Possible involvement of free radicals in lipopolysaccharide-induced labyrinthitis in the guinea pig: a morphological and functional investigation

BACKGROUND: There are few published placebo-controlled clinical trials demonstrating the efficacy of the newer antidepressants in markedly or severely depressed hospitalized patients. This study demonstrates the efficacy of nefazodone compared with placebo in the treatment of patients hospitalized for major depression. METHOD: Nefazodone and placebo treatment were compared in a 6-week trial of 120 patients hospitalized for DSM-III-R diagnosed major depression (without psychosis) at 2 study centers. Efficacy was evaluated using standard psychiatric rating scales, and patients were monitored for safety. RESULTS: Nefazodone treatment resulted in a significant reduction (p < .01) of the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score compared with placebo from the end of the first treatment week through the end of the study (-12.2 nefazodone vs. -7.7 placebo). At the end of the trial, significantly more nefazodone-treated patients (50%) than placebo-treated patients (29%) had responded, as indicated by their Clinical Global Impressions-Improvement score (p = .021) or by a > or = 50% reduction in their HAM-D-17 scores (p = .017). Significantly more patients treated with nefazodone (36%) than placebo-treated patients (14%) had a HAM-D-17 score < or = 10 at the end of treatment (p = .004). Significant treatment differences (p < .01) in favor of nefazodone were also seen in the Montgomery-Asberg Depression Rating Scale; the HAM-D retardation, anxiety, and sleep disturbance factors; and HAM-D item 1 (depressed mood). Patients with dysthymia in addition to major depression also showed significant improvement (p < .05) when treated with nefazodone, with significant differences in response rates seen as early as week 2 and through the end of the trial. The mean nefazodone dose was 491 mg/day at the end of week 2 and 503 mg/day at the end of treatment. Nefazodone was well tolerated, and the number of patients discontinuing owing to adverse events was small, with no significant safety issues noted in either treatment group. Fewer nefazodone-treated than placebo-treated patients discontinued owing to lack of efficacy. CONCLUSION: Nefazodone was superior to placebo in the treatment of marked to severe major depression in patients requiring hospitalization. The clinical benefit of nefazodone was evident as early as the first week of treatment as judged by several measures of efficacy, with significant differences from placebo sustained throughout the trial.     

Characteristics of fluoxetine versus placebo responders in a randomized trial of geriatric depression

Results from placebo-controlled trials of antidepressants can be used to identify patients most likely to benefit from medication. Using data from a randomized clinical trial of fluoxetine versus placebo for 671 elderly outpatients with major depression, we evaluated characteristics of those who improved with and without active medication. We found that the choice of outcome measure made a difference when evaluating the effectiveness of fluoxetine relative to placebo and determining the accuracy of predictive variables in both treatment groups. Generally, less severe depression predicted favorable response (greater than 50% improvement on the 21-item Hamilton Rating Scale for Depression [HAM-D-21], less than 3 on the Clinical Global Impressions [CGI] and Patient Global Impressions [PGI] improvement scales) and remission (less than 9 on 6-week HAM-D-21) with both fluoxetine and placebo. Less anxiety/somatization was associated with favorable fluoxetine response, and lower levels of cognitive and sleep disturbance were associated with remission in the placebo group. By contrast, higher levels of psychomotor retardation in the placebo group were associated with clinician and patient ratings of much or very much improved. The similarities among responders in both groups may indicate that some in the fluoxetine group would have improved with placebo.     

