Hyperhidrosis: oral glycopyrronium bromide

Evidence review: efficacy

No randomised controlled trials examining the effectiveness of oral glycopyrronium bromide for treating hyperhidrosis were identified.

Four case series were identified which examined the use of oral glycopyrronium bromide in people with primary (idiopathic) hyperhidrosis (3 in mainly adult populations and 1 in children or young people), and 1 case series that examined oral glycopyrronium bromide in people with compensatory hyperhidrosis after thoracic or lumbar sympathectomy.

Bajaj and Langtry (2007) retrospectively reviewed the case notes of 24 adults with primary hyperhidrosis (mean age 33 [range 19–62 years]; 70% female) who had been treated with oral glycopyrronium bromide between 2001 and 2004 at Sunderland Royal Hospital. Hyperhidrosis was focal in 15 people (most commonly axillae in 9 people, and palms of hands or soles of feet in 6 people) and generalised in 9. Previous treatments (aluminium chloride in 17, beta-blockers in 7, diltiazem in 4, clonidine in 3 and propantheline in 2) were either ineffective or not tolerated. Three people had tried no previous treatment.

Oral glycopyrronium bromide tablets were given at a dose of 2 mg twice daily initially and increased to 2 mg 3 times daily depending on response and tolerability. One person took 4 mg twice daily and 1 person took 2 mg once daily. Duration of treatment is not reported.

Follow-up was available for 19 people, 15 of whom (79%) had hyperhidrosis that responded to glycopyrronium bromide according to their case notes. The degree of treatment response could not be accurately assessed from the patients' case notes, so the absolute responses were recorded. Four people stopped treatment because of lack of effectiveness. Eight of the 19 people completed a 10-point linear analogue scale reporting the severity of their hyperhidrosis and quality of life before and after treatment. Response was rated as excellent (an improvement of 9 points or more) in 3 people, improved (an improvement of up to 8 points) in 4 people and no improvement in 1 person.

Lee et al. (2012) retrospectively reviewed the case notes of 36 people with primary hyperhidrosis (mean age 28±14.9 years; 58% female) who had attended a pain clinic in South Korea between 2007 and 2009, and had accepted treatment with oral glycopyrronium bromide. Participants were newly diagnosed with hyperhidrosis and had received no previous treatment for this condition. Fifty-three per cent of participants had symptoms in 3 or more body areas, 28% in 2 areas and 19% in only 1 area of the body.

Oral glycopyrronium bromide tablets were given at a dose of 1 mg twice daily initially and increased by 2 mg per day, depending on response and tolerability, up to a maximum of 8 mg daily. Response to treatment was assessed by questionnaire before and after treatment. This included questions from the Keller scale and Milanez de Campos scale, which examined any improvement in hyperhidrosis symptoms. The Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were used to assess psychological effects, and Short Form 36 (SF-36) was used to assess effects on quality of life. The function of the autonomic nervous system was assessed on a 90-question test (the Autonomic Nervous System [ANS] scale). Duration of treatment was not reported.

A total of 66 people were given oral glycopyrronium bromide; results are only reported for the 36 who completed follow-up and all questions on the questionnaire. After treatment, 75% of 36 people showed a decrease in sweating on the Keller scale. The mean score reduced from 60 before treatment to 35.9 after treatment (p<0.01). No further details are reported on this scale, such as what the total score is or the change in score that would indicate a clinically significant improvement. The mean score on the Milanez de Campos scale reduced from 57.9 before treatment to 38.7 after treatment (p<0.01). The authors reported that this scale measures the discomfort level of hyperhidrosis in everyday life, but no further details on this scale were given. Glycopyrronium bromide had no effect on BDI or ANS scores, but improved BAI scores (mean score change from 12.1 to 9.7; p=0.03). SF-36 results were not reported.

Walling (2012) retrospectively reviewed the case notes of 59 people (mean age 29 [range 14–59 years]; 63% female) who had been treated with oral therapy for primary hyperhidrosis at the University of Iowa's Department of Dermatology between 1993 and 2005. A total 71 people had been treated with oral medications during this time; 59 had follow-up data available (mean duration 19.5 months) and were included in the analysis. Seventy-one per cent of the 59 participants (n=42) had focal hyperhidrosis of the axillae, palms or soles; 14% (n=8) had focal hyperhidrosis of the face and scalp; and 15% (n=9) had generalised hyperhidrosis. In 95% of participants (n=56), their condition had failed to respond to other treatments, including aluminium chloride (n=55); iontophoresis (n=13); oral medications, such as propranolol, clonidine, benzodiazepines, and in 3 people glycopyrronium bromide (n=13), botulinum toxin (n=1) and sympathectomy (n=1).

