Oxybutynin-associated Cognitive Impairment: Evidence and Implications for Overactive Bladder Treatment.

Anticholinergic medications have long been a mainstay of overactive bladder (OAB) treatment. Oxybutynin, a first-generation anticholinergic, still accounts for more than half of all OAB medication prescriptions, despite associations with impaired memory and cognition, as well as mounting evidence that it may increase the risk of incident dementia. This review details the current literature regarding oxybutynin and cognition, including evidence from preclinical, clinical, and real-world studies that show that oxybutynin binds nonspecifically to muscarinic receptors in the brain and is associated with adverse cognitive outcomes. We also discuss society recommendations to reduce use of oxybutynin and other anticholinergics to treat OAB.

Long-term evaluation of the safety and efficacy of a novel 20% oxybutynin hydrochloride lotion for primary palmar hyperhidrosis: An open-label extension study.

The long-term safety and efficacy of 52-week application of oxybutynin hydrochloride 20% lotion (20% OL) for the treatment of primary palmar hyperhidrosis (PPHH) in Japanese patients aged ≥12 years were evaluated in an open-label extension (OLE) of a 4-week, randomized, double-blind (DB) study. The OLE included 114 patients who completed the DB study and wished to continue treatment and 12 new patients. In the safety analysis population (125 patients), the incidence of adverse events (AEs) and adverse drug reactions (ADRs) was 79.2% and 36.0%, respectively. Serious AEs were observed in two patients but were considered unrelated to the investigational drug. The incidence of AEs that led to study discontinuation was 1.6%. The incidence of application site AEs and ADRs was 35.2% and 26.4%, respectively. The severity of most events was mild. The incidence of anticholinergic AEs related to dry mouth was 3.2% for thirst and 0.8% for dry throat. The long-term efficacy of 20% OL was confirmed by a long-lasting reduction in sweat volume and improvement in the Hyperhidrosis Disease Severity Scale and Dermatology Life Quality Index. This study has several limitations: First the results may include some bias because most of the participants were from the prior DB study; second, the results may not be generalizable because only a few participants were in the age group most susceptible to PPHH (i.e., < 15 years old); and third, the study did not obtain safety information from treatment for more than 52 weeks, so this information must be collected in clinical practice in the future. No reduced therapeutic effect was observed in patients with PPHH in this study after 52-week application of 20% OL. Also, few patients experienced serious AEs or AEs that led to study treatment discontinuation.

A novel lotion formulation of 20% oxybutynin hydrochloride for the treatment of primary palmar hyperhidrosis: A randomized, placebo-controlled, double-blind, phase III study.

BACKGROUND: No previous controlled studies have been specifically designed or adequately powered to show the efficacy of topical oxybutynin for palmar hyperhidrosis by using quantitative measures. OBJECTIVE: To evaluate efficacy of 20% oxybutynin hydrochloride lotion (20% OL) in reducing palmar sweat volume in patients with primary palmar hyperhidrosis (PPHH). METHODS: In a randomized controlled trial, Japanese patients with PPHH aged 12 years and older received either 20% OL (n = 144) or placebo (n = 140) on both palms once daily for 4 weeks. Palmar sweat volume was measured by the ventilated capsule method. For the primary outcome, response was defined as a reduction of sweat volume of at least 50% from baseline. RESULTS: At week 4, the responder rate for sweat volume was significantly higher in the 20% OL arm than in the placebo arm (52.8% vs 24.3%, respectively; treatment difference, 28.5% [95% CI, 17.7% to 39.3%]; P < .001). No serious adverse events occurred, and no adverse events led to treatment discontinuation. LIMITATIONS: The treatment period was only 4 weeks. CONCLUSIONS: In patients with PPHH, 20% OL is superior to placebo in reducing palmar sweat volume.

Efficacy and safety of a new peeling formulated with a pool of PHAs for the treatment of all skin types, even sensitive.

