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Biomedical subjects

M Liebowitz

Publications and source records attributed to M Liebowitz.

At least 19 recordsLinked to original sources

Open trial of nefazodone among Hispanics with major depression: efficacy, tolerability, and adherence issues.

The efficacy and tolerability of nefazodone in the treatment of major depression among Spanish-monolingual Hispanics was examined and compared to historical controls among English-speaking, predominantly non-Hispanic subjects. Fifty monolingual Hispanic outpatients with major depression and a HAM-D17 score > or = 18 were treated with nefazodone in a flexible-dose 8-week open-label protocol. Sixty-three percent of the intent-to-treat (ITT) sample with > or = 1 efficacy visit were considered responders according to CGI-I criteria, falling within the range of response rates (58-69%) reported in six prior nefazodone trials with non-Hispanic subjects. Significant improvement was found for the ITT and completer samples in HAM-D17, HAM-D28, and SCL-90 scores and in two measures of psychosocial functioning. Endpoint mean dose in the ITT sample was 379 mg/day (SD = 170), also within the range of previous trials (321-472 mg/day). Adverse effects were not elevated, with only dry mouth (8%) reported by > 6% of subjects. However, 42% of the sample dropped out of treatment before study termination, usually because of side effects or due to family or work difficulties, a higher rate than previously reported for nefazodone (21-33%). This open trial finds nefazodone to be an efficacious treatment for major depression among monolingual Hispanics, with comparable efficacy to previous controlled trials among non-Hispanic subjects. Double-blind studies are required to confirm this comparable efficacy. Mean endpoint doses and adverse effect rates similar to previous trials do not support the need for reduced doses of nefazodone among Hispanics. However, an elevated rate of treatment discontinuation threatens treatment efficacy among this population. Causes for this elevated rate require explanation, given the apparently unremarkable pattern of adverse effect reports.

Adult↗

Serum leptin levels increase following acute myocardial infarction.

Leptin is secreted into the circulation and communicates the peripheral nutritional status to specific hypothalamic centers. Recent studies suggest that leptin may be involved in the acute response to stress, and that its interaction with the hypothalamo-pituitary-adrenal axis and the inflammatory cytokine system may be of clinical importance. Since these systems are activated during acute myocardial infarction (AMI), we studied leptin and cortisol levels during hospitalization in 30 consecutive patients admitted for AMI. The results show that leptin reached its peak on the second day of hospitalization, with a 2-fold increase from its baseline level on admission (p < 0.02). On day 3, leptin levels declined, and were 46%, 9%, and 6% above baseline on days 3, 4 and 5, respectively. The mean cortisol level was elevated on day 1 and decreased toward normal levels thereafter (p < 0.001). The cortisol level did not correlate with leptin concentration throughout the study. These findings suggest that leptin may have a role in the metabolic changes taking place during the first days after an AMI.

Aged↗

Disability and quality of life in pure and comorbid social phobia. Findings from a controlled study.

Social phobia is increasingly recognized as a prevalent and socially impairing mental disorder. However, little data is available regarding the general and disease-specific impairments and disabilities associated with social phobia. Furthermore, most studies have not controlled for the confounding effects of comorbid conditions. This study investigates: (a) the generic quality of life; (b) work productivity; and, (c) various other disorder-specific social impairments in current cases with pure (n = 65), comorbid (n = 51) and subthreshold (n = 34) DSM-IV social phobia as compared to controls with no social phobia (subjects with a history of herpes infections). Social phobia cases reported a mean illness duration of 22.9 years with onset in childhood or adolescence. Current quality of life, as assessed by the SF-36, was significantly reduced in all social phobia groups, particularly in the scales measuring vitality, general health, mental health, role limitations due to emotional health, and social functioning. Comorbid cases revealed more severe reductions than pure and subthreshold social phobics. Findings from the Liebowitz self-rated disability scale indicated that: (a) social phobia affects most areas of life, but in particular education, career, and romantic relationship; (b) the presence of past and current comorbid conditions increases the frequency and severity of disease-specific impairments; and, (c) subthreshold social phobia revealed slightly lower overall impairments than comorbid social phobics. Past-week work productivity of social phobics was significantly diminished as indicated by: (a) a three-fold higher rate of unemployed cases; (b) elevated rates of work hours missed due to social phobia problems; and (c) a reduced work performance. Overall, these findings underline that social phobia in our sample of adults, whether comorbid, subthreshold, or pure was a persisting and impairing condition, resulting in considerable subjective suffering and negative impact on work performance and social relationships. The current disabilities and impairments were usually less pronounced than in the past, presumably due to adaptive behaviors in life style of the respondents. Data also confirmed that social phobia is poorly recognized and rarely treated by the mental health system.

