Iontophoresis uses a medical device, water, and a direct electrical current to pass an ionized substance through intact skin. The process has been used to treat palmar and plantar hyperhidrosis for more than 70 years. In fact, tap water iontophoresis has long been considered by many dermatologists to be the first line of treatment for hyperhidrosis of the palms and soles.[7,134] Iontophoresis can also be used to treat axillary hyperhidrosis, but the process tends to be more cumbersome and less effective when for the underarms.
Usually, simple tap water iontophoresis is enough to achieve desired results but in some cases clinicians may need to add baking soda to "soft water" or use iontophoresis to deliver anticholinergics or other medications to hyperhidrotic areas affected. (More information on this below.)
In the 18th century, not long after electricity was discovered, people started trying to use it to treat various human conditions. Pivati is reported to have used iontophoresis to treat arthritis in 1740. Research during the late 19th century and 20th century demonstrated that iontophoresis is an efficient method for the delivery of medications into the body through the skin. Interestingly, the sweat glands are the main portal of entry for any pharmaceutical agents delivered through the skin, since electrical resistance is lowest by that route.[7,47] In 1936, Ichikasa discovered that iontophoresis of medications led to a reduction of sweating in the affected area. In the 1940s, Takata and Shelley independently found that anhidrosis could be obtained by iontophoresis with tap water. The treatment became increasingly popular after 1968, when F. Levit published a paper on a practical device for iontophoresis.[7,85] Dermatologists have since tried iontophoresis for a host of conditions, including vitiligo and scleroderma. But, currently, hyperhidrosis is said to be the only clear indication for iontophoresis, in part because this use has proven to be both successful and popular.[7,131] Indeed, patients who prefer to self-manage their hyperhidrosis treatment at home may find that, after they have learned the treatment process from a healthcare professional, iontophoresis is a very attractive option. In addition, many health insurance organizations in the U.S. consider treatment with iontophoresis for hyperhidrosis medically necessary when antiperspirants have been ineffective or have resulted in skin irritation.
Mechanism of Action
The manner in which iontophoresis halts or diminishes sweating is not yet fully understood but there are several theories. One of the physical principles of electricity is that molecules with the same charge repel one another and those with opposite charge attract one another. In iontophoresis, a charged molecule is delivered across the skin by placing it near the electrode of like charge, while the electrode of opposite charge is placed elsewhere on the body. This physical explanation for how particles are transported across the skin does not, however, explain the mechanism of action of tap water iontophoresis in reducing sweat output.
An early theory was that iontophoresis leads to a plugging of sweat gland ducts. This concept was based on the development of iatrogenic miliaria when iontophoresis was done on the back, chest, or arms of patients. Microscopic analysis showed keratin plugs obstructing sweat ducts. However, light and electron microscopy of sweat glands in a patient with palmar hyperhidrosis did not show ductal obstruction. This finding led to the theory that iontophoresis may cause a functional impairment of the sweat gland, either by completely blocking sympathetic nervous system transmission to the gland, raising the threshold for transmission of sympathetic nerve impulse, or changing the cellular secretory physiology. However, neurotransmitter levels in the eccrine gland or surrounding microcirculation do not change after iontophoresis. It's also postulated that decreased pH in the sweat duct due to an increase in H+ ions during tap water iontophoresis may contribute to eccrine gland dysfunction. Anodal current has been found to have a better inhibitory effect on sweating than cathodal current, and this may be due to the lowering of pH. Use of saline in iontophoresis has not been found to be as effective as use of tap water; researchers Sato and colleagues also found that the pH of anodal water did not drop during saline iontophoresis.
The regimen recommended for iontophoresis will vary with the device used, the areas to be treated, and whether the treatment is to be carried out in the clinic or at home.[3,7,86,134]. Some general advice:
Treatment usually begins in the medical office under the direct care and instruction of a healthcare professional. Once the desired dryness has been accomplished, or once it appears that the patient is ready, willing, and fully trained enough, it may be determined that treatments can continue in the home environment under the patient's self-management utilizing a device purchased or rented for home use.
- Scratches and cuts on the surface to be treated should be covered with a thin layer of petroleum jelly.[86,134] Coat the skin around the axilla with petroleum jelly if treating that area. Keep in mind, however, that petroleum jelly inhibits the iontophoresis process at the coated area so use only as necessary.
- Use nondeionized tap water (from the faucet).
- Fill the trays with just enough water to cover the hands (or feet).
- After placing the body part in the device tray (or, if treating the underarms, after applying the device or wet pads) turn the machine on. Slowly increase the amperage until a tingling that is not unpleasant is felt in the affected area,[86,145] or to a maximum of 20 mA.[4,134,145]
- Treat for 20 minutes a session every two to three days or for ten minutes three to five times a week. Initially, iontophoresis treatments are required on a frequent basis. A Monday, Wednesday, Friday schedule is often recommended in the beginning and until the condition improves. Then, treatments can be tapered down to as few as one treatment per week. 
