Faculty Bibliography

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.

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.

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.

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.

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.

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.

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.