Adult↗

Childhood trauma and dissociative symptoms in panic disorder.

OBJECTIVE: Childhood trauma has been associated with increased risk for both panic disorder and dissociative symptoms in adulthood. The authors hypothesized that among individuals with a primary diagnosis of panic disorder, those experiencing depersonalization/derealization during panic attacks would be more likely to have a history of childhood trauma. METHOD: Rates of traumatic events were compared between panic disorder patients with (N=34) and without (N=40) prominent depersonalization/derealization during panic attacks. Symptom severity in the two groups was also examined. RESULTS: Contrary to the authors' hypothesis, no evidence was found that depersonalization/derealization during panic attacks was associated with childhood trauma. Minimal differences in severity of illness were found between patients with dissociative symptoms and those without such symptoms. CONCLUSIONS: This finding is consistent with a multifactorial model of dissociation. Factors other than childhood trauma and general psychopathology may underlie vulnerability to dissociative symptoms in panic disorder.

Adolescent↗

Disability and quality of life in pure and comorbid social phobia--findings from a controlled study.

Social phobia is increasingly recognized as a prevalent and socially impairing mental disorder. However, little data is available regarding the general and disease-specific impairments and disabilities associated with social phobia. Furthermore, most studies have not controlled for the confounding effects of comorbid conditions. This study investigates: (a) the generic quality of life; (b) work productivity; and, (c) various other disorder-specific social impairments in current cases with pure (n = 65), comorbid (n = 51) and subthreshold (n = 34) DSM-IV social phobia as compared to controls with no social phobia (subjects with a history of herpes infections). Social phobia cases reported a mean illness duration of 22.9 years with onset in childhood or adolescence. Current quality of life, as assessed by the SF-36, was significantly reduced in all social phobia groups, particularly in the scales measuring vitality, general health, mental health, role limitations due to emotional health, and social functioning. Comorbid cases revealed more severe reductions than pure and subthreshold social phobics. Findings from the Liebowitz self-rated disability scale indicated that: (a) social phobia affects most areas of life, but in particular education, career, and romantic relationship; (b) the presence of past and current comorbid conditions increases the frequency of disease-specific impairments; and, (c) subthreshold social phobia revealed slightly lower overall impairments than comorbid social phobics. Past week work productivity of social phobics was significantly diminished as indicated by: (a) a three-fold higher rate of unemployed cases; (b) elevated rates of work hours missed due to social phobia problems; and, (c) a reduced work performance. Overall, these findings underline that social phobia in our sample of adults, whether comorbid, subthreshold, or pure was a persisting and impairing condition, resulting in considerable subjective suffering and negative impact on work performance and social relationships. The current disabilities and impairments were usually less pronounced than in the past, presumably due to adaptive behaviors in life style of the respondents. Data also confirmed that social phobia is poorly recognized and rarely treated by the mental health system.

Adult↗

Serotonergic function in social phobia: comparison to normal control and obsessive-compulsive disorder subjects.

Eighteen patients with social phobia, 21 normal control subjects, and 42 obsessive-compulsive disorder (OCD) control subjects were challenged with single doses of the partial serotonin agonist oral m-chlorophenylpiperazine (m-CPP) and placebo. Social phobics did not significantly differ from normal or OCD control subjects in prolactin response to m-CPP. There was a significant difference across groups in cortisol response to m-CPP, such that female social phobics had more robust cortisol responses to the m-CPP challenge. Pairwise comparisons only reached trend significance, perhaps due to the relatively small sample sizes. This study offers preliminary evidence for serotonin dysfunction in social phobia, particularly in female social phobics, but needs to be replicated in a larger sample size.

