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PubMed2003

Transdermal estradiol therapy for advanced prostate cancer--forward to the past?

PURPOSE: Current hormonal therapies for prostate cancer are associated with significant morbidities, including symptoms of andropause and osteoporosis. Oral estrogens prevented many of these problems but were abandoned due to cardiovascular toxicity attributed to hepatic effect. In contrast, parenteral estrogens prevent first pass hepatic metabolism and substantially reduce cardiovascular risk, and long-term transdermal estradiol therapy is believed to be cardioprotective. We report preliminary results of a pilot study using transdermal estradiol therapy to treat men with advanced prostate cancer. MATERIALS AND METHODS: A total of 20 patients with advanced prostate cancer were enrolled in a before and after study that examined the impact of estradiol patches on hormones, disease, thrombophilia, vascular flow, osteoporosis and quality of life. RESULTS: Median followup is 15 months. Estradiol levels greater than 1,000 pmol./l. were achieved using 2 patches and higher levels were obtained by increasing the number of patches. All patients achieved castrate levels of testosterone within 3 weeks and had biochemical evidence of disease regression. One patient died of disease at 14 months and 1 cardiovascular complication occurred. Thrombophilic activation was avoided and vascular flow improved. Bone mineral density was significantly increased. Mild or moderate gynecomastia occurred in 80% of patients but no patient had hot flushes. All other functional and symptomatic quality of life domains improved. CONCLUSIONS: Transdermal estradiol therapy produced an effective tumor response. Cardiovascular toxicity was substantially reduced compared with that expected of oral estrogen, and other morbidity (gynecomastia) was negligible. Transdermal estradiol therapy prevented andropause symptoms, improved quality of life scores and increased bone density. Transdermal estradiol costs a tenth of current therapy cost, with the potential for considerable economic savings over conventional hormone therapies.

Administration, Cutaneous↗
PubMed1986

Influence of transdermal nitrates on exercise capacity in patients with stable angina.

Twenty patients completed a double-blind cross-over study to determine the influence of a transdermal preparation of Nitroglycerin on exercise performance in stable angina. Angiographically proven two or three vessel coronary disease was present in all. After a base-line exercise test the active device was titrated to efficacy or side effects and the number of patches thereafter remained constant (2-6 patches per day; mean 3.5). Patients were randomly allocated to active treatment or placebo, and further exercise tests were performed at 2 hours and 26 hours after application of the device. Patients were then crossed over after one days rest to the opposite treatment group, and exercise studies repeated. Two hours after application of transdermal nitroglycerin total exercise duration increased (mean 14.0 minutes) compared to placebo (12.5 minutes) and control (12.0 minutes) (p less than 0.05). This effect was maintained at 26 hours. Exercise time to anginal threshold (angina + 1.5 mm ST segment depression) was increased at 2 hours and 26 hours with active drug by 11% compared to placebo and by 22% in comparison to control. Double product of heart rate and blood pressure was not significantly different in treated and placebo groups. Oral nitroglycerin consumption assessed during the titration phase was reduced by 71%. It is concluded that transdermal nitroglycerin significantly increases exercise capacity in patients with stable angina, with an effect that is maintained over a 24-hour period using a single dose application.

Administration, Topical↗
PubMed1994

Efficacy of intermittent (eight hours off) transdermal nitrate therapy in stable angina.

