PubMed Health⌕ Search

Biomedical subjects

D Michelson

Publications and source records attributed to D Michelson.

At least 19 recordsLinked to original sources
PubMed2005

ADHD Rating Scale IV: psychometric properties from a multinational study as a clinician-administered instrument.

The development of rating scales for attention-deficit/hyperactivity disorder (ADHD) has traditionally focused on parent-or teacher-rated scales. However, clinician-based instruments are valuable tools for assessing ADHD symptom severity. The ADHD Rating Scale IV (ADHD RS), clinician administered and scored, has been validated as a useful instrument to assess ADHD symptoms among American children and adolescents. In this study, we assessed the psychometric properties of the scale in a recent clinical trial conducted mainly in Europe with over 600 children and adolescents diagnosed with ADHD. The trial was conducted in 11 European countries plus Australia, Israel, and South Africa. Results based on data in the study indicate that this version of the scale has acceptable psychometric properties including inter-rater reliability, test-retest reliability, internal consistency, factor structure, convergent and divergent validity, discriminant validity, and responsiveness. There were low-to-moderate ceiling and floor effects. The psychometric properties were comparable with other validated scales for assessing ADHD symptom severity. These results were consistent across the 14 countries participating in this trial. Overall, the data from this study support the use of the ADHD RS as a clinician-rated instrument for assessing the severity of ADHD symptoms in children and adolescents in Europe.

Adolescent↗
PubMed2001

Abnormalities in response to vasopressin infusion in chronic fatigue syndrome.

Several neuroendocrine studies have suggested hypoactivation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome. One possible determinant of this neuroendocrine abnormality, as well as the primary symptom of fatigue, is reduced hypothalamic secretion of corticotropin-releasing hormone (CRH). Because CRH and vasopressin secreted from the hypothalamus act synergistically at the pituitary to activate ACTH secretion, the ACTH response to peripheral infusion of vasopressin can provide an indirect measure of hypothalamic CRH secretion. We measured the ACTH and cortisol response to a one hour infusion of arginine vasopressin in 19 patients with chronic fatigue syndrome and 19 age and sex matched healthy volunteers. Patients with chronic fatigue syndrome had a reduced ACTH response to the vasopressin infusion and a more rapid cortisol response to the infusion. These results provide further evidence of reduced hypothalamic CRH secretion in patients with chronic fatigue syndrome.

Adrenocorticotropic Hormone↗
PubMed2001

Efficacy of usual antidepressant dosing regimens of fluoxetine in panic disorder: randomised, placebo-controlled trial.

BACKGROUND: Although serotonin reuptake inhibitors are effective in panic disorder, questions concerning whether doses associated with antidepressant efficacy are also effective for panic disorder remain. AIMS: To assess the efficacy of the usual antidepressant dose of fluoxetine in treating full panic attacks. METHOD: Patients with panic disorder were randomised to placebo or to fluoxetine initiated at 10 mg daily for 1 week and then increased to 20 mg daily. The trial lasted 12 weeks, but after 6 weeks patients who had failed to achieve a satisfactory response were eligible for dose escalation to a maximum of 60 mg of fluoxetine daily. RESULTS: Fluoxetine was associated with a statistically significantly greater proportion of panic-free patients compared with placebo after 6 weeks and at end-point. CONCLUSIONS: Fluoxetine at a dose of 20 mg daily is safe and efficacious in reducing symptoms of panic disorder. Patients who fail to obtain a satisfactory response at 20 mg daily may benefit from further dose increases.

Adult↗
PubMed2001

Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study.

