The effect of teriparatide compared with risedronate on reduction of back pain in postmenopausal women with osteoporotic vertebral fractures.

UNLABELLED: The effect of teriparatide and risedronate on back pain was tested, and there was no difference in the proportion of patients experiencing a reduction in back pain between groups after 6 or 18 months. Patients receiving teriparatide had greater increases in bone mineral density and had fewer vertebral fractures. INTRODUCTION: This study aimed to understand the effect of teriparatide in reducing back pain in patients with prevalent back pain and vertebral fracture compared to risedronate. METHODS: In an 18-month randomized, double-blind, double-dummy trial, we investigated the effects of teriparatide (20 µg/day) vs. risedronate (35 mg/week) in postmenopausal women with back pain likely due to vertebral fracture. The primary objective was to compare the proportion of subjects reporting ≥30% reduction in worst back pain severity from baseline to 6 months as assessed by a numeric rating scale in each treatment group. Pre-specified secondary and exploratory outcomes included assessments of average and worst back pain at additional time points, disability and quality of life, bone mineral density, incidence of fractures, and safety. RESULTS: At 6 months, 59% of teriparatide and 57% of risedronate patients reported ≥30% reduction in worst back pain and there were no differences between groups in the proportion of patients experiencing reduction in worst or average back pain at any time point, disability, or quality of life. There was a greater increase from baseline in bone mineral density at the lumbar spine (p = 0.001) and femoral neck (p = 0.02) with teriparatide compared to risedronate and a lower incidence of vertebral fractures at 18 months (4% teriparatide and 9% risedronate; p = 0.01). Vertebral fractures were less severe (p = 0.04) in the teriparatide group. There was no difference in the overall incidence of adverse events. CONCLUSIONS: Although there were no differences in back pain-related endpoints, patients receiving teriparatide had greater skeletal benefit than those receiving risedronate.

Fluoxetine in medically stable, depressed geriatric patients: effects on weight.

This study assessed the effect of fluoxetine 20 mg/day on weight loss in older patients treated for major depression in a multicenter, double-blind placebo-controlled, 6-week clinical trial. Thirty U.S. outpatient clinics affiliated with psychiatric programs participated in the study that involved 671 medically stable outpatients at least 60 years old who had normal cognition and met DSM-III-R criteria for major depression. Weight was recorded at weekly visits. As a measure of adiposity, patients were categorized into two groups, high and low/normal body mass index (BMI) groups. Analyses were done for each group. The high BMI group, but not the low/normal BMI group, had a statistically greater proportion of fluoxetine-treated patients who lost at least 5% of their baseline weight. Overall mean weight change for the fluoxetine-treated patients was about 1% compared with essentially no change for placebo-treated patients. Only one patients, who was treated with fluoxetine and in the low/normal BMI group, discontinued from the study because of weight loss. Although 5% weight loss occurred in more fluoxetine-treated than placebo-treated patients, most of the patients who lost weight had higher adiposity at baseline. There was not a statistically significant difference in the proportion of fluoxetine-treated and placebo-treated patients in the low/normal group who had at least 5% weight loss. Medically relevant weight loss in older patients treated with fluoxetine was uncommon.

Twice-daily dosing of loracarbef 200 mg versus 400 mg in the treatment of patients with acute maxillary sinusitis.

Loracarbef is an oral synthetic beta-lactam antibiotic in the new carbacephem class. We conducted a multicenter, randomized, double-blind, parallel-group study to compare the efficacy and safety of loracarbef 200 mg twice daily (BID) and 400 mg BID when given orally for 10 days to patients 12 years of age and older with acute maxillary sinusitis. Because sinus aspirates for culture are not routinely obtained in the management of acute maxillary sinusitis, antimicrobial therapy usually is selected empirically. This study was designed to provide data simulating the usual clinical practice of treatment without sinus aspiration. Two hundred nine patients who met the entry criteria, which included abnormal pretherapy sinus radiographs compatible with acute maxillary sinusitis and symptoms of fewer than 4 weeks' duration, qualified for the clinical analyses. Of the 106 clinically qualified patients assigned to the 200-mg BID group, favorable clinical responses (cure and improvement) were noted in 86 (81.1%) patients. Of the 103 clinically qualified patients assigned to the 400-mg BID group, 84 (81.6%) patients had favorable clinical responses. These results compare favorably with accepted clinical response rates of 70% to 80% for beta-lactams selected on an empiric basis. At the end of the treatment period, favorable radiologic responses (resolved and improved) and favorable clinical responses occurred in 55 (51.9%) of the 106 clinically qualified patients in the 200-mg BID group and in 57 (55.3%) of the 103 clinically qualified patients in the 400-mg BID group. Mean roentgenogram scores for the clinically qualified patients were 2.3 for both groups before therapy and 1.3 and 1.5 after therapy for the 200-mg BID and 400-mg BID groups, respectively. The mean change from pretherapy to posttherapy by patient was 1.0 for the 200-mg BID group and 0.8 for the 400-mg BID group. There were no statistically significant differences between treatment groups in the incidence of specific adverse events reported during therapy. These data suggest that loracarbef 200 mg BID is comparable in efficacy and safety to loracarbef 400 mg BID in the treatment of patients with acute maxillary sinusitis.