The efficacy of intermittent (16 h on/8 h off) transdermal nitrate therapy (0.4 mg/h) was assessed in 46 patients with chronic stable angina, all but one of whom were on concomitant beta-blocker and/or calcium antagonist therapy. The study was a randomised, double-blind placebo-controlled crossover with two consecutive 7-day treatment periods, conducted at two centres. Prior to entry into the study patients were screened for exercise test reproducibility and nitrate response. Patch efficacy was determined by maximal symptom limited treadmill stress testing (Bruce protocol) and subjective diary card data. Analysis of variance showed that active treatment significantly improved time to onset of angina (P < 0.001), time to 1 mm ST-segment depression (P < 0.001) and total exercise duration (P < 0.001) compared with placebo from 385.7, 310.8 and 458.1 s to 455.7, 385.2 and 497.1 s, respectively. Nitrate patch therapy significantly reduced diastolic and systolic blood pressures without significantly increasing resting heart rate. There was a marginal reduction in the incidence of angina attacks and sublingual nitroglycerine consumption during active treatment. We conclude that intermittent transdermal nitrate therapy significantly improves exercise tolerance in patients with chronic angina pectoris and that this improvement occurs in addition to conventional anti-anginal therapy.

Administration, Cutaneous↗
PubMed2005

Transdermal iontophoretic delivery of apomorphine in patients improved by surfactant formulation pretreatment.

The objective of the present study is to evaluate the efficacy and the safety of transdermal iontophoretic delivery of R-apomorphine, a potent dopamine agonist, in combination with surfactant pretreatment in patients with advanced Parkinson's disease. Iontophoresis patches were applied in 16 patients for 3.5 h, with 0.5 h of passive delivery followed by 3 h of current application at a current density of 250 microA/cm2. Eight of these patients were treated with a surfactant formulation prior to iontophoresis. The pharmacokinetics, pharmacodynamic effects, systemic and local side effects of R-apomorphine were assessed. The plasma concentration vs. time profiles upon iontophoresis of R-apomorphine were described successfully by a novel pharmacokinetic model. The model suggests that only 1.9% of the dose that has been released from the patch accumulated in the skin. The patients treated with the surfactant formulations showed a statistically significant increase of bioavailability (from 10.6+/-0.8% to 13.2+/-1.4%) and of the steady state input rate (from 75.3+/-6.6 to 98.3+/-12.1 nmol/cm2 h) compared to the control patients (iontophoresis without absorption enhancers). In five out of eight patients in the study group and in three out of eight patients in the control group, clinical improvement was observed.

Administration, Cutaneous↗
PubMed1989

A review of contact dermatitis associated with transdermal therapeutic systems.

The literature is reviewed for contact dermatitis associated with transdermal therapeutic systems. Clonidine, nitroglycerin, scopolamine, estradiol and testosterone are utilized in such applications, and fentanyl is under investigation. Most cutaneous reactions are limited to localized dermatitis; however, generalized systemic effects may occur. Investigators are reporting skin-related side-effects in up to 50% of patients using transdermal clonidine; however, with the other agents, this is demonstrated much less frequently. Reactivation of the dermatitis via oral medication, following sensitization to the patch, is noted in rare instances.

Administration, Cutaneous↗
PubMed1997

Selegiline percutaneous absorption in various species and metabolism by human skin.

PURPOSE: A Selegiline Transdermal System (STS) is under development for indications which may not be optimally or safely treated with oral selegiline. Studies were conducted to evaluate the in vitro penetration and skin metabolism of selegiline in order to better understand the toxicological findings and the observed plasma levels of selegiline and its metabolites in animals and man. METHODS: In vitro penetration studies were conducted in four different species (male hairless mice, male and female rats, female dog and male Micropig) and compared to human skin. In another study, viable human skin was used to estimate the extent of metabolism of selegiline by human skin using Franz diffusion cells. RESULTS: Results indicated that female dog and male Micropig skin were reasonable animal models for 24 hour in vitro selegiline penetration through human skin. Penetration of selegiline through rat skin and hairless mouse skin was 2-fold and 3-fold higher than through human skin, respectively. Metabolism was negligible in human skin. Selegiline metabolites (L-methamphetamine and N-desmethylselegiline but not L-amphetamine) were detected at all time points but the extent of selegiline metabolism was negligible. The cumulative 24 hour in vitro selegiline permeation from a 1.83 mg/cm2 STS through human skin was 5.0 mg. This was similar to the in vivo permeation in humans as assessed by residual patch analysis. CONCLUSIONS: The similarity of dog and human skin permeation results support the use of the dog as a species for evaluating the toxicology of transdermally-administered selegiline. Selegiline is not metabolized cutaneously and hence the metabolic profile following STS administration is likely due to hepatic metabolism only.

