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Biomedical subjects

W K Goodman

Publications and source records attributed to W K Goodman.

87 records · Page 5Linked to original sources
PubMed1989

Fluvoxamine as an antiobsessional agent.

The studies reviewed here suggest that the potent and selective serotonin reuptake inhibitor fluvoxamine is an effective treatment for OCD. Response to the antiobsessional effects of fluvoxamine is independent of baseline levels of depression. Additional studies are currently underway to determine if fluvoxamine is actually more effective in OCD than less potent blockers of serotonin reuptake (e.g., desipramine) (Goodman et al. unpublished data). However, since the clinical response to potent serotonin reuptake blockers is often incomplete or, in as many as one-third of patients, absent, the precise relevance of the monoamine reuptake blocking properties of these medications to the pathogenesis of OCD remains unclear.

Antidepressive Agents↗
PubMed1988

Carbon dioxide-induced anxiety. Behavioral, physiologic, and biochemical effects of carbon dioxide in patients with panic disorders and healthy subjects.

Carbon dioxide was administered for 15 minutes to patients with panic disorders (5% CO2, n = 14) and healthy subjects (5% CO2, n = 11; 7.5% CO2, n = 8). Following administration of CO2 and air placebo, changes in behavioral ratings, vital signs, and plasma levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol, cortisol, growth hormone, and prolactin were measured over three hours. In the healthy subjects, CO2 produced dose-related increases in anxiety, somatic symptoms, vital signs, and plasma cortisol levels. In the patients, the frequency of panic attacks (in eight of 14 patients) and the increases in anxiety and somatic symptoms induced by 5% CO2 exceeded those in the healthy subjects and were similar to those induced by 7.5% CO2 in the healthy subjects. The physiologic and biochemical measurements obtained did not elucidate the mechanisms underlying CO2-induced anxiety or the greater anxiogenic effects of CO2 seen in patients with panic disorders.

Adult↗
PubMed1988

Serotonin function in obsessive-compulsive disorder. A comparison of the effects of tryptophan and m-chlorophenylpiperazine in patients and healthy subjects.

To evaluate the role of serotonin (5-HT) function in obsessive-compulsive disorder (OCD), behavioral and biochemical responses to the 5-HT receptor agonist m-chlorophenylpiperazine (MCPP) and the 5-HT precursor tryptophan were examined in healthy subjects and patients with OCD. Baseline prolactin levels and the prolactin rise following MCPP were significantly reduced in female patients compared with female healthy subjects. In contrast, the increase in prolactin level following tryptophan administration was not significantly different between male or female patients with OCD and the respective sex-matched healthy subjects. The prolactin responses to MCPP and tryptophan were both significantly higher in female patients and healthy subjects than in their male counterparts. The cortisol and growth hormone responses to MCPP and tryptophan were similar in the patients and healthy subjects and were not related to gender. The behavioral responses to MCPP or tryptophan were not consistently different between patients and healthy subjects, and neither MCPP nor tryptophan had effects on obsessive or compulsive symptoms. These results lend only partial support to the hypothesis that 5-HT dysfunction may be linked to the pathophysiology of OCD and point to the need for the evaluation of other neurotransmitter systems in future investigations of OCD.

Adult↗
PubMed1988

Elevated CSF dynorphin A [1-8] in Tourette's syndrome.

A recent neuropathological study has reported decreased levels of dynorphin A immunoreactivity in striato-pallidal fibers in the brain of a patient with severe Gilles de la Tourette's syndrome (TS). This observation, taken with the neuroanatomic distribution of dynorphin and its broad range of motor and behavioral effects, has led to speculation concerning its role in the pathobiology of TS. We report on the presence of elevated concentrations of dynorphin A [1-8] in the CSF of 7 TS patients, aged 20 to 45 years. The increase in CSF dynorphin was found to be associated with the severity of the obsessive compulsive symptoms but not with tic severity in these patients. Although CSF studies lack the precision necessary to address questions of selective involvement of neuronal system in specific CNS locations, these findings suggest that endogenous opioids are involved in the pathobiology of TS and related disorders. Tourette's syndrome (TS) is a chronic neuropsychiatric disorder of childhood onset that is characterized by multiple motor and phonic tics that wax and wane in severity and an array of behavioral problems including some forms of obsessive compulsive disorder (OCD) (1). Once thought to be a rare condition, the prevalence of TS is now estimated to be one case per 1,000 boys and one case per 10,000 girls, and milder variants of the syndrome are likely to occur in a sizeable percentage of the population (2). Although the etiology of TS remains unknown, the vertical transmission of TS within families follows a pattern consistent with an autosomal dominant form of inheritance (3,4). Neurobiologic and pharmacological data have implicated central monoaminergic and neuropeptidergic systems in the pathophysiology of TS, and basal ganglia structures remain the prime candidates as the neuroanatomical origin for TS and related conditions (1). Endogenous opioids, including dynorphin and met-enkephalin are concentrated in structures of the basal ganglia (5), are known to interact with central dopaminergic neurons (6, 7), and may play an important role in the control of motor functions (8). Post-mortem brain studies have directly implicated opioids in the pathophysiology of Parkinson's disease (9), Huntington's disease (10), and most recently in TS (11). The neuropathological study of Haber et al. (11) reported decreased levels of dynorphin A [1-17] immunoreactivity in striatal fibers projecting to the globus pallidus in the brain of a patient with severe TS. This ovservation, taken with the neuroanatomic distribution of dynorphin and its broad range of motor and behavioral effects, has led to speculation concerning its role in the pathobiology of TS.(ABSTRACT TRUNCATED AT 400 WORDS)

