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Biomedical subjects

W K Goodman

Publications and source records attributed to W K Goodman.

At least 73 records · Page 4Linked to original sources
PubMed1992

Assessment of severity and change in obsessive compulsive disorder.

Useful clinician-rated measures of OCD are now available. The Y-BOCS and NIMH Global OC both seem suitable for monitoring outcome in drug trials of OCD. These two scales seem relatively specific for symptoms of OCD and are sensitive to drug-induced changes in symptoms. Neither the Y-BOCS nor the NIMH Global OC confuse trait with state. There are ample data suggesting that the Y-BOCS is reliable and valid scale. Unlike some of the symptom inventories, such as the LOI and MOCI, final scores on the NIMH Global OC and Y-BOCS are not influenced directly by the type or number of obsessions and compulsions present. A computer-administered version of the Y-BOCS has been developed. Currently available patient-rated instruments suffer from serious shortcomings, including insensitivity to change and poor representation of patients with mono-symptomatic clinical pictures (e.g., hoarding alone). Some rating scales have been adapted for use in children with OCD. Several groups, including our own, have elected to use change scores on the 10-item Y-BOCS and a global measure of OCD, such as the NIMH Global OC or modified OGI, as the principal outcome variables in drug trials in patients with OCD. Several studies have selected a 35% decrease in Y-BOCS scores from baseline as indicative of clinically significant improvement. A limitation of all single-item global measures is that they cannot be resolved into smaller components. The more fine-grained analysis that is possible with the multi-item Y-BOCS makes it more desirable as a primary outcome measure, with a global scale as a secondary outcome measure.

Adult↗
PubMed1992

The serotonin hypothesis of obsessive compulsive disorder: implications of pharmacologic challenge studies.

Demonstration of the efficacy of serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors such as clomipramine in the treatment of obsessive compulsive disorder has fueled interest in the neurobiological basis of this illness. Results of treatment studies, investigations of biological markers, and pharmacologic challenges are reviewed and implications for a 5-HT theory of obsessive compulsive disorder discussed. While the nature of the dysregulation in serotonin transmission that may attend obsessive compulsive disorder has yet to be fully elucidated, evidence accumulates that 5-HT function in part modulates obsessive compulsive symptoms. Development of more specific probes and new brain imaging techniques will further enhance understanding of the pathophysiology of obsessive compulsive disorder.

Biomarkers↗
PubMed1992

Pharmacotherapy of obsessive compulsive disorder.

The authors briefly review studies of the efficacy of potent serotonin reuptake inhibitors (SRIs) (e.g., clomipramine, fluvoxamine) in obsessive compulsive disorder (OCD) and compare the use of antidepressants in the treatment of depression and OCD. They propose an algorithm for those patients with OCD who fail to respond to an adequate trial with a potent SRI and discuss the promise and limitations of adding tryptophan, fenfluramine, lithium, buspirone, or a neuroleptic to ongoing SRI therapy. Other biological approaches (e.g., ECT, psychosurgery) are considered in terms of their narrowly defined roles in the treatment of patients with SRI-resistant OCD.

1-Naphthylamine↗
PubMed1991

Cerebral laterality, perception of emotion, and treatment response in obsessive-compulsive disorder.

Patients with obsessive-compulsive disorder (OCD) had lower right-ear advantages than healthy controls on five different language-related dichotic listening tests of cerebral laterality. This abnormality was more pronounced in patients with more severe illness. Stimulus pairs in one test consisted of one word with a positive emotional valence and one emotionally neutral word. Pairs in another test consisted of one negative and one neutral word. Patients with OCD tended to hear fewer emotion-related words than did healthy controls, a finding also noted in depressed patients. Moreover, OCD patients who responded to treatment with serotonin reuptake inhibitors heard fewer emotion-related words than did nonresponders.

Adolescent↗
PubMed1991

Current treatment approaches to obsessive-compulsive disorder.

The two most useful treatments in obsessive-compulsive disorder are pharmacotherapy with potent serotonin reuptake-blocking agents and behavioral techniques, such as exposure and response prevention. Based on the authors' cumulative clinical experience, it is suggested that patient education, cognitive therapy, and psychodynamic psychotherapy are helpful adjuncts during various treatment stages of obsessive-compulsive disorder. The patient's strengths and knowledge of the illness can be used by the nurse-therapist to determine the implementation and timing of these therapeutic measures. Specific behavioral and cognitive techniques that may be useful in treating specific symptoms of obsessive-compulsive disorder are highlighted. Suggestions for future nursing research are outlined.

Behavior Therapy↗
PubMed1991

A controlled trial of lithium augmentation in fluvoxamine-refractory obsessive-compulsive disorder: lack of efficacy.