Adult↗

A 2-year study of sertraline in the treatment of obsessive-compulsive disorder.

The present study investigated the tolerability, safety profile, and anti-obsessional efficacy of sertraline, a selective serotonin reuptake inhibitor, during long-term treatment of patients with obsessive-compulsive disorder (OCD). Fifty-nine OCD patients who had completed a 1 year double-blind, fixed dose study comparing sertraline and placebo subsequently entered a 1-year open extension. Among the 51 patients who had been treated with sertraline during the double-blind phase, the mean total duration of sertraline treatment was 690 days. Only treatment responders who completed the 52-week double-blind treatment phase were permitted to enter the open extension. The higher rate (p < 0.02) of sertraline patients (51 out of 241) than of placebo patients (eight out of 84), who responded to treatment and entered the open-label phase is therefore consistent with the greater mean improvement observed in the sertraline group during double-blind treatment. Placebo responders differed from sertraline responders in that they were less impaired at baseline of the double-blind study [Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) of 18.5 versus 23.4] and they exhibited less improvement during double-blind treatment (-6.1 versus -11.4). In the open-label phase all patients received sertraline at a starting dose of 50 mg once a day, titrated in 50 mg increments to a maximum dose of 200 mg according to clinical response. At end-point the mean Y-BOCS score for all patients decreased by a further 3.6 points. Patients previously treated with placebo showed greater improvement after being switched to sertraline than those who received continued sertraline treatment. Patients who completed the study and received 2 full years of sertraline treatment (n = 38) exhibited a mean improvement of 15.6 points using the Y-BOCS. Sertraline was well tolerated during both the double-blind phase and the open extension, and the incidence of adverse experiences was generally reduced during the second year of treatment. Three patients discontinued open treatment because of adverse experiences. Long-term sertraline treatment did not appear to be associated with the emergence, increased incidence, or increased severity of adverse experiences or clinically significant abnormalities in laboratory tests, vital signs, or the electrocardiogram. The study supports the long-term safety and tolerability of sertraline over a 2-year treatment course and the sustained efficacy of sertraline in patients with OCD.

1-Naphthylamine↗

Treatment of obsessive-compulsive disorder with fluvoxamine: a multicentre, double-blind, placebo-controlled trial.

One hundred and sixty patients with a primary diagnosis of obsessive-compulsive disorder were enrolled in a multicentre, randomized, double-blind, placebo-controlled study of fluvoxamine. After a placebo washout phase, patients were randomized to treatment with placebo or fluvoxamine (100-300 mg/day) for 10 weeks. Seventy-eight patients in each group were evaluable for efficacy. Fluvoxamine was significantly more effective than placebo as assessed by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the National Institute of Mental Health Obsessive-Compulsive (NIMH-OC) scale and the Global Improvement item of the Clinical Global Impression (CGI) scale. The percentage of patients classified as "responders" (much or very much improved according to the Global Improvement item) was also significantly higher in the fluvoxamine group from Week 6 onwards, with 33.3% of fluvoxamine-treated patients and 9.0% of those given placebo classified as "responders" at endpoint. The "responders" to fluvoxamine experienced a substantial clinical benefit as reflected in decreases in their Y-BOCS and NIMH-OC scores. Fluvoxamine was well tolerated with the majority of adverse events considered mild or moderate.

Adult↗

Double-blind parallel comparison of three dosages of sertraline and placebo in outpatients with obsessive-compulsive disorder.

BACKGROUND: Anecdotal evidence suggests patients with obsessive-compulsive disorder (OCD) are treated with selective serotonin uptake inhibitors at dosages significantly higher than those used with depressed patients. The current study examined the efficacy, safety, and optimal dosing strategy of sertraline in patients with OCD. METHODS: Three hundred twenty-four nondepressed outpatients with OCD from 11 sites followed identical protocols using a double-blind parallel design. Following 1 week of single-blind placebo, patients were randomly assigned to 12 weeks of treatment with one of three fixed dosages of sertraline (50, 100, or 200 mg/d) or placebo. RESULTS: Sertraline patients exhibited significantly greater improvement (P < .05) at end point than placebo patients on all three main efficacy measures in the 50-mg/d and 200-mg/d groups and on one measure in the 100-mg/d group. The placebo response was larger in this population of subjects with OCD than in those previously studied. Adverse experiences were common in the sertraline and placebo groups and appeared to be dose-related in the sertraline-treated patients. CONCLUSIONS: Results support the safety and efficacy of daily dosages of 50, 100, and 200 mg of sertraline in the short-term treatment of patients with OCD.