A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression

BACKGROUND: Depression is a major cause of morbidity and mortality in children and adolescents. To date, randomized, controlled, double-blind trials of antidepressants (largely tricyclic agents) have yet to reveal that any antidepressant is more effective than placebo. This article is of a randomized, double-blind, placebo-controlled trial of fluoxetine in children and adolescents with depression. METHODS: Ninety-six child and adolescent outpatients (aged 7-17 years) with nonpsychotic major depressive disorder were randomized (stratified for age and sex) to 20 mg of fluoxetine or placebo and seen weekly for 8 consecutive weeks. Randomization was preceded by 3 evaluation visits that included structured diagnostic interviews during 2 weeks, followed 1 week later by a 1-week, single-blind placebo run-in. Primary outcome measurements were the global improvement of the Clinical Global Impressions scale and the Children's Depression Rating Scale--Revised, a measure of the severity depressive symptoms. RESULTS: Of the 96 patients, 48 were randomized to fluoxetine treatment and 48 to placebo. Using the intent to treat sample, 27 (56%) of those receiving fluoxetine and 16 (33%) receiving placebo were rated "much" or "very much" improved on the Clinical Global Impressions scale at study exit (chi 2 = 5.1, df = 1, P = .02). Significant differences were also noted in weekly ratings of the Children's Depression Rating Scale--Revised after 5 weeks of treatment (using last observation carried forward). Equivalent response rates were found for patients aged 12 years and younger (n = 48) and those aged 13 years and older (n = 48). However, complete symptom remission (Children's Depression Rating Scale--Revised < or = 28) occurred in only 31% of the fluoxetine-treated patients and 23% of the placebo patients. CONCLUSION: Fluoxetine was superior to placebo in the acute phase treatment of major depressive disorder in child and adolescent outpatients with severe, persistent depression. Complete remission of symptoms was rare.     

Hypothyroidism and hyperthyroidism in major depression revisited

BACKGROUND: The aim of our study was to evaluate the prevalence of thyroid abnormalities among depressed outpatients and to examine the response to treatment of those subjects with relatively low or high thyroid hormone levels. METHOD: Outpatients (N = 200) 18 to 65 years of age who met DSM-III-R criteria for major depression were screened for the presence of thyroid abnormalities using a number of thyroid indices. Of these patients, 166 were then treated openly with the antidepressant fluoxetine for 12 weeks. We assessed whether patients with relatively low or high thyroid hormone levels had a different response to treatment compared with other patients. The 17-item Hamilton Rating Scale for Depression (HAM-D-17) was administered during the study to assess changes in depressive symptoms. Thyroid function was assessed by measuring T3, T4, free T4 index (FT4I), T3 uptake (T3U), and serum thyroid-stimulating hormone (TSH) levels. RESULTS: No clinical cases of hyperthyroidism or hypothyroidism were detected. Of the patients examined, 5 (2.6%) had slightly elevated TSH levels (range, 4.7-8.2); none of these had T4 or FT4I levels below the normal range. Subnormal levels of T4 or FT4I were found in 1 subject (0.5%). T3 and T3U levels were below the normal range in a larger number of patients (7.6% and 15.0% respectively), but only 1 of these patients had elevated TSH levels. None of the patients had levels of TSH below the normal range, and only 3 subjects (1.5%) had T4 levels above the normal range. No relationship was found between response rate (assessed as either change in HAM-D-17 score or as remission of depressive symptoms with a HAM-D-17 score < or = 7 for 3 consecutive weeks) and each of the thyroid tests, even after adjusting for baseline severity of depression. CONCLUSION: In depressed outpatients, it appears that hypothyroidism and hyperthyroidism are extremely uncommon and that the presence of subtle thyroid function abnormalities does not have an impact on treatment outcome.     

The relationship between fluoxetine use and suicidal behavior in 654 subjects with anxiety disorders

