Excessive Sweating Caused by Antidepressants: Measurement and Treatment With Glycopyrrolate (AIDES-G)

Overview

The study consists of measurement of antidepressant-induced excessive sweating and its treatment with an experimental medication, glycopyrrolate (approved to treat ulcers), which will be added to the antidepressant. This is an open-label study (no placebo group or concealment of the nature of the treatment) that will last 8 weeks, including two weeks of baseline measurement without treatment with the study medication followed by six weeks of treatment with the study medication. The study is pilot study by Dr. Rajnish Mago that is based on the hypothesis that glycopyrrolate will be effective in reducing the severity of excessive sweating caused by antidepressant treatment, and will have minimal side-effects.

Sweating is a common and bothersome adverse effect of treatment with antidepressants. Tricyclics and selective serotonin reuptake inhibitors (SSRIs) have both been clearly shown to cause sweating. Increased sweating has been reported with venlafaxine (Pierre and Guze, 2000) and bupropion (Feighner et al. 1984) as well. It is unclear to what extent tolerance develops to antidepressant-induced sweating. It may continue to be a problem even after 6 or more months on the antidepressant (e.g., Mavissakalian et al., 2002). The prevalence of sweating with SSRIs is estimated to be between 7% and 19% depending on the drug (Ashton \& Weinstein 2002). According to the Physician's Desk Reference, excessive sweating occurs in 3-11% patients in clinical trials of SSRIs. Considering the fairly high prevalence of excessive sweating during antidepressant use and its consequences of patient distress and treatment noncompliance, it is important that more intensive efforts be made to understand the phenomenon and to systematically study potential treatments for it. The mechanism of antidepressant-induced sweating has not been clearly elucidated and there is no generally accepted treatment for it. Initially, a reduction in the dose may be attempted to resolve antidepressant-induced sweating. However, a reduction of dose may not always be helpful (Leeman, 1990; Ashton \& Weinstein 2002) as it has been noted that the presence of sweating is not a clear dose-related symptom. As well, reducing the dose of the antidepressant may lead to a worsening of depression and therefore be an unrealistic alternative. Antiadrenergic drugs like clonidine and terazosin (Feder, 1995; Mago and Monti, 2007; Mago et al., 2009) may be effective for the treatment of antidepressant-induced excessive sweating because the nervous system control of sweating is initially mediated by adrenergic receptors. However, antiadrenergic treatment may be associated with a decrease in blood pressure in some patients, which may lead to dizziness, especially on standing up. Also, the improvement in excessive sweating may not be complete. Therefore, additional approaches are needed. Sweat glands are innervated by nerve fibers that release acetylcholine. Anticholinergic medications could be used as a potential treatment for the excessive sweating. In case reports, the anticholinergic drug benztropine has been successfully used to treat antidepressant-induced excessive sweating (Garber and Gregory, 1997; Feder and Guze, 2000). However, this has not been confirmed in a clinical trial. Also, benztropine readily crosses the blood-brain barrier; therefore, in addition to its desired effect peripherally on the sweat glands, it tends to cause cognitive side effects through its central effects. Glycopyrrolate is an anticholinergic medication that is preferred for a variety of clinical uses because it does not cross the blood-brain barrier to a great extent. It has been used for many years by anesthesiologists to dry secretions during surgical procedures. In a case series based on chart review (Tran et al., 2009), it was found to be effective for antidepressant-induced excessive sweating.