Animals↗
PubMed1996

Transdermal oestrogen for treatment of severe postnatal depression.

BACKGROUND: Postnatal depression can have long-term adverse consequences for the mother, for the marital relationship, and for the infant's psychological development. Such depressions can be severe and resistant to both support and counselling and to therapy with antidepressant drugs. We investigated the antidepressant efficacy of oestrogen given transdermally. METHODS: In a double-blind, placebo-controlled study, 61 women with major depression, which began within 3 months of childbirth and persisted for up to 18 months postnatally, were allocated randomly active treatment (n=34; 3 months of transdermal 17 beta-oestradiol 200 micrograms daily alone, then 3 months with added cyclical dydrogesterone 10mg daily for 12 days each month) or placebo (n=27; placebo patches and tablets according to the same regimen). The women were assessed monthly by self-ratings of depressive symptoms on the Edinburgh postnatal depression scale (EPDS) and by clinical psychiatric interview (schedule for affective disorders and schizophrenia [SADS]-change scale). FINDINGS: On pretreatment assessments the women in both groups were severely depressed (mean EPDS score 21.8 [SD 3.0] active group, 21.3 [2.9] placebo group; SADS scores, 66.3 [11.4] and 64.3 [10.7]). During the first month of therapy the women receiving oestrogen improved rapidly, and to a significantly greater extent than controls (mean EPDS scores 13.3 [SD 5.7] vs 16.5 [5.3]. Patients receiving placebo also improved over time but, on average, their scores did not fall below the screening threshold for major depression for at least 4 months. The estimated overall treatment effect of oestrogen on the EPDS was 4.38 points (95% Cl 1.89-6.87). None of a range of other factors (age, psychiatric, obstetric and gynaecological history, severity and duration of current episode of depression, and concurrent antidepressant medication), influenced the response to oestrogen. INTERPRETATION: This study has shown that transdermal oestrogen is an effective treatment for postnatal depression. Further studies are required to establish the minimum effective dose and shortest necessary duration of treatment as well as the mechanism of antidepressant action of oestrogen.

Administration, Cutaneous↗
PubMed2004

A two-year study on the effects of nicotine and its withdrawal on mood and sleep.

Acute administration of nicotine has beneficial effects on a variety of neurological and psychiatric disorders. The purpose of this study was to determine the long-term effects of transdermal nicotine on sleep and major depression. Under a single blind protocol study where patients initially received nicotine and then switched to placebo. Fourteen non-smoking patients with major depression (Hamilton Rating > or = 18) served as subjects. Transdermal nicotine (17.5 mg), was administered five days weekly for six months, three days weekly on month 7 and one day per week on month 8. From the 9th to the 24th month, once a week a patch without nicotine substituted the nicotine patch. Sleep and depression was assessed throughout. REM sleep latency changed from 32.6 min. to 78.2 min. at the end of the study, wakefulness decreased, slow wave sleep increased throughout the study and a transient decrease of REM sleep duration upon nicotine withdrawal was observed. Hamilton scores went from an initial mean score of 29.7 to a final score of 10.8. The results support the possible therapeutical effects of long-term transdermal nicotine on sleep and mood, with a carryover effect into the withdrawal period, even though, the conclusions should be taken with caution due to the design applied.

Administration, Cutaneous↗
PubMed2006

New transdermal bioadhesive film containing oxybutynin: In vitro permeation across rabbit ear skin.