BACKGROUND: In the past few years, there has been controversy over the relationship between suicidal behavior and fluoxetine use. This report examines the relationship between fluoxetine use and suicidal behavior in the Harvard/Brown Anxiety Disorders Research Program (HARP). METHOD: HARP is a naturalistic, prospective, longitudinal anxiety disorders study. Probabilities of suicidal behavior for 654 subjects were examined using life table analysis for the study group as a whole and stratified by depression status at intake. RESULTS: Subjects not using fluoxetine during follow-up had almost twice the probability of making a suicide attempt or gesture during the follow-up than subjects who were using fluoxetine, although this difference was not statistically significant. Subjects having episodes of major depressive disorder (MDD) at intake were more likely than those not having an episode to receive fluoxetine during follow-up (74/166 [45%] vs. 118/488 [24%], chi squared= 24.85, df= 1, p < .0001). Among those subjects having episodes of MDD at intake, there was a statistically significantly lower probability of suicide attempts/gestures for those taking fluoxetine than for those not using fluoxetine during follow-up (log-rank chi squared= 5.10, df= 1, p= .02). CONCLUSION: We found no evidence that fluoxetine use is associated with increased risk of suicide attempts or gestures. However, we did find that subjects with more suicide risk factors at intake were more likely to use fluoxetine than those without these risk factors.     

A multicenter evaluation of the efficacy and safety of 150 and 300 mg/d sustained-release bupropion tablets versus placebo in depressed outpatients

This multicenter, randomized, double-masked, placebo-controlled, parallel-group study compared the antidepressant efficacy and safety of bupropion sustained-release (SR) tablets (150 mg QD or 150 mg BID) with placebo in outpatients with moderate-to-severe depression. The study consisted of a 1-week placebo phase followed by 8 weeks of active treatment with bupropion SR 150 mg/d (150 mg QD, n = 121) or 300 mg/d (150 mg BID, n = 120) or placebo (n = 121). Efficacy was measured by changes in scores on the 17-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions for Severity of Illness (CGI-S) and Clinical Global Impressions for Improvement of Illness (CGI-I) scales. Safety was monitored by regular assessment of vital signs and adverse events as well as by pretreatment and posttreatment physical and clinical laboratory examinations. By day 56, both bupropion SR treatments were more effective in relieving the symptoms of depression than was placebo. Compared with those receiving placebo, patients in the bupropion SR 150- and 300-mg/d groups had significantly reduced symptoms by treatment day 56, as measured on the 17-item HAM-D, CGI-S, and CGI-I scales (P < 0.05). Bupropion SR was well tolerated, with no serious adverse events reported by bupropion-treated patients; 95% of all reported adverse events were of mild or moderate intensity. No clinically significant changes in vital signs, laboratory test results, or physical findings were observed. A greater mean weight loss was observed at the end of treatment in both the bupropion SR 150-mg (0.5 kg) and bupropion SR 300-mg (1.0 kg) group compared with placebo (0.2 kg). We found that bupropion SR 150 mg administered either once or twice daily was more effective than placebo in treating depression and that once-daily dosing appears to be at least as effective as twice-daily dosing. Should this prove true, depressed patients may be able to benefit from the convenience and improved tolerability associated with once-daily dosing.     

The relationship between adult attachment style and therapeutic alliance in individual psychotherapy: A meta-analytic review.

The present study examined the relationship between adult attachment style and therapeutic alliance in individual psychotherapy. Search procedures yielded 17 independent samples (total N = 886, average n = 52, standard deviation = 24) for inclusion in the meta-analysis. Results indicated that greater attachment security was associated with stronger therapeutic alliances, whereas greater attachment insecurity was associated with weaker therapeutic alliances, with an overall weighted effect size of r = .17, p .10) with the exception of the source of alliance ratings; results indicated that patient-rated alliance demonstrated a significantly larger relationship with attachment compared with therapist-rated alliance (Qbetween = 3.95, df = 1, p = .047). Implications for clinical practice and future research are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Sociocultural influences and care of dying children in Japan and the United States

