No gender differences in placebo responses of patients with major depressive disorder.

BACKGROUND: This study was designed to compare placebo responses in men and women. METHODS: Data for 501 women and 375 men with major depressive disorder treated with placebo from seven investigational randomized double-blind trials comparing fluoxetine with placebo were analyzed. Changes in major depressive disorder symptoms with placebo administration were measured as changes in total Hamilton Depression Rating Scale scores and adverse (nocebo) effects were measured by comparing treatment-emergent signs and symptoms. RESULTS: Both women and men with major depressive disorder showed significant symptomatic improvement following placebo administration, similar in magnitude and time course of response. Women on placebo reported slightly more nocebo effects than men. CONCLUSIONS: The finding that women and men with major depressive disorder demonstrated a similar therapeutic outcome after placebo administration suggests that gender is not a predictor of placebo response.

Adverse events and treatment discontinuations in clinical trials of fluoxetine in major depressive disorder: an updated meta-analysis.

BACKGROUND: A 1993 meta-analysis of US Investigational New Drug clinical trials of fluoxetine reinforced this agent's more favorable adverse-event profile compared with tricyclic antidepressants (TCAs). OBJECTIVES: The present meta-analysis sought to provide a reanalysis of updated adverse-event and discontinuation data for fluoxetine 20 to 80 mg/d compared with TCAs and placebo in the treatment of major depressive disorder (MDD) in adults. A subanalysis to assess the safety profile of the most commonly used effective dose of fluoxetine in MDD (20 mg) was also conducted. METHODS: Data were obtained from 25 double-blind clinical trials involving 4016 patients with MDD randomized to treatment with fluoxetine 20 to 80 mg/d, TCAs, or placebo. The subanalysis included data from 6 trials involving 1258 patients treated with fixed 20-mg doses of fluoxetine or placebo. Spontaneously reported treatment-emergent adverse events, reasons for discontinuation, and events leading to discontinuation were compared between groups. RESULTS: The age of the 4016 randomized patients ranged from 12 to 90 years, with a mean age of 46 years. Most patients were white (92%), and 62% were female. The age of the 1258 patients in the 20-mg fixed-dose population ranged from 18 to 90 years, with a mean age of 54 years; as in the total population, most of these patients were white (92%), and 57% were female. The adverse-event profiles of fluoxetine and TCAs in these trials were consistent with the typical profiles of selective serotonin reuptake inhibitors and TCAs. At a dose of 20 mg/d, fluoxetine-treated patients had a discontinuation rate due to adverse events that was not statistically significantly different from that in placebo recipients. Discontinuation rates due to lack of efficacy were not significantly different between fluoxetine and TCAs. However, significantly more TCA-treated patients discontinued therapy because of adverse events and significantly fewer completed treatment compared with fluoxetine-treated patients (both, P < 0.001). The most common events (> or = 2%) leading to discontinuation were asthenia, dizziness, insomnia, nausea, nervousness, somnolence, and tremor in fluoxetine-treated patients and abnormal vision, agitation, constipation, dizziness, dry mouth, headache, nausea, nervousness, rash, somnolence, sweating, and tremor in TCA-treated patients. CONCLUSIONS: Data from this large series of clinical trials confirm that fluoxetine is well tolerated in the acute treatment of MDD in adults, especially at a dosage of 20 mg/d, and is better tolerated than the recommended doses of TCAs.

Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment.

BACKGROUND: The effects of extended selective serotonin reuptake inhibitor (SSRI) treatment on weight are not well characterized. Also unknown is whether different agents have differential effects. To examine these questions, we assessed weight changes in patients randomly assigned to long-term treatment with fluoxetine, sertraline, or paroxetine. METHOD: Patients (N = 284) with major depressive disorder (DSM-IV) were randomly assigned to double-blind treatment with fluoxetine (N = 92), sertraline, (N = 96), or paroxetine (N = 96) for a total of 26 to 32 weeks. The mean percent change in weight was compared for each group, as was the number of patients who had > or = 7% weight increase from baseline. RESULTS: Patients (fluoxetine, N = 44; sertraline, N = 48; paroxetine, N = 47) who completed the trial were included in these analyses. Paroxetine-treated patients experienced a significant weight increase, fluoxetine-treated patients had a modest but nonsignificant weight decrease, and patients treated with sertraline had a modest but nonsignificant weight increase. The number of patients whose weight increased > 7% from baseline was significantly greater for paroxetine-treated compared with either fluoxetine-treated or sertraline-treated patients. CONCLUSION: Risk of weight gain during extended SSRI treatment differs depending on which SSRI is used.

Efficacy, adverse events, and treatment discontinuations in fluoxetine clinical studies of major depression: a meta-analysis of the 20-mg/day dose.

