Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.
Donepezil and Memantine for Moderate-Severe AD
Source: Howard R, et al. N Engl J Med 2012;366:893-903.
The choice of if and when to employ pharmacotherapy in the management of Alzheimer's disease (AD) is not an easy one. Early in the disease process (mild-moderate AD) where clinical trials have demonstrated beneficial outcomes, albeit of debatable clinically relevant magnitude clinicians and caregivers may be least motivated to treat, since disease status is relatively less problematic and measureable benefits are smaller. In moderate-severe AD, memantine (MEM) has demonstrated beneficial effects. A single, never-replicated trial of the addition of MEM to donepezil (DON) in mild-moderate AD had favorable outcomes. Data on whether cholinesterase inhibitors provide improved outcomes as the disease progresses to the moderate-severe stages have been lacking. Indeed, there is some support for discontinuation of cholinesterase inhibition when AD progresses to the severe stage.
Howard et al randomized patients (n = 295) with moderate-severe AD already on treatment with DON to one of four groups: continued DON alone, MEM alone, continued DON plus MEM, or placebo alone. Patients were followed for 1 year, measuring outcomes by means of the Standardized Mini-Mental State Examination (SMMSE) and Bristol Activities of Daily Living Scale (BADLS). The minimum clinically important difference on these scales is 1.4 points and 3.5 points, respectively.
At 1 year, scores in the group that continued DON were superior to the placebo group as measured by the SMMSE (1.9 points difference); on the BADLS, the score was statistically significantly improved but failed to meet the minimum clinically important difference threshold. Neither substitution of MEM for DON nor addition of MEM to DON provided clinically important improvement.
In moderate-severe AD, these data support continuation of DON, but not substitution or augmentation with MEM.
Treating Hyperhidrosis with Systemic Therapy
Source: Walling HW. J Am Acad Dermatol 2012;66:387-392.
Even though hyperhidrosis (HHD) has a prevalence almost three times as great as rheumatoid arthritis (± 3% vs ± 1%), clinician awareness and management of this disorder are often suboptimal. Although the palms of the hands and plantar surfaces of the feet are the most commonly involved sites, axillary, craniofacial, and multisite involvement is reported. The HHD disease severity scale describes moderate HHD as "tolerable but sometimes interferes with daily activities," and severe as "barely tolerable to intolerable, that frequently to always interferes with daily activities." HHD is not just a quality-of-life issue; skin infections are more common in HHD sufferers.
The mainstay of HHD treatment for several decades has been topical drying agents, especially with those containing aluminum chloride. Iontophoresis, botulinum toxin, and even sympathectomy have demonstrated some efficacy, but the expense and inconvenience of such interventions is an obstacle.
Walling performed a chart review of HHD patients seen in an academic department of dermatology who had received one of three systemic agents to treat HHD: glycopyrrolate, oxybutynin, or clonidine.
Glycopyrrolate was effective in 30 of 45 patients; among glycopyrrolate treatment failures, six of 15 were nonresponders, and nine had adverse anticholinergic effects (e.g., dry mouth). Clonidine was effective in six of 13 patients; among clonidine treatment failures, three were nonresponders and four experienced hypotension. A single patient responded favorably to oxybutynin (an anticholinergic typically used for overactive bladder).
Because no one treatment for HHD is uniformly effective, clinicians must become aware of alternative therapies. Previous literature has suggested that systemic treatments might not be well tolerated, yet efficacy in this data set was good with no serious adverse effects. Systemic treatments may help patients with HHD.
Can Male Pattern Baldness Predict BPH?
Source: Arias-Santiago S, et al. J Am Acad Dermatol 2012;66:401-408.
Aside from genetic influences, testosterone (TST) and dihydrotestosterone (d-TST) play an important role in both benign prostatic hyperplasia (BPH) and male pattern baldness (also known as androgenetic alopecia). For BPH, conversion of TST to d-TST by means of 5-alpha-reductase (5-AR) results in stimulus for prostate gland growth. In the prostate, 5-AR of both type 1 and type 2 are operant. 5-AR blockers (e.g., finasteride, dutasteride) have been shown to shrink prostate size.
In the scalp, only 5-AR type 2 is functional. In susceptible individuals, conversion of TST to d-TST in the scalp results in follicular diminution, producing hair loss. Might the same susceptibility to male pattern baldness be reflected in an increased incidence or severity of BPH?
Arias-Santiago et al compared metrics pertinent to BPH in men with and without early-onset male pattern baldness. Although there was no difference between groups in levels of testosterone, prolactin, other gonadal steroids, or testosterone-binding proteins, the men with early male pattern baldness had significantly greater levels of PSA, more lower urinary tract symptoms consistent with BPH, greater prostate gland size as measured by ultrasound, and lower urinary flow rates.
Clinicians may wish to look for BPH-related symptoms in men with early androgenetic alopecia.
The choice of if and when to employ pharmacotherapy in the management of Alzheimer's disease (AD) is not an easy one.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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