Depression is a common cause of sexual dysfunction, but also antidepressant medication is often associated with sexual side effects. This article includes two related studies. The first double-blind, placebo-controlled study was conducted in men with lifelong rapid ejaculation and aimed to assess putative differences between the major selective serotonin reuptake inhibitors (SSRIs) (fluoxetine, fluvoxamine, paroxetine, and sertraline) with regard to their ejaculation-delaying effect. Sixty men with an intravaginal ejaculation latency time (IELT) of 1 minute or less were randomly assigned to receive fluoxetine 20 mg/day, fluvoxamine 100 mg/day, paroxetine 20 mg/day, sertraline 50 mg/day, or placebo for 6 weeks. During the 1-month baseline and 6-week treatment periods, the men measured their IELT at home using a stopwatch. The trial was completed by 51 men. During the 6-week treatment period, the geometric mean IELT in the placebo group was constant at approximately 20 seconds. Analysis of variance revealed a between-groups difference in the evolution of IELT delay (p = 0.0004); in the paroxetine, fluoxetine, and sertraline groups there was a gradual increase to about 110 seconds, whereas in the fluvoxamine group, IELT was increased to only approximately 40 seconds. The paroxetine, fluoxetine, and sertraline groups differed significantly (p < 0.001, p < 0.001, p = 0.017, respectively) from placebo but the fluvoxamine group did not (p = 0.38). Compared with baseline, paroxetine exerted the strongest delay in ejaculation, followed by fluoxetine and sertraline. There was no clinically relevant delay in ejaculation with fluvoxamine. In men with lifelong rapid ejaculation, paroxetine delayed ejaculation most strongly, whereas fluvoxamine delayed ejaculation the least. The second double-blind, placebo-controlled study was carried out in men with lifelong rapid ejaculation (IELT < or = 1 minute) and in men with lifelong less-rapid ejaculation (IELT > 1 minute) to investigate whether data about SSRI-induced delayed ejaculation in men with rapid ejaculation may be extrapolated to men with less-rapid ejaculation. After measurement of IELT at home (using a stopwatch) during a 1-month baseline assessment, 32 men with an IELT of 1 minute or less (group 1) or more than 1 minute (group 2) were randomly assigned to receive paroxetine 20 mg/day or placebo for 6 weeks in a double-blind manner. Patients continued to measure their IELTs at home during the 6 weeks of the study. At baseline, 24 patients consistently had IELTs of one minute or less (group 1), and eight patients had IELTs of more than 1 minute (group 2). The geometric mean IELT was 14 seconds in group 1 and 83 seconds in group 2. Twelve patients in group 1 and five in group 2 were randomized to the paroxetine 20 mg/day. The percentage increase in the geometric mean IELT compared with baseline in patients treated with paroxetine was 420% (95% confidence interval [CI], 216-758%) in group 1 and 480% (95% CI, 177-1,118%) in group 2 (p = 0.81). After 6 weeks of treatment with paroxetine, the geometric mean IELT was 92 seconds in group 1 and 602 seconds in group 2 (p < 0.001). Therefore, the paroxetine-induced percentage increase in IELT seems to be independent of the baseline IELT. This suggests that ejaculation-delaying side effects of some SSRIs investigated in men with lifelong rapid ejaculation may be generalized to men with less-rapid ejaculation.     

A randomized controlled trial of fluoxetine and cognitive behavioral therapy for bulimia nervosa: short-term outcome

This study compared and combined fluoxetine and individual cognitive behavioral therapy in the treatment of bulimia nervosa. Participants were 76 women who sought treatment at the Eating Disorders Program of the Toronto Hospital and who met DSM-III-R criteria for bulimia nervosa. Subjects were randomly assigned to receive fluoxetine alone, cognitive behavior therapy alone, or the two in combination and were treated over 16 weeks. Short-term outcome revealed that all three treatment conditions were associated with clinical improvement across a wide range of parameters. The combination of pharmacotherapy and psychotherapy was superior to pharmacotherapy alone on specific parameters and there was no statistically significant advantage to the combination over psychotherapy alone. Limitations to the study include the absence of a placebo pill group and a waiting list control group as well as a substantial dropout rate across all three treatment conditions.     