Of the 59 participants who had been treated with oral therapy in this case review, 45 had received oral glycopyrronium bromide tablets. Three-quarters of those treated (n=34) took this in addition to other treatment (including aluminium chloride, botulinum toxin and iontophoresis).

Thirty out of 45 participants (67%) had hyperhidrosis that responded to treatment with oral glycopyrronium bromide according to their case notes. Absolute responses to therapy were recorded because degrees of response could not be determined from most patient records. The dose of glycopyrronium bromide was titrated depending on response and tolerability. Among 'responders' the most common dose was 1 mg once daily (n=12), followed by 1 mg twice daily (n=6), 2 mg twice daily (n=5), 2 mg once daily (n=4), 3 mg once daily (n=2) and 3 mg twice daily (n=1).

Of the 30 'responders', 14 people reported a degree of improvement. This was reported as 'great', 'excellent' or 'more than 75%' in 6 people and 'some', 'moderate' or 'more than 50%' in 8 people. Of the 15 people whose condition did not respond to treatment with oral glycopyrronium bromide, 6 out of 45 (13%) were defined as 'non-responders' (a person who reported 'no', 'slight' or 'less than 50% improvement', or stopped treatment because of lack of efficacy) and 9 out of 45 (20%) had experienced adverse effects leading to treatment withdrawal.

Paller et al. (2012) retrospectively reviewed the case notes of 31 children or young people (aged 3–17 years; mean age at hyperhidrosis onset 10.3 years; mean age when prescribed oral glycopyrronium bromide 14.8 years; 74% female) with primary hyperhidrosis focal to the palms, soles and/or axillary areas (greater than 6 months duration and of a severity that interfered with daily activity), who were treated with at least 1 dose of oral glycopyrronium bromide between 2001 and 2010 at a children's hospital in Chicago. Almost all children (97%) had tried previous topical therapy with 20% aluminium chloride, 11% had tried botulinum toxin and 7% iontophoresis.

Oral glycopyrronium bromide tablets were given at a dose of 1 mg once or twice daily initially and increased by 1 mg per day, depending on response and tolerability, to a maximum of 3 mg twice daily (2 mg twice daily if less than 12 years of age). Thereafter the dose was tapered to maintain control. The mean daily dose was 2.2±1.3 mg. Just over a quarter of children continued with aluminium chloride intermittently as needed to maintain control.

Overall 90% (28) of 31 children or young people experienced an improvement in hyperhidrosis with oral glycopyrronium bromide treatment. Based on case notes or verbal interview, this was defined as 'major improvement' in 20 children or young people and 'adequate improvement' in 8. Three children (10%) had no improvement but the condition worsened in none. The duration of treatment ranged from 4 months to 10 years in children who found improvement, and less than 1 month in the 3 who found it ineffective. In all children, the response was lost within a day or 2 of stopping glycopyrronium bromide treatment.

Gong and Kim (2013) retrospectively reviewed the case notes of 19 adults or young people (age range 15–76 years) who had received oral glycopyrronium bromide to treat compensatory hyperhidrosis after thoracic or lumbar sympathectomy at a pain clinic in South Korea between 2007 and 2012 and had complete follow-up available. Compensatory hyperhidrosis develops in other parts of the body unrelated to the area treated by surgery. The site of primary hyperhidrosis varied (hand, foot, face, neck or axillae), as did the site of compensatory hyperhidrosis, which included the chest, back, abdomen and thighs.

Oral glycopyrronium bromide tablets were given at a dose of 1 mg twice daily initially and increased by 2 mg per day depending on response and tolerability up to a maximum of 8 mg daily. Response to treatment was assessed by questionnaire at baseline and after 1 month of treatment. This included the Milanez de Campos scale, which measures the everyday discomfort from hyperhidrosis symptoms, the modified Beck Depression and Anxiety Inventories (mBDI and BAI) to assess psychological effects, and the ANS scale, to assess the function of the autonomic nervous system.

At 1 month, 17 of the 19 participants (89%) who received oral glycopyrronium bromide and had complete follow-up had a reduction in Milanez de Campos score from baseline (mean score reduced from 60.4 to 34.2; p<0.05). The mBDI score also decreased in 89% of participants (mean score reduced from 17.8 to 12.8; p<0.05) and the BAI score decreased in 79% of participants (mean score reduced from 12.5 to 9.3; p<0.05). There was no statistically significant effect on the ANS scale.