Two- and 4-week double-blind placebo-controlled trials of lithium augmentation of ongoing fluvoxamine treatment trials were conducted in 20 and 10 patients, respectively, with primary obsessive-compulsive disorder (OCD) who had failed to respond to fluvoxamine alone. Although 2 weeks of double-blind lithium augmentation produced a small but statistically significant reduction in obsessive-compulsive symptoms, most patients did not have a clinically meaningful response. Furthermore, there was no statistical or clinical improvement in obsessive-compulsive symptoms during the subsequent 4-week double-blind, placebo-controlled trial of lithium augmentation. On the basis of treatment response criteria, only 18% and 0% of the patients responded to lithium augmentation of fluvoxamine during the 2- and 4-week treatment trials, respectively. In light of the previously reported 44% response rate to lithium augmentation in treatment-resistant depressed patients on fluvoxamine, the results of this study suggest that pathophysiological differences may exist between OCD and depression. The routine use of lithium augmentation in the management of patients with OCD who are refractory to serotonin reuptake inhibitors is not supported by these findings.

Adult↗
PubMed1990

Specificity of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder. Comparison of fluvoxamine and desipramine.

To evaluate whether serotonin reuptake inhibition is critical to the treatment of obsessive-compulsive disorder, 40 outpatients with a principal diagnosis of obsessive-compulsive disorder were randomized in a double-blind fashion to 8 weeks of treatment with either the serotonin reuptake inhibitor fluvoxamine maleate (n = 21) or the norepinephrine reuptake inhibitor desipramine hydrochloride (n = 19). Fluvoxamine was significantly better than desipramine in reducing the severity of obsessive-compulsive symptoms, as measured by the Yale-Brown Obsessive Compulsive Scale and by the global response rate ("responder" equaling "much improved"). Eleven of 21 patients were responders with fluvoxamine compared with 2 of 19 patients with desipramine. Fluvoxamine, but not desipramine, was also effective in reducing the severity of "secondary" depression. Fluvoxamine-induced improvement in symptoms of obsessive-compulsive disorder was not correlated with the severity of baseline depressive symptoms. This study provides additional evidence that the acute serotonin reuptake properties of a drug are predictive of its anti-obsessive-compulsive efficacy. It is hypothesized that the mechanism of action of serotonin reuptake inhibitors in obsessive-compulsive disorder may be related to chronic treatment-induced adaptive changes in presynaptic serotonin receptor function (eg, autoreceptor desensitization) and/or indirect influences on dopaminergic function (eg, in the basal ganglia).

Adult↗
PubMed1990

Fluvoxamine treatment of coincident autistic disorder and obsessive-compulsive disorder: a case report.

This is a single-case report of fluvoxamine treatment of comorbid autistic disorder (AD) and obsessive-compulsive disorder (OCD). Psychological, neuroanatomical, and neurochemical parallels are drawn between AD and OCD. The implications of this case of coincident AD and OCD, as well as the response to fluvoxamine, are discussed with respect to nosology, pathophysiology, and treatment of these disorders.

Adult↗
PubMed1990

Clinical studies of 5-HT function using i.v. L-tryptophan.

1. Preclinical studies reveal that long-term treatment with antidepressant drugs induces significant changes in serotonergic (5-HT) receptor sensitivity. Similarly, clinical studies suggest that brain 5-HT function is abnormal in depression. Of the available methodologies for conducting such clinical studies, the pharmacological challenge strategy has proven particularly useful. 2. I.v. L-TRP has emerged as the most frequently used challenge agent in diagnostic and neuropsychopharmacological studies of 5-HT function. I.v. L-TRP increases serum prolactin (PRL) in humans, probably via 5-HT mechanisms. Under carefully standardized conditions, this PRL response to L-TRP appears to be a reasonably sensitive and valid measure of net 5-HT function. 3. The PRL response to L-TRP is blunted in depressed patients compared with healthy controls. Blunting has not been observed in panic disorder, obsessive compulsive disorder, or schizophrenia, although preliminary findings suggest it may occur in bulimia. 4. The PRL response to L-TRP is enhanced by certain classes of thymoleptic drugs (TCAs, MAOIs, 5-HT reuptake inhibitors, lithium) in a differentially time-dependent fashion. So-called "atypical" antidepressants (trazodone, mianserin) and benzodiazepines have no effect. Such findings are generally consistent with preclinical electrophysiological findings. 5. These clinical studies of the PRL response to L-TRP, in conjunction with emerging evidence that experimentally reduced plasma TRP can reverse the therapeutic effects of some antidepressants, suggest that antidepressant drug action may be more accurately conceptualized as 5-HT dependent rather than 5-HT enhancing. The availability of more selective 5-HT-active drugs promises to further clarify 5-HT mechanisms of neuropsychiatric disease and drug action at the clinical level.

Animals↗
PubMed1990

Neuroleptic addition in fluvoxamine-refractory obsessive-compulsive disorder.

Nine of 17 patients with obsessive-compulsive disorder responded when neuroleptic was added to fluvoxamine with or without lithium. Comorbid occurrence of tic spectrum disorders or of schizotypal personality disorder was associated with response. Abnormalities in brain dopamine and serotonin may be implicated in such patients.

Adult↗
PubMed1990

Fluvoxamine/pimozide treatment of concurrent Tourette's and obsessive-compulsive disorder.