Efficacy and safety of tramadol HCl in breakthrough musculoskeletal pain attributed to osteoarthritis

OBJECTIVE: To evaluate the efficacy of tramadol as adjunctive therapy in patients with musculoskeletal pain attributed to osteoarthritis (OA) who experienced breakthrough pain while taking a nonsteroidal antiinflammatory drug (NSAID). METHODS: This single center, parallel, placebo controlled, 2 phase study was conducted in adults who experienced breakthrough OA pain while undergoing stable NSAID therapy. In a 24 h open label phase, patients took 100 mg of tramadol followed by 50 mg every 6 h (total 250 mg) in addition to their daily NSAID regimen. Supplemental analgesics were prohibited. Patients who met entry criteria and were willing to continue therapy were randomized to a 13 day double blind phase of adjunctive therapy with tramadol (50-100 mg every 4-6 h as needed for pain) or placebo; NSAID therapy was continued. The primary efficacy endpoint was the time to exit from the study because of therapeutic failure (i.e., insufficient pain relief or an inability to perform activities of daily living). RESULTS: The time to exit from the study because of insufficient pain relief tended to be longer in the tramadol group (250 mg/day) compared with the placebo group (p = 0.066). At the end of the double blind phase, pain at rest was significantly less severe in tramadol treated patients (p = 0.046). In addition, severity of pain on motion tended to be less severe in tramadol treated patients (p = 0.059). General severity of current pain and ability to perform activities of daily living were not significantly different with tramadol or placebo. Patients' overall assessment of therapy (p = 0.022) and investigator's rating of global improvement (p = 0.004) were significantly better with tramadol than with placebo. CONCLUSION: Tramadol may have a role as adjunctive treatment for breakthrough pain in patients receiving NSAID therapy for musculoskeletal pain attributed to OA.     

Effects of fluoxetine versus bright light in the treatment of seasonal affective disorder

BACKGROUND: Disturbances of serotonergic neurotransmission appear to be particularly important for the pathophysiology of winter depression. This study investigated whether fluoxetine has antidepressant effects comparable to bright light in the treatment of seasonal affective disorder (winter type). METHOD: A randomized, parallel design was used with rater and patients blind to treatment conditions. One week of placebo (phase I) was followed by 5 weeks of treatment (phase II) with fluoxetine (20 mg per day) and a placebo light condition versus bright light (3000 lux, 2 h per day) and a placebo drug. There were 40 patients (20 in each treatment condition) suffering from seasonal affective disorder (SAD) according to DSM-III-R who had a total score on the Hamilton Depression Scale of at least 16. RESULTS: Forty patients entered phase II and 35 completed it (one drop-out in the fluoxetine group and four in the bright light group). Fourteen (70%) of the patients treated with bright light and 13 (65%) of those treated with fluoxetine were responders (NS). The remission rate in the bright light group tended to be superior (bright light 50%, fluoxetine 25%; P = 0.10). Light therapy improved HDRS scores significantly faster, while fluoxetine had a faster effect on atypical symptoms. Light treatment in the morning produced a significantly faster onset of improvement, but at the end of treatment the time of light application seemed not to be crucial. CONCLUSION: Both treatments produced a good antidepressant effect and were well tolerated. An apparently better response to bright light requires confirmation in a larger sample.     

Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). Ramipril Efficacy in Nephropathy