- Halfway through the 20-minute session, reverse current flow to switch the anode site to opposite side, or keep one side in the anodal pan each session until euhidrosis is reached and then switch sides.
- It is possible to treat hands and feet simultaneously, with hands and feet going into separate trays.
- Maintenance treatment frequency will vary, but one to three times a week is usually necessary.[7,86] If mineral content of tap water is low (if water is "too soft"), insufficient current flow may occur. This can be corrected by adding a teaspoon of baking soda to each tray.
- If a patient fails to respond to tap water iontophoresis alone, one can add an anticholinergic to the water trays. For instance, glycopyrrolate 2-mg tablets can be crushed and added to each tray (see section on use of anticholinergics in iontophoresis below).
- Irritation developing along the water line can be treated with 1% hydrocortisone cream.
- Patients who don't respond to iontophoresis may be candidates for a combination therapy, such as one including iontophoresis and antiperspirants for greater symptom relief, patient convenience, and/or compliance. 
Women who are pregnant or patients with pacemakers or substantial metal implants (in the path of the electrical current, such as joint replacements), cardiac conditions, or epilepsy should not use iontophoresis. Children can be treated with iontophoresis, but some may not be able to tolerate the same current levels used by adults.[86,130]
FDA Device Regulation
A note regarding iontophoresis devices and their regulation: when FDA review is needed prior to marketing a medical device (such as an iontophoresis device), the FDA will either:
- "Clear" the device after reviewing a premarket notification, or
- "Approve" the device after reviewing a premarket approval application.
An observational study of iontophoresis in 113 patients with palmoplantar hyperhidrosis published in 1952 demonstrated a response rate of 91% for palmoplantar hyperhidrosis and showed that adding ionizable agents to the water did not improve the results.
In another study, 30 patients with palmoplantar hyperhidrosis were successfully treated with iontophoresis using different pan and electrode configurations, current levels, and duration of sessions. Patients were treated 6 days a week until sweating stopped. Patients were found to require 2 to 3 weeks of 6-days-per-week treatment to reach that endpoint and remained in remission for an average 6.3 months. Observing that some patients could not tolerate the usual current level when the electrodes were placed in separate pans, one group of patients was treated with both electrodes in the same pans. This configuration required longer times to reach anhidrosis despite higher current levels.
In another study, a group of 18 patients with palmar hyperhidrosis had iontophoresis treatment for one hand with the other hand serving as the control. Patients were treated with 12 to 20 mA for 20 minutes 3 times a week for 3 weeks. The results showed that 15 of 18 participants had markedly reduced sweat production in their treated hands.
In 1989, a double-blind controlled study of 11 patients with palmar hyperhidrosis used a sham treatment of one involved hand as placebo. After a median of 10 treatments using current from 2 to 10 mA, sweat production was measured by gravimetry and compared to baseline. A median reduction of 38% from baseline was found for the treated hands. After maintenance treatment every other week for 3 months, there was an 81% median reduction of sweat production (P<0.05).
Similarly, a 2002 controlled trial of 112 patients diagnosed with palmar hyperhidrosis showed that, after 8 treatments, sweating was reduced 81.2% from baseline. This reduction was seen 20 days after the eighth treatment, with the mean return of symptoms occurring at 35 days. 
Study of portable device for home use
While most iontophoresis devices require a plug, portable devices are available. A study of one such device was carried out on 27 treatment sites in 22 patients: sites included 10 palms, 9 feet, and 8 axillae. Patients used the device on the involved area, using the opposite side as control, for 30 minutes twice a day for 5 days followed by 30 minutes daily. Sweat production was assessed using a computerized image analysis of chemically treated paper applied to the involved area. Two axillae and one foot did not respond to treatment. It took 2 weeks for 80% of palms to respond, and by 20 days 100% of hands, 78% of feet, and 75% of axillae responded. Of the 24 sites that had at least a 50% improvement in subjective symptoms, there was a statistically significant decrease in mean sweat production after 1 month of treatment compared to controls (P<0.001 for palms and soles and P<0.01 for axillae). Follow-up 1 month after therapy was halted found that only the palms showed a continued statistically significant difference in sweat production. The authors concluded that the device has a role in treating hyperhidrosis but may require twice-daily treatment for more than 2 weeks for some patients and that retreatment is necessary 2 weeks after stopping treatment.
Study with gravimetric follow-up
To investigate whether a current other than the standard direct current (DC) would lessen side effects of iontophoresis, 25 patients with palmar hyperhidrosis were treated in a double-blind manner with standard DC, alternating current (AC), or an alternating current with a DC offset (AC/DC). Patients were treated 4 times a week until resolution, and then once weekly as maintenance. Gravimetric measurement of sweat production was performed. Those treated with standard DC had improvement in hyperhidrosis after an average of 11 treatments, as well as the usual side effects, including the occasional mild shock due to incorrect technique (i.e. moving hands in or out of the water bath too quickly). Those on AC treatments had no resolution of hyperhidrosis after a total of 25 treatments. Those on the AC/DC protocol improved at the same rate as those on DC, but there were no signs of skin irritation or discomfort. The authors concluded that the AC with a DC offset “should become the treatment of choice.”