Oxybutynin is used extensively in the treatment of patients with overactive bladder. The aim of this work was to realize and test in vitro a new transdermal bioadhesive film containing oxybutynin. Transdermal films were prepared by dissolving in water an adhesive (Plastoid), a film-forming polymer (polyvinyl alcohol), a plasticizer (sorbitol) and the drug. The mixture was then spread on siliconized paper and oven-dried. Permeation experiments were conducted in Franz-type diffusion cells using rabbit ear skin as barrier. The donor compartment contained a water solution, the prepared film (with or without backing) or the commercial patch (Oxytrol). The experiments were performed for 24h. Oxybutynin showed good permeation characteristics across the skin. When the film was applied in occlusive conditions the release profiles were much higher than in non-occlusive conditions, reaching 50% of drug permeated after 24h. Compared to the commercial patch Oxytrol, the film was more efficient suggesting that a smaller area or a lower drug loading could be employed. The results obtained show that the bioadhesive film can be a promising and innovative therapeutic system for the transdermal administration of oxybutynin.

Administration, Cutaneous↗
PubMed1996

Antihypertensive effects of a new transdermal delivery system for clonidine in genetic and experimental hypertensive rats.

The antihypertensive effects of a new transdermal delivery system for clonidine (CAS 4205-90-7, clonidine tape, M-5041T) were investigated in spontaneously hypertensive rats (SHR), 2-kidney, 1-clip renal hypertensive rats (RHR) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. M-5041T (0.5-4.5 mg/kg) elicited a long-lasting hypotensive effect that was accompanied by bradycardia in a dose-dependent manner during 24-h patching on the backs of rats in all three hypertensive rat models. The hypotensive effect of M-5041T was more persistent than that of oral administration of clonidine (50 and 100 micrograms/kg) in both SHR and RHR. The most pronounced hypotensive effect of M-5041T was observed in DOCA-salt hypertensive rats. Plasma clonidine concentrations following transdermal application of M-5041T (1.5 mg/kg) were approximately 2-3 fold higher in DOCA-salt hypertensive rats compared with SHR. Electrical conductance of the skin surface, an index of the water content of the stratum corneum, was greater in DOCA-salt hypertensive rats than in SHR, suggesting that the delivery of clonidine may have been enhanced as a result of an increase in skin permeability due to the increase in water content of the stratum corneum in DOCA-salt hypertensive rats. Co-administration of M-5041T (0.5 mg/kg) with either trichloromethiazide (1 mg/kg, orally) or nifedipine (3 mg/kg, orally) at each sub-dose which affected both systolic blood pressure and heart rate produced significant hypotensive and bradycardic effects in SHR. Following repeated daily applications of M-5041T (1.5 mg/kg) for 7 consecutive days in SHR, significant hypotensive and bradycardic effects were produced at 6 h post-patching and then disappeared at 24 h post-patching in each trial. The plasma clonidine concentrations at 6 and 24 h post-patching were similar from the first to the seventh trial. No significant changes in blood pressure and heart rate were observed after termination of the regimen. These findings suggest that M-5041T could serve as an efficient and useful antihypertensive transdermal delivery system in humans without producing tolerance to the hypotensive effect and withdrawal syndrome after abrupt cessation of the treatment when used alone or with either a diuretic or a calcium channel blocker.

Administration, Cutaneous↗
PubMed1997

Transdermal clonidine therapy and blood pressure nocturnal fall in mild hypertensive male subjects.

