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Professor Tim Watson is an Abstract Reviewer for the World Confederation for Physical Therapy.

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Iontophoresis

Basic Principles
Ionic Penetration
Acid / Alkaline Reactions
Anodal and Cathodal Reactions in response to Iontophoresis
Application Devices
Polarity, Current Intensity and Drug Concentrations
General Principles of Application
Safe Current Density
Electrodes
Preparation and Delivery
References


Iontophoresis is a technique which uses an electric current to deliver a medicine or other chemical through the skin. In popular (lay)  terms it is sometimes called "an injection without the needle". In the past it has sometimes been called Electromotive Drug Administration, though in modern therapy, this is a rarely employed term.

This is not a new technique - there is recorded iontophoresis activity way back to the 1700's, though most authorities agree that it was not until the work of Le Duc in the early 1900's that the technique really gained momentum, though its use since that time has been sporadic.

Formally, the modality can be defined thus :  ". . . a non-invasive method of propelling high concentrations of a charged substance, (normally a medication or bioactive agent), transdermally by repulsive electromotive force using a small electrical charge applied to an iontophoretic chamber containing a similarly charged active agent and its vehicle". The term iontophoresis is simply defined as ion transfer (ionto = ion; phoresis = transfer).

Iontophoresis is used in therapy, but is not exclusive to this arena, and there are applications in medicine, dentistry, lab sciences and physiology. A literature search will quickly identify thousands of references, though only a relatively small proportion of them will be directly relevant to therapy type applications. There have been several reviews over the years (see references at the end of this material) which will assist those with an interest in following up on the key literature.

There are relatively few practitioners using iontophoresis in the UK, but in the USA it is a mainstream application. In Europe there are pockets of activity, and strong support from many practitioners. The use of iontophoresis worldwide is patchy - with areas of high use and areas where it is almost never employed.

IONTOPHORESIS is NOT the same as PHONOPHORESIS which involves driving ions across the skin with therapeutic ultrasound.

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Basic Principles

In order to 'drive' the ions into the tissues, a DIRECT (Galvanic) CURRENT needs to be employed. Some authorities suggest that the current needs to be continuous, though others have argued that so long as the current is monophasic in nature, a pulsed application can be used. Continuous (classic) DC is most commonly used in practice. 

Essentially, the substance to be driven into the tissues NEEDS to be IONIC in nature, and MUST be placed under the electrode with the SAME CHARGE (i.e. positively charged ions placed under the positive electrode (ANODE) and the reverse for a negatively charged ion).

The positively charged chamber, called the anode, will repel a positively charged chemical into the skin.

The negatively charged chamber, called the cathode, will repel a negatively charged chemical into the skin.

The positively charged chamber, called the anode, will repel a positively charged chemical into the skin.

The negatively charged chamber, called the cathode, will repel a negatively charged chemical into the skin.

Conventionally, the electrode under which the ionic solution is placed is called the ACTIVE electrode (other terms include TREATMENT electrode or DELIVERY electrode). The other electrode, which is used to complete the circuit is most commonly called the DISPERSIVE, INDIFFERENT, INACTIVE or RETURN electrode. For consistency in this document the terms ACTIVE and INDIFFERENT electrodes will be used. 

Ions with a polarity which is the same as that of the stimulating electrode are repelled into the skin

 

Iontophoresis_1

It is assumed that the effects of the treatment are attributed to the delivered ions and not the direct current - though interestingly, this basic premise has not actually been fully established. Given the wealth of evidence in favour of various DC applications, including a recent resurgence of High Voltage Pulsed Current (HVPC) and the developing use of MICROCURRENT based therapies, it would be surprising if the DC current had no effect in its own right.

The ions are driven into the skin via the pores - hair follicles, sweat gland ducts - rather than through the stratum corneum per se (the stratum has a high resistance, thus limited current passes through it - the ducts are lower resistance, will allow greater passage of current, thus the route of preference).

The ions (ionic solution) used will depend on the therapeutic effects which are intended. The table in this document identifies some of the more commonly employed solutions, their use and the electrode under which they need to be placed in order for the iontophoretic effect to be achieved. These substances range from tap water through to steroid based medicines, and the regulations concerning their use will vary from country to country depending on prescription and therapist autonomy.

