Faculty Bibliography

BACKGROUND:Changes in sexual interest/satisfaction and function are frequently associated with major depression and the use of some antidepressant treatments. This study compares the effects of antidepressant medication, psychotherapy, and combined treatment on sexual interest/satisfaction and function in patients with chronic major depression. METHOD/METHODS:Outpatients with chronic forms of DSM-IV major depressive disorder (N = 681) were randomly assigned to 12 weeks of nefazodone, Cognitive Behavioral Analysis System of Psychotherapy (CBASP), or combined nefazodone/CBASP. The Modified Rush Sexual Inventory was used to assess sexual functioning, and the 24-item Hamilton Rating Scale for Depression was used to assess depressive symptoms. RESULTS:At baseline, 65% of men and 48% of women reported some sexual dysfunction. Statistically significant linear improvement in sexual interest/satisfaction was noted across all 3 treatment groups (p < .001). Additionally, significant improvement in sexual function was observed across all 3 treatment groups on a composite measure of female sexual function (p < .001). Controlling for depressive symptoms and gender, combined treatment produced greater improvement in total sexual interest/satisfaction than CBASP alone (p = .007), but was not significantly different from nefazodone alone. Improvement in depressive symptoms was associated with improved sexual interest/satisfaction for men and women and, for men, improved sexual functioning. CONCLUSION/CONCLUSIONS:Chronic depression is associated with high rates of sexual dysfunction. Treatment with nefazodone, CBASP, and combined treatment improved sexual interest/satisfaction, with greatest improvement observed with combined treatment.

BACKGROUND:The antidepressant nefazodone and the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) were recently found to have significant, additive effects in a large multicenter study of chronic forms of major depression. As nefazodone-mediated blockade of serotonin-2 receptors may directly relieve insomnia associated with depression, we examined the more specific effects of CBASP and nefazodone, singly and in combination, on sleep disturbances. METHOD/METHODS:A total of 597 chronically depressed outpatients (DSM-III-R criteria) with at least 1 insomnia symptom were randomly assigned to 12 weeks of treatment with nefazodone (mean final dose = 466 mg/day), CBASP (mean = 16.0 sessions), or the combination (mean dose = 460 mg/day plus a mean of 16.2 CBASP sessions). Continuous and categorical insomnia outcomes, derived from standard clinician- and self-rated assessments, were compared. RESULTS:Patients receiving nefazodone (either alone or in combination with CBASP) obtained significantly more rapid and greater ultimate improvement in insomnia ratings when compared with those treated with CBASP alone. This difference was maximal by the fourth week of therapy and sustained thereafter. Combined treatment did not result in markedly better insomnia scores than treatment with nefazodone alone on most measures, although patients receiving both CBASP and nefazodone were significantly more likely (p < .001) to achieve > or = 50% decrease in insomnia severity. CONCLUSION/CONCLUSIONS:Despite comparable antidepressant efficacy, monotherapy with nefazodone or CBASP resulted in markedly different effects on the magnitude and temporal course of insomnia symptoms associated with chronic forms of major depression. Patients receiving the combination of psychotherapy and pharmacotherapy benefited from both the larger and more rapid improvements in insomnia associated with nefazodone therapy and the later-emerging effects of CBASP on the overall depressive syndrome.

Generalized anxiety disorder (GAD) is a chronic disorder that often precedes the development of, and is comorbid with, depression. Investigation of the neurobiological basis of GAD has provided suggestive evidence to implicate dysfunction of serotonergic and noradrenergic systems in the expression of GAD, as well as the depressive disorders. Hence, there may be a neurobiological link between GAD and depression through the activity of the serotonin and norepinephrine systems. The use of various anxiolytics and antidepressants, including benzodiazepines, tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors in the treatment of GAD is reviewed. The neurobiological relationship between GAD and depression, and the frequent comorbidity of these disorders, suggests that agents with a dual action on the serotonin and norepinephrine systems may potentially offer superior benefits in the management of patients with anxiety and depressive disorders.

which of these effects provides a differential benefit in anxiety versus depression?

The omnipresent worry and anxiety that are characteristic of generalized anxiety disorder (GAD) significantly reduce social and occupational functioning. Yet many clinical investigations of GAD fail to evaluate treatment-related changes in function. As a consequence, many patients who respond to pharmacologic treatment (defined as having a > or = 50% reduction in symptoms) still exhibit subsyndromal symptoms that predispose to relapse. This is particularly true for patients with GAD who have comorbid psychiatric or medical conditions. In recent years, the goal of treatment for anxiety disorders has been set toward the achievement of full remission--that is, a virtually asymptomatic state. Remission indicates an improvement not only of symptoms but also of functionality. Benzodiazepines, azapirones, and antidepressants are the three main classes of agents currently used in the treatment of GAD. Some antidepressants have been shown to better facilitate remission. This article will summarize evidence for the clinical utility of pharmacotherapeutic agents commonly used in the treatment of GAD.

Social anxiety disorder (SAD) is a prevalent anxiety disorder with the potential for considerable impairment. A patient with SAD is presented and treatment options are discussed. Novel concepts guiding our understanding of the neurobiology of SAD are presented, including the concept of sensory maps of the body, which is used to speculate on the nature of internal representations of relationships and their potential role in triggering anxiety in SAD. Understanding the neural circuitry mediating social relationships and its role in the threat response in SAD may be important for the development of new treatments for this disorder.