UNLABELLED: Treatment of mild hypertension with an antihypertensive drug administered by means of a transdermal therapeutic system (TTS) could produce favorable results, when compared with a traditional oral regimen. PURPOSE: Using 24-h ambulatory blood pressure (BP) monitoring (ABPM) in mild hypertensive male subjects, to analyze three aspects which have not been completely clarified: a) whether a latency in the antihypertensive effect may be present, recording BP already from the first day of application of the patch, b) the eventual hazardous enhancement of circadian nocturnal fall in BP values in treated mild hypertensive patients and, c) the possible overlapping of antihypertensive effect between the administration of two consecutive patches. SUBJECTS AND METHODS: In 12 caucasian male outpatients (yrs 55 +/- 3 SEM) with uncomplicated essential mild hypertension, a patch containing placebo was applied for the first week (T 0 period). At the end of the T 0 period, a 5 mg TTS-2 clonidine patch was applied for one week, and, subsequently, a new patch of 5 mg TTS-2 clonidine was kept for another week. ABPM was performed on the last day of the placebo period (T 0) and on the 1st day (T1), the 7th day (T2) and the 14th day (T3) of transdermal clonidine therapy. RESULTS: Both systolic and diastolic BP (24 h mean, day-night-time) decreased on the 1st, 7th and 14th day, when compared with T0. However, no significant differences were documented between the BP levels on the 1st and the 7th day of treatment. The incidence of nocturnal fall in systolic and diastolic BP was evaluated and no significant differences were found, when compared with night-time reference values. CONCLUSIONS: When compared with the placebo period, TTS-2 clonidine lowers SBP and DBP within the first 24 hours of application. The antihypertensive effect persists at the end of the first week, as well as after 14 days. The lowest values of systolic-diastolic BP documented were not below the levels reported in normotensive men. Therefore, TTS-2 clonidine seems to act as an antihypertensive agent rather than a hypotensive drug since it normalizes BP without lowering it below physiological levels.

Administration, Cutaneous↗
PubMed1992

Plasma lipid and lipoprotein effects of transdermal administration of estradiol and estradiol/norethisterone acetate.

To evaluate the effect of transdermal sequential treatment with estradiol and estradiol/norethisterone acetate on lipoprotein metabolism, 25 postmenopausal women received treatment for 12 cycles of 4 weeks each (2 weeks estradiol 50 micrograms/day and 2 weeks a combined patch delivering norethisterone acetate 0.25 mg/day and estradiol 50 micrograms/day). Blood samples for lipoprotein analyses were drawn before treatment and in estrogen and combined phases in cycles 3 and 12. Plasma total cholesterol, low (LDL) and high (HDL) density lipoprotein were all significantly reduced in both estrogen and combined phases. Eighteen of the women continued the treatment for 36 cycles. In this group the HDL-cholesterol had returned to baseline values in combined phase in cycle 24. Plasma cholesterol and LDL-cholesterol values remained significantly reduced throughout the whole study compared to the pre-trial values. The present study by transdermal sequential hormonal treatment results in a lipid and lipoprotein pattern with reduced total cholesterol and LDL cholesterol in postmenopausal women.

Administration, Cutaneous↗
PubMed2003

Postoperative pain management using fentanyl patches in dogs.

To the ability of the fentanyl patch to control pain in a postoperative canine model, we provided two male beagles with 25-mg/h patches and two with 50-mg/h patches 24 h prior to surgery. Each animal underwent a major abdominal surgical procedure to place three separate catheters with associated vascular access ports. Serum plasma levels of fentanyl were analyzed at multiple time points throughout the study period. Animals were subjectively assessed for postoperative pain by using a Simple Descriptive Scale at regular intervals postoperatively. Other parameters observed and recorded included heart and respiration rates, rectal temperature, appetite, and activity. The fentanyl patch appeared to adequately control postoperative pain in our canine abdominal surgical model. Three animals demonstrated mild pain 1 to 2 h postoperatively. Two animals, one from each dose group, showed mild pain 8 h postoperatively. Mild pain is commensurate with USDA category C, which encompasses procedures that do not result in more than momentary or slight pain or distress and do not require intervention. At no other time points were any of the animals considered to be in pain. Our study also suggested that increased subcutaneous fat delayed the rate of absorption of fentanyl. The lower body-weight beagles, which had the 25-mg/h patches, reached reported human serum analgesic levels within 8 h after placement, whereas the heavier beagles with the 50-mg/h patches reached human serum analgesic levels 12 h after placement. Fentanyl concentrations remained at the reported human analgesic levels in all animals between 2 to 4 h after the patches were removed. Regardless of the dose, decreases in heart rate, respiration rate, and temperature were observed in all four animals 12 h after placing the patches. Issues regarding the regulatory requirements to prevent drug abuse, the side effects and potency of fentanyl, and the prolonged duration of action as a transdermal system should be addressed by the veterinarian when considering usage of this analgesic method.