BACKGROUND: Actually, the use of chemical peels in cosmetics and dermatology continues to grow due to their versatility, clinical endpoint-directed predictability, and favorable risk profile in comparison to lasers. The chemical peel is a generally safe method for treatment of some skin disorders and to refresh and rejuvenate the skin. The major challenge of chemical peels is the tolerability, that is because of sensitive skin which is one of the most common skin disorders. AIM: The aim of this study was to evaluate the effectiveness of the new Miamo Renewal Peel Serum formulated with a pool of new generation acids (ELPA25™) on sensitive skin with respect to mandelic acid serum only and with respect to placebo comparison. MATERIALS AND METHODS: The "in vivo" study following the half-face experimental protocol active versus placebo involved 30 healthy Caucasian female volunteers between 25 and 64 years, with sensitive skin, who were divided into two different groups. ELPA25™ serum was applied in one group three times a week for 8 weeks. The other group, with the same protocol, applied an active serum containing mandelic acid, as control, versus placebo. In particular, skin moisturizing, skin viscoelastic properties, skin surface smoothness, wrinkle reduction, and stratum corneum renewal were evaluated. RESULTS: Renewal Peel Serum was very well tolerated from sensitive skin. A significant decrease in skin roughness and wrinkle breadth, and an improvement in firmness and in skin elasticity, was observed after 2 months of treatment with respect both to mandelic acid serum and to placebo comparison. CONCLUSIONS: Scientific protocol using self-controlled study methodology and noninvasive skin bioengineering techniques with adequate statistical methods were able to evaluate both the safety and the efficacy of the new Miamo Renewal Peel Serum. This study highlighted that the Miamo Renewal Peel Serum formulated with a patent-pending mixture of new generation acids (ELPA25™) exerts many beneficial effects and it can be successfully employed for sensitive skin.

The Differential Risk of Mortality Among Users of Overactive Bladder Anticholinergic Medications and ß3 Agonists.

Anticholinergic overactive bladder (OAB) medications have been studied in large observational studies to determine if they are associated with a greater risk of mortality (potentially because of their effects on the heart or the brain). Studies in different populations of old adults have shown that oxybutynin is associated with a significantly higher risk of mortality of 26-58% in comparison to other OAB anticholinergic medications or ß3 agonists. In general, anticholinergic OAB medications may increase the risk of mortality, and a single multicountry study showed that ß3 agonist users had a 20% lower risk of mortality compared to OAB anticholinergic users. PATIENT SUMMARY: Older adults who started using a traditional type of medication for overactive bladder (oxybutynin) had a higher risk of dying compared to people who used newer types of anticholinergic medications and to people who used overactive bladder medications that work in a different way.

Dosing Variability and Clinical Outcomes of Oxybutynin: A Pediatric Cohort of Patients With Neurogenic Bladder.

Background: Despite the therapeutic advancements of the last several decades, neurogenic bladder remains a significant source of morbidity for patients with a spinal pathology. Oxybutynin is a mainstay of treatment in pediatric populations despite significant side effects and highly variable bioavailability. Objectives: To characterize the use of oxybutynin in a cohort of pediatric patients with neurogenic bladder. Methods: Retrospective data were collected of dosing, drug interactions, and urodynamics parameters in the 100 consecutive patients in a spinal differences clinic who had an appointment between October 7, 2015, and December 30, 2015. In addition to descriptive statistics, a linear regression model of oxybutynin dose versus age and sex was developed to examine the impact of age on dosing variability. Results: One hundred patients (52% female) with a median age of 6.8 years were included. The median daily dose of oxybutynin was 0.36 mg/kg (interquartile range, 0.28-0.54 mg/kg). Of the 48 patients with a recent urodynamics study, 13 had a detrusor leak point pressure (DLPP) greater than the typical cutoff of 40 cm H2O, indicating a need for management escalation. However, of these 13 patients, 38% were already on or exceeding oxybutynin's maximum recommended dose. Conclusion: The wide dosing variability and high DLPPs despite maximal dosing indicate a need for further investigation of oxybutynin's bioavailability in this population compared to its side effects and clinical outcomes. If variability in response to the medication is due to differences in bioavailability, then a precision-dosing model based on patient genomics could be developed for oxybutynin.