Depression is associated with marked suffering, morbidity, and high risk of recurrence and/or chronicity. As a result, the disorder represents a considerable public health problem and economic burden on society. Treatment of patients with depression to a state of remission is associated with a significantly improved long-term outcome, including a reduced risk of relapse and improved functioning. Thus, remission (which can be defined as attainment of a total score < or = 7 on the Hamilton Rating Scale for Depression) should be the goal of the acute phase of pharmacotherapy. Although it is widely assumed that available antidepressants are comparably effective, comparisons of the efficacy of antidepressants in clinical trials are flawed by a number of factors. Most notable problems are higher-than-expected placebo effects and low statistical power. Double-blind, comparative studies are also compromised by relatively high attrition rates and the often underestimated effects of patient nonadherence. Large study groups (in the order of 300 patients per treatment group) are needed to differentiate between a good and a potentially better antidepressant. The statistical technique of meta-analysis has been used to examine the results of studies of various antidepressants; these meta-analyses have shown that the selective serotonin reuptake inhibitors (SSRIs) have overall "within group" comparability and, overall, an efficacy profile comparable to the previous standard, tricyclic antidepressants (TCAs). However, in studies of hospitalized patients, TCAs affecting both serotonergic and noradrenergic systems (eg, amitriptyline or clomipramine) have been found to have greater efficacy when compared with SSRIs. Results of some individual studies, as well as a pooled analysis of the outcomes of more than 2,000 depressed patients, indicate that venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, may have a similar advantage relative to SSRIs across a broader range of patients. These findings suggest antidepressants that affect both serotonergic and noradrenergic neurotransmission may be more likely to accomplish the goal of remission. Compared with TCAs, the better safety profile of venlafaxine has established the drug as a more appropriate first-line treatment option.

BACKGROUND:Although it is known that antidepressant treatment improves psychosocial functioning, whether such changes occur independent of depressive symptoms is not known. This study compared efficacy of nefazodone, psychotherapy, and their combination in improving psychosocial functioning in chronically depressed outpatients. METHODS:Patients with chronic forms of major depressive disorder were randomized to 12 weeks of nefazodone, Cognitive Behavioral Analysis System of Psychotherapy (CBASP), or combined nefazodone/CBASP. Psychosocial assessments measured overall psychosocial functioning, work functioning, interpersonal functioning, and general health. RESULTS:Relative to community norms, patients with chronic major depression evidenced substantially impaired psychosocial functioning at baseline. Combined treatment produced significantly greater psychosocial improvement than either CBASP alone or nefazodone alone on all primary measures. Combined treatment remained superior to nefazodone on primary measures of work, social, and overall functioning, and superior to CBASP on social functioning when depressive symptoms were controlled. Unlike the two groups receiving nefazodone, CBASP alone's effect on psychosocial function was relatively independent of symptom change. Psychosocial functioning improved more slowly than depressive symptoms, and moderate psychosocial impairments remained at end point. CONCLUSIONS:Combined treatment had greater effect than either monotherapy. Change in depressive symptoms did not fully explain psychosocial improvement. Moderate residual psychosocial impairment remained, suggesting the need for continuation/maintenance treatment.

Generalized anxiety disorder (GAD) is a common disorder marked by excessive anxiety, worry, and somatic manifestations lasting over 6 months. GAD occurs relatively early in life in the majority of individuals; it is often chronic and comorbid with other anxiety disorders, affective disorders, and/ or medical conditions. GAD is as functionally debilitating as major depression even without comorbidity and, hence, is associated with considerable economic and societal burdens as well as health care utilization. Underrecognition of GAD and undertreatment of this disorder are major factors contributing to the individual and societal burden of GAD. Earlier long-term studies in GAD reported low remission rates despite treatment. More recent data support the potential for achieving remission in GAD with appropriate treatment. There is a critical need to enhance mental health literacy programs and translate the efficacy data into effectiveness schemes in clinical practice by improving disease management strategies. A conceptual basis for achieving these goals is provided by moving from a disorder model to a disease model in psychiatric practice. This move allows for staging of psychiatric illnesses, with GAD as a prototypical example. For the clinician, the critical paradigm shift is in modifying the treatment goal from the attenuation of symptoms, as in a "response," to the achievement of a state of "remission" (i.e., a virtually asymptomatic state). Remission of symptoms allows for improvement of psychosocial functioning and quality of life and potentially wellness. In this review, a synopsis of the epidemiology, natural history, economic and social cost, and clinical management issues is given as a road map to dissolving the burden of GAD.

The diagnosis of anxiety disorders and major depression can be reliably made based on signs and symptoms. However there are significant limitations to the current system of classification including overlapping criteria, high comorbidity, and the issue of subthreshold syndromes. The literature on treatment response documents that selective serotonin reuptake inhibitors are effective in the treatment of the various anxiety disorders, including when comorbid major depression is present. The literature also suggests that tricyclic antidepressant medications have superior benefits over selective serotonin reuptake inhibitors in major depression. Examination of the functional anatomy of the fear and reward systems may shed light on the underlying processes in the anxiety and depressive disorders. Such an approach points out the importance of addressing avoidance behaviors, which may be more responsive to cognitive behavioral treatments than pharmacological agents.