BACKGROUND: The Ramipril Efficacy In Nephropathy (REIN) study found that in patients with chronic nephropathies and proteinuria of 3 g or more per 24 h, ramipril safely reduced the rate of decline of the glomerular filtration rate (GFR) and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF), as compared with placebo plus conventional antihypertensive drugs at the same level of blood pressure control. At the end of the core study patients continued on or shifted to ramipril and were formally enrolled into the REIN follow-up study. METHODS: 97 patients entered the follow-up study. Patients originally randomised to ramipril continued with the same daily dose (n=51), whereas those originally on placebo plus conventional antihypertensive drugs switched to ramipril after the first visit of the follow-up study (n=46). Ramipril (1.25 to 5.00 mg/day) and conventional antihypertensive therapy were targeted at achieving diastolic blood pressure under 90 mm Hg. The main efficacy variables were GFR decline and ESRF (need for dialysis). Analysis was by intention to treat. FINDINGS: During the follow-up study the mean rate of GFR decline per month decreased from 0.44 (SD 0.54) mL/min per 1.73 m2 in the core study to 0.10 (0.50) mL/min per 1.73 m2 in patients originally randomised to ramipril (p=0.017), and from 0.81 (1.12) to 0.14 (0.87) mL/min per 1.73 m2 in those originally randomised to placebo plus conventional antihypertensive therapy (p=0.017). At the final visit, mean absolute GFR values were 12 mL/min per 1.73 m2 higher (33% better) in patients randomised to ramipril than in those assigned placebo (n=26 and 17, respectively: 35.5 [19.0] vs 23.8 [9.4] mL/min per 1.73 m2, p=0.01). 19 of the patients originally on ramipril versus 35 switched from placebo to ramipril progressed to ESRF (p=0.027) during the whole observation period; of these, six (8%) versus 14 (16%) reached that endpoint during the follow-up study; and the risk ratios were 1.86 (95% CI 1.07-3.26) over the whole observation period and 2.95 (1.13-7.68) during follow-up. Beyond follow-up at month 36, the incidence of ESRF was zero in patients originally randomised to ramipril but 30% in patients on placebo plus conventional antihypertensive therapy. INTERPRETATION: In patients with chronic nephropathy and high risk of rapid progression to ESRF, ramipril reversed the tendency of GFR to decline with time. Moreover, a treatment period of sufficient duration (> or =36 months) eliminated the need for dialysis. Even patients previously treated with antihypertensive drugs other than angiotensin-converting-enzyme inhibitors benefited from shifting to ramipril.     

Estimated number of patients with chronic renal failure but not with end-stage renal disease in Japan: comparisons between two estimation methods

BACKGROUND: A significant number of American women of childbearing age are troubled by premenstrual symptoms, but the underlying cause is not understood, resulting in inadequate therapy. OBJECTIVES: To use basal levels of cortisol to differentiate women with low symptom (LS) patterns of turmoil-type premenstrual symptoms from women with premenstrual symptom (PMS) patterns and from women with premenstrual magnification (PMM) patterns of turmoil-type premenstrual symptoms. METHOD: Symptom and cortisol patterns of women were monitored for three consecutive menstrual cycles. Three distinct groups of women were identified based on symptom patterns and types. RESULTS: Significant differences in symptom severity among groups were observed during the follicular (F = 203; df= 2, 24; p < .0001) and luteal phases (F= 51.3; df= 2, 24; p< .0001) of the cycle. There were no statistically significant differences in cortisol among groups for the follicular phase, but there were during the luteal phase (F= 4.0; df= 2, 24; p= .03). CONCLUSIONS: Altered regulation of the stress axis may be involved in mediating turmoil-type PMS.     

Fluoxetine, smoking, and history of major depression: A randomized controlled trial.

The study was a randomized placebo-controlled trial testing whether fluoxetine selectively enhances cessation for smokers with a history of depression. Euthymic smokers with (H+, n = 109) or without (H-, n = 138) a history of major depression received 60 mg fluoxetine or placebo plus group behavioral quit-smoking treatment for 12 weeks. Fluoxetine initially enhanced cessation for H+ smokers (p = .02) but subsequently impaired cessation regardless of depressive history. Six months after quit date, fluoxetine-treated participants were 3.3 times more likely to be smoking (p = .02). Further research is warranted to determine why high-dose fluoxetine produces continuing effects that oppose tobacco abstinence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Glimepiride, a new once-daily sulfonylurea. A double-blind placebo-controlled study of NIDDM patients. Glimepiride Study Group