Several side effects are seen during tap water iontophoresis but usually these are mild and do not necessitate discontinuation of treatment. Some effects can be prevented by proper preparation and patient education. For instance, to prevent mild shocks, patients should be reminded to keep their hands or feet in the water trays while the device is in use and to avoid touching the electrodes. Open wounds (cuts, abrasions, hangnails) on the treated surface can be covered with petroleum jelly to minimize discomfort during the procedure. Petroleum jelly may also be applied along the water line to help prevent erythema of that region. [86, 133, 134]
In a series of patients treated with iontophoresis, a few side effects were commonly reported. Vesiculation in the effected area has been reported, but is usually transient. Eight of 112 patients reported vesiculation in a 2002 study. Redness of the skin, often along the water line, is also commonly reported. Twelve of 122 patients reported erythema in the 2002 study previously mentioned. Discomfort, either as a burning sensation or “pins and needles,” is also common.[70,133] All patients in one series complained of “pins and needles,” and 20 of 112 complained of the burning sensation.
Both erythema and vesiculation can be treated with 1% hydrocortisone cream should these symptoms persist. Sometimes the skin becomes dry and cracked or fissured, necessitating the use of moisturizers or decreasing the frequency of iontophoresis sessions.
Studies of iontophoresis and other agents
Since sweat glands are the main route for absorption of medications delivered by iontophoresis, using this method to deliver agents to treat hyperhidrosis is a logical approach. Several studies compared tap water iontophoresis to iontophoresis of an anticholinergic medication, and another compared combined iontophoresis of aluminum chloride and an anticholinergic to tap water iontophoresis.
In one study, the anticholinergic agent poldine methylsulfate or tap water was delivered by iontophoresis to the palms, soles, and axillae of 13 patients, using one side either as placebo control or for the other treatment. Poldine was more effective than tap water overall, and two patients with sweating unresponsive to tap water had an excellent response to poldine iontophoresis. The greatest effect of poldine was on the palms, and the worst response was in the axillae, where only 2 of 5 patients had a response. Systemic side effects were seen, most commonly dry mouth. Similar to tap water iontophoresis, continued treatment once or twice weekly with poldine was needed, as only a few patients had longer remissions.
Another study evaluated the use of a 0.1% solution of glycopyrronium bromide delivered by iontophoresis to 27 patients with various combinations of palmar, plantar, and axillary hyperhidrosis. Treatment results for tap water iontophoresis in 26 other patients were reported for comparison. The group treated with tap water all responded after a variable number of treatments, but most required continued weekly or twice-weekly treatment to maintain dryness. Patients with planter and axillary symptoms required more treatments to reach sufficient dryness. Those treated with glycopyrronium fared better, however. Except for those with axillary hyperhidrosis, a prolonged period of hypohidrosis was achieved—an average of 33.7 and 47.2 days between treatments for palmar and plantar hyperhidrosis, respectively. Axillary patients continued to need treatment about once per week. All patients had signs of systemic absorption of the anticholinergic. Dryness of the mouth usually persisted for 6 to 24 hours after therapy. Occasional visual, GI, and urinary difficulties were reported. The reason for the prolonged effect with glycopyrronium is unknown, and the author speculated that the drug is held in the epidermis and slowly released.
In a third study, the combination of 0.01% glycopyrrolate and 2% aluminum chloride was delivered by iontophoresis to patients with palmar hyperhidrosis. One group had the opposite hand treated with tap water in a double-blind study, and a second group received the combined treatment to both hands. Combined iontophoresis used changing periods of time for delivery of glycopyrrolate and aluminum chloride over 4 days: on the first day the anticholinergic alone was given over 30 minutes, and on the second day 20 minutes were used for delivery of glycopyrrolate and 10 minutes for aluminum chloride. This ratio was reversed for the third day, and on the fourth day the patients received aluminum chloride alone. Using this approach, the investigators hoped to suppress sweating with the anticholinergic in order to enhance the absorption of aluminum chloride into the sweat gland. Each day the treatment was repeated with reversed polarity, leading to an overall treatment duration of 1 hour. In the double-blind study, the decrease in severity as measured by iodine-starch paper patterns was higher in the palms treated with combination therapy (P=0.084). The mean remission duration after the 4-day treatment was 3.5 days for tap water iontophoresis and 20 days for combination therapy (P=0.098). In the observational study, 87% of patients responded to the treatment and had a mean remission duration of 32 days. Only 1 patient complained of mouth dryness. Although no specific data on treatment of the axillae by this method are reported, the authors state that the axillary hyperhidrosis responded as well as palmar symptoms. Two patients had 5 months of remission of axillary sweating after a single 4-day treatment.
In summary, iontophoresis has a long history of safe and effective use for the treatment of palmar and plantar hyperhidrosis. With the use of home device and a solid foundation of patient training and education, this can be a convenient and cost effective treatment option for many patients and should not be overlooked.