Possible monoamine oxidase inhibitor-serotonin uptake inhibitor interaction: fluoxetine clinical data and preclinical findings.

The primary objective of this article is to review information pertinent to and emphasize the seriousness of a potential adverse monoamine oxidase inhibitor (MAOI)-serotonin uptake inhibitor interaction by considering, within the context of preclinical data, clinical cases in which an MAOI and fluoxetine hydrochloride, a specific serotonin uptake inhibitor, were administered in close temporal proximity. Clinical cases were identified by a review of spontaneous adverse event reports submitted voluntarily to Eli Lilly and Company through its drug surveillance program and by a review of reports of MAOI interactions published in the scientific literature. A discussion of eight selected clinical cases of acute adverse reactions (seven with fatal outcomes; one with a favorable response after cyproheptadine therapy) reported to Eli Lilly and Company in which an MAOI was initiated concurrently or shortly after the discontinuation of fluoxetine and a review of preclinical data suggest a possible role of serotonin and/or serotonin-dopamine interactions in the hypermetabolic state that may occur when a serotonin uptake inhibitor and an MAOI are coadministered, although alternative etiologic processes are possible as well. Data reviewed reinforce the idea that the administration of an MAOI in close temporal proximity to fluoxetine is contraindicated.

Analyses of suicidality in double-blind, placebo-controlled trials of pharmacotherapy for weight reduction.

BACKGROUND: The obese who seek therapy may also have depression and thus a risk for suicidality (suicidal acts and ideation). For this reason and because of interest in the potential impact of a medication with antidepressant properties on suicidality in a population without a primary diagnosis of depression, we performed a comprehensive analysis of suicidality data from clinical trials in patients seeking weight-reduction therapy. METHOD: Suicidality data from 11 double-blind controlled trials in the United States Investigational New Drug fluoxetine obesity clinical trial data base (3819 randomized outpatients) were reviewed. Trials lasted 6 to 60 weeks (continuous and intermittent therapy designs). They included obese men and women (median body mass index, 35.0 kg/m2). Trials excluded patients treated with antidepressants. Incidence of suicidality was analyzed by the incidence difference method. RESULTS: No fatal suicidal acts occurred. One suicide attempt was reported in a patient receiving placebo after prior fluoxetine therapy (intermittent therapy trial). The overall incidence of suicidal ideation among fluoxetine-treated and placebo-treated patients in the obesity clinical trials was 0.24%. The difference in incidence of emergent suicidal ideation in fluoxetine-treated (0.23%) and placebo-treated patients (0.27%) was not statistically significant. CONCLUSION: Based on these analyses of controlled clinical trials, suicidality occurs but has a low incidence rate in the obese who seek pharmacologic weight-reduction therapy. Fluoxetine-treated and placebo-treated patients did not differ statistically significantly in the incidence of suicidality either during or after discontinuation of therapy.

Lack of association between fluoxetine and suicidality in bulimia nervosa.

