Faculty Bibliography

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.

BACKGROUND:Limited information is available on treatment response of anxiety symptoms in chronic forms of major depression. Concurrent anxiety disorders are prevalent in chronic depression, but the responsiveness of patients with such comorbidity to different treatments is largely unknown. This study investigated the comparative efficacy of nefazodone, Cognitive Behavioral Analysis System of Psychotherapy (CBASP), and their combination in improving anxiety symptoms in patients with chronic forms of major depression, including those with a concurrent anxiety disorder. METHOD/METHODS:681 patients with chronic major depressive disorder (DSM-IV criteria) participated in a multicenter study of 12 weeks of acute treatment with nefazodone (N = 226), CBASP (N = 228), or the combination (N = 227). The Hamilton Rating Scale for Anxiety (HAM-A), the HAM-A psychic anxiety factor, and the anxiety/arousal subscale of the 30-item Inventory for Depressive Symptomatology-Self Report (IDS-SR-30) were used to assess anxiety symptoms. RESULTS:In the full sample. without controlling for change in depressive symptoms, combination therapy was superior to both monotherapies on all 3 anxiety measures both in the rate of change and at endpoint. When change in depressive symptoms was controlled for, there were no treatment differences in rate of change from baseline to week 12 on any of the 3 anxiety measures. In those patients with a concurrent anxiety disorder, however, the combination was superior to CBASP on the HAM-A and the IDS-SR-30. Nefazodone alone and combination therapy were both superior to CBASP on the HAM-A psychic anxiety factor. CONCLUSION/CONCLUSIONS:For patients with chronic depression, combination therapy is superior to CBASP or nefazodone alone. Among patients with a concurrent anxiety disorder, nefazodone. either alone or in combination with CBASP, improves anxiety symptoms faster than CBASP alone, independent of depressive symptom reduction.

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 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.

To determine whether (1) insight in obsessive-compulsive disorder (OCD) improves when OCD symptoms improve, and whether (2) degree of insight in OCD predicts response to sertraline, data were obtained from five sites participating in a larger multisite study of relapse in OCD. During the first 16 weeks of the study, 71 patients received open-label treatment with sertraline and were assessed using the Yale-Brown Obsessive-Compulsive Rating Scale (Y-BOCS) and a rating scale to evaluate insight, the Brown Assessment of Beliefs Scale (BABS), at study baseline and termination. Baseline total BABS score was not significantly correlated with change in Y-BOCS score. Change in BABS total score and change in Y-BOCS total score were significantly correlated. There was no significant difference in mean endpoint Y-BOCS scores for patients with poor insight (n = 14) compared to patients with good insight at baseline (n = 57). Thus, insight improved with decrease in OCD symptom severity. Degree of insight at baseline did not predict response to sertraline, i.e., patients with poor insight were just as likely to respond to sertraline as patients with good insight.

Anxiety disorders are common mental disorders, encompassing a group of conditions that share extreme or pathological anxiety as the primary disturbance in mood or emotional tone. Anxiety disorders include generalized anxiety disorder (GAD), panic disorder, agoraphobia, specific phobias, social anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder. Individual anxiety disorders have considerable symptomatic overlap in their expression. The life-time prevalence of all anxiety disorders in the general population is about 25%. There is familial aggregation of anxiety and mood disorders such as major depression. Genetic factors and life experiences both contribute to the likelihood of developing anxiety disorders. GAD is characterized by excessive anxiety and uncontrollable worry, is present for longer than 6 months, and tends to occur comorbidly with other conditions, including other anxiety disorders and major depression as well as general medical conditions. GAD, given its chronic nature, is associated with significant impairment. GAD is responsive to pharmacological treatments, such as anxiolytics and antidepressants, as well as psychotherapies such as cognitive therapy.