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Biomedical subjects

M R Liebowitz

Publications and source records attributed to M R Liebowitz.

At least 73 records · Page 4Linked to original sources

Medication therapy for social phobia.

Social phobia, though the third most common psychiatric disorder in the United States, has received little systematic attention until recently. Chronic and disabling symptoms usually precede other disorders in individuals with comorbidity, including alcohol abuse. Though about 80% of individuals do not seek treatment, controlled trials have demonstrated efficacy for several medications, of which phenelzine (an irreversible monoamine oxidase inhibitor [MAOI]) is the best studied. The benzodiazepines, clonazepam and alprazolam, also hold promise. New reversible MAOIs such as moclobemide and brofaromine are under investigation; fluoxetine and other serotonin selective reuptake inhibitors need further controlled study. The benefits of group cognitive-behavioral therapy also appear substantial. Issues for future investigation include long-term outcome, differential therapeutics, diagnostic subtyping, and combination treatments.

Benzamides↗

Physical disability and social phobia.

The DSM-III-R excludes persons with socially phobic symptoms secondary to axis III conditions from the diagnostic category of social phobia. This exclusion exists without empirical basis. A series of eight clinical cases is presented in which patients suffered from excessive levels of secondary social anxiety relative to their disfiguring or disabling physical conditions. All subjects had a good response to the monoamine oxidase inhibitor phenelzine, which enabled them to live in a less-inhibited and less-restrictive manner. Their medication response to monoamine oxidase inhibitors parallels the psychopharmacologic response patterns of generalized or DSM-III-R social phobics. This study suggests a novel application of the drug phenelzine for a patient group formerly overlooked with regard to treatment options. The similarity of this group's psychopharmacologic responsivity and clinical characteristics to those of DSM-III-R social phobics also lends support to the relaxation of the axis III exclusion in DSM-IV's definition of social phobia.

Adult↗

Timing of neuroendocrine responses and effect of m-CPP and fenfluramine plasma levels in OCD.

The present study assesses the timing of and relationship between neuroendocrine response and metabolite blood levels following the partial serotonin (5-HT) agonist m-CPP and the 5-HT releaser/reuptake blocker fenfluramine. Cortisol levels peaked significantly earlier than did prolactin, m-CPP, fenfluramine, or norfenfluramine blood levels by time-to-peak analysis. This earlier cortisol response to both 5-HT agents raises the possibility that peripheral mechanisms may play a role in cortisol release. Since peak m-CPP level correlated even more closely to peak prolactin rise than did peak fenfluramine, this suggests that prolactin response to oral m-CPP challenge is useful in assessing 5-HT function.

Adult↗

Panic attacks during placebo procedures in the laboratory. Physiology and symptomatology.

Heart rate, respiratory measurements, and Acute Panic Inventory symptoms of 17 patients with panic disorder who experienced panic attacks during a placebo infusion (situationally provoked panic) were analyzed and compared with similar data from a group of 19 patients with panic disorder who panicked during lactate infusion. Previously, it was shown that the group with lactate-induced panic attacks exhibited increased minute ventilation compared with normal control subjects and nonpanicking patients with panic disorder during lactate infusion. The group with situationally provoked panic attacks exhibited significant increases in both heart rate and minute ventilation immediately preceding the onset of the panic attack. The increase in minute ventilation appeared to be caused more by increase in tidal volume than in respiratory frequency. The increase in heart rate in the group with situationally provoked panic attacks was very similar to that seen in the group with lactate-induced panic attacks, but the group with situationally provoked panic attacks appeared to have somewhat greater increase in minute ventilation than the group with lactate-induced panic attacks. This suggests that the metabolic alkalosis produced by lactate infusion might actually blunt the full expression of panic-associated respiratory stimulation. These data validate the belief that significant cardiorespiratory stimulation occurring during panic attacks in the laboratory is not simply secondary to the intrinsic physiologic effects of panic-inducing substances such as lactate, yohimbine, and carbon dioxide.

Adult↗

A direct interview family study of social phobia.

Risks for DSM-III-R anxiety and affective disorders and "subdisorder" (nonimpairing) irrational social fears, among directly interviewed first-degree relatives (n = 83) of probands who met criteria for social phobia but for no other lifetime anxiety disorder diagnosis, were contrasted to risks for disorder among similarly evaluated relatives (n = 231) of never mentally ill controls. Relatives of social phobia probands had a significantly increased risk for social phobia (16% vs 5%, relative risk = 3.12) but not for other anxiety disorders. These results suggest a familial contribution to the development of some cases of social phobia. The specificity of the pattern of intergenerational transmission is consistent with the current nosologic distinction between social phobia and other anxiety disorders.