OBJECTIVE: To compare the efficacy and safety of two daily doses of the new sulfonylurea, glimepiride (Amaryl), each as a once-daily dose or in two divided doses, in patients with NIDDM. RESEARCH DESIGN AND METHODS: Of the previously treated NIDDM patients, 416 entered this multicenter randomized double-blind placebo-controlled fixed-dose study. After a 3-week placebo washout, patients received a 14-week course of placebo or glimepiride 8 mg q.d., 4 mg b.i.d., 16 mg q.d., or 8 mg b.i.d. RESULTS: Fasting plasma glucose (FPG) and HbA1c values were similar at baseline in all treatment groups. The placebo group's FPG value increased from 13.0 mmol/l at baseline to 14.5 mmol/l at the last evaluation endpoint (P < or = 0.001). In contrast, FPG values in the four glimepiride groups decreased from a range of 12.4-12.9 mmol/l at baseline to a range of 8.6-9.8 mmol/l at endpoint (P < or = 0.001, within-group change from baseline; P < or = 0.001, between-group change [vs. placebo] from baseline). Two-hour postprandial plasma glucose (PPG) findings were consistent with FPG findings. In the placebo group, the HbA1c value increased from 7.7% at baseline to 9.7% at endpoint (P < or = 0.001), whereas HbA1c values for the glimepiride groups were 7.9-8.1% at baseline and 7.4-7.6% at endpoint (P < or = 0.001, within-group change from baseline; P < or = 0.001, between-group change from baseline). There were no meaningful differences in glycemic variables between daily doses of 8 and 16 mg or between once- and twice-daily dosing. Adverse events and laboratory data demonstrate that glimepiride has a favorable safety profile. CONCLUSIONS: Glimepiride is an effective and well-tolerated oral glucose-lowering agent. The results of this study demonstrate maximum effectiveness can be achieved with 8 mg q.d. of glimepiride in NIDDM subjects.     

Bacteriological activity of trovafloxacin, a new quinolone, against respiratory tract pathogens

BACKGROUND: Corpus callosum (CC) morphology has recently been investigated in schizophrenia using refined imaging and analytic techniques; however, methodological problems and small sample sizes have led to inconsistent findings. METHODS: This study used a large sample of male schizophrenics (n = 79) and male controls (n = 65) to investigate size and shape of the CC on midsagittal magnetic resonance images. Size was determined by tracing the area of the CC, and shape was determined using a landmark-based analysis. In addition, the relationship between CC morphology and phenomenologic variables such as age of onset, length of illness, exposure to medications, and symptom severity was explored. RESULTS: After controlling for age, height, and parental socioeconomic status, there was a main effect of diagnosis on CC size (F = 5.05, df = 1,139, p < .03), with patients' CCs being significantly smaller. No difference was found between patients and controls in CC shape (F = 1.07, df = 18,125, p > .38) or orientation (F = 0.79, df = 18,125, p > .70), using a landmark-based technique. Finally, there was a significant inverse correlation between size of CC and severity of negative symptoms. CONCLUSIONS: These findings support previous studies that have found a decrease in size of the CC in patients with schizophrenia. Moreover, the decrement in volume is generalized, not regional, and is related to the severity of negative symptoms.     

Effectiveness and cost of selective decontamination of the digestive tract in critically ill intubated patients. A randomized, double-blind, placebo-controlled, multicenter trial

