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Biomedical subjects

M R Liebowitz

Publications and source records attributed to M R Liebowitz.

At least 19 recordsLinked to original sources

Noradrenergic function in panic disorder. Effects of intravenous clonidine pretreatment on lactate induced panic.

To assess the role of noradrenergic stimulation during lactate-induced panic, ten patients with panic disorder who panicked during a standard sodium-lactate infusion underwent a repeat infusion following intravenous clonidine pretreatment. Although clonidine significantly lowered prelactate systolic blood pressure, the drug did not significantly lower prelactate anxiety levels, as reflected by the Acute Panic Inventory (API). Clonidine blocked lactate-induced panic in four of ten subjects, a significant effect. Clonidine treatment also significantly attenuated lactate-panic symptoms, as reflected by time to panic and API comparison between trials. Nevertheless, over half the subjects still panicked in response to lactate despite clonidine. This preliminary study suggests that reduction of central noradrenergic activity by clonidine, at least at the dosage levels employed in the current study, only partially attenuates panic response to lactate. Noradrenergic theories of panic may not therefore fully account for lactate panicogenesis.

Adult

Serotonergic function in obsessive-compulsive disorder. Behavioral and neuroendocrine responses to oral m-chlorophenylpiperazine and fenfluramine in patients and healthy volunteers.

To evaluate serotonergic (5-hydroxytryptamine) function in obsessive-compulsive disorder, behavioral and neuroendocrine responses to m-chlorophenylpiperazine (m-CPP; 0.5 mg/kg orally) and fenfluramine hydrochloride (60 mg orally) were examined in 20 patients and 10 healthy controls under double-blind, placebo-controlled conditions. Following m-CPP, but not fenfluramine or placebo, 55% (11/20) of the patients with obsessive-compulsive disorder experienced a transient exacerbation of obsessive-compulsive disorder. Prolactin response was blunted in patients following m-CPP but not following fenfluramine. Patients with greater behavioral response to m-CPP had smaller prolactin responses. Cortisol response to m-CPP and fenfluramine did not significantly differ between the groups. Behavioral and neuroendocrine responses appeared divergent. This does not suggest simply upregulation or downregulation of 5-hydroxytryptamine receptors, but rather complex mechanisms involving multiple neurotransmitter and neuromodulator systems.

Administration, Oral

Social phobia. Comorbidity and morbidity in an epidemiologic sample.

Selected sociodemographic and clinical features of social phobia were assessed in four US communities among more than 13,000 adults from the Epidemiologic Catchment Area study. Rates of social phobia were highest among women and persons who were younger (age, 18 to 29 years), less educated, single, and of lower socioeconomic class. Mean age at onset was 15.5 years, and first onsets after the age of 25 years were uncommon. Lifetime major comorbid disorders were present in 69% of subjects with social phobia and usually had onset after social phobia. When compared with persons with no psychiatric disorder, uncomplicated social phobia was associated with increased rates of suicidal ideation, financial dependency, and having sought medical treatment, but was not associated with higher rates of having made a suicide attempt or having sought treatment from a mental health professional. An increase in suicide attempts was found among subjects with social phobia overall, but this increase was mainly attributable to comorbid cases. Social phobia, in the absence of comorbidity, was associated with distress and impairment, yet was rarely treated by mental health professionals. The findings are compared and contrasted with prior reports from clinical samples.

Adolescent

Phenelzine vs atenolol in social phobia. A placebo-controlled comparison.

Seventy-four patients who met DSM-III criteria for social phobia completed 8 weeks of double-blind, randomly assigned treatment with the monoamine oxidase inhibitor phenelzine sulfate, the cardioselective beta-adrenergic blocker atenolol, or placebo. The overall response rates were 64% for phenelzine, 30% for atenolol, and 23% for placebo. Phenelzine was widely superior to both atenolol and placebo on independent rater analyses and, to a lesser extent, on self-report, with no significant differences between atenolol and placebo. At the end of 16 weeks, phenelzine was still significantly superior to placebo, while atenolol showed an intermediate response that did not differ significantly from either of the other treatments. Patients with generalized social phobia constituted 76% of the sample, and they were preferentially responsive to phenelzine. The small size of the discrete social phobic sample precluded separate outcome analyses for this subtype. Overall, the findings support the responsivity of social phobia to monoamine oxidase inhibitors.

Adolescent

The neuropsychiatric manifestations of Lyme borreliosis.

Lyme borreliosis (Lyme disease), a tick-borne spirochetal illness, has multisystemic involvement and is rapidly increasing in certain areas of the United States. Although its neurologic manifestations are becoming increasingly well recognized, its psychiatric presentations are not well known. The first section of this paper will provide an overview of Lyme borreliosis and a review of the relevant neuropsychiatric literature. The second section will provide clinical descriptions of some common neuropsychiatric symptoms as well as a discussion of the problems typically faced by patients with this illness. Guidelines to assist the clinician in working with these patients will be presented.

Adult

Effects of fenfluramine on plasma homovanillic acid in healthy subjects.

The specificity of fenfluramine as a pharmacological probe of the serotonin system has been questioned, since animal studies with high dose l-fenfluramine show increases in striatal levels of the dopamine metabolite homovanillic acid. To test the specificity of fenfluramine in humans with clinical doses, we compared plasma homovanillic acid (pHVA) concentration in healthy volunteers after administration of fenfluramine (60 mg) and placebo. There were no significant effects on pHVA, which supports previous findings that at doses used in pharmacological challenge paradigms, the effect of fenfluramine on the dopamine system is insufficient to alter measures of its change.

Dopamine

Reaction time to threat stimuli in panic disorder and social phobia.