OBJECTIVE: Atomoxetine is an investigational, nonstimulant pharmacotherapy being studied as potential treatment for attention-deficit/hyperactivity disorder (ADHD). It is thought to act via blockade of the presynaptic norepinephrine transporter in the brain. We assessed the efficacy of 3 doses of atomoxetine compared with placebo in children and adolescents with ADHD. METHODS: A total of 297 children and adolescents who were 8 to 18 years of age and had ADHD as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, were randomized to placebo or atomoxetine dosed on a weight-adjusted basis at 0.5 mg/kg/day, 1.2 mg/kg/day, or 1.8 mg/kg/day for an 8-week period. ADHD symptoms, affective symptoms, and social and family functioning were assessed using parent and investigator rating scales. RESULTS: Approximately 71% of children enrolled were male, approximately 67% met criteria for mixed subtype (both inattentive and hyperactive/impulsive symptoms), and the only common psychiatric comorbidity was oppositional defiant disorder (approximately 38% of the sample). At baseline, symptom severity was rated as moderate to severe for most children. At endpoint, atomoxetine 1.2 mg/kg/day and 1.8 mg/kg/day were consistently associated with superior outcomes in ADHD symptoms compared with placebo and were not different from each other. The dose of 0.5 mg/kg/day was associated with intermediate efficacy between placebo and the 2 higher doses, suggesting a graded dose-response. Social and family functioning also were improved in the atomoxetine groups compared with placebo with statistically significant improvements in measures of children's ability to meet psychosocial role expectations and parental impact. Discontinuations as a result of adverse events were <5% for all groups. CONCLUSION: Among children and adolescents aged 8 to 18, atomoxetine was superior to placebo in reducing ADHD symptoms and in improving social and family functioning symptoms. Atomoxetine was associated with a graded dose-response, and 1.2 mg/kg/day seems to be as effective as 1.8 mg/kg/day and is likely to be the appropriate initial target dose for most patients. Treatment with atomoxetine was safe and well tolerated.

Adolescent↗
PubMed2000

Hormonal markers of stress response following interruption of selective serotonin reuptake inhibitor treatment.

Depressive illness is associated with loss of the usual regulation of stress-responsive hormonal and neurotransmitter systems, and antidepressants have intrinsic effects reducing the activity of these systems. Abrupt interruption of treatment with some antidepressants has been associated with a self-limited syndrome of physical and psychological symptoms distinct from relapse, of which drug half-life appears to be the major determinant. We hypothesized that reactivation of stress-response systems could play a role in this syndrome and studied the effects of treatment interruption in patients successfully treated with the antidepressant fluoxetine, paroxetine or sertraline. During placebo substitution, interruption of paroxetine was associated with statistically significant increases in plasma IGF-1 and heart rate. These data suggest that some activation of physiologic stress-responses may accompany symptom increases during treatment interruption of shorter half-life agents.

Adult↗
PubMed2000

Female sexual dysfunction associated with antidepressant administration: a randomized, placebo-controlled study of pharmacologic intervention.

OBJECTIVE: Few controlled trials of pharmacologic intervention in women with antidepressant-associated sexual dysfunction have been reported, and there is uncertainty about the usefulness of putative treatments and the assessment methodologies. The authors evaluated the efficacy of buspirone and amantadine in the treatment of sexual dysfunction associated with fluoxetine administration. METHOD: Women who had been successfully treated with fluoxetine for at least 8 weeks and who had reported a deterioration in sexual function not present before the initiation of fluoxetine entered a 4-week assessment period. After assessment they were randomly assigned to an 8-week treatment trial with buspirone (N=19), amantadine (N=18), or placebo (N=20). Outcomes were assessed by using a patient-rated daily diary and a clinician-rated structured interview. RESULTS: While the amantadine-treated women did report significantly greater improvements in energy levels than women in the placebo group, all treatment groups experienced improvement in overall sexual function as well as in most individual measures. There were no statistically significant differences among the three groups. CONCLUSIONS: Neither buspirone nor amantadine was more effective than placebo in ameliorating antidepressant-associated sexual dysfunction. All groups experienced marked nonspecific improvement during treatment, which suggests the importance of placebo-controlled trials for this condition.

Adult↗
PubMed2000

Brain kinetics of paroxetine and fluoxetine on the third day of placebo substitution: a fluorine MRS study.

OBJECTIVE: This study tested whether a relationship exists between concentration and response following discontinuation of selective serotonin reuptake inhibitors. METHOD: Eight patients with remitted major depression who were taking 20 mg/day of either fluoxetine or paroxetine underwent placebo substitution for 3 days. Serum drug and brain fluorine levels were obtained before and after placebo substitution. RESULTS: With placebo substitution, a mean of 88% (SD=13%) of brain fluorine signal from fluoxetine (plus fluorinated metabolites) remained, compared with a mean of 38% (SD=17%) of the brain fluorine signal from paroxetine (plus fluorinated metabolites). Among patients taking paroxetine, adverse events during placebo substitution correlated highly with steady-state brain drug levels. CONCLUSIONS: The correlation of clinical effects with brain drug levels in the paroxetine group suggests that relationships between drug response and brain drug concentrations merit further investigation.

Adult↗
PubMed2000

Interruption of selective serotonin reuptake inhibitor treatment. Double-blind, placebo-controlled trial.

