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Biomedical subjects

M R Liebowitz

Publications and source records attributed to M R Liebowitz.

At least 109 records · Page 6Linked to original sources

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 Patients withdrawn from active drugs had relapsed by week 24, providing additional support for the efficacy of the active drugs.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↗

Noradrenergic function in obsessive-compulsive disorder: behavioral and neuroendocrine responses to clonidine and comparison to healthy controls.

To evaluate noradrenergic (NE) function in obsessive-compulsive disorder (OCD), behavioral, physiological, and neuroendocrine responses to the alpha 2-adrenergic agonist clonidine were examined in 18 patients with OCD and 10 healthy subjects. Subjects received single i.v. doses of 2 micrograms/kg of clonidine administered under double-blind, placebo-controlled, random-assignment conditions. Following clonidine, but not following placebo, patients transiently experienced a significant reduction of obsessions and compulsions. Significant drowsiness and a reduction in anxiety were also noted, but the antiobsessional effect appeared independent of the soporific and antianxiety effects. Growth hormone (GH), cortisol, and 3-methoxy-4-hydroxyphenylglycol responses to clonidine did not differentiate patients from healthy controls. Blood pressure and pulse in response to clonidine did not differ between groups. Improvement in OCD symptoms after clonidine significantly correlated with GH response to clonidine, suggesting specific noradrenergic mediation. This finding lends only partial support for a primary defect of noradrenergic function in OCD.

Adolescent↗

Effects of chronic fluoxetine treatment on behavioral and neuroendocrine responses to meta-chlorophenylpiperazine in obsessive-compulsive disorder.

To investigate the effect of fluoxetine on serotonergic sensitivity in obsessive-compulsive disorder (OCD), the partial serotonin agonist metachlorophenylpiperazine (mCPP) was compared to placebo under double-blind conditions in six patients with OCD before and during treatment with fluoxetine. Readministration of oral mCPP (0.5 mg/kg) after at least 12 weeks of fluoxetine treatment did not increase obsessive-compulsive (OC) symptoms, in contrast to exacerbation of OC symptoms produced by mCPP before treatment. Chronic fluoxetine treatment resulted in a significant increase in prolactin and cortisol response to mCPP. This may be accounted for, however, by substantially increased plasma mCPP levels during fluoxetine treatment. Chronic fluoxetine treatment diminished the behavioral sensitivity to mCPP and did not diminish, but may have partially normalized, the neuroendocrine response to mCPP in patients with OCD. These adaptive homeostatic effects may reflect fluoxetine's antiobsessional mechanism.

Adult↗

Cognitive-behavior therapy for panic disorder delivered by psychopharmacologically oriented clinicians.

A cognitive-behavioral treatment program for panic disorder was delivered by staff members of a psychiatric center that traditionally utilizes pharmacological methods. Psychiatrists, a nurse practitioner, and psychologists not previously exposed to behavioral techniques were trained by a behavioral psychologist to utilize a treatment program consisting of breathing control, cognitive restructuring, and exposure to panic-eliciting somatic cues. Of the 24 patients treated as part of this training in panic control therapy, 14 were panic-free after treatment and three additional patients showed moderate improvement and decreased frequency of panic. A case example is presented to demonstrate the application of behavioral techniques to individual patients. Discussion is focused on issues surrounding training in behavioral methods and problems in exporting behavioral technology to centers that emphasize psychopharmacological approaches to treatment.

Adult↗

A pilot follow-up study of childhood soft signs and the development of adult psychopathology.

A subgroup of subjects (4 of 12) with childhood soft signs and adolescent anxiety-withdrawal disorders were followed up into adulthood and assessed for soft signs and psychiatric diagnoses. These subjects continued to have soft-sign abnormalities and most had adult anxiety or affective disorders, including obsessive-compulsive disorder (OCD). In contrast, control subjects with childhood soft signs but no adolescent anxiety disorders had fewer soft signs at follow-up and no discrete adult anxiety or affective disorders, but they did have obsessive-compulsive symptoms that did not meet criteria for OCD.

Adolescent↗

Hypochondriasis and obsessive compulsive disorder: overlaps in diagnosis and treatment.

BACKGROUND: Hypochondriasis is a disorder for which there are no established effective treatments. Hypochondriacs, in their obsessions about illness, compulsions to check with others, and failure to be reassured, share many features in common with those who have obsessive compulsive disorder (OCD). METHOD: The authors present a case series of six patients with DSM-III-R hypochondriasis, five of whom also had a history of OCD. Two of the six agreed to be treated with doses of fluoxetine typically used to treat OCD. RESULTS: Both patients, one of whom had no past history of OCD, showed a marked improvement in hypochondriacal symptoms. CONCLUSION: These findings suggest that a subgroup of patients with hypochondriasis may be particularly responsive to serotonin reuptake blockers.

Adult↗

Treatment of social phobia with drugs other than benzodiazepines.