Administration, Cutaneous↗
PubMedDate not supplied

Transdermal nicotine therapy and primary care. Importance of counseling, demographic, and participant selection factors on 1-year quit rates. The Nebraska Primary Practice Smoking Cessation Trial Group.

OBJECTIVE: To evaluate the smoking cessation efficacy of nicotine patch therapy as an adjunct to low-intensity, primary care intervention. DESIGN: Randomized, placebo-controlled, double-blind, multisite trial. SETTINGS: Twenty-one primary care sites in Nebraska. PATIENTS: A total of 369 smokers of 20 or more cigarettes per day. INTERVENTION: Two brief primary care visits for smoking intervention with 10 weeks of active or placebo-patch therapy. MAIN OUTCOME MEASURES: Confirmed self-reported abstinence 3, 6, and 12 months after the quit day. RESULTS: Compared with placebo control subjects, participants assigned nicotine patches had higher 3-month (23.4% vs 11.4%; P < .01) and 6-month (18.5% vs 10.3%; P < .05) abstinence rates. The 1-year abstinence rates for the active and placebo patch groups were 14.7% and 8.7%, respectively (P = .07). Of smokers aged 45 years and older, 9 (18.8%) of 48 using active patches compared with 0 of 31 using placebo patches achieved 12-month abstinence (chi 2 = 6.56; P < .05). Among those with high nicotine dependency scores (Fagerstrom score > or = 7), 1-year abstinence rates were significantly higher in the nicotine patch group (19.1%) compared with the placebo group (5.0%) (chi 2 = 10.7; P = .001). However, there was no significant difference in 1-year quit rates for participants with low Fagerstrom scores (< 7). CONCLUSIONS: Nicotine patch therapy enhanced 6 month quit rates as an adjunct to brief primary care intervention. The highest quit rates were achieved by participants who specifically contacted the site to enroll in the study or to obtain a prescription for nicotine patches. Differences in participant selection factors may account, in part, for the lower smoking cessation rates associated with primary care intervention. Duration of counseling, patient age, and Fagerstrom scores may be important factors related to the long-term smoking cessation success of nicotine patch therapy.

Administration, Cutaneous↗
PubMed2000

Assessing the impact of heat on the systemic delivery of fentanyl through the transdermal fentanyl delivery system.

OBJECTIVES: To examine the effects of locally applied heat on the systemic delivery of fentanyl through the Transdermal Fentanyl Delivery System. DESIGN: Open, 2-period crossover randomized study conducted in the anesthesia department of a university teaching hospital. METHOD: Six healthy adult volunteers received a fentanyl 25-microg/h patch with and without local heat for 240 minutes followed by administration without heat for an additional 20 hours. Participants then crossed over. Venous blood was drawn at baseline and hourly for 24 hours. Peak plasma concentration (CMax) of fentanyl was measured and the area under the curve (AUC) of the plasma fentanyl concentration versus time post administration graph was evaluated. RESULTS: Difference in CMax and AUC were not statistically significant over the entire 24-hour study period. However, for the 4-hour period of heat application statistically significant differences were seen in both mean CMax (heat, 0.4 ng/mL versus no heat, 0.1 ng/mL (P =.030)) and mean AUC (heat, 40 ng/mL x min versus no heat, 10 ng/mL x min (P =.010)). CONCLUSION: Local heat can speed the onset of steady state fentanyl concentration in the Fentanyl Transdermal Drug Delivery System thus limiting the delay in onset of analgesia and allowing earlier identification and treatment of side effects.