BACKGROUND: Abrupt interruption of therapy with selective serotonin reuptake inhibitors (SSRIs) has been associated with somatic and psychological symptoms. AIMS: Systematically to assess symptoms and effects on daily functioning related to interruption of SSRI therapy. METHOD: Patients treated with fluoxetine, setraline or paroxetine underwent identical five-day periods of treatment interruption and continued active treatment under double-blind, order-randomised conditions, with regular assessment of new symptoms. RESULTS: Placebo substitution for paroxetine was associated with increases in the number and severity of adverse events following the second missed dose, and increases in functional impairment at five days. Placebo substitution for sertraline resulted in less pronounced changes, while interruption of fluoxetine was not associated with any significant increase in symptomatology. CONCLUSIONS: Abrupt interruption of SSRI treatment can result in a syndrome characterised by specific physical and psychological symptoms. Incidence, timing and severity of symptoms vary among SSRIs in a fashion that appears to be related to plasma elimination characteristics.

Adult↗
PubMed1999

Changes in weight during a 1-year trial of fluoxetine.

OBJECTIVE: Fluoxetine has been associated with weight loss during acute treatment, but no controlled studies of weight change during long-term treatment with fluoxetine or other selective serotonin reuptake inhibitors have been reported. Weights were assessed for patients whose depressive symptoms had disappeared with acute fluoxetine treatment. Patients were then randomly assigned to continuation treatment with fluoxetine or placebo. METHOD: Patients whose illness had remitted after 12 weeks of treatment with fluoxetine, 20 mg/day, were randomly assigned to receive up to 38 weeks of treatment with fluoxetine or placebo. Weight was assessed at each visit. Change in weight was analyzed during the initial 12 weeks of acute treatment and after 14, 26, and 38 weeks. Relationships between weight change and body mass index and between weight change and appetite change were assessed. RESULTS: During the initial 4 weeks of therapy, a mean absolute weight decrease of 0.4 kg was observed for all patients. Among patients who completed 50 weeks of therapy, the mean absolute weight increase during continuation treatment was similar for both the placebo- and fluoxetine-treated groups. Weight increase was not related to initial body mass index but was related to both poor appetite at study entry and to improvement in appetite after recovery. No patients discontinued therapy because of weight gain. CONCLUSIONS: Acute therapy with fluoxetine is associated with modest weight loss. After remission of depressive symptoms, weight gain for patients taking fluoxetine for longer periods is not different from that for patients taking placebo and is most likely related to recovery from depression.

Adult↗
PubMed1999

Continuing treatment of panic disorder after acute response: randomised, placebo-controlled trial with fluoxetine. The Fluoxetine Panic Disorder Study Group.

BACKGROUND: Data concerning appropriate treatment in panic disorder following an initial response to acute therapy are limited. AIMS: To assess the safety and efficacy of continued fluoxetine treatment following successful acute therapy of panic disorder. METHOD: Patients who responded to acute fluoxetine treatment were randomised to 24 weeks of continued fluoxetine or placebo. RESULTS: Fluoxetine responders randomised to continue on their acute-phase fluoxetine dose experienced statistically significant improvement in panic attack frequency and phobia rating scale score over 24 weeks of therapy, while those switched to placebo experienced statistically significant worsening in Hamilton Anxiety (HAM-A), Hamilton Depression (HAM-D) and SCL-90-R rating scores. CONCLUSIONS: Fluoxetine was associated with improved clinical outcomes compared with placebo during continuation therapy.

Adult↗
PubMed1999

Changes in adverse events reported by patients during 6 months of fluoxetine therapy.

BACKGROUND: Although a period of 6 to 12 months of antidepressant therapy is recommended for most patients with depression, systematic examinations of the course of adverse events over time, the resolution of early-onset events, and the possible emergence of later-onset events are limited. We examined the safety of fluoxetine, 20 mg/day, in a large, prospective, long-term treatment trial, and we report a comparison of early- and late-onset adverse events and the course of adverse events over 26 weeks of treatment. METHOD: Adverse events were recorded at each visit in a uniform format by open-ended questioning, regardless of perceived causality. New or worsened events reported in either the first 4 weeks of treatment (early-reporting interval) or weeks 22 through 26 of treatment (late-reporting interval) were compared. RESULTS: Patients (N = 299) whose depression (DSM-III-R) remitted with 12 weeks of fluoxetine treatment entered continuation therapy, and 174 completed 26 weeks of therapy. All events that occurred in > or =5% of patients early in treatment decreased in frequency over time (p<.05), and no events occurred significantly more frequently during continuation therapy. No previously uncommon adverse events became common during long-term treatment. CONCLUSION: Common adverse events associated with initiating fluoxetine treatment in depressed patients, including nausea, insomnia, nervousness, and somnolence, resolve in the majority of patients and become significantly less frequent with continued treatment over a 6-month period. No adverse events present initially become more frequent late in treatment. Therapy with fluoxetine, 20 mg/day, is well tolerated over 6 months, and most adverse events observed early in treatment resolve.

