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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Thomas Jefferson University
Sponsor:
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT01588717
First received: April 26, 2012
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Hyperhydrosis
Depression
Drug: Glycopyrrolate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study to Measure and Treat Antidepressant-Induced Excessive Sweating With Glycopyrrolate (AIDES-G)

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • Clinical Global Impression- Improvement scores [ Time Frame: 9 weeks per subject ] [ Designated as safety issue: No ]
    The main comparison will be the end-of-study mean v. the baseline mean


Secondary Outcome Measures:
  • change in mean of patient rated severity of sweating for each week, and change in mean skin conductance for each week [ Time Frame: 9 weeks per subject ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: April 2012
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: glycopyrrolate
glycopyrrolate 2 to 6 mg/day
Drug: Glycopyrrolate
glycopyrrolate 2 to 6mg/day
Other Names:
  • Cuvposa®
  • Robinul®
  • Robinul® Forte

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01588717

Contacts
Contact: Kelly Huhn, BS 215-503-1662 Kelly.Huhn@Jefferson.edu

Locations
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Kelly Huhn    215-503-2833      
Principal Investigator: Rajnish Mago, MD         
Sponsors and Collaborators
Thomas Jefferson University
Investigators
Principal Investigator: Rajnish Mago, MD Thomas Jefferson University
  More Information

No publications provided

Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT01588717     History of Changes
Other Study ID Numbers: AIDES-G
Study First Received: April 26, 2012
Last Updated: February 4, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Thomas Jefferson University:
Hyperhydrosis
Excessive Sweating
Sweating
Depression
Antidepressant

Additional relevant MeSH terms:
Hyperhidrosis
Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Sweat Gland Diseases
Skin Diseases
Antidepressive Agents
Glycopyrrolate
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Adjuvants, Anesthesia
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014