Clinical Trial↗
PubMedDate not supplied

Transdermal glyceryl trinitrate (nitroglycerin) in healthy persons: acute effects on skin temperature and hemodynamic orthostatic response.

In order to find an explanation for individual reactions to transdermal glyceryl trinitrate (GTN) we studied the skin temperature and hemodynamic reactions in 63 healthy persons. The data were obtained before and after the application of GTN and Glycerin (GL) placebo patches, during one hour. The skin temperature was measured on both forearms, the local (left sided) and systemic (right sided) reaction on GTN was related to the skin fold and the calculated body fat content. The bilateral rise of skin temperature and its duration was higher and longer in obese than in lean persons mainly in obese women. The UV induced thermo and the later photothermoreaction (Erythema) was reduced on the left forearm after the application of GTN and GL patches. The observed hemodynamic GTN effect confirmed known postural reactions, such as decreased arterial pressure (delta mAP = -2.9%), increased heart rate (delta HR = +7.4%) and QTc prolongation (delta QTc = +4.9%) in upright position. An adverse drug effect with increased mean blood pressure (delta mAP = +12%) and increased heart rate (delta HR = +10.4%) mainly in supine position was observed in 11% of the participants, but only in men. Such a reaction was already described by Murell, 1879. Individual GTN effects were analyzed and related to habits and family history. In male smokers and in persons with hypertensive and diabetic close relatives, the hypotensive GTN effect was accentuated in supine position. In the upright position the group with hypertensives in the family presented a moderate hypotensive reaction without secondary tachycardia and the smokers presented only a slightly increased heart rate. Our observations suggest that individual reactions to transdermal glyceryl trinitrate (GTN) with its active component nitric oxide (NO) depends on physiological conditions, related to endogenous vasoactive substances, mainly the interaction with EDRF (the endogenous NO) and the activity of the Renin-Angiotensin System.

Administration, Cutaneous↗
PubMed2006

Selegiline transdermal system for the treatment of major depressive disorder: an 8-week, double-blind, placebo-controlled, flexible-dose titration trial.

OBJECTIVE: This study investigated the efficacy, safety, and tolerability of the selegiline transdermal system (STS) administered in a dose range of 6 mg/24 hours to 12 mg/24 hours for treating major depressive disorder (MDD). METHOD: Patients meeting DSM-IV criteria for MDD (N = 265) were randomly assigned to blinded treatment with STS or a matching placebo patch for 8 weeks. Patients failing to meet or maintain protocol-defined therapeutic response criteria at predetermined time points had their STS (or placebo) dose increased. Assessments were conducted at weeks 1, 2, 3, 5, 6, and 8. Patients were not required to follow a tyramine-restricted diet. The study ran from September 2001 through August 2002. RESULTS: Selegiline transdermal system treatment resulted in significantly greater improvement (p < or = .05) compared with placebo treatment on the 3 depression rating scales: the 28-item Hamilton Rating Scale for Depression (HAM-D28) (primary outcome measure), the Montgomery-Asberg Depression Rating Scale, and the Inventory for Depressive Symptomatology-Self Rated. The treatment effect measured by the HAM-D28 was modest, primarily due to insomnia side effects. The antidepressant efficacy of STS was substantiated further by the significantly greater improvement in core depression symptoms (HAM-D Bech-6 subscale). The side effects of highest incidence were application site reactions and insomnia. There were no safety concerns based on routine clinical laboratory and electrocardiogram monitoring, and there were no occurrences of hypertensive crisis. CONCLUSION: Results of this double-blind, placebo-controlled, dose titration trial provide evidence of short-term efficacy, safety, and tolerability of STS in the dose range of 6 mg/24 hours to 12 mg/24 hours for treatment of MDD. Selegiline transdermal system has an improved margin of safety compared with oral monoamine oxidase inhibitors and represents a useful addition to the existing array of antidepressants.

Administration, Cutaneous↗