BACKGROUND: The efficacy and safety of fluoxetine in adults with moderate-to-severe major depression are well established. However, most analyses combined dosages (20-80 mg/day) of the compound. We hypothesized that in patients taking 20 mg/day, efficacy would be maintained but the incidence of adverse events would be lower. We present a meta-analysis of efficacy and safety data for fluoxetine, 20 mg/day. METHOD: Data were from 3 double-blind studies (N = 417) that included patients with moderate-to-severe major depression (DSM-III or DSM-III-R criteria) who received placebo or fixed-dose 20-mg/day treatment with fluoxetine. Efficacy was assessed using the Hamilton Rating Scale for Depression (HAM-D; HAM-D-17 total score and anxiety/somatization, retardation, sleep disturbance, and cognitive disturbance factors) and response and remission rates. Safety assessments included treatment-emergent adverse events, reasons for discontinuation, and adverse events leading to discontinuation. Adverse events were evaluated to determine the emergence of activation and/or sedation. RESULTS: At 20 mg/day, fluoxetine-treated patients demonstrated significantly greater remission and response rates and mean changes on HAM-D-17 total score and anxiety/somatization, retardation, and cognitive disturbance factor scores than placebo-treated patients (p < .001). The incidence of specific adverse events leading to discontinuation and the frequency of study discontinuations due to adverse events were similar among fluoxetine-treated and placebo-treated patients (6.1% vs. 5.8%, p = .879). Several adverse events (insomnia, asthenia, somnolence, gastroenteritis, decreased libido, chills, and confusion) occurred significantly more frequently among fluoxetine-treated patients. A significant change in sedation, but not activation, occurred in patients in the fluoxetine 20-mg/day group compared with the placebo group. CONCLUSION: These data affirm that fluoxetine at 20 mg/day is efficacious, safe, and of similar activation potential when compared with placebo in patients with major depression.

Fluoxetine versus sertraline and paroxetine in major depression: tolerability and efficacy in anxious depression.

BACKGROUND: Major depression with high levels of anxiety (anxious depression) is a common subtype of depression associated with greater psychosocial impairment and poorer response to antidepressant treatment. It is unclear whether in this population there are differences in efficacy or tolerability across selective serotonin reuptake inhibitors. For this reason, using head-to-head acute treatment comparison, we compared efficacy and tolerability of fluoxetine, sertraline, and paroxetine among depressed patients with high levels of anxiety. METHODS: Patients (N = 108) with DSM-IV major depression and high levels of anxiety (a HAM-D-Anxiety/Somatization Factor score > or =7) were randomized to fluoxetine, sertraline, or paroxetine treatment in a double-blind fashion. Changes in overall depression and anxiety were assessed. RESULTS: Patients demonstrated similar baseline-to-endpoint improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores. Patients also demonstrated similar change-over-time improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores, except at week one where fluoxetine- and sertraline-treated patients had statistically significantly greater improvement than paroxetine-treated patients in the HAM-D-Anxiety/Somatization Factor score. There were no significant differences across treatments in percentages of patients with substantial emergence, any worsening, or improvement at endpoint in individual HAM-D Items 9 (agitation), 10 (psychic anxiety), and 11 (somatic anxiety). Overall, all treatments were well tolerated. CONCLUSION: These data showed no significant differences in efficacy and tolerability of fluoxetine, sertraline, and paroxetine in patients with high levels of baseline anxiety symptoms during the acute treatment of major depression. Each treatment was similarly effective in improving depression in this subtype of patients with anxious depression.

Persisting dysphagia after uvulopalatoplasty performed with steel scalpel.

OBJECTIVES/HYPOTHESIS: The aim of the present study was to determine the incidence of postoperative persisting dysphagia after uvulopalatoplasty performed with conventional steel scalpel (UPP) and to videoradiographically evaluate the oral and pharyngeal phases of swallowing in patients reporting persisting dysphagia. The hypothesis to be tested was that patients treated with UPP would demonstrate a lower incidence of persisting dysphagia than previously found after uvulopalatoplasty performed with laser technique (LUPP). STUDY DESIGN: Retrospective. METHODS: Sixty-eight of 76 consecutive patients treated with UPP answered a questionnaire concerning outcome and late complications after the operation. The patients who reported postoperative dysphagia were additionally interviewed at a minimum of 1 year postoperatively, and the oral and pharyngeal phases of swallowing were videoradiographically examined in those with persisting dysphagia. RESULTS: The incidence of persisting dysphagia after UPP was 29%. Videoradiographically 71% of the dysphagic patients showed a deviant pharyngeal swallowing pattern. CONCLUSION: The incidence of persisting dysphagia after UPP did not differ from that reported after laser uvulopalatoplasty. Dysphagia after UPP was mostly associated with videoradiographic signs of deviant pharyngeal swallowing function. Patients should be informed that there is a risk of developing dysphagia after uvulopalatoplasty.

[The Stockholm project: drunken drivers are given supervision instead of prison sentences]. / Stockholmsprojekt: rattfyllerister får vård i stället för fängelse.

