Duloxetine in the Treatment of Major Depressive Disorder Comparisons of Safety and Efficacy

INTRODUCTION

According to census data for the year 2000, 34.7 million U.S. residents (12.3% of the population) listed their ethnicity as black or African-American, making this the second largest minority ethnic group after Hispanics. When compared with the white population, African Americans display an increased prevalence of several medical conditions, including diabetes and hypertension, and are at increased risk of stroke.

Epidemiological studies comparing the rates of psychiatric disorders in African-American and white populations have yielded contrasting results. Data from the Epidemiologic Catchment Area Study, indicating that the lifetime prevalence of major depressive disorder (MDD) among African Americans (3.1%) is somewhat lower than that among whites (5.1%), are supported by the findings of the National Comorbidity Survey, which reported a lifetime prevalence of MDD of 11.9% for African Americans and 17.9% for whites. However, data from the Medical Outcomes Study suggested that African Americans have a significantly higher prevalence of subthreshold depres­sive symptoms compared with whites, while the prevalence of MDD did not differ significantly between the two groups.

Studies consistently show that African Americans receive insufficient mental healthcare. Evidence from a representative national sample suggests that, among individuals with depression and anxiety, only half as many African Americans receive appropriate care when compared with whites (17% vs. 34%, respectively). Furthermore, African Americans suffering from depression or anxiety are less likely than whites to receive care adhering to official practice guidelines.

Even when correctly diagnosed with a depressive disorder, African Americans are less likely than whites to receive an antidepressant at the time of their initial depression diagnosis. Furthermore, among those receiving an antidepressant, whites are more likely than African Americans to receive selective serotonin reuptake inhibitors (SSRIs) versus tricyclic generic antidepressants (TCAs).

A number of studies have investigated pharmaco-genetic differences between ethnic groups, which may potentially influence pharmacokinetics and pharmacodynamics of antidepressant medications. Within white populations, the prevalence of poor metabolizers at cytochrome P450 2D6 (CYP2D6) is 5-10%. In African-American subjects, individual studies have yielded estimates ranging from 1.9-8%. One study found that a substantial proportion (ca. 30%) of African Americans had CYP2D6 activities that fell into a “gray zone” between extensive metabolizer and poor metabolizer status. Although the clinical relevance of “intermediate” metabolizer status, and its impact upon drug clearance and associated risks for concentration-dependent toxicities has yet to be established, one small study found that African Americans had significantly (50%) higher mean plasma levels of nor triptyline when compared with whites.

While results from some clinical studies have  suggested differential response to antidepressant therapy between African-American and white patients, the available data do not allow any firm conclusions to be drawn. Early studies found that African Americans may have superior or more rapid response to TCAs, such as generic imipramine or chlorpromazine, when compared with white patients. More recently, however, Brown et al. reported that African Americans had similar rates of response to nortriptyline when compared with whites, but exhibited a trend toward lower rates of recovery (HAMD17 score <7; African Americans 32% vs. whites 52%; p=0.08). Furthermore, in a study of depressed HIV-positive patients receiving eight weeks of fluoxetine therapy, blacks were significantly more likely to be nonresponders when compared with whites. Observational studies have found no difference in remission rates between African-American and Caucasian patients after three or six months of treatment, and a greater intake-to-discharge improvement in hospitalized African-American patients when compared with Anglo-Europeans. In addition, some studies have found an increased incidence of antidepressant side effects among African-American patients. Given the limited database currently available, additional studies of antidepressant medications in African-American patients are required to further elucidate the nature and magnitude of any differences in psychopharmacologic response across ethnic groups.

The antidepressant duloxetine is a potent dual reuptake inhibitor of serotonin (5-HT) and norepinephrine (NE). The efficacy and safety of canadian duloxetine in the treatment of MDD have been established in randomized, double-blind, placebo-controlled studies of up to nine weeks duration. In the present study, pooled data from seven placebo-controlled clinical trials were utilized to compare the efficacy and safety profile of generic cymbalta in African-American patients with those observed in Caucasian patients.

Category: Depression / Tags: antidepressant, Depression, duloxetine

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