Ionic Penetration

It is usually considered that the penetration of the ions into the tissues is likely to be less than 1mm. Any deeper penetration is considered to be due to local capillary circulation effects. There is no evidence that the current itself is responsible for penetrations beyond this level (though some authors claim - without explicit evidence - that the ions are driven much further into the tissues. The bulk of the ions that enter the tissues accumulate under the stimulating electrode and it may be possible that recombination of the substance can occur under this (active) electrode, though this remains a controversial issue which has not been fully resolved by the available research evidence.

It is possible that different ions will travel varying distances into the tissues - in other words, there is not a 'set' penetration which is equal for all different substances. This issue has also yet to be fully resolved.

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Acid / Alkaline Reactions

Will get ACID accumulation under the POSITIVE (anode) electrode (weak HYDROCHLORIC ACID) because the negatively charged chloride ions (Cl- from NaCl) will transit (be attracted) towards the anode.

Will get ALKALINE accumulation under the NEGATIVE (cathode) electrode (SODIUM HYDROXIDE) because the positively charged sodium ions (Na+ from NaCl) will move towards the cathode. The Na+ ions react with water to form sodium hydroxide (NaOH). N.B. it is suggested that the reaction at the negative (cathode) electrode will bring about a softening of the skin, hence is growing use by beauty therapy clinics.

A reactive hyperaemia will ne observable under BOTH electrodes due to (chemically mediated) local vasodilation.

The magnitude of the local reaction (independent of the ions utilised) will depend on :

  • Current Intensity (more current, greater reaction)
  • Time (longer time, stronger reaction)
  • Tissue Resistance (greater resistance, stronger reaction)

The evidence is summarised by Belanger (2010) who concludes that based on the available evidence (e.g. Banga et al, 1998 and Anderson et al, 2003) the penetration of the ions is greatest in the region of the pores, the penetration of the substance through the skin is in proportion to the current magnitude, but that the substance is most likely deposited below the stratum corneum, thus acting as a depot. Onward migration of the substance to the deeper tissues is achieved by diffusion rather than being 'driven' deeper by the applied current.

Interestingly, it is also suggested that if there is a strong vasodilation in the blood vessels of the skin, there will be a less effective diffusion to the deeper tissues on the basis that the increased local flow will serve to dilute the subepidermal deposit.

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Anodal and Cathodal Reactions in response to Iontophoresis
 

Cathode Anode
NEGATIVE electrode POSITIVE electrode
Attraction of +ve ions Attraction of -ve ions
Alkaline reaction by the formation of NaOH Acid reaction by the formation of HCl
Increased density of proteins Decreased density of proteins
Increased nerve excitability via a depolarisation effect Decreased nerve excitability via a hyperpolarisation effect (sometimes called anode blockade)

Application Devices

There are many specific (dedicated) machines sold which are solely designed to deliver this type of treatment. Several are for patient home use (especially for the treatment of hyperhydrosis). Most modern multifunction devices will include iontophoresis type currents in their menu options.

Dedicated Iontophoresis device Multimodal Iontophoresis device
Dedicated Iontophoresis device Iontophoresis multimodal device
Examples of dedicated IONTOPHORESIS devices Examples of MULTIMODAL devices which include IONTOPHORESIS facilities

Additionally, the so called 'wireless' application devices are gaining popularity, eespecially for home use. The delivery system is 'self contained' in that the electrodes (self adhesive) and stimulator are in a single housing which the patient applied to the affected area. The electrode patch is preconfigured and delivers a smaller current than is normally employed in the department or clinic (typically 0.1mA). The patch is applied for 12 - 24 hours (depending on the intended dose) after which time, it is removed and disgarded (they can not be reused). The illustration of electrode systems (below) includes one such option (top right)

Optimal Current Variables used in Iontophoresis (after Rothstein et al, 1998)
 

Current Type DC
Current Amplitude 1.0 - 4.0 mA
Treatment Duration 20 - 40 minutes
Total Current delivered 40-80mA/min

There are some authors who identify very specific substance concentrations, volumes, electrode sizes, current intensity and treatment duration (the critical parameters for an iontophoresis treatment). Others provide general guidance, saying that it is not possible to be specific for a particular patients with a particular clinical presentation.

