MDD include antidepressant medication, psychotherapy, and neuromodulatory strategies. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are two classes of antidepressants with a better safety profile than the traditional drugs, such as the tricyclic antidepressants.10 A recent literature evaluate by Cipriani et al11 identified differences in terms of both efficacy and acceptability among commonly prescribed antidepressants in favor of escitalopram and sertraline. In particular, this meta-analysis showed that venlafaxine, escitalopram, mirtazapine, and sertraline were more effective in terms of response than duloxetine, paroxetine, reboxetine, fluoxetine, and fluvoxamine. In terms of acceptability, escitalopram, citalopram, bupropion, and sertraline experienced better overall performance than other second-generation antidepressants. Another review by Cipriani et al12 recognized some statistically significant differences favoring escitalopram over other antidepressive brokers for acute-phase treatment of major depression in terms of efficacy (citalopram and fluoxetine) and acceptability (duloxetine). However, there was insufficient evidence to detect a difference between escitalopram and other antidepressants in early response to treatment. Another paper by Aguglia et al13 reported that use of SSRIs increased from 7.5% (2003) to 13.1% (2009) while the utilization of SNRIs increased from 0.8% to 2.5%. The most important increase over the VPREB1 6-12 months period was explained for escitalopram (+2.78%). A higher persistence in therapy was reported for SSRIs versus SNRIs (15.1% versus 13.0%), and escitalopram.