Weeks Of Maintenance Treatment Research Articles

Treatment of seborrhoeic dermatitis of the scalp with a topical solution of urea, lactic acid, and propylene glycol (K301): results of two double‐blind, randomised, placebo‐controlled studies

Alternative treatments for seborrhoeic dermatitis are needed because of the increasing risk of anti-fungal resistance to existing therapies. To investigate the efficacy, safety and tolerability of topical scalp treatment with K301 solution. Two multi-centre, randomised, double-blind studies were conducted. Study I: 4 weeks of once-daily treatment with either one form of K301 (a or b) or placebo, followed by 4 weeks of maintenance treatment three times-per-week. Study II: 4 weeks of K301 (a) or placebo once-daily. Study I: 98 patients enrolled (K301a + b, n = 51; placebo, n = 47) and 83 completed; 201 entered Study II (K301a, n = 136; placebo, n = 65) and 195 completed. Erythema and desquamation sum score at 4 weeks, mean (SD) values were 2.4 (2.0) for K301a + b and 3.2 (2.2) for placebo in Study I (P = 0.025) and 2.5 (1.9) for K301a and 3.2 (1.8) for placebo in Study II (not significant). In both studies, 4-week desquamation scores were significantly improved for K301 vs. placebo (P < 0.05). Both studies showed significant improvements in symptomatic investigator and patient assessments for K301 over placebo after 4 weeks (P < 0.05). Treatment-related adverse events were generally mild and included some smarting or burning upon application. The K301 was well tolerated and associated with clinically meaningful improvements in seborrhoeic dermatitis endpoints.

Big Costs for Little Gain in Ovarian Cancer

Big Costs for Little Gain in Ovarian Cancer

Eslicarbazepine Acetate

Eslicarbazepine acetate, a prodrug of eslicarbazepine (S-licarbazepine), is a novel, voltage-gated sodium channel antagonist under development for the adjunctive treatment of adult patients experiencing treatment-refractory partial-onset seizures. * In phase III trials, eslicarbazepine acetate 800 and 1200 mg once daily significantly reduced seizure frequency compared with placebo over 12 weeks of maintenance treatment in adults experiencing partial-onset seizures who were taking 1-3 concomitant antiepileptic drugs. * During long-term, open-label treatment for up to 1 year, eslicarbazepine acetate at a median dosage of 800 mg once daily produced sustained reductions from baseline in seizure frequency. * Long-term treatment with eslicarbazepine acetate significantly improved from baseline health-related quality of life as assessed by the Quality-of-Life in Epilepsy Inventory-31 instrument. Similarly, eslicarbazepine acetate significantly reduced depressive symptoms assessed by the Montgomery-Asberg Depression Rating Scale. * Eslicarbazepine acetate was generally well tolerated in clinical trials. The majority of treatment-emergent adverse events were of mild to moderate severity and most occurred early in treatment.

Preliminary evidence for gender‐specific effects of topiramate as a potential aid to smoking cessation

Study aims were threefold: (i) to determine the feasibility, potential efficacy and safety of topiramate as an aid to smoking cessation; (ii) to examine potential predictors of abstinence including gender; and (iii) to explore topiramate's effects on tobacco withdrawal and post-cessation weight gain. Randomized, double-blind, placebo-controlled, 11-week clinical trial with a 6-week dosage titration period and 5 weeks of maintenance treatment. Single-site, out-patient, randomized clinical trial. Thirty-eight adult male and 49 female chronic smokers who smoked an average of > 10 cigarettes per day and who were motivated to try to quit smoking. Random assignment to receive either topiramate (n = 43) up to 200 mg daily in divided doses or placebo (n = 44) orally combined with brief counseling over an 11-week period. Carbon monoxide (CO)-confirmed 4-week prolonged abstinence rate during weeks 8-11. Changes in tobacco withdrawal, body weight and safety parameters were also assessed. Overall, no significant increase in the prolonged abstinence rate was detected, but logistic regression analysis indicated significant gender-specific differences. Men treated with topiramate were nearly 16 times more likely to quit smoking than women on topiramate [37.5% versus 3.7%; odds ratio (OR) = 15.6; P = 0.016] and were roughly four times more likely to quit smoking than placebo-treated men (37.5% versus 13.6%; OR = 3.8; P = 0.098). Topiramate-treated men reported significantly lower tobacco withdrawal scores than both women taking topiramate and men on placebo. On average, male cessators on placebo gained 3.30 kg, whereas topiramate led to a 0.72 kg weight loss (P = 0.03). Study discontinuation rates due to adverse events (AEs) were significantly higher in the topiramate group (topiramate 23% versus placebo 2%). The most commonly reported AEs in the topiramate arm were paraesthesia, fatigue, difficulty with concentration/attention and nervousness. Topiramate produced gender-specific effects on smoking cessation. Male smokers had markedly greater quit rates than female smokers and men were roughly four times more likely to quit smoking when treated with topiramate as compared to placebo. Topiramate was fairly well tolerated, although higher discontinuation rates were seen. Topiramate's triple effects aiding smoking abstinence, attenuating nicotine withdrawal and preventing post-cessation weight gain might make it a promising agent for treating tobacco addiction, at least in men.