Oxybutynin nanosuspension gel for enhanced transdermal treatment for overactive bladder syndrome.

Oxybutynin (OXY) is the most common drug to treat overactive bladder (OAB) syndrome. Transdermal administration is a more ideal route replacing oral administration to resolve problems of low bioavailability and severe side effects. However, commercial transdermal products of OXY frequently cause skin irritation and low permeation efficiency arising discontinued medication. Here, oxybutynin nanosuspension (OXY-NS) and its gel preparation (OXY-NG) were constructed to resolve these issues. In vitro permeation test and in vivo pharmacokinetics study confirmed that OXY-NG significantly enhanced the transdermal permeation of OXY, about 4-fold and 3-fold higher than oxybutynin coarse suspension (OXY-CG), respectively, and in vitro retention test certified that OXY-NG increased OXY concentration especially in viable epidermis (VE) and Dermis (about 3 times that of OXY-CG), consequently improving the bioavailability. Skin irritation assay demonstrated that OXY-NG would not trigger skin adverse effects. In addition, selectively blocking hair follicles test evidenced that hair follicles pathway played an important role in OXY-NS transdermal delivery. In general, by virtue of excellent drug loading, low toxicity and ease of scale-up, OXY-NG is a promising strategy to ameliorate skin permeation of insoluble OXY for better transdermal treatment for OAB, hence increasing its bioavailability, reducing adverse effects, and achieving good patient compliance.

The Twilight Zone: Oxybutynin Overuse Exacerbating Delirium.

Anticholinergic medications, such as oxybutynin, are first-line pharmacologic therapies in overactive bladder. However, the cognitive adverse effect profiles of frequently used anticholinergic medications are extensive and limit their use in older patients. Additionally, many older patients continue on anticholinergic therapy if adverse effects are not self-reported by the patient or detected by the provider.Here, we present a case of a 73-year-old male with a history of major neurocognitive disorder, in which unreported oxybutynin overuse led to repeated delirious states, erratic driving, and subsequent psychiatric hospitalizations. During his hospitalizations, he displayed progressively more linear thought processes and improved insight without clear etiology. After a more thorough history of his medication use was obtained, he disclosed that he would often take additional doses of oxybutynin to prevent incontinence during car rides and had done so prior to recent hospitalizations.Our example highlights the importance of thorough history taking, medication review, reducing polypharmacy, careful patient education about medications with psychiatric adverse effects, and, importantly, the avoidance of anticholinergic medication prescription in older patients.

The cognitive effect of anticholinergics for patients with overactive bladder.

Overactive bladder (OAB) is often treated with medications that block the cholinergic receptors in the bladder (known as anticholinergics). The effect of this medication class on cognition and risk of dementia has been increasingly studied over the past 40 years after initial studies suggested that the anticholinergic medication class could affect memory. Short-term randomized clinical trials demonstrated that the administration of the anticholinergic oxybutynin leads to impaired memory and attention, and large, population-based studies showed associations between several different anticholinergic medications and dementia. However, trials involving anticholinergics other than oxybutynin have not shown such substantial effects on short-term cognitive function. This discordance in results between short-term cognitive safety of OAB anticholinergics and the long-term increased dementia risk could be explained by the high proportion of patients using oxybutynin in the OAB subgroups of the dementia studies, or a study duration that was too short in the prospective clinical trials on cognition with other OAB anticholinergics. Notably, all studies must be interpreted in the context of potential confounding factors, such as when prodromal urinary symptoms associated with the early stages of dementia lead to an increase in OAB medication use, rather than the use of OAB medication causing dementia. In patients with potential risk factors for cognitive impairment, the cautious use of selected OAB anticholinergic agents with favourable physicochemical and pharmacokinetic properties and clinical trial evidence of cognitive safety might be appropriate.

