Standardized assessment of new electromagnetic field generators in an interventional radiology setting.

PURPOSE: Two of the main challenges associated with electromagnetic (EM) tracking in computer-assisted interventions (CAIs) are (1) the compensation of systematic distance errors arising from the influence of metal near the field generator (FG) or the tracked sensor and (2) the optimized setup of the FG to maximize tracking accuracy in the area of interest. Recently, two new FGs addressing these issues were proposed for the well-established Aurora(®) tracking system [Northern Digital, Inc. (NDI), Waterloo, Canada]: the Tabletop 50-70 FG, a planar transmitter with a built-in shield that compensates for metal distortions emanating from treatment tables, and the prototypical Compact FG 7-10, a mobile generator designed to be attached to mobile imaging devices. The purpose of this paper was to assess the accuracy and precision of these new FGs in an interventional radiology setting. METHODS: A standardized assessment protocol, which uses a precisely machined base plate to measure relative error in position and orientation, was applied to the two new FGs as well as to the well-established standard Aurora(®) Planar FG. The experiments were performed in two different settings: a reference laboratory environment and a computed tomography (CT) scanning room. In each setting, the protocol was applied to three different poses of the measurement plate within the tracking volume of the three FGs. RESULTS: The two new FGs provided higher precision and accuracy within their respective measurement volumes as well as higher robustness with respect to the CT scanner compared to the established FG. Considering all possible 5 cm distances on the grid, the error of the Planar FG was increased by a factor of 5.94 in the clinical environment (4.4 mm) in comparison to the error in the laboratory environment (0.8 mm). In contrast, the mean values for the two new FGs were all below 1 mm with an increase in the error by factors of only 2.94 (Reference: 0.3 mm; CT: 0.9 mm) and 1.04 (both: 0.5 mm) in the case of the Tabletop FG and the Compact FG, respectively. CONCLUSIONS: Due to their high accuracy and robustness, the Tabletop FG and the Compact FG could eliminate the need for compensation of EM field distortions in certain CT-guided interventions.

Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression.

OBJECTIVE: This study compared the efficacy and safety of paroxetine and imipramine with that of placebo in the treatment of bipolar depression in adult outpatients stabilized on a regimen of lithium. METHOD: In a double-blind, placebo-controlled study, 117 outpatients with DSM-III-R bipolar disorder, depressive phase, were randomly assigned to treatment with paroxetine (N=35), imipramine (N=39), or placebo (N=43) for 10 weeks. In addition to lithium monotherapy, patients may have received either carbamazepine or valproate in combination with lithium for control of manic symptoms. Patients were stratified on the basis of trough serum lithium levels determined at the screening visit (high: >0.8 meq/liter; low:

Treatment of major depression with nortriptyline and paroxetine in patients with ischemic heart disease.

OBJECTIVE: This study compared the efficacy, tolerability, and safety of paroxetine and nortriptyline in depressed patients with ischemic heart disease. METHOD: After a 2-week, single-blind placebo lead-in phase, 81 outpatients with DSM-III-R-defined nonpsychotic unipolar major depression and ischemic heart disease were randomly assigned to double-blind treatment with paroxetine or nortriptyline for 6 weeks. Paroxetine was administered at a fixed-flexible dose of 20-30 mg/day. Nortriptyline dose was adjusted with the use of blood-level monitoring to reach a plasma concentration of 50-150 ng/ml. RESULTS: Twenty-seven of the 41 patients who started treatment with paroxetine and 29 of the 40 patients who started treatment with nortriptyline had an improvement of at least 50% in their Hamilton Depression Rating Scale scores. Significantly more patients taking nortriptyline discontinued treatment prematurely (35% versus 10%), and more patients taking nortriptyline had adverse events resulting in termination (25% versus 5%). CONCLUSIONS: Both treatments were efficacious. Sixty-three percent of all patients improved at least 50%, and of these, 90% met the criteria for remission. Paroxetine was better tolerated than nortriptyline and less likely to produce cardiovascular side effects.