A randomized trial of bupropion and/or nicotine gum as maintenance treatment for preventing smoking relapse

To investigate the efficacy of maintenance treatment with bupropion and/or nicotine gum for reducing smoking relapse. A 48-week study was conducted at a university-based smoking cessation clinic between February 2001 and October 2005. A total of 588 smokers received bupropion and nicotine patch in 8 weeks of open-label treatment (OLT); 289 abstainers during the last 4 weeks of OLT were randomized in double-blind placebo-controlled fashion to one of four arms for 16 weeks of maintenance treatment (MT) followed by 24 weeks of non-treatment follow-up (NTFU). Bupropion (300 mg/day) and 2 mg nicotine gum, used alone or combined, and comparable placebo pill and placebo gum. Behavioral counseling at all visits. Time to relapse (TTR) from randomization. Relapse is defined as the first 7 consecutive days of smoking. Abstinence verified by carbon monoxide <or= 8 parts per million. TTR was longer with extended active treatments compared to placebo (median days to relapse: bupropion + placebo = 136, nicotine + placebo = 98, bupropion + nicotine = 90, double placebo = 71). Hazard ratios (HR) for relapse were statistically significant for bupropion + placebo versus double placebo during MT (HR = 0.59, 95% CI = 0.37-0.92) and to the end of NTFU (HR = 0.66, 95% CI = 0.42-0.96). However, bupropion's advantage dissipated upon stopping the drug. Gum use was low, preventing a valid assessment; but analysis restricted to gum users suggested a weak effect of extended nicotine gum. Maintenance treatment with bupropion exerted a modest benefit for preventing smoking relapse; the optimum duration of bupropion treatment was unclear. Further research is needed to ascertain the merits of extended use of nicotine gum, other nicotine replacement agents and other treatments known to aid smokers for preventing relapse once abstinence is achieved.

Gender Differences in Bipolar Disorder Type 1

To explore gender differences in bipolar I disorder, we compared the longitudinal treatment outcome and baseline demographic and clinical characteristics of 27 male and 45 female adult subjects who were treated for an acute affective episode and longitudinally followed for a period of up to 48 weeks. Females were more likely to report a history of suicidal gestures and a comorbid panic disorder; males were more likely to present with a comorbid obsessive-compulsive disorder, and there was a trend for a more frequent history of alcohol or substance abuse. No significant differences were found between the genders for the time to remission from the index episode, number of recurrences, and time spent with any clinical or subclinical mood symptom during the 48 weeks of maintenance treatment. Although differences may exist between bipolar I male and female subjects, prospective course does not seem to reveal differences in a 48-week period, at least when similar treatment strategies are adopted.

Use of Calcipotriene Cream (Dovonex?? Cream) Following Acute Treatment of Psoriasis Vulgaris with the Calcipotriene/Betamethasone Dipropionate Two-Compound Product (Taclonex??)