Anxiety↗
PubMed1998

Pathophysiologic and somatic investigations of hypothalamic-pituitary-adrenal axis activation in patients with depression.

Preclinical studies of inflammatory and autoimmune illnesses have demonstrated the importance of central components of the HPA axis in disease pathophysiology. The implications of these data for human illness are poorly understood. We have studied the pathophysiology of the hypercortisolism seen in two human illnesses involving the central nervous system, multiple sclerosis (MS) and depression, and looked for demonstrable somatic changes that may be associated with such hypercortisolism. Data from a study of medication-free patients with multiple sclerosis not in acute exacerbation suggest that compared with depression, MS is associated with increased prominence of hypothalamic vasopressin secretion (p < 0.05). Data from studies of depressed patients with mild to moderate hypercorticolism (assessed by 24-hour urinary free cortisol excretion) demonstrate marked reductions in bone mineral density compared to healthy, carefully matched controls (p < 0.001), as well as changes in markers of bone metabolic activity similar to those seen in patients with Cushing's disease or exogenous glucocorticoid treatment (p < 0.05). Taken together, these studies suggest HPA axis dysregulations demonstrated in preclinical models of autoimmune and inflammatory illness also occur in human illness and may have important and lasting somatic sequelae.

Adrenocorticotropic Hormone↗
PubMed1998

Safety of abrupt discontinuation of fluoxetine: a randomized, placebo-controlled study.

Selective serotonin reuptake inhibitors may be associated with new adverse events after abrupt discontinuation. Hypothesizing that the long half-life of fluoxetine would be protective, this study analyzed the effects of abrupt fluoxetine discontinuation during a randomized, double-blind, placebo-controlled study of depression maintenance treatment. After 12 weeks of fluoxetine treatment (20 mg/day), 395 responders were abruptly randomized to placebo (N = 96) or to continued fluoxetine (N = 299). Patients were seen at weeks 1, 2, 4, and 6 after randomization. Reports of new or worsened adverse events were similar for both groups at each visit after randomization. Patient discontinuations related to adverse events were also similar in both groups. Mild, self-limited lightheadedness or dizziness occurred in a small percentage of patients who discontinued fluoxetine treatment but was of little clinical significance. No cluster of symptoms suggestive of a discontinuation syndrome was observed. Abrupt discontinuation of fluoxetine treatment was well tolerated and did not seem to be associated with significant clinical risk. Fluoxetine may offer a potential safety advantage over shorter-acting agents with respect to treatment interruption and/or discontinuation and may be a better choice for those patients who are likely to miss doses because of travel or forgetfulness.

Adult↗
PubMed1998

Outcome assessment and clinical improvement in panic disorder: evidence from a randomized controlled trial of fluoxetine and placebo. The Fluoxetine Panic Disorder Study Group.

OBJECTIVE: Although panic attacks account for only a portion of the morbidity of panic disorder and panic attack frequency assessments are unreliable, studies of drug efficacy in panic disorder have generally used reduction in panic attack frequency as the primary measure of improvement. The authors studied the efficacy of fluoxetine treatment in panic disorder and measured the relative contributions of changes in symptoms to overall improvement. METHOD: Patients with a diagnosis of panic disorder (N = 243) were randomly assigned to treatment with 10 or 20 mg/day of fluoxetine or placebo. Primary outcome measures were change in panic attack frequency and clinician-rated Clinical Global Impression improvement scores. Other assessments included a panic attack inventory, clinician-rated and patient-rated versions of the Panic and Phobic Disorder Change Scale, a phobia rating scale, the Hamilton Anxiety Rating Scale, the 21-item Hamilton Depression Rating Scale, and the Sheehan Disability Scale. Correlations were determined between outcomes in individual symptom domains and overall clinical outcome. RESULTS: Fluoxetine, particularly the 20-mg/day dose, was associated with more improvement than was placebo in patients with panic disorder across multiple symptom measures, including global improvement, total panic attack frequency, phobic symptoms, and functional impairment. Global improvement was most highly correlated with reductions in overall anxiety and phobic symptoms and least correlated with reduction in panic attacks. Fluoxetine treatment for panic disorder was well tolerated, with a safety profile consistent with that observed for fluoxetine in other disorders. CONCLUSIONS: These data provide support for the efficacy and safety of fluoxetine treatment in reducing panic attacks, phobic symptoms, anxiety, and depressive symptoms in patients with panic disorder. Reductions in panic attack frequency in subjects given either fluoxetine or placebo were less closely related to overall clinical improvement than reductions in phobic avoidance, anxiety, depressive symptoms, and functional impairment, suggesting that outcome measures in this disorder should be more broadly based.