BACKGROUND: The coincidence of major depressive disorder in bulimia nervosa ranges from 35% to 80%. Because of this comorbidity and because suicidality (suicidal acts and ideation) is an inherent part of depression, assessment of the risk of suicide in patients with bulimia nervosa is of considerable interest. METHOD: Data from United States Investigational New Drug double-blind, placebo-controlled fluoxetine clinical trials in bulimia nervosa were analyzed comprehensively to assess the potential association between fluoxetine treatment and suicidality in 785 patients with DSM-III-R bulimia nervosa. Patients were predominantly women (98%), aged 17 to 63 years; of the randomly assigned patients, 16.9% exhibited 17-item Hamilton Rating Scale for Depression (HAM-D) total scores of 17 or greater at baseline (range, 0-31). Incidence of suicidality was analyzed by the incidence difference method. RESULTS: No fatal suicidal acts occurred; 9 (1.15%) of 785 patients made nonfatal attempts; 24 (3.06%) experienced emergent (text-defined) suicidal ideation. No statistically significant increases in the incidence of suicidal acts or suicidal ideation were observed among fluoxetine-treated compared with placebo-treated patients. A smaller percentage of fluoxetine-treated (2.0%) than placebo-treated (3.8%) patients experienced emergence of substantial suicidal ideation (change in baseline HAM-D Item 3 [suicide item] score of 0 or 1 to 3 or 4 during therapy). A statistically significantly greater proportion of fluoxetine-treated than placebo-treated patients experienced improvement in suicidal ideation (decrease in HAM-D Item 3 score) from baseline to endpoint (p = .026). CONCLUSION: Analyses of the incidence of suicidal acts and suicidal ideation did not indicate an increased risk of suicidality in patients with bulimia nervosa treated with fluoxetine compared with those treated with placebo.

Fluoxetine: no association with suicidality in obsessive-compulsive disorder.

Since (a) obsessive-compulsive disorder (OCD) may involve serotonergic neural transmission abnormalities also though to be related to regulation of suicide and aggression, (b) comorbidity between OCD and depression is substantial, and (c) depression is a major risk factor for suicide, a comprehensive analysis of clinical trial data was undertaken to assess the potential association of fluoxetine, a serotonin uptake inhibitor, and suicidality (suicidal acts and ideation). Pooled data from clinical trials comparing fluoxetine (n = 266) and placebo (n = 89) in patients with DSM-IIIR OCD were analyzed retrospectively. No suicidal acts occurred during placebo lead-in or double-blind therapy. Mean Hamilton Depression Scale item 3 (suicide item) scores improved statistically significantly with fluoxetine compared with placebo. Worsening in suicidal ideation was statistically significantly more frequent with placebo than with fluoxetine. Emergence of substantial suicidal ideation (change in baseline item 3 score of 0 or 1 to 3 or 4) was numerically greater with placebo than with fluoxetine (3.6% vs. 1.7%; not statistically significant). The incidence of suicidality in fluoxetine-treated patients with OCD was low, compared favorably with rates in corresponding placebo-treated patients, and was well within the range of estimates in previous studies of patients with OCD. These controlled clinical trial results suggest no undue risk of suicidality in patients with OCD treated with fluoxetine.

Fluoxetine: a review of receptor and functional effects and their clinical implications.

Downregulation of serotonin 5-HT1 receptors is the most frequently reported central nervous system neural effect of subchronic exposure to fluoxetine in rodents. However, downregulation of these receptors has not been universally demonstrated. Effects of subchronic exposure on 5-HT2 receptors are mixed. Fluoxetine exposure appears to have no effect on cholinergic muscarinic receptors. Effects on beta-adrenergic receptors are controversial, as only one laboratory has reported downregulation. The majority of studies have failed to show an effect on beta-adrenergic-receptor-stimulated cAMP generation. Electrophysiologic studies support the concept that fluoxetine facilitates net serotonergic transmission through downregulation of presynaptic inhibitory autoreceptors. Data suggest that its subchronic specificity and selectivity distinguish fluoxetine from members of other classes of available antidepressants, making it a distinct therapeutic option.

Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression.