A calcipotriene/betamethasone dipropionate two-compound product (Taclonex ointment) has been shown to be safe and effective in the treatment of psoriasis over 4 weeks. Since treatment of psoriasis is generally long-term, the objective of this study was to investigate the efficacy and safety of transferring patients to maintenance treatment with calcipotriene cream (Dovonex cream) following a 4-week treatment period with the two-compound product. Patients with psoriasis were randomized to one of the following three treatment groups: 4 weeks of the two-compound product followed by 8 weeks of calcipotriene cream (calcipotriene cream group); 4 weeks of the two-compound product followed by 8 weeks of calcipotriene cream on weekdays and the two-compound product on weekends (alternating group); 4 weeks of the two-compound product followed by 8 weeks of vehicle of calcipotriene cream (vehicle group). All medications were applied once daily. A total of 1136 patients were randomized: 383 to the calcipotriene cream group, 377 to the alternating group, and 376 to the vehicle group. The mean percentage change in the Psoriasis Area and Severity Index from baseline to the end of the trial was -44.5% in the calcipotriene cream group, -58.4% in the alternating group, and -33.1% in the vehicle group. The mean difference between the calcipotriene cream and vehicle groups (primary treatment comparison) was -11.7% (95% CI -17.9, -5.5), which was statistically significant (p<0.001), and the mean difference between the alternating and vehicle groups was -24.7% (95% CI -30.9, -18.5), which was also statistically significant (p<0.001). For the investigators' global assessment of disease severity at the end of the trial, the differences between the calcipotriene cream and vehicle groups, and between the alternating and vehicle groups, were statistically significant (p<0.001), showing superior efficacy in the nonvehicle groups. The results were similar for the patients' global assessment of response to treatment. There were 43 patients (11.3%) with adverse drug reactions in the calcipotriene cream group, 28 (7.6%) in the alternating group, and 32 (8.6%) in the vehicle group. There were no statistically significant differences in the incidence of adverse drug reactions in the calcipotriene cream group relative to the vehicle group (odds ratio 1.36; 95% CI 0.84, 2.21; p=0.21), or in the alternating group relative to the vehicle group (odds ratio 0.87; 95% CI 0.51, 1.48; p=0.61). Four weeks of treatment with the calcipotriene/betamethasone dipropionate two-compound product followed by 8 weeks of maintenance treatment with calcipotriene cream is effective and safe. As an alternative maintenance regimen, treatment with calcipotriene cream on weekdays and the two-compound product on weekends is also effective and safe.

Efficacy of Sertraline in Preventing Relapse of Posttraumatic Stress Disorder

Objective: The study examined the efficacy of sertraline, compared with placebo, in sustaining improvement and preventing relapse over 28 weeks in patients with posttraumatic stress disorder (PTSD) who had completed a 12-week double-blind, placebo-controlled acute treatment study and a subsequent 24-week open-label study of continuation treatment with sertraline. Method: Ninety-six patients were randomly assigned, in a double-blind design, to 28 weeks of maintenance treatment with sertraline (50–200 mg, N=46; 78% were women) or placebo (N=50; 62% were women). Measures used in biweekly assessments included the Clinician-Administered PTSD Scale, the Impact of Event Scale, and the Clinical Global Impression severity and improvement ratings. Kaplan-Meier analyses were used to estimate time to discontinuation from the study due to relapse, relapse or study discontinuation due to clinical deterioration, and acute exacerbation. Results: Continued treatment with sertraline yielded lower PTSD relapse rates than placebo (5% versus 26%). Patients who received placebo were 6.4 times as likely to experience relapse as were patients who received sertraline. Kaplan-Meier analyses confirmed the protective effect of sertraline in significantly extending time in remission. The ability of sertraline to sustain improvement was comparable across the three core PTSD symptom clusters (reexperiencing/intrusion, avoidance/numbing, and hyperarousal). A regression analysis found early response during acute treatment to be associated with a more than 16-fold reduced risk of relapse after placebo substitution. Sertraline, at a mean endpoint dose of 137 mg, was well tolerated, with no sertraline-related adverse events observed at a rate of 10% or higher. Conclusions: The results provide evidence for the ability of sertraline both to sustain improvement in PTSD symptoms and to provide prophylactic protection against relapse.