Dynorphins↗
PubMed1987

Effects of yohimbine in obsessive compulsive disorder.

The alpha 2-adrenergic receptor antagonist yohimbine was administered to 12 drug-free patients with obsessive compulsive disorder (OCD) and to 12 healthy subjects. Changes in behavior, cardiovascular symptoms, and in plasma levels of cortisol and the norepinephrine metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), were assessed. Yohimbine had no significant effect on OCD symptoms. The OCD patients did not differ from healthy controls in their behavioral and MHPG response to yohimbine. In contrast to healthy subjects, OCD patients, like previous reports of depressed and panic disorders patients, had an increased cortisol response to yohimbine. These data suggest it is unlikely that abnormal noradrenergic function plays a primary role in the pathogenesis of OCD.

Adult↗
PubMed1987

Serotonin function in anxiety. II. Effects of the serotonin agonist MCPP in panic disorder patients and healthy subjects.

To assess the role of serotonin function in the development of panic anxiety, the behavioral and biochemical responses to the serotonin receptor agonist, m-chlorophenylpiperazine (MCPP) was examined in healthy subjects and agoraphobic and panic disorder patients. MCPP had anxiogenic effects in both the healthy subjects and patients. Panic attacks meeting DSM-III criteria occurred following MCPP in 12 of 23 patients and 6 of 19 healthy subjects (NS) and other ratings of anxiety also did not distinguish the two groups. MCPP resulted in significant but similar increases in cortisol, prolactin, and growth hormone in the healthy subjects and patients. The results of this investigation suggest that serotonin neuronal dysfunction may not be of etiologic significance in most panic disorder patients. However, the observed anxiogenic properties of MCPP suggest that additional studies of the role of serotonin systems in the pathophysiology of human anxiety disorders are indicated.

Adult↗
PubMed1987

Neurobiological mechanisms of panic anxiety: biochemical and behavioral correlates of yohimbine-induced panic attacks.

The effects of yohimbine, an alpha 2-adrenergic receptor antagonist, on anxiety, blood pressure, heart rate, and plasma levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and cortisol were determined in 20 healthy subjects and 68 patients who had agoraphobia with panic attacks or panic disorder. Yohimbine produced panic attacks meeting DSM-III criteria in 37 patients and one healthy subject. The patients reporting yohimbine-induced panic attacks had significantly larger increases in plasma MHPG, cortisol, systolic blood pressure, and heart rate than the healthy subjects. These findings support the hypothesis relating high noradrenergic neuronal activity to the pathophysiology of panic attacks in a subgroup of panic disorder patients.

Adult↗
PubMed1987

Treatment of severe obsessive-compulsive disorder with fluvoxamine.

Ten obsessive-compulsive patients received single-blind treatment with fluvoxamine, a selective serotonin reuptake inhibitor, for several weeks following at least 2 weeks of placebo. The group showed significant improvement, as measured by several clinical scales and self-ratings; six patients were judged responders. Fluvoxamine appears effective in treating severe obsessive-compulsive disorder.

Adult↗
PubMed1987

A case of alprazolam, but not lorazepam, inducing manic symptoms.

A patient developed manic symptoms during treatment with alprazolam. These symptoms remitted upon discontinuation of treatment, but reemerged during a second trial with alprazolam. Subsequent administration of an equivalent dosage of lorazepam did not induce manic symptoms. The clinical and theoretical implications of these findings are discussed in relation to the possible mechanisms of action of alprazolam, a novel benzodiazepine.

Adult↗
PubMed1986

Carbon dioxide sensitivity in panic anxiety. Ventilatory and anxiogenic response to carbon dioxide in healthy subjects and patients with panic anxiety before and after alprazolam treatment.

