Abstract
Not all medications arrive from a disciplined path of translational drug development; sometimes, the route of discovery involves serendipity. A drug developed for controlling urinary urgency, oxybutynin, is reviewed here as a highly effective treatment for excessive sweating (hyperhidrosis). Its use in Parkinson disease is described in a case report.
Not all medications arrive from a disciplined path of translational drug development; sometimes, nothing more than serendipity is the route of discovery for a useful treatment. This has been the situation for a “hidden gem” described here: a brief publication that its author re-discovered many years later. 1 The topic is a highly effective treatment for excessive sweating, using a drug initially developed for controlling urinary urgency. Oxybutynin treatment of hyperhidrosis (HH), which can be defined as excessive and inappropriate sweating, is reviewed here in a case report illustrating its effectiveness against this relatively common and challenging non-motor feature of Parkinson disease (PD).
For dissipating body heat, sweating is a physiological response generated by thermoregulatory centers of the anterior hypothalamus. Sweating also can be enacted via activation of limbic system circuitry. Causes for HH include certain medications
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and various neurological disorders (including PD3–6). Some patients with PD experience this problem in the form of generalized and drenching sweats.
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For these patients, episodic HH can arise from the peak effects of levodopa or, most commonly, during the wearing off of its drug action.3,5,7,8 HH can also be experienced unrelated to the timing of medications and, in some patients, even prior to the start of dopaminergic therapy. In his 1888 textbook on diseases of the nervous system, the British neurologist William Gowers MD reported that some of his PD patients affected by HH might experience an initial sense of feeling hot “…very frequently accompanied by increased perspiration, which may be general and profuse on the least exertion of the body or mind. One patient could not dictate the simplest letter, even in winter, without first having his coat taken off, so intense was the perspiration caused.” [
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, page 1009]
Although topical antiperspirants like aluminum salts and the anticholinergic drug glycopyrrolate have been used for HH in various clinical situations,
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improvements offered by these treatment options are quite limited. Intradermal botulinum toxin injections can provide localized relief of HH but this treatment is painful, costly, and not suitable for large skin territories. For patients with HH associated with dyskinesia or wearing-off, adjustment of levodopa dosing may ameliorate the triggering of HH. However, a clinical observation from 1988 (initially reported as the treatment
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for a unique clinical syndrome of hypothermia and HH
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) has led to another effective option for treating excessive sweating in idiopathic HH14,15 and, in the author's experience, also in PD: At age 63, this patient started to experience unpredictable episodes of profuse bilateral sweating located to her scalp and at the back of her neck and shoulders. She needed a towel to mop up sweat in these regions. These events occurred several times daily, at random times unrelated to dosing, dyskinesia, or wearing off of levodopa effect. Although for many years she has experienced mild anxiety (and regularly uses alprazolam 0.125 mg three times per day), she does not associate sweating episodes with anxious feelings or stressful situations. Sweating episodes never occurred prior to age 63 and have not been associated with exercise, sleep, or other symptoms of autonomic impairment or hyperactivity. She does not experience excessive axillary sweating. Over 8 years of stereotyped diaphoretic attacks, there has been no change in their frequency or other features. After several months of episodic sweating, oxybutynin was prescribed (5 mg each morning). Immediately afterwards and continuing 8 years later, there have been no recurrences of HH. No adverse effects from oxybutynin have been reported, Two trials of discontinuing oxybutynin demonstrated that the use of the drug did not result in impairment of short-term recall or other cognitive operations. These off-medication trials also confirmed the drug's continuing benefits against HH.
Although oxybutynin treatment of HH has not been evaluated in a randomized controlled clinical trial, the author's additional experience in prescribing this drug for other PD patients has been mostly positive (both for its efficacy and tolerability). Oxybutynin is not without the risk for adverse reactions, however, as it can cause cognitive impairment and it can add to the anticholinergic burden of concomitant medications.18,19 In addition to typical anticholinergic effects, the regular use of oxybutynin has also been associated with anxiety and depression 20 and in one instance, with clinically-significant hyperthermia. 21 For treating HH, an optimal dose has not been established but reported clinical experience suggests that it is within the range of drug intake used for treating overactive bladder spasms (5–10 mg/day).14,15
In summary, the serendipitous discovery of oxybutynin as an effective therapy for HH 1 offers the potential for controlling this relatively common problem experienced by some PD patients.4,6 Like several other repurposed and off-label medications found to be useful for symptomatic treatment of PD, this “hidden gem” of pharmacological intervention offers a strategy for easing the one of the many burdens of living with this disorder.
Footnotes
Funding
The author received no financial support for the research, authorship, and/or publication of this article.
Declaration of conflicting interests
The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.