Real-life experience with oral oxybutynin long-term continuous therapy in severe hyperhidrosis and systematic review of the literature.

Hyperhidrosis is a disorder of excessive sweating severely impacting on patient's quality of life (Qol). Several studies have been published about oral oxybutynin, but no studies focused on the achievement of complete clinical and Qol response. The aim of this study was to report our real-life experience with oral oxybutynin in patients with severe hyperhidrosis significantly affecting their Qol. In this cohort retrospective study, we enrolled, in a 3-year period, patients affected by severe hyperhidrosis with poor Qol, continuously treated with oral oxybutynin. Our outcome was the obtainment of complete clinical and Qol improvement. A systematic review of the literature was also performed reporting efficacy and safety of oral oxybutynin for primary hyperhidrosis. We enrolled 62 patients, of which 53 (85.5%) received a mean daily dose of 10 mg and nine (15.5%) of 5 mg. Complete clinical response was achieved in 77.4% (48/62) of cases, while complete Qol improvement occurred in 51.6% (32/62) of cases. Adverse events were only reported as mild, with dry mouth being the most frequently observed (16.1%). Kaplan-Meier survival analysis highlighted that both median clinical and Qol complete responses were reached after 1 year of continuous therapy with oral oxybutynin. The main limitation of our study is the small number of patients enrolled. Long-term therapy with oral oxybutynin for severe hyperhidrosis, continuously administered at a mean daily dosage of 5 to 10 mg, allowed the majority of our patients to reach both clinical and Qol complete improvement, without significant adverse events.

Craniofacial hyperhidrosis: Clinical characteristics and response to treatment in a cohort of 97 patients treated with oral oxybutynin.

The term craniofacial hyperhidrosis (HH) refers to HH that affects the face and/or scalp. Few studies have focused on this specific location, and even fewer distinguish between the two areas. Our study aims are to describe the clinical characteristics of patients with craniofacial HH, specifying whether the condition affects the scalp, face or both, and to compare these cases with those recorded at other locations. As secondary objectives, we determine the effectiveness and adverse effects of oral oxybutynin (OOx), and assess patients' adherence to treatment. This prospective observational study was carried out with respect to the period 2007-2019. All patients diagnosed with HH of the scalp and/or face and who were treated with OOx at our HH unit were included in the study group. Of 292 patients treated with OOx, 97 (33.2%) had craniofacial HH. Of these, 4 (4.1%) presented HH exclusively on the scalp, 56 (57.7%) exclusively on the face and 37 (38.1%) in both locations. The patients in the latter category (compared with those with exclusively facial HH) were significantly older than the others, had a later onset of HH, a greater frequency of secondary HH, less simultaneous involvement of the classical areas of primary focal HH (the palms, soles, and armpits) and greater generalized HH and of the trunk. No significant differences were observed between the three locations (face, scalp, or both) regarding the efficacy and side effects of OOx. The patients with exclusively facial HH presented greater adherence to treatment.

Effect of Antimuscarinic Drugs on Cognitive Functions in the Management of Overactive Bladder in Elderly.