There is a need to compile a national database on drunken driving, since experience from other countries is not necessarily applicable to Swedish conditions. Legislation, drinking habits, and public attitudes to drinking and driving differ markedly from country to country. Since 1990, the driving licence unit of the Magnus Huss Clinic has been collaborating with a probation office unit of the National Prisons and Probation Administration and the Offender Aid Society on a non-institutional drunk driving program of at least one year's duration, often linked with several years' follow-up. The article outlines experience and results derived from this program. Among other things, blood alcohol content is questioned as an indicator of the severity of a drinking problem.

The location of the upper oesophageal sphincter and its behaviour during bolus propagation--a simultaneous cineradiographic and manometric investigation.

By means of simultaneous cineradiographic and manometric examinations using closely positioned microtransducers the maximal pressure of the upper oesophageal sphincter was found at a level 20 mm below the plane of the vocal folds and 6 mm above the level of the cricoid arch. The sum of these 2 distances is in accordance with the distance between the vocal fold level and the lower border of the cricoid arch given in the literature. This implies that the high pressure zone of the upper oesophageal sphincter corresponds to the pars fundiformis of the cricopharyngeus muscle. The lower part of the inferior pharyngeal constrictor and the upper circular muscle fibres of the oesophagus contribute to the sphincter. When the bolus approached the sphincter, the pressure decreased and during bolus passage the pressure was below or well below half of the resting pressure. The pressure profile disclosed no signs of muscular dyscoordination or discontinuity of the upper oesophageal sphincter.

Mobility of the upper esophageal sphincter in relation to the cervical spine: a morphologic study.

If the posterior part of the upper esophageal sphincter (UES) were to lag behind due to the presence of dense tissue strands between the sphincter and the prevertebral ligament, as suggested in the literature, it would be impossible to use the larynx as a radiographic indicator of the location of the UES at intraluminal pressure measurements. The goal of this investigation was to study UES behavior during induced movements in autopsy specimens and to search for dense fibrous strands between the UES and the prevertebral fascia. Histologic studies of frozen sections and paraffin sections showed a loose fatty tissue in the prevertebral space. There were no dense connective tissue strands. Autopsy specimens were used in experiments mimicking the laryngeal/UES elevation during swallowing. The results of this study indicate that the larynx and the UES move as one entity. When one is attempting to register the UES movement during swallowing, the laryngeal skeleton can therefore serve as a radiographic indicator of the UES movements.

The hypopharyngeal diverticulum. A simultaneous cineradiographic and manometric examination.

The upper esophageal sphincter (UES) was studied in 10 patients with symptomatic hypopharyngeal diverticulum during rest and at deglutition using simultaneous cineradiography and manometry by means of triple pressure microtransducers. In all 10, cineradiographic examinations were performed. Occurrence of double pressure peaks was examined in 8/10. In 7/10, the length and resting pressure of the UES could be determined. In 5/10, the UES pressure could be recorded when the bolus was in the pharynx and in 6/10 when it reached the UES. The pressure below the neck of the diverticulum at the time when the bolus reached the diverticular entrance, was of the same magnitude or exceeded the resting pressure of the UES in 4 patients and was approximately 0 kPa in 2 patients. In 3 patients the UES contraction was elicited as soon as the bolus entered the pharynx and remained so till it had passed the UES. In 3 patients the contrast bolus was seen to pass simultaneously into the diverticulum and into the esophagus, even though the sphincter was contracted. It is plausible that the pharyngeal wall gives way when a bolus is forced against the contracted UES by the high peristaltic pressure forming a pulsion diverticulum as postulated already by Zenker in 1878. Double pressure peaks were registered in the UES at rest in 6 patients indicating a split between the muscle bundles in the sphincter.

The upper esophageal sphincter during normal deglutition. A simultaneous cineradiographic and manometric investigation.

The upper esophageal sphincter was studied during deglutition in 7 healthy subjects using simultaneous cineradiography and manometry. The pressure measuring device consisted of 3 sensors distally placed, and separated by 10 mm. They recorded pressure obliquely to the right at an angle of 15 to 45 degrees anteriorly. During the swallowing sequence a pressure sensor initially placed in the high pressure zone of the sphincter easily slid out of position due to asynchronous movements of the sphincter and the pressure measuring device. These movements can result in erroneous interpretation of pressure recordings. Continuous radiologic monitoring during the entire swallowing sequence thus seems to be mandatory. Immediately before the bolus entered the upper esophageal sphincter, the sphincter relaxed and low or even negative pressures were registered. When the bolus had passed onwards the sphincter contracted gradually, to resume its pre-swallow pressure.

Movement of the upper esophageal sphincter and a manometric device during deglutition. A cineradiographic investigation.

A cineradiographic examination of 9 healthy subjects showed asynchronous movement of a manometric device in relation to movement of the upper esophageal sphincter (UES) during deglutition. A single sensor placed within the UES high pressure zone at rest registered pressures existing outside this zone during the major part of deglutition. The manometric device must therefore comprise at least three sensors placed at different levels and about 10 mm apart if consistent pressure recording within this zone is to be achieved. In order to evaluate the pressure profile within the sphincter adequately, cineradiographic determination of the orientation of the measuring device is necessary. This was made possible by insertion of two mutually perpendicular radiopaque indicators into the catheter.