We evaluated the effect of selective decontamination of the digestive tract (SDD) on the incidence of ventilator-associated pneumonia (VAP) and its associated morbidity and cost in a mixed population of intubated patients. Two hundred seventy-one consecutive patients admitted to the intensive care units (ICUs) of five teaching hospitals and who had an expected need for intubation exceeding 48 h were enrolled and received topical antibiotics or placebo. Uninfected patients additionally received ceftriaxone or placebo for 3 d. VAP occurred in 11.4% of SDD-treated and 29.3% of control-group patients (p < 0.001; 95% confidence interval [CI]: 7.8 to 27.9). The incidence of nonrespiratory infections in the two groups was 19.1% and 30.7%, respectively (p = 0.04; 95% CI: 0.7 to 22.7). Among survivors, the median length of ICU stay was 11 d (interquartile range: 7 to 21.5 d) for the SDD-treated group and 16. 5 d (10 to 30 d) for the control group (p = 0.006). Mean cost per survivor was $11,926 for treated and $16,296 for control-group patients. Mortality was 38.9% and 47.1%, respectively (p = 0.57). In decontaminated patients, the prevalence of gram-negative bacilli fell within 7 d from 47.4% to 13.0% (p < 0.001), whereas colonization with resistant gram-positive strains was higher (p < 0. 05) than in the placebo group. In a mixed population of intubated patients, SDD was associated with a significant reduction of morbidity at a reduced cost. Our findings support the use of SDD in this high-risk group.     

Differential effects of migraine drugs on cerebral blood flow autoregulation

OBJECTIVE: To compare the efficacy and tolerability of mirtazapine and fluoxetine in depressed inpatients and outpatients. METHOD: Patients with a major depressive episode (DSM-III-R), a baseline score of > or=21 on the 17-item Hamilton Rating Scale for Depression (HAM-D), and > or=2 on HAM-D Item 1 (depressed mood) were randomly assigned to a 6-week treatment with either mirtazapine (N=66, 15-60 mg/day) or fluoxetine (N=67, 20-40 mg/day). The upper limit of the mirtazapine dose range was above the dose range approved in the United States (15-45 mg/day). Efficacy was evaluated by the HAM-D, Clinical Global Impressions, the Visual Analogue Mood Rating Scale (VAMRS), and the Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ). The efficacy analyses were performed on the intent-to-treat group using the last-observation-carried-forward method. RESULTS: Mean total 17-item HAM-D scores at baseline were 26.0 for the mirtazapine- and 26.1 for the fluoxetine-treated group. The decrease from baseline on the HAM-D was larger in the mirtazapine than in the fluoxetine group throughout the treatment period, reaching statistical significance at days 21 and 28. At assessments from day 21 and onward, the absolute difference between the 2 study groups favoring mirtazapine ranged from 3.7 to 4.2 points, the magnitude of difference usually seen between an efficacious antidepressant drug and placebo. Mean dosages at weeks 1-4 were 36.5 mg/day for mirtazapine and 19.6 mg/day for fluoxetine; the respective dosages at weeks 5-6 were 56.3 mg and 35.8 mg. Similar numbers of patients dropped out due to adverse events; tolerability profiles were comparable except for changes in body weight from baseline which were statistically significantly more pronounced in the mirtazapine group compared to the fluoxetine group. CONCLUSION: We found that mirtazapine was as well tolerated as fluoxetine and significantly more effective after 3 and 4 weeks of therapy.     

Fluoxetine in depressed alcoholics. A double-blind, placebo-controlled trial

BACKGROUND: The selective serotonergic medication fluoxetine has demonstrated efficacy in the treatment of major depression and has suggested efficacy in the treatment of alcoholism. However, no completed trials with any selective serotonergic medication have been reported in patients who display both major depression and alcoholism, despite previous observations that both depression and alcoholism are associated with low serotonergic functioning. METHODS: Fifty-one patients diagnosed as having comorbid major depressive disorder and alcohol dependence were randomized to receive fluoxetine (n = 25) or placebo (n = 26) in a 12-week, double-blind, parallel-group trial. Weekly ratings of depression and alcohol consumption were obtained throughout the 12-week course of the study. RESULTS: The improvement in depressive symptoms during the medication trial was significantly greater in the fluoxetine group than in the placebo group. Total alcohol consumption during the trial was significantly lower in the fluoxetine group than in the placebo group. CONCLUSIONS: Fluoxetine is effective in reducing the depressive symptoms and the alcohol consumption of patients with comorbid major depressive disorder and alcohol dependence. It is unknown whether these results generalize to the treatment of less depressed and less suicidal alcoholics.