Faculty Bibliography

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.

Pharmacokinetic interactions between medications can have clinically significant effects. Concern usually arises when a medication is added to a continuing regimen, though discontinuation of a medication can also have an impact. A case is presented of a patient who experienced benzodiazepine withdrawal symptoms on discontinuation of nefazodone, an antidepressant that inhibits the cytochrome P450 3A4 isoenzyme. Plasma levels of alprazolam, a substrate for the 3A4 isozyme, fell rapidly when nefazodone was discontinued, presumably because of renewed 3A4 isoenzyme activity. The management of the patient's withdrawal symptoms is described.

Compulsive buying is a syndrome characterized by the impulsive and/or compulsive buying of unneeded objects that results in personal distress, impairment in vocational or social functioning, and/or financial problems. Results from a two-site, double-blind, placebo-controlled 13-week trial of fluvoxamine are presented. Subjects had problematic buying behavior that they could not control for the previous 6 months or longer and met DSM-IV criteria for impulse control disorder-not otherwise specified (ICD-NOS) and the University of Cincinnati criteria for compulsive buying. Assessments included clinician-rated scales-the Yale-Brown Obsessive Compulsive Scale modified for compulsive buying, the Clinical Global Impression Scale, the Global Assessment of Functioning, and the Hamilton Rating Scale for Depression-and patient self-reports using daily diaries, which measured episodes of compulsive buying. Forty-two subjects gave informed consent, with 37 subjects providing evaluable information and 23 completing the study. Current or past psychiatric comorbidity was present in 74% of subjects. Intent-to-treat and completer analyses failed to show a significant difference between treatments on any measures of outcome. A high placebo-response rate, possibly from the behavioral benefits of maintaining a daily diary, prevents any definitive statement on the efficacy of fluvoxamine in treating compulsive buying.

Impulse control disorders (ICDs) are characterized by irresistible urges to perform acts that result in a reduction of tension and possibly gratification, but also have negative consequences. Trichotillomania, an ICD, is characterized by a recurrent failure to resist impulses to pull out one's hair, resulting in noticeable hair loss. Limited information is available about structural and neurochemical differences in individuals with trichotillomania. Cognitive behavioral techniques are promising treatments for trichotillomania. Pharmacologic treatments have focussed on clomipramine and venlafaxine as potentially effective for the short term control of symptoms in trichotillomania. Selective serotonin reuptake inhibitors, though promising in open trials, seem to be largely ineffective in reducing hair pulling in controlled studies. Durability of pharmacologic benefit for the symptoms of trichotillomania, both in a small trial and in clinical experience, appears to be poor.

BACKGROUND:The major treatments reported to be effective in the treatment of trichotillomania are cognitive-behavioral therapy (CBT) with habit reversal and serotonin-norepinephrine reuptake inhibitors such as clomipramine. However, the 2 treatments have not been previously compared with each other. This study examines the efficacy of CBT and clomipramine compared with placebo in the treatment of trichotillomania. METHOD/METHODS:Twenty-three patients with trichotillomania as determined by the Structured Clinical Interview for DSM-III-R entered and 16 completed a 9-week, placebo-controlled, randomized, parallel-treatment study of CBT and clomipramine. Efficacy was evaluated by the Trichotillomania Severity Scale, the Trichotillomania Impairment Scale, and the Clinical Global Impressions-Improvement scale, which were conducted by an independent assessor blinded to the treatment condition. RESULTS:CBT had a dramatic effect in reducing symptoms of trichotillomania and was significantly more effective than clomipramine (p = .016) or placebo (p = .026). Clomipramine resulted in symptom reduction greater than that with placebo, but the difference fell short of statistical significance. Placebo response was minimal. CONCLUSION/CONCLUSIONS:Clinicians should be aware of the potential treatments available for trichotillomania. A larger and more definitive study comparing CBT and a serotonin-norepinephrine reuptake inhibitor is indicated.

BACKGROUND:Serotonin reuptake inhibitors (SRIs) have demonstrated consistent efficacy in the treatment of obsessive-compulsive disorder (OCD), while agents that are primarily norepinephrine reuptake inhibitors have not. Comparable efficacy has been demonstrated for SRI and non-SRI antidepressants in uncomplicated major depressive disorder (MDD). This multicenter trial is the first comparison of an SRI (sertraline) and a non-SRI antidepressant (desipramine) in the treatment of OCD with concurrent MDD. METHODS:One hundred sixty-six patients diagnosed using structured clinical interviews and recruited from 16 treatment sites were randomly assigned to double-blind treatment with either sertraline (up to 200 mg/d) or desipramine (up to 300 mg/d) over 12 weeks. Measures of severity of OCD and MDD symptoms, as well as adverse effects of the medications, were monitored over the course of the treatment period. RESULTS:Patients assigned to sertraline responded significantly better at end point on measures of OCD and MDD symptoms compared with patients assigned to desipramine. Sertraline was also associated with a significantly greater number of patients who achieved a "robust" improvement in OCD symptoms (> or =40% reduction) compared with desipramine. More patients receiving desipramine than sertraline discontinued treatment because of adverse events. CONCLUSIONS:The SRI sertraline was more effective in reducing MDD and OCD symptoms than the primarily norepinephrine reuptake inhibitor desipramine for patients with concurrent OCD and MDD.

Venlafaxine is a medication available by prescription in the U.S. both in an immediate release and an extended release formulation. Preclinical studies indicate it has the effect of potently blocking the serotonin and norepinephrine transporters. Venlafaxine is approved by the FDA for the treatment of major depressive disorder and generalized anxiety disorder. Suggestive evidence, mostly from open label case series, indicates efficacy of venlafaxine in several other conditions including panic disorder, social anxiety disorder, obsessive compulsive disorder, trichotillomania, ADHD, chronic pain, and fibromyalgia. The limited evidence supporting efficacy in these conditions is reviewed. Additional randomized clinical trials with placebo controls are indicated.