Paroxetine treatment of generalized social phobia (social anxiety disorder): a randomized controlled trial.

CONTEXT: The generalized type of social phobia (social anxiety disorder) is a severe and often disabling form of social anxiety that affects approximately 5% of the general population. Earlier research has shown monoamine oxidase inhibitors or benzodiazepines to be effective in treating this condition, but neither has achieved widespread use. OBJECTIVE: To compare the efficacy of paroxetine, a selective serotonin reuptake inhibitor, with placebo in adults with generalized social phobia. DESIGN: Twelve-week, multicenter, randomized, double-blind trial. SETTING: Thirteen centers across the United States and 1 in Canada. PARTICIPANTS: Between April 13, 1995, and February 28, 1996, 187 persons meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for generalized social phobia were randomized (and 183 returned for at least 1 efficacy assessment) to treatment. INTERVENTION: After a 1-week, single-blind, placebo, run-in period, patients received a double-blind, 11-week course of either paroxetine or matching-image placebo. The initial daily dosage of paroxetine (or placebo) was 20 mg with increases of 10 mg/d weekly (flexible dosing to a maximum of 50 mg/d) permitted after the second week of treatment. MAIN OUTCOME MEASURES: Number of responders based on the Clinical Global Impression Global Improvement Item ("much improved" or "very much improved"); mean change from baseline on the Liebowitz Social Anxiety Scale total score. RESULTS: Fifty (55.0%) of 91 persons taking paroxetine and 22 (23.9%) of 92 persons taking placebo were much improved or very much improved at the end of treatment (odds ratio [OR], 3.88; 95% confidence interval [CI], 2.81-5.36). Mean Liebowitz Social Anxiety Scale total scores were reduced by 39.1% (the mean baseline score of 78.0 declined by a mean of 30.5 points at follow-up) in the paroxetine group compared with 17.4% (the mean baseline score of 83.5 declined 14.5 points at follow-up) in the placebo group, a difference of 21.7% (95% CI, 8.7%-34.7%) favoring paroxetine. CONCLUSIONS: Paroxetine is an effective treatment for patients with generalized social phobia. Short-term (ie, 11-week) treatment results in substantial and clinically meaningful reductions in symptoms and disability. Future research should test whether these may be further reduced by extended treatment or supplementation with specific educational-cognitive-behavioral techniques.

Efficacy studies of paroxetine in panic disorder.

The optimal assessment of treatment outcome for studies assessing the efficacy of treatments for panic disorder has been a controversial topic. A recent National Institute of Mental Health (NIMH)-sponsored consensus conference addressed this important topic, and a summary paper regarding assessment of essential elements of the disorder resulted. Among other conclusions, it was agreed that several different domains should be considered as essential. This article reviews three pivotal studies assessing the efficacy of paroxetine for the treatment of panic disorder, and evaluates these studies for inclusion of those variables considered essential. Additionally, some data were reanalyzed to determine the percentage of individuals in these studies who are unequivocal responders (i.e., were both panic-free and rated on global assessment as responders). A longer-term treatment and relapse study is also mentioned briefly.

Comparison of paroxetine and nortriptyline in depressed patients with ischemic heart disease.