OBJECTIVE: A comprehensive meta-analysis of clinical trial data was performed to assess the possible association of fluoxetine and suicidality (suicidal acts and ideation). DESIGN: Retrospective analysis of pooled data from 17 double blind clinical trials in patients with major depressive disorder comparing fluoxetine (n = 1765) with a tricyclic antidepressant (n = 731) or placebo (n = 569), or both. MAIN OUTCOME MEASURES: Multiple data sources were searched to identify patients with suicidal acts. Suicidal ideation was assessed with item 3 of the Hamilton depression rating scale, which systematically rates suicidality. Emergence of substantial suicidal ideation was defined as a change in the rating of this item from 0 or 1 at baseline to 3 or 4 during double blind treatment; worsening was defined as any increase from baseline; improvement was defined as a decrease from baseline at the last visit during the treatment. RESULTS: Suicidal acts did not differ significantly in comparisons of fluoxetine with placebo (0.2% v 0.2%, p = 0.494, Mantel-Haenszel adjusted incidence difference) and with tricyclic antidepressants (0.7% v 0.4%, p = 0.419). The pooled incidence of suicidal acts was 0.3% for fluoxetine, 0.2% for placebo, and 0.4% for tricyclic antidepressants, and fluoxetine did not differ significantly from either placebo (p = 0.533, Pearson's chi 2) or tricyclic antidepressants (p = 0.789). Suicidal ideation emerged marginally significantly less often with fluoxetine than with placebo (0.9% v 2.6%, p = 0.094) and numerically less often than with tricyclic antidepressants (1.7% v 3.6%, p = 0.102). The pooled incidence of emergence of substantial suicidal ideation was 1.2% for fluoxetine, 2.6% for placebo, and 3.6% for tricyclic antidepressants. The incidence was significantly lower with fluoxetine than with placebo (p = 0.042) and tricyclic antidepressants (p = 0.001). Any degree of worsening of suicidal ideation was similar with fluoxetine and placebo (15.4% v 17.9%, p = 0.196) and with fluoxetine and tricyclic antidepressants (15.6% v 16.3%, p = 0.793). The pooled incidence of worsening of suicidal ideation was 15.3% for fluoxetine, 17.9% for placebo, and 16.3% for tricyclic antidepressants. The incidence did not differ significantly with fluoxetine and placebo (p = 0.141) or tricyclic antidepressants (p = 0.542). Suicidal ideation improved significantly more with fluoxetine than with placebo (72.0% v 54.8%, p less than 0.001) and was similar to the improvement with tricyclic antidepressants (72.5% v 69.8%, p = 0.294). The pooled incidence of improvement of suicidal ideation was 72.2% for fluoxetine, 54.8% for placebo, and 69.8% for tricyclic antidepressants. The incidence with fluoxetine was significantly greater than with placebo (p less than 0.001) and did not differ from that with tricyclic antidepressants (p = 0.296). CONCLUSIONS: Data from these trials do not show that fluoxetine is associated with an increased risk of suicidal acts or emergence of substantial suicidal thoughts among depressed patients.

Fluoxetine in tricyclic refractory major depressive disorder.

Data regarding open-label treatment with fluoxetine following failure to respond to tricyclic antidepressants (TCAs) or intolerance of TCA side effects, suggest a response rate between 51.4% and 62.1%, depending on the definition of TCA refractoriness employed. Double-blind study of this issue would extend these findings. Fluoxetine is well tolerated in patients unable to tolerate TCAs. Within this population, more than 80% of patients unable to tolerate TCAs found fluoxetine acceptable. Fluoxetine, as an alternative to polypharmaceutical augmentation, may represent a logical choice as the next step in therapy for a patient who has initially been treated with a TCA and has proven refractory or intolerant.

Fetal feminization and female gender identity in the testicular feminizing syndrome of androgen insensitivity.

Interview data on aspects of sex and eroticism from a sample of 10 chromosomally male (XY) patients with the complete testicular feminization (androgen insensitivity) syndrome and from a sample of 23 patients with the late-treated adrenogenital syndrome showed marked differences. Homosexual experiences and/or dreams were lacking in the androgen-insensitive group as compared with the adrenogenital group (p[Symbol: see text]0.01).The androgen-insensitive group reported lower frequency of sexual arousal from visual stimuli than did the adrenogenital group (p[Symbol: see text]0.05).Findings on different aspects of sexual behavior suggest a tendency for the androgen-insensitive patients as a group to have a lower sex drive, to be less keenly aware of their sex drive, to be less assertive in heterosexual relations, and to be less versatile in coitus than the adrenogenital patients. No case of exclusive lesbianism, transsexualism, or transvestism was reported from either patient group. Although the two groups differed in sexual and erotic behavior, both were within the range of what in our culture is accepted as feminine. Nonetheless, the androgen-insensitive patients conformed more closely to the conventional feminine stereotype. Regarding explicit satisfaction with female sex role and with cosmetic and clothing interests, the androgen-insensitive group was characteristically feminine. Findings on the Draw-a-Person Test and the Guilford-Zimmerman Temperament Survey are compatible with the results of normal females, but are in sharp contrast with those of normal males. Interview and psychometric data thus concur in showing the androgen-insensitive patients to be unmistakably feminine in behavior and outlook. Their femininity is best conceived of as a product of hormonal nonandrogenization, prenatally and later, in combination with the social experiences of rearing and development, after initial assignment as a girl.