One hypothesis that could account for the anxiogenic response to breathing air supplemented with carbon dioxide seen in panic anxiety patients is that panic patients might have abnormally high central medullary chemoreceptor sensitivity. Chemoreceptor sensitivity was assessed by using a rebreathing technique to measure the ventilatory response to CO2 in 14 medication-free patients with agoraphobia and panic attacks and 23 healthy subjects. Ventilatory response to CO2 was similar in patients and controls (mean +/- SEM, 1.58 +/- 0.16 vs 1.58 +/- 0.14 L/min/mm Hg), suggesting that abnormal chemoreceptor sensitivity does not explain the behavioral sensitivity of panic patients to CO2. Anxiety ratings increased markedly during rebreathing both in patients and controls; anxiety increases were significantly greater in patients than in healthy subjects matched for age, sex, and rebreathing duration. Alprazolam treatment in eight patients markedly attenuated anxiety increases during rebreathing. Differences in anxiogenic sensitivity to CO2 between patients and controls may be due to differences in the regulation of noradrenergic or other neuronal systems.

Adult↗
PubMed1986

Ineffectiveness of clonidine in the treatment of the benzodiazepine withdrawal syndrome: report of three cases.

The effectiveness of clonidine hydrochloride in the treatment of abrupt withdrawal from long-term, therapeutic doses of benzodiazepines was studied in three patients under double-blind, placebo-controlled conditions. The intensity, severity, and duration of the abstinence syndrome were not altered by clonidine at a dose sufficient to markedly reduce blood pressure and plasma free 3-methoxy-4-hydroxyphenylglycol. These results contrast with the established efficacy of clonidine in the opiate withdrawal syndrome and suggest that many of the symptoms of benzodiazepine withdrawal may not be caused by hyperactivity of the noradrenergic system.

Adult↗
PubMed1986

Drug treatment of panic disorder: the comparative efficacy of imipramine, alprazolam, and trazodone.

Data from 74 patients with panic disorder were evaluated to determine the comparative efficacy of imipramine, alprazolam, and trazodone. All patients were treated with placebo for 3 weeks and were then blindly switched to active treatment for 8 weeks. Both imipramine and alprazolam were highly effective in reducing the symptoms of generalized anxiety, the frequency of panic attacks, and phobic avoidance. However, the time course of these effects differed; alprazolam demonstrated therapeutic properties during the first week, whereas the therapeutic efficacy of imipramine was not clearly apparent until the fourth week of treatment. Relative to imipramine and alprazolam, trazodone was not an effective treatment for panic disorder and was poorly tolerated; only 17 trazodone-treated patients completed at least 4 weeks of treatment, and only 2 patients were considered good or complete responders. These findings support the hypotheses that drugs that are efficacious in the treatment of panic disorders act by altering noradrenergic function and that drugs with primary actions on serotonin function are likely to be less effective treatments. The different time courses of therapeutic action of imipramine and alprazolam indicate that these drugs ameliorate panic anxiety via different mechanisms. The possible therapeutic applications of this observation are discussed.

Agoraphobia↗
PubMed1985

Therapeutic applications and mechanisms of action of monoamine oxidase inhibitor and heterocyclic antidepressant drugs.

Tricyclic antidepressants, monoamine oxidase inhibitors, and antidepressants of atypical structure are used in a variety of psychiatric and nonpsychiatric disorders. The efficacy of antidepressant drugs in major depression, panic disorder, obsessive-compulsive disorder, peptic ulcer disease, enuresis, chronic pain, migraine, bulimia, and attention deficit disorder is briefly reviewed. The rationale that led to each of these therapeutic applications is examined, and the possible mechanism of action is discussed in light of recent advances in neurobiologic research. It is concluded that improved understanding of antidepressant drugs' mechanisms of action may help elucidate the etiology of these disorders and yield more effective treatments.

Antidepressive Agents↗
PubMedDate not supplied

Tic-related vs. non-tic-related obsessive compulsive disorder.

Obsessive compulsive disorder (OCD) is a chronic condition characterized by an array of intrusive, upsetting thoughts and interfering, repetitive behaviors. Some forms of OCD may be etiologically related to Tourette's syndrome (TS). This cross-sectional study examines a range of obsessive compulsive (OC) symptoms which have been hypothesized to distinguish tic-related OCD from non-tic-related OCD. One hundred and seventy-seven patients with a primary DSM-IIIR diagnosis of OCD, aged 16 to 72, participated in the study. Patients with tic-related OCD (n = 56) reported more OC symptoms, including more aggressive, religious, and sexual obsessions as well as checking, counting, ordering, touching, and boarding compulsions than did patients with non-tic-related OCD (n = 121). Contrary to our expectation, these two groups of OCD patients did not differ with regard to the presence of "just right" phenomena or symptoms of psychasthenia. "Just right" phenomena and symptoms of psychasthenia, however, were both found to be associated with the current severity of OC symptoms.

Adult↗