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

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.

Inclusion Criteria:

1. Age 18 years or older

2. Presence of excessive sweating by self-report

3. Within 2 months of initiation of an antidepressant or increase in the dose, there was
a clear and substantial increase in sweating not explained by undue external warmth,
exercise, or other reason. If treatment with the antidepressant was interrupted, did
not persist for more than 6 weeks during that interruption

4. Treatment with the antidepressant is deemed to be clinically necessary due to
substantial benefit from the antidepressant that is causing the excessive sweating,
and failure to respond to or tolerate an alternative antidepressant

5. Decrease in dose of the antidepressant is either not clinically viable due to the
benefit obtained at the current dose OR decrease in dose of the antidepressant has
been tried but was not effective.

6. Excessive sweating has persisted for at least 4 weeks prior to baseline assessment

7. The excessive sweating is rated by the patient as at least moderately bothersome.

8. Episodes of excessive sweating occur at least twice a week for last 4 weeks

9. Use of effective contraception (e.g., sterilization, oral contraceptives, condom with
spermicide, etc)

Exclusion Criteria:

1. Presence of another known disease that could potentially cause excessive sweating

2. Failure to respond in the past to anticholinergic treatment for excessive sweating

3. Previous allergic reaction to glycopyrrolate

4. Narrow angle glaucoma

5. Significant cardiac disease including cardiac or heart block

6. Patients with known hot-flashes or who are menopausal

7. History of urinary retention

8. History of seizures

9. Pregnancy or breastfeeding

10. Other significant medical illness or laboratory abnormalities that, in the judgment
of the PI, would increase risk to the patient