1-Naphthylamine↗

Memory bias does not generalize across anxiety disorders.

Individuals with social phobia were compared with normal controls on their memory for socially-related threat words in contrast to positive and neutral words. A memory paradigm used in a previous study of panic disorder patients [Cloitre, M. & Liebowitz, M. R. (1991) Cognitive Therapy and Research, 15, 609-619] was applied to test the generalizability of findings of threat-biased memory in a semantic memory task (free recall) and a perceptual memory task (high-speed recognition) to social phobics. No evidence of threat-related memory bias among social phobics was obtained. Since both the social phobic and control groups showed better memory for affectively valenced (threat and positive) compared to neutral information, it is unlikely that the absence of threat-biased memory among social phobics was the result of insensitive measurement.

Adult↗

Subsyndromal ("mixed") anxiety--depression in primary care.

OBJECTIVE: To determine in primary care settings the prevalence, clinical characteristics, and functional status of patients who have anxious and depressive symptoms who did not meet diagnostic criteria for major mood and anxiety diagnoses. DESIGN: Patients were screened with the General Health Questionnaire and interviewed if they exceeded the cutoff score of 5. Also, one patient whose score was below the cutoff was interviewed for every two patients whose scores were above the cutoff. SETTING: Five primary care sites in the United States, France, and Australia. PATIENT: Two hundred sixty-seven patients presenting to their primary care physicians for general medical care and follow-up. METHODS: Structured diagnostic interviews were conducted and ratings of anxiety, depression, and functional impairment were obtained by trained interviewers. RESULTS: After adjustments for sampling, 5% of the patients had symptoms of anxiety, depression, and functional impairment, without meeting formal criteria for a major DSM-III-R mood or anxiety disorder. This was comparable to the prevalence of diagnosable DSM-III-R mood disorders but only one-fourth the prevalence of diagnosable anxiety disorders. These patients who had subsyndromal symptoms had rates of lifetime psychiatric disorders and prior psychiatric treatment comparable to those of patients meeting criteria for major mood and anxiety disorders. CONCLUSION: The comparable rates of symptomatic distress, functional impairment, and prior psychiatric illness and treatment suggest that patients with subsyndromal anxiety and depressive symptoms warrant clinical recognition and possibly specific treatment.

Anxiety↗

Brain event-related potential correlates of overfocused attention in obsessive-compulsive disorder.

A hypothesis of overfocused attention in obsessive-compulsive disorder was investigated by measuring auditory event-related potentials (ERPs) during a selective attention task. Unmedicated patients (n = 18) with this disorder showed significantly larger attention-related processing negativity (PN), with earlier onset and longer duration, than did normal controls (n = 15). In the N200 region (160-250 ms), PN was larger in patients with fewer nonspecific neurological soft signs. This task, however, did not yield any group differences in mismatch negativity (N2a) or classical N200 (N2b). P300 amplitudes for attended targets were smaller for patient than normal groups, but the reverse was true for P300 and positive slow wave amplitudes for unattended nontargets. Collectively, these ERP abnormalities suggest a misallocation of cognitive resources. Because of the importance of the frontal lobe in the control of selective attention, PN enhancement in patients with obsessive-compulsive disorder may reflect hyperactivation of this region. This conceptualization is consistent with recent functional neuroimaging findings.

Adult↗

The DSM-IV field trial for mixed anxiety-depression.