CONTEXT: Depression and ischemic heart disease often are comorbid conditions and, in patients who have had a myocardial infarction, the presence of depression is associated with increased mortality. Patients with heart disease need a safe and effective treatment for depression. OBJECTIVE: To compare the efficacy, cardiovascular effects, and safety of a specific serotonin reuptake inhibitor, paroxetine, with a tricyclic antidepressant, nortriptyline hydrochloride, in depressed patients with ischemic heart disease. DESIGN: Two-week placebo lead-in followed by a double-blind randomized 6-week medication trial. SETTING: Research clinics in 4 university centers. PATIENTS: Eighty-one outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder and with documented ischemic heart disease. INTERVENTIONS: Treatment with either paroxetine, 20 to 30 mg/d, or nortriptyline targeted to a therapeutic plasma level, 190 to 570 nmol/L (50-150 ng/mL), for 6 weeks. MAIN OUTCOME MEASURES: For effectiveness of treatment, a decline in the score of the Hamilton Rating Scale for Depression by 50% and final score of 8 or less; for cardiovascular safety, heart rate and rhythm, supine and standing systolic and diastolic blood pressures, electrocardiogram conduction intervals, indexes of heart rate variability, and rate of adverse events. RESULTS: By intent-to-treat analysis, 25 (61%) of 41 patients improved during treatment with paroxetine and 22 (55%) of 40 improved with nortriptyline. Neither drug significantly affected blood pressure or conduction intervals. Paroxetine had no sustained effects on heart rate or rhythm or indexes of heart rate variability, whereas patients treated with nortriptyline had a sustained 11% increase in heart rate from a mean of 75 to 83 beats per minute (P<.001) and a reduction in heart rate variability, as measured by the SD of all normal R-R intervals over a 24-hour period, from 112 to 96 (P<.01). Adverse cardiac events occurred in 1 (2%) of 41 patients treated with paroxetine and 7 (18%) of 40 patients treated with nortriptyline (P<.03). CONCLUSIONS: Paroxetine and nortriptyline are effective treatments for depressed patients with ischemic heart disease. Nortriptyline treatment was associated with a significantly higher rate of serious adverse cardiac events compared with paroxetine.

Double-blind, fixed-dose, placebo-controlled study of paroxetine in the treatment of panic disorder.

OBJECTIVE: This study was designed to determine the minimum paroxetine dose effective for treating panic disorder. METHOD: Of 425 patients with DSM-III-R panic disorder with or without agoraphobia who underwent a 2-week drug-free screening period, 278 patients were randomly assigned to double-blind treatment with a 10-week course of placebo or paroxetine at a dose of 10, 20, or 40 mg/day. RESULTS: At 40 mg/day, paroxetine was superior to placebo across the majority of outcome measures. Despite a mean of 9.5 to 11.6 full panic attacks during the screening period, 86.0% of the patients taking 40 mg of paroxetine, 65.2% of those taking 20 mg, 67.4% of those taking 10 mg, and 50.0% of the placebo-treated patients were free of full panic attacks during the 2 weeks ending at week 10. The 40-mg paroxetine group experienced significantly greater global improvement than the placebo group and significantly greater improvement in frequency of full and limited-symptom panic attacks, intensity of full panic attacks, phobic fear, anxiety, and depressive symptoms, usually evident by week 4. All doses of paroxetine were well tolerated, and adverse effects were consistent with those associated with selective serotonin reuptake inhibitors. CONCLUSIONS: Paroxetine is an effective and well-tolerated short-term treatment of panic disorder. The minimum dose demonstrated to be significantly superior to placebo was 40 mg/day, although some patients did respond at lower doses.

The effects of scopolamine and clonidine upon the performance and learning of a motor skill.

Twenty-eight subjects practised a task involving procedural knowledge in which a moving target has to be followed for two 3-min sessions. They were then randomly allocated to receive an IV injection of 0.4 mg scopolamine, 0.15 mg clonidine or saline. General impairment due to both active treatments was seen 20 min later in significantly decreased tracking performance. Subjects then had to learn a mirror-reversed version of the tracking task. This involved acquiring novel procedural knowledge. Subjects who had either saline or clonidine treatment showed rapid temporary improvements and also considerable permanent learning. Subjects treated with scopolamine, however, showed only slow temporary improvement and little permanent improvement in their performance at this task. This result suggests that a normally functioning cholinergic system is necessary not only for an efficient working memory but also for the long term acquisition of some kinds of procedural knowledge.