Adult↗
PubMed1998

Optimal length of continuation therapy in depression: a prospective assessment during long-term fluoxetine treatment.

OBJECTIVE: The purpose of this study was to determine prospectively the optimal length of therapy in a long-term, placebo-controlled continuation study of patients who responded to acute fluoxetine treatment for major depression (defined by DSM-III-R). METHOD: The study was conducted at five outpatient psychiatric clinics in the United States. Patients who met criteria for remission after 12 or 14 weeks of open-label acute fluoxetine therapy, 20 mg/day (N=395 of 839 patients), were randomly assigned to one of four arms of a double-blind treatment study (50 weeks of placebo, 14 weeks of fluoxetine and then 36 weeks of placebo, 38 weeks of fluoxetine and then 12 weeks of placebo, or 50 weeks of fluoxetine). Relapse rate was the primary outcome measure. Both Kaplan-Meier estimates and observed relapse rates were assessed in three fixed 12-week intervals after double-blind transfers from fluoxetine to placebo at the start of the double-blind period and after 14 and 38 weeks of continued fluoxetine treatment. RESULTS: Relapse rates (Kaplan-Meier estimates) were lower among the patients who continued to take fluoxetine compared with those transferred to placebo in both the first interval, after 24 total weeks of treatment (fluoxetine, 26.4%; placebo, 48.6%), and the second interval, after 38 total weeks of treatment (fluoxetine, 9.0%; placebo, 23.2%). In the third interval, after 62 total weeks of treatment, rates were not significantly different between the groups (fluoxetine, 10.7%; placebo, 16.2%). CONCLUSIONS: Patients treated with fluoxetine for 12 weeks whose depressive symptoms remit should continue treatment with fluoxetine for at least an additional 26 weeks to minimize the risk of relapse.

Adult↗
PubMed1997

The effect of assessment method and respondent population on utilities elicited for Gaucher disease.

Measured preferences have been reported to vary with the method of elicitation and respondent population surveyed. We elicited utilities for Gaucher disease using a multimedia implementation of the time trade-off, standard gamble, and a conceptually different, largely untested approach, the risk-risk trade-off, from those who are healthy, those with a chronic illness and those with Gaucher disease. The risk-risk trade-off produced significantly lower utilities than the other two preference assessment methods and had the poorest test-retest reliability. The respondent's self-rated current health state utility was the most important determinant of utility values elicited by the time trade-off and standard gamble for the hypothetical health states. Our results do not support the use of our implementation of the risk-risk trade-off method. In eliciting preferences for hypothetical health states from the general population, the subjective rating of a respondent's own health state should be considered in determining representative population groups.

Adult↗
PubMed1997

Hormonal and metabolic responses to exercise across time of day and menstrual cycle phase.

Two studies, each utilizing short-term treadmill exercise of a different intensity, assessed the metabolic and hormonal responses of women to exercise in the morning (AM) and late afternoon (PM). In study 1, plasma concentrations of growth hormone, arginine vasopressin, catecholamines, adrenocorticotropic hormone, cortisol, lactate, and glucose were measured before, during, and after high-intensity exercise (90% maximal O2 uptake) in the AM and PM. In study 2, plasma concentrations of adrenocorticotropic hormone, cortisol, lactate, and glucose were measured before, during, and after moderate-intensity exercise (70% maximal O2 uptake) in the AM and PM in the follicular (days 3-9), midcycle (days 10-16), and luteal (days 18-26) phases of the menstrual cycle. The results of studies 1 and 2 revealed no significant diurnal differences in the magnitude of responses for any measured variable. In addition, study 2 revealed a significant time-by-phase interaction for glucose (P = 0. 014). However, net integrated responses were similar across cycle phases. These data suggest that metabolic and hormonal responses to short-term, high-intensity exercise can be assessed with equal reliability in the AM and PM and that there are subtle differences in blood glucose responses to moderate-intensity exercise across menstrual cycle phase.

Adult↗