Adult↗

Neuropsychiatric impairment in impulsive personality disorders.

It has been suggested that impulsivity and aggression are associated with neuropsychiatric impairment. Neurological soft signs may be a useful marker of nonspecific brain damage, and may therefore be increased in impulsive and aggressive patients compared with normal control subjects. A structured examination was used to evaluate neurological soft signs in 28 patients with personality disorders characterized by impulsivity and 28 healthy control subjects. All of the patients met DSM-III-R criteria for borderline personality disorder, and 10 also met criteria for antisocial personality disorder. All patients were questioned about past history of physical aggression, and a subset of 18 patients underwent neuropsychological testing with a select battery. Left-sided neurological soft signs were significantly increased in patients compared with normal control subjects. Patients with a history of aggression, however, had significantly more right-sided neurological soft signs than those without a history of aggression. Increased neurological soft signs were associated with impairment on the Wisconsin Card Sort, a test of frontal lobe executive function. Specific neuropsychiatric abnormalities, such as lateralized neurological soft signs and associated impairment on select neuropsychological tests, may be present in patients with personality disorders characterized by impulsivity.

Adult↗

Computed tomography and neurological soft signs in obsessive-compulsive disorder.

Computed tomography was used to compare the following three groups: obsessive-compulsive disorder (OCD) patients with high scores on a soft neurological sign examination, OCD patients with low soft neurological sign scores, and control subjects. Neuranatomical structures were measured using quantitative volumetric analysis. OCD patients with high soft sign scores had significantly increased ventricular volumes compared with OCD patients with low soft sign scores and control subjects. Caudate and lenticular nucleus volumes did not differ between groups.

Adult↗

The effect of acetazolamide on ventilation in panic disorder patients.

OBJECTIVE: Patients with panic disorder are behaviorally hypersensitive to CO2 inhalation and may also be biologically hypersensitive. A report by Mathew et al. showed, however, that administration of the carbonic anhydrase inhibitor acetazolamide, which is believed to increase brain CO2 level, did not cause panic in panic disorder patients. The authors of the present study noted that respiratory frequency did not increase in the earlier experiment and wondered whether respiratory stimulation occurred during acetazolamide administration, as would be expected if CO2 level increases significantly. METHOD: Ten patients with panic disorder and six normal control subjects received injections of acetazolamide, 1 g i.v., as per the Mathew et al. protocol, during breath by breath measurement of both tidal volume and frequency of respiration. RESULTS: Three patients had panic attacks, one before receiving acetazolamide, one during the injection, and one 2 minutes after injection. Only the last of these attacks appeared possibly attributable to acetazolamide. None of the control subjects panicked. Neither patients nor control subjects exhibited meaningful change in tidal volume, respiratory frequency, or minute ventilation, and both groups experienced a trend toward significant decrease in overall levels of anxiety and dyspnea after acetazolamide injection. CONCLUSIONS: The authors replicated the earlier finding that acetazolamide is not panicogenic in patients with panic disorder but also showed that at the dose given, there is no meaningful effect on ventilation. If acetazolamide does affect CO2 levels it does so in a way that does not stimulate ventilation. Therefore, the acetazolamide injection results of Mathew et al. and of the present study do not challenge hypotheses linking panic attacks to hypersensitive respiratory control mechanisms.

Acetazolamide↗

Diagnostic and substance specificity of carbon-dioxide-induced panic.

OBJECTIVE: The authors assessed the substance and diagnostic specificity of carbon-dioxide-induced panic since, in addition to the specific biochemical effects of inhaled carbon dioxide (CO2), simple physiologic distress is also frequently implicated as a panicogenic factor during respiratory challenge studies with CO2 in patients with anxiety disorders. METHOD: Eighteen patients with panic disorder, 20 with social phobia, and 23 psychiatrically normal subjects inhaled a mixture of 35% CO2 and 65% O2 for 30 seconds through a face mask. They also breathed for 30 seconds through a valve reducing the diameter of the airway. A double-blind, counterbalanced, randomized design was used. RESULTS: In spite of important similarities between the two interventions, including the induction of equal amounts of subjective respiratory distress, carbon dioxide inhalation was significantly more potent than increased airway resistance in provoking panic in the anxiety disorder patients. The patients with panic disorder were significantly more sensitive to CO2 than were the patients with social phobia or the normal subjects. CONCLUSIONS: Carbon dioxide inhalation appears to have a specific panicogenic effect in panic patients that goes beyond simple breathlessness.

Administration, Inhalation↗

Neurobiology of impulsivity and the impulse control disorders.