BACKGROUND: overactive bladder (OAB) affects 17-41% older adults in community dwelled setting. For several years, antimuscarinics have been validated as the first-line medical treatment for OAB. Despite abundant data obtained from clinical trials provisions the use of antimuscarinics, investigation about the effect of this drug on cognitive function in elderly remains scarce. The objective of this study is to investigate the effect of antimuscarinics therapy on cognitive functions in OAB geriatric patients. METHODS: this study design is a systematic review and meta-analysis. Studies were collected using several search engines; those were PubMed, Science Direct, Cochrane, and EBSCOhost using predetermined MeSH keywords with Boolean operators. Selection of studies was done by three reviewers. Studies which fulfilled the inclusion and exclusion criteria underwent full-text review. For every selected full text, we extracted the following data if available: patients demographics, types of antimuscarinics used, placebo, dose, follow-up period, and Mini-Mental State Examination (MMSE) total score. RESULTS: a total of 8 studies from an initial 146 publications were selected. There were 8 antimuscarinic agents evaluated in the studies, including Oxybutynin, Darifenacin, Tolterodine, Trospium, Imidafenacin, Propiverine hydrochloride, Fesoterodine, and Solifenacin. Oxybutynin was shown to have largest effect towards the decline of MMSE score [Mean difference: -2.90; 95% CI: -4.07, -1.73]. Darifenacin and Tolterodine were also shown to be significant in the decline of total MMSE score, although still inferior to Oxybutynin. CONCLUSION: the use of most antimuscarinics medication has little to no effect towards the cognitive function in the management of overactive bladder in elderly patients. However, Oxybutynin, Darifenacin, and Tolterodine was shown to have significant decrease in cognitive functions, as shown in the decline of total MMSE score.

Oxybutynin in primary hyperhidrosis: A long-term real-life study.

Hyperhidrosis is a condition of excessive sweating beyond physiological parameters that can seriously impair quality of life. This study aims to evaluate the oral oxybutynin effectiveness in hyperhidrosis, besides its tolerance and safety. In a real-life long-term study, 30 patients with primary hyperhidrosis and Hyperhidrosis Disease Severity Scale (HDSS) with score of at least two were submitted to a questionnaire to assess demographic data, HDSS and side effects of oxybutynin. Most patients were women (n = 23, 76.7%), median age was 40 years (range 12-70, SD 17.5) and 17(56.7%) had family history of hyperhidrosis. The most common hyperhidrosis form was axillary (n = 15, 50.0%), followed by palmoplantar (n = 8, 26.7%), cranio-facial (n = 11, 36.7%) and trunk (n = 5, 16.7%). Median duration of treatment was 2.4 years (range 1-6 years, SD 1.3). Thus, all patients used oxybutynin for at least 1 year, 30% for 2 years, 20% 3 years, 17% 4 years, and 3% 6 years. There was a significant improvement in HDSS score of patients (P < .001). This real life study suggests that oxybutynin is effective and safe for treatment of hyperhidrosis, both in children and adults, with mild and tolerable side effects, with significant improvement in HDSS.

Survival study of treatment adherence by patients given oral glycopyrrolate for hyperhidrosis following treatment failure with oral oxybutynin.

Oral anticholinergics such as oxybutynin (OOx) and glycopyrrolate (OGly) are frequently used in the management of hyperhidrosis. Although OOx is considered currently the anticholinergic drug of first choice, OGly is a safe and effective alternative if OOx fails. The aim of this study was to identify the main variables associated with treatment adherence by patients receiving OGly, for whom previous treatment with OOx had failed. A prospective study was conducted of patients with hyperhidrosis receiving treatment with OGly in the period 2012 to 2019. Epidemiological variables, treatment details, effectiveness and adverse effects were recorded. A total of 58 patients (41 women), with a mean age of 35.9 years, were included in the study. The median follow-up period was 32 months. At 3 months, 70.7% of the patients had responded to treatment (excellent response: 75.6%), and adverse effects were reported by 70.7%. At 12 months, 53.4% had responded (excellent response: 74.2%), with adverse effects in 70.9%. The variables associated with poorer adherence were affected areas: palms of the hands, soles of the feet and armpits. The only variable associated with greater adherence was the generalized presence of hyperhidrosis. Our results provide valuable insights into the outcomes achieved when OGly is used to treat hyperhidrosis.

Tolerance of oral oxybutynin in the treatment of hyperhidrosis.