OBJECTIVE: This field trial was designed to answer four questions. First, are patients presenting with anxious or depressed symptoms that are associated with significant impairment but do not meet DSM-III-R definitional thresholds for axis I anxiety or mood disorders? Second, is the impairment experienced by these patients simply the consequence of the severity of their medical conditions? Third, what percent of these patients present with depressive symptoms only, anxious symptoms only, and a mixture of both? Fourth, how should the operational criteria for the syndrome(s) presented by these patients be defined? METHOD: A total of 666 patients from five primary care medical sites and two outpatient mental health sites were administered a semistructured psychiatric interview. RESULTS: Patients presenting with affective symptoms that did not meet definitional thresholds for DSM-III-R axis I disorders were at least as common as patients with several of the already established anxiety and mood disorders in each of the seven sites, and their disorders were associated with significant distress or impairment. A nonspecific pattern of anxious and depressed symptoms was the modal presentation among these patients with currently subdefinitional threshold disorders, and they could be significantly differentiated in terms of current symptoms from patients presenting with a principal diagnosis of generalized anxiety disorder, major depressive episode, or panic disorder with agoraphobia. CONCLUSIONS: The authors recommend that a mixed anxiety-depression category be included in the DSM-IV appendix for proposed diagnostic categories that need further study. A criteria set is proposed.

Ambulatory Care↗

Neuropsychiatric and neuropsychological findings in conduct disorder and attention-deficit hyperactivity disorder.

Neuropsychiatric and neuropsychological evaluations were performed in a pilot study of adolescents with DSM-III-R disruptive behavior disorders, including conduct disorder (CD) and attention-deficit hyperactivity disorder (ADHD). The following comparisons were made: 1) CD comorbid with ADHD vs. CD only; 2) all subjects with ADHD vs. all non-ADHD; and 3) all subjects with CD vs. all non-CD. The CD + ADHD group had increased left-sided soft signs compared with the CD group. CD + ADHD subjects significantly underperformed CD subjects on several executive functioning measures, with no differences on Verbal IQ subtests. Results are discrepant with previous findings of deficient verbal functioning in delinquent populations. However, findings may not be generalizable because of sampling limitations.

Adolescent↗

Quantitative electroencephalographic subtyping of obsessive-compulsive disorder.

Current neuropsychological, electrophysiological, and other imaging data strongly suggest the existence of a neurobiological basis for obsessive-compulsive disorder (OCD), which was long considered to be exclusively of psychogenic origin. The positive response of some OCD patients to neurosurgery, as well as the efficacy of agents that selectively block serotonin reuptake, lends further support to a biological involvement. However, a survey of the treatment literature reveals that only 45-62% of OCD patients improve with these specific medications. In a pilot study using a quantitative electroencephalographic (QEEG) method known as neurometrics, in which QEEG data from OCD patients were compared statistically with those from an age-appropriate normative population, we previously reported the existence of two subtypes of OCD patients within a clinically homogeneous group of patients who met DSM-III-R criteria for OCD. Following pharmacological treatment, a clear relationship was found between treatment response and neurometric cluster membership. In this study, we have expanded the OCD population, adding patients from a second site, and have replicated the existence of two clusters of patients in an enlarged, statistically more robust population. Cluster 1 was characterized by excess relative power in theta, especially in the frontal and frontotemporal regions; cluster 2 was characterized by increased relative power in alpha. Further, 80.0% of the members of cluster 1 were found to be nonresponders to drug treatment, while 82.4% of the members of cluster 2 were found to be treatment responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Psychopharmacologic treatment of child and adolescent obsessive compulsive disorder.

Recent evidence now suggests that OCD is much more common in young people than previously thought, affecting up to 200,000 children and adolescents in the United States alone. Unlike many childhood disorders, OCD appears remarkably similar for children and adults in terms of both clinical presentations and treatment response. The treatments of choice for OCD are antidepressants with potent serotonergic reuptake blocking effects such as fluoxetine and clomipramine. Both medications appear to be equally effective in terms of symptom remission, with different investigators reporting response rates in the range of 50% to 75%. Recent evidence suggests, however, that fluoxetine may be tolerated more easily than clomipramine and may be associated with less relapse upon discontinuation. Behavior therapy, either alone or in combination with medication, has been shown to be an effective alternative treatment. In spite of the increasing recognition of the disorder in both adults and children, only a handful of treatment outcome studies of child and adolescent OCD have been conducted and much work remains to be done in this area.

Adolescent↗