Clinical impulsivity has been characterized in both dimensional and categorical terms. Whereas DSM-III-R classifies personality disorders characterized by impulsivity and impulse control disorders as discrete entities, impulsive symptoms and traits can also be conceived in terms of an underlying behavioral dimension. The authors review research on impulsivity and the impulse control disorders from a biological perspective. In particular, they critically review evidence that the serotonin neurotransmitter system mediates symptoms and traits of impulsive personality disorders and the impulse control disorders.

Adult↗

Alpidem in the treatment of panic disorder.

Alpidem, an imidazopyridine that acts at the gamma-aminobutyric acid/benzodiazepine receptor complex, has been reported to be an effective anxiolytic with a more favorable side effect profile than benzodiazepines. The effect of alpidem was investigated in an 8-week, open, clinical trial in 13 patients with panic disorder, with or without agoraphobia. Three patients were responders (much improved or very much improved), five patients were nonresponders, and five patients dropped out after less than 6 weeks of treatment. Significant improvement was seen in the sample as a whole for spontaneous panic attacks, phobic avoidance, and anticipatory anxiety. Most improvement occurred during the first 4 weeks of treatment, and responders had milder panic disorder at baseline. Adverse effects were generally mild. After 8 weeks of treatment, taper of medication over 2 weeks occurred without significant worsening of panic disorder symptoms. The efficacy of alpidem in the treatment of panic disorder remains uncertain and requires assessment in a controlled trial.

Adolescent↗

Fluoxetine for hypochondriacal patients without major depression.

Hypochondriasis without concomitant depression is often considered to be unresponsive to pharmacotherapy. Given marked similarities between hypochondriasis and obsessive-compulsive disorder, we decided to conduct an open trial of high-dose fluoxetine for patients with DSM-III-R hypochondriasis who did not meet criteria for major depression. Ten of 16 patients were much improved at the end of 12 weeks. A comparison of baseline and week 12 scores by the use of a paired-samples t-test revealed a statistically significant reduction in hypochondriacal concerns, as measured by the Heightened Illness Concern Clinical Global Impression Severity scale, the Whiteley Index of Hypochondriasis, and the Heightened Illness Concern Questionnaire. These results suggest that fluoxetine may be a useful therapy for hypochondriacal patients without marked depressive features--a group previously considered to be treatment refractory.

Adult↗

Pharmacotherapy of social phobia.

The Liebowitz Social Anxiety Scale (LSAS) was developed to help clinicians evaluate data by examining fear and avoidance together in order to provide a fuller understanding of anxiety disorders. A number of pharmacologic agents have been studied in social phobia, including monoamine oxidase inhibitors, serotonin selective reuptake inhibitors, tricyclics, and benzodiazepines. This paper reviews the findings of several open and double-blind clinical trials using the LSAS and other measures. Promising results have been achieved with some pharmacologic agents, although further controlled trials are necessary.

Adult↗

Reversible monoamine oxidase-A inhibitors in social phobia.

Placebo-controlled studies of standard and reversible monoamine oxidase-A (MAO-A) inhibitors in social phobia are reviewed. Four studies utilized several common measures, including the Liebowitz Social Anxiety Scale and the Hamilton Anxiety Scale. Efficacy for phenelzine, moclobemide, and brofaromine appeared comparable across studies on both categorical and dimensional measures, as did placebo results. In terms of patient characteristics, baseline social phobia ratings were similar across studies, but initial Hamilton Anxiety Scale scores differed. Although the reason for this is uncertain, it is more likely due to rater differences than to patient differences.

Humans↗

Psychiatric manifestations of Lyme borreliosis.

BACKGROUND: Lyme borreliosis (Lyme disease), a tick-borne spirochetal illness, has later manifestations that may include arthritic, neurologic, ophthalmologic, and cardiac symptoms. Recent reports suggest psychiatric symptoms may also be part of the clinical picture. METHOD: Using a structured interview (SCID), we interviewed three patients who had developed a psychiatric disorder for the first time after infection with Borrelia burgdorferi. RESULTS: During Lyme borreliosis, one patient had major depression and panic disorder, one patient had an organic mood syndrome with both depression and mania, and the third patient had panic disorder. These disorders remitted after adequate antibiotic treatment. CONCLUSION: While depression has been previously linked to neuroborreliosis, this is the first report to link panic disorder and mania with borrelial infection. Because of the rapid rise of Lyme borreliosis nationwide and the need for antibiotic treatment to prevent severe neurologic damage, mental health professionals need to be aware of its possible psychiatric presentations.

Adult↗