Oral oxybutynin (OOx) is an effective and safe treatment for the treatment of hyperhidrosis (HH). However, in some patients a loss of efficacy during prolonged treatment has been observed. Analysis of these cases could enable us to identify patients susceptible to OOx tolerance. An alternative treatment might then be considered. To assess tolerance to OOx in the treatment of HH. Secondarily, to assess epidemiological data and the duration of efficacy, together with the probable causes of any loss in this respect. Retrospective study of patients who started treatment with OOx for HH during the period 2007 to 2017 and who either abandoned this treatment due to loss of efficacy or needed higher daily doses to maintain the initial efficacy. Epidemiological data were collected, the duration of the efficacy of OOx was recorded and the possible causes of loss of efficacy were considered. The development of tolerance was suspected in 18 patients (8.5%) of the 211 who had previously responded to OOx. Thirteen patients abandoned OOx due to its lack of efficacy and five had to increase the dose in order to maintain efficacy. In seven patients, tolerance to the drug appeared in the first year of treatment, while in the remaining 11, the tolerance appeared later. Most patients achieved and maintained good control of HH with long-term OOx. However, in some cases the efficacy of the drug decreases. The study analysis did not produce findings enabling us to predict a loss of treatment efficacy.

Long-term results of the treatment of primary hyperhidrosis with oxybutynin: follow-up of 1,658 cases.

BACKGROUND: Hyperhidrosis (HH) is characterized by exaggerated sweating in a specific region due to hyperfunction of the sweat glands. In the late 2000s, we started treating patients with an anticholinergic, oxybutynin, that was not being used until then. OBJECTIVES: To present, after 12 years of utilizing this medication in our service, the substantial experience obtained with the use of oxybutynin as an initial treatment of HH in a large series of 1,658 patients. METHODS: We analyzed 1,658 patients treated with oxybutynin for HH from May 2006 to June 2018. The patients were divided into four groups according to the main site of HH: the plantar group, the axillary group, the facial group, and the palmar group. To measure the degree of satisfaction, a quality of life (QoL) questionnaire was used. RESULTS: Pre-treatment QoL was poor or very poor in more than 94% of the cases, and the palmar group had the worst quality of life. After treatment, we observed an improvement in the quality of life in 77% of patients. More than 70% of the patients in all groups present moderate or optimal subjective clinical improvement in sweating after treatment. The group with the best result was the facial group. Intense dry mouth was reported in 24.9% of all patients in all groups. CONCLUSIONS: This study included a large number of patients followed for a long period and demonstrated the good effectiveness of treatment with oxybutynin for hyperhidrosis in the main sites of sweating.

Comparative study of efficacy and safety of 45% mandelic acid versus 30% salicylic acid peels in mild-to-moderate acne vulgaris.

BACKGROUND: Chemical peels have become a popular modality in the treatment of acne vulgaris (AV). Mandelic acid (MA) is a new emerging peeling agent for AV owing to its antibacterial and anti-inflammatory properties. Hence, it is worthwhile to evaluate the effectiveness and safety profile of this newer agent and to compare it with an older established peeling agent, salicylic acid (SA) in the treatment of AV. OBJECTIVE: Comparison between therapeutic efficacy and safety of 45% MA peel with 30% SA peel in Indian patients suffering from mild-to-moderate facial AV. METHODS: A total of 50 patients suffering from mild-to-moderate AV were randomly divided into two groups, with one receiving 30% SA peels and the other receiving 45% MA peels at an interval of 2 weeks for six sessions. Total duration of the study was 12 weeks. Michaelsson acne scores (MAS) and clinical photographs were used to evaluate the efficacy of therapy objectively. Adverse effects of both the agents were also noted at each visit. RESULTS: Both agents showed almost equal efficacy in improving mild-to-moderate AV. Salicylic acid was found better in treating noninflammatory lesions, while MA had an upper hand in treating inflammatory lesions. Overall, there was no significant difference between the two peels in improving MAS and percentage decrease in MAS. However, adverse effects were lesser with MA peels. CONCLUSION: About 45% MA peel was found to be equally effective as 30% SA peel in mild-to-moderate facial AV. However, safety and tolerability of MA peel were better than SA peel.