Social phobia is emerging as an important cause of psychiatric morbidity. Reasons for this are described, as are clinical issues of importance to social phobia, including the extensive associated distress and disability. The use of phenelzine, atenolol, buspirone, fluoxetine, and moclobemide are described. Diagnostic and transcultural aspects of social phobia are described.

Adolescent↗

Obsessive compulsive disorder, depression, and fluoxetine.

BACKGROUND: Fluoxetine, a selective serotonin reuptake blocker, is an antidepressant medication that has also been shown in open clinical trials and one controlled trial to be effective in the treatment of obsessive compulsive disorder (OCD). OCD is often complicated by depression, and depressive symptoms may interfere with response to both pharmacologic and behavioral treatments. METHOD: We describe pilot data from 10 outpatients who met DSM-III-R criteria for OCD in whom the possibility of a depressive reaction or lack of antidepressant response occurred during an open trial of fluoxetine. RESULTS: Rapid increase in fluoxetine dose to high doses was associated with depressive symptoms in 6 patients. In 8 patients, improvement in depression was associated with addition of a tricyclic antidepressant to fluoxetine treatment. In 5 patients, both OCD and depressive symptoms improved when the patient was switched to the partially selective serotonin reuptake blocker clomipramine. CONCLUSION: This paper serves to alert clinicians to the possibility of a depressive reaction, or lack of antidepressant response, to fluoxetine in OCD patients. This possibility can only be resolved scientifically by adequately controlled experimental trials. If depression occurs, combined fluoxetine and tricyclic treatment, or a switch to a partially selective serotonin reuptake inhibitor, may be helpful. Special considerations and side effects of combined fluoxetine-tricyclic treatment are described.

Adolescent↗

High-dose carbon dioxide challenge test in anxiety disorder patients.

Many investigators have shown that panic disorder patients and possibly social phobics are hypersensitive to the anxiogenic effects of inhaled carbon dioxide (CO2). In this study we administered double-breath inhalation of 35% CO2 and 65% oxygen (O2) to panic disorder patients, social phobics, and normal controls. At baseline, panic disorder patients were characterized by higher pulse, anxiety score, and evidence of hyperventilation. Panic patients and social phobics panicked more often to 35% CO2 than to room air; normal controls did not have a higher rate of panic to CO2 than to room air. However, we did not find significant group differences in anxiety level, physiological measures, or biochemical measures in response to CO2 breathing compared with room air breathing. These results confirm earlier reports of baseline hyperventilation in panic disorder patients. However, 35% CO2 may be too high a dose to differentiate respiratory responses of patients compared with normals.

Administration, Inhalation↗

Signs of central nervous system dysfunction in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) has been linked to altered neurological function following head trauma, encephalitis, abnormal birth events, and Gilles de la Tourette's syndrome. Abnormalities in computed tomographic scans, electroencephalograms, positron emission tomographic scans, and evoked potentials have been described in this disorder, but are neither consistent nor pathognomonic of OCD. Neurological soft signs are nonlocalizing signs of deviant performance on a motor or sensory test where no other sign of a neurological lesion is present. We studied 41 medication-free patients with OCD who met DSM-III-R criteria, as well as 20 normal controls, matched for age, sex, and handedness, on 20 individual tasks that involved fine motor coordination, involuntary movements, and sensory and visuospatial function. There were significantly more signs of central nervous system dysfunction in the OCD group, as shown by abnormalities in fine motor coordination, involuntary and mirror movements, and visuospatial function. An excess of findings on the left side of the body and abnormalities of cube drawing may suggest right hemispheric dysfunction in a subgroup of patients with OCD. Soft signs correlated with a severity of obsessions. There was also a correlation between abnormalities in visual memory and recognition on neuropsychological testing and total soft signs. These findings provided additional evidence for a neurological deficit in some patients with OCD. However, further comparisons with other psychiatric populations are needed to determine whether these findings are unique to OCD or are a property of other psychiatric disorders as well.

Adolescent↗

Familial transmission of simple phobias and fears. A preliminary report.

Preliminary data from a blind direct interview family study indicate a significantly higher risk for simple phobia among first-degree relatives (n = 49) of simple phobic probands (who had no other anxiety disorder) as compared with first-degree relatives (n = 119) of never mentally ill controls (31% vs 11%, relative risk = 3.3). Female relatives were more likely to be affected than male relatives (48% vs 13%), though this difference did not reach conventional significance in an age-corrected analysis. Significant between-group differences were not found in risks for (1) other anxiety, affective, and substance abuse disorders, and (2) simple irrational fears that did not meet disorder criteria. The results suggest that simple phobia is a highly familial disorder that does not transmit increased risk for other phobic or anxiety disorders. The specificity of increased risk among the relatives of simple phobics is consistent with the distinction between simple phobia, social phobia, and agoraphobia. However, complete delineation of the transmissional relationship between these illnesses requires assessment of the extent to which risk for simple phobia can be transmitted by individuals with other phobic or anxiety disorders. Replication of these preliminary findings in larger clinically and epidemiologically selected samples is needed.

Adult↗