Site variability in treatment outcome in antidepressant trials

Objective: Site-specific differences in treatment outcome during multisite antidepressant drug trials may contribute to a negative or failed clinical trial. As part of a five-site, long-term, double-blind, placebo-controlled, relapse prevention trial with fluoxetine in major depression, the authors examined site-specific variability in outcome ratings. Methods: Data from 390 patients with major depression who participated in a 64-week, placebo-controlled trial were retrospectively analyzed. χ 2 Analyses and Kaplan–Meier survival estimates were used to examine site-specific differences in relapse rates during 14 weeks of maintenance treatment following randomization to fluoxetine or placebo after remission with fluoxetine treatment. Results: Results from χ 2 analysis ( P<.001) and Kaplan–Meier survival rates ( P<.001) following randomization to placebo after 12 weeks of fluoxetine treatment showed a fluoxetine superiority over placebo among all five sites combined. Individually, however, only three of the five sites (60%) were able to distinguish fluoxetine superiority. In contrast, there was no fluoxetine versus placebo difference observed among all five sites after randomization following 26 weeks of fluoxetine treatment ( P=.11, Fisher's exact test). However, one site (20%) individually could still distinguish a drug versus placebo difference ( P<.05). Limitations: Analyses were performed retrospectively, with individual sites not specifically powered to distinguish a drug–placebo difference. Conclusion: Substantial site differences were observed in the ability to distinguish drug superiority over placebo, and this variability may contribute to a negative or failed clinical drug trial.

Deaths in the first two weeks of maintenance treatment in NSW in 1994: identifying cases of iatrogenic methadone toxicity

A study was undertaken to estimate the frequency of iatrogenic methadone toxicity in the first 2 weeks of maintenance treatment in NSW. Cases were identified from a list of all 1994 methadone-associated deaths using data on methadone patients held by the NSW and Queensland Health Departments. The likely causes of death were determined from data collected from coronial files. A forensic toxicologist experienced in the area gave an independent opinion. Of the 14 deaths in the first 2 weeks of maintenance, at least 10 were primarily caused by the toxic effects of methadone prescribed by NSW doctors. The rate of fatal iatrogenic methadone toxicity was 2.2 per thousand admissions to maintenance. Victims of fatal iatrogenic toxicity often displayed signs of methadone intoxication in the days before their death. They invariably died several hours after taking the fatal dose, usually after seeming to go to sleep. Often friends or family were concerned about their welfare, were unable to rouse them from their "sleep" and frequently reported the deceased was "snoring" loudly for some time before their demise. The author recommends that patients entering methadone maintenance should be informed of the risks and should be required to give written consent to treatment. To prevent fatal methadone toxicity, patients should receive daily medical assessment during the first 1-2 weeks of maintenance.

A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in adults with previously untreated epilepsy

In the last 5 years oxcarbazepine (OXC) has been registered in many countries for use as first-line and add-on treatment for partial seizures with or without secondarily generalized seizures (PS) and generalized tonic-clonic seizures without partial onset (GTCS). Its use as monotherapy in adults with newly diagnosed epilepsy was investigated in this double-blind, randomized, parallel-group comparison with phenytoin (PHT). A total of 287 adult patients, with either PS or GTCS, were randomized. After retrospective baseline assessment, patients were randomized to OXC or PHT in a 1:1 ratio. The double-blind treatment phase was divided into two periods: a flexible titration period of 8 weeks, followed by 48 weeks of maintenance treatment. In the efficacy analyses, no statistically significant differences were found between the treatment groups. Seventy patients (59.3%) in the OXC group and 69 (58.0%) in the PHT group were seizure-free during the maintenance period. A total of 56 of the patients in the OXC group discontinued treatment prematurely (five because of tolerability reasons) compared to 61 in the PHT group (16 for tolerability reasons). The number of premature discontinuations due to adverse experiences showed a statistically significant difference in favour of OXC. There was no statistically significant difference between the groups with respect to the total number of premature discontinuations. This trial provides further support for the efficacy and safety of OXC as first-line treatment in adults with PS and GTCS. In addition, the results show that OXC has significant advantages over PHT in terms of tolerability.