Two studies assessed response time among clinically anxious subjects and normal controls when presented with threat, positive and neutral stimuli under perceptual (lexical decision) and semantic (category decision) task conditions. In Study 1, panic disorder subjects' (n = 14) performance was compared to that of matched normal controls (n = 14) while in Study 2 social phobic subjects (n = 24) were compared to matched normal controls (n = 24). Relative to matched normal controls, panic disorder subjects but not social phobics tended to show greater slowing in performance on the more cognitively complex (category) task. A second finding, consistent across both studies was that, compared to the normal control groups, both panic and social phobic groups showed significantly slowed responses to threat words in both the perceptual and semantic tasks. Such findings are directly counter to the predictions of a mood congruence hypothesis. This apparent contradiction is resolved by a review of the literature which indicates that mood-related facilitation effects are obtained only in tasks which tap awareness of threat information rather than speed of response. It is suggested that while anxiety may produce enhanced awareness of threat, it may inhibit responsiveness to it. The results of these studies are seen as consistent with ethological theories of inhibited motoric responses under certain threat conditions. Furthermore, the findings suggest that caution is indicated in interpreting slowed reaction time to threat stimuli in tasks such as the Stroop color naming task as purely the result of attentional processes.

Adult

Body dysmorphic disorder. Diagnostic issues and related disorders.

This article reviews diagnostic issues about body dysmorphic disorder and discusses its relationship to other disorders. Diagnostic and symptomatic overlap with obsessive-compulsive disorder is explored; associated features, course of illness, presumed etiology, and treatment outcome are compared; and similarities and differences are reviewed. Other illnesses with similar features, such as anorexia nervosa, social phobia, and the disorders associated with cosmetic surgery are mentioned. These findings are discussed in light of the development of DSM-IV diagnostic criteria.

Adolescent

Open trial of intravenous clomipramine in five treatment-refractory patients with obsessive-compulsive disorder.

In a preliminary trial, five oral-clomipramine-refractory patients with obsessive-compulsive disorder (OCD) were treated openly with 14 intravenous clomipramine infusions each. Using standardized assessments, three patients were rated as much improved, one as unchanged, and one as minimally improved. Statistically significant improvements were noted on both the Yale-Brown Obsessive Compulsive Scale and the NIMH Global OCD scores. No patient discontinued treatment because of side effects. Although the results are provocative in that three of five patients were much improved at the end of the protocol, conclusions about preferential efficacy for the intravenous route must await a placebo-controlled trial.

Administration, Oral

Pharmacotherapy of social phobia. A controlled study with moclobemide and phenelzine.

In a double-blind, parallel group trial, 78 subjects with social phobia received moclobemide (a new reversible inhibitor of monoamine oxidase A) phenelzine, or placebo. After eight weeks, both active drugs-phenelzine somewhat more than moclobemide--were clinically and statistically significantly more effective than placebo, as assessed by rating scales. There was some further improvement between weeks 8 and 16, particularly in the moclobemide group; at week 16, 82% of the moclobemide and 91% of the phenelzine-treated patients were almost asymptomatic. Moclobemide was, however, much better tolerated than phenelzine. Patients withdrawn from active drugs had relapsed by week 24, providing additional support for the efficacy of the active drugs.

Adult

Serotonergic medications for sexual obsessions, sexual addictions, and paraphilias.

BACKGROUND: Paraphilias and related disorders have recently been thought of as sexual addictions. However, it has also been argued that these disorders are sexual compulsions. The question arises as to whether these disorders and obsessive compulsive disorder respond in the same way to pharmacotherapy. METHOD: We retrospectively reviewed outcome in 13 patients who presented with sexual symptoms and were treated with serotonin reuptake blockers. Symptoms were divided into paraphilias, nonparaphilic sexual addictions, and sexual obsessions. RESULTS: Paraphilias had the least improvement, while sexual obsessions had the best response to medication. CONCLUSION: Paraphilias and related disorders may be less responsive than sexual obsessions or compulsions to serotonin reuptake blockers. Perhaps paraphilias and related disorders are on the impulsive rather than the compulsive end of the spectrum of obsessive compulsive disorders. Controlled trials are, however, necessary to replicate these preliminary findings.

Adolescent

Treatment outcome of obsessive compulsive disorder with comorbid social phobia.

BACKGROUND: Treatment of obsessive compulsive disorder (OCD) with serotonin reuptake blockers has been demonstrated effective in 50% to 60% of patients in open and placebo-controlled studies. However, some reports indicate that comorbid Axis II psychopathology, including avoidant personality disorder, and deficiency of social skills could be predictors of a poor response to treatment in OCD patients. METHOD: A retrospective review elicited 12 patients who met DSM-III-R diagnostic criteria for both OCD and social phobia and were treated in our clinic last year with adequate trials of serotonin reuptake blockers or MAOIs. RESULTS: Only 3 (27%) of the 11 patients treated with serotonin reuptake blockers had a substantial improvement of OCD symptoms. Among them, only 1 (11%) of 9 patients with generalized subtype of social phobia versus 2 (100%) of 2 patients with the nongeneralized subtype responded to serotonin reuptake blockers. Four (80%) of 5 patients with comorbid generalized social phobia receiving phenelzine had marked improvement of OCD symptoms. In general, response of social phobia occurred parallel to that of OCD. CONCLUSION: Comorbid generalized social phobia seems to be associated with a poor response to serotonin reuptake blockers in OCD patients. Deficient social skills, as well as distinct biological mechanisms, may be involved. MAOIs might be an effective alternative medication in refractory cases. Larger and controlled studies are needed to define the implications of the association of OCD and social phobia.

Adult