A 25-year-old man with a history of Tourette's syndrome presented for treatment of OCD symptoms. Fluvoxamine worsened tics, led to coprolalia, and did not help the OCD. The addition of pimozide dramatically reduced both OCD and Tourette's symptoms. Double-blind sequential discontinuation of fluvoxamine and pimozide confirmed that pimozide alone reduced only tics and the combination of fluvoxamine and pimozide was required for the improvement in OCD. Tics may reflect a subtype of OCD. Some OCD patients unresponsive to a 5-HT reuptake inhibitor alone may benefit from the addition of a dopamine antagonist.

Adult↗
PubMed1990

Clinical data on the role of serotonin in the mechanism(s) of action of antidepressant drugs.

In view of evidence that brain serotonin (5-HT) function is abnormal in depression, the ability to alter 5-HT function has been studied as a mechanism of antidepressant drug action. In preclinical studies, antidepressants had significant effects on 5-HT receptor sensitivity. In the clinical setting, the pharmacologic challenge paradigm has generated interest as a means of studying 5-HT function. Most frequently used in these studies has been intravenous L-tryptophan (L-TRP), which increases serum prolactin (PRL). The authors review the neuroendocrine effects of intravenous L-TRP in depression and other conditions, as well as the effects of thymoleptic drugs on the PRL response to L-TRP. Findings are discussed in light of recent evidence that experimentally reduced plasma TRP can reverse the therapeutic effects of some antidepressants.

Antidepressive Agents↗
PubMed1990

Beyond the serotonin hypothesis: a role for dopamine in some forms of obsessive compulsive disorder?

It seems unlikely that a solitary disturbance in serotonin function can fully account for the pathophysiology of obsessive compulsive disorder. The authors propose that some forms of obsessive compulsive disorder, e.g., obsessive compulsive disorder with a history of Tourette's syndrome, may involve a relative or absolute derangement in both brain serotoninergic and dopaminergic systems. A role for dopamine in the pathophysiology of obsessive compulsive disorder is supported by a review of the preclinical and clinical evidence. Additional studies are needed to more directly evaluate dopamine function in patients with obsessive compulsive disorder.

Dopamine↗
PubMed1989

Efficacy of fluvoxamine in obsessive-compulsive disorder. A double-blind comparison with placebo.

A six- to eight-week double-blind placebo-controlled trial of the potent and selective serotonin reuptake inhibitor fluvoxamine was conducted in 42 patients with primary obsessive-compulsive disorder (OCD). Approximately one half of the patients also had symptoms of major depression. Fluvoxamine was significantly better than placebo on all measures of obsessive-compulsive symptoms. Nine of 21 patients were responders ("much improved") with fluvoxamine compared with no responders with placebo, and fluvoxamine was effective in patients with OCD both with and without secondary depression. Response of OCD was not correlated with severity of baseline depression. These data lend partial support to the serotonin hypothesis of OCD. However, since a number of patients failed to respond to fluvoxamine, the role of other neurochemical systems in this disorder needs to be explored.

Adult↗
PubMed1989

The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability.

The Yale-Brown Obsessive Compulsive Scale was designed to remedy the problems of existing rating scales by providing a specific measure of the severity of symptoms of obsessive-compulsive disorder that is not influenced by the type of obsessions or compulsions present. The scale is a clinician-rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms) (total range, 0 to 40), with separate subtotals for severity of obsessions and compulsions. In a study involving four raters and 40 patients with obsessive-compulsive disorder at various stages of treatment, interrater reliability for the total Yale-Brown Scale score and each of the 10 individual items was excellent, with a high degree of internal consistency among all item scores demonstrated with Cronbach's alpha coefficient. Based on pretreatment assessment of 42 patients with obsessive-compulsive disorder, each item was frequently endorsed and measured across a range of severity. These findings suggest that the Yale-Brown Scale is a reliable instrument for measuring the severity of illness in patients with obsessive-compulsive disorder with a range of severity and types of obsessive-compulsive symptoms.

Adult↗
PubMed1989

The Yale-Brown Obsessive Compulsive Scale. II. Validity.

The development design and reliability of the Yale-Brown Obsessive Compulsive Scale have been described elsewhere. We focused on the validity of the Yale-Brown Scale and its sensitivity to change. Convergent and discriminant validity were examined in baseline ratings from three cohorts of patients with obsessive-compulsive disorder (N = 81). The total Yale-Brown Scale score was significantly correlated with two of three independent measures of obsessive-compulsive disorder and weakly correlated with measures of depression and of anxiety in patients with obsessive-compulsive disorder with minimal secondary depressive symptoms. Results from a previously reported placebo-controlled trial of fluvoxamine in 42 patients with obsessive-compulsive disorder showed that the Yale-Brown Scale was sensitive to drug-induced changes and that reductions in Yale-Brown Scale scores specifically reflected improvement in obsessive-compulsive disorder symptoms. Together, these studies indicate that the 10-item Yale-Brown Scale is a reliable and valid instrument for assessing obsessive-compulsive disorder symptom severity and that it is suitable as an outcome measure in drug trials of obsessive-compulsive disorder.

Adult↗