 

Polarity, Current Intensity and Drug Concentrations

In general terms, low current intensities appear to achieve favourable results. The treatment is usually applied with currents up to 5mA and with low ionic concentrations – up to 5%, though there are certainly reports and treatment suggestions that take the current intensity up to higher levels and employ 'stronger' substance concentrations. Treatment times are typically in the 20 - 40 minute range.

There is evidence to suggest that using a higher concentration of the substance does not serve to increase the effectiveness of the therapy, and does not increase the amount of the drug delivered to the tissues - low concentrations of drug (or substance) (typically 2-5%) and a low current intensity (up to 5mA) appears to be the most effective delivery method.

It has been suggested that  commonly, the NEGATIVE electrode is made larger (relative to the positive electrode) to avoid skin irritation (whether the ionic driving electrode or not). Figures often cited suggest that the negative (cathode) electrode should be 2 x larger than the positive (anode) electrode.

General Principles of Application

It is preferable to utilise a direct current stimulator, commonly a dedicated iontophoresis device, or the DC/Iontophoresis output on a multi-modal machine. 

Constant current is preferable to constant voltage - thus, whatever changes occur in terms of skin resistance, the magnitude of the applied current will not exceed the preset level. Some machines offer you and a choice - and if that is the case, constant current will give you an effective and the most safe application (smaller risk of skin burn).

Constant voltage stimulation can result in a burn more easily (in this case, the voltage is set by the operator. If the skin resistance changes, the current flow through the tissues will vary - and thus give rise to an increased risk of burn)

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Safe Current Density

It is important to note that the current density (how strong the current is and also how concentrated it is), measured in mA/cm2, is an important factor in these treatments. If the current density reaches too high a level, tissue damage, and especially skin burn, may ensue.

It is suggested (see Belanger, 2010 for the full argument), that a current density of no more than 0.5mA/cm2 is applicable at the negative(cathode) electrode and 1.0mA/cm2 at the positive(anodal) electrode.

If a current of 2mA is delivered using an electrode of 6cm2, the current density will be 2(mA)/6(cm2) = 0.33mA/cm2, which is safe at either the positive (anode) or negative (cathode) electrode.

It is possible, using a transposition of the equation, to establish the maximal current that can be applied with a particular electrode whilst ensuring a safe treatment.

Maximum Current (mA) = Maximum Safe Current Density (mA/cm2) x Electrode area (cm2)

E.g.

If the (active) electrode to be used is 6cm2
If the active electrode is to be made NEGATIVE (cathode)
The maximum safe current density is 0.5mA/cm2
The maximum current that can be safely applied is therefore :

= 0.5mA/cm2) x 6 (cm2) = 3mA

Electrodes

The electrodes can be special pre gelled disposable electrodes or standard metal electrodes of various types.

Some commercial iontophoresis electrodes have special wells or receptacle areas for the drug in question.

 
Iontophoresis electrode system Iontophoresis electrode system
Iontophoresis electrode system Iontophoresis electrode system
Examples of commercialliy available iontophoresis electrode systems

It is not necessary to use these (commercial) electrodes, and for many years, therapists have used various metal / foil electrodes with the substance needed for the treatment applied to the wet/damp gauze between the metal electrode and the skin surface.

Preparation and Delivery

The skin should be abrasion / cut free and the area carefully washed (soap & water is fine).

Some authorities have advocated the application of heat prior to the iontophoresis, but the experimental evidence does not support this. In fact, it appears to reduce the amount of drug passing through the epidermis and as identified in a previous section, increasing blood flow through the skin and superficial tissues may simply serve to reduce the size of the 'depot' in the skin.

Ensure that all electrode pads are thoroughly soaked in either tap water or other appropriate solution prior to application. Dry electrodes are inappropriate and should not be used.

If pregelled electrodes are being used, ensure that a good even contact is achieved.

Adequate fixation of the electrode and pad to the skin needs to be carefully maintained. Uneven current distribution can easily lead to skin burns and/or irritation

Explain to the patient what is expected and ensure that they know to report immediately if any untoward or painful sensations are felt.

Turn the current up slowly to the required amount

At the end of the treatment time, ensure that the current is turned down slowly.

Table of Commonly Used Medications and Solutions with Iontophoresis (after Rothstein et al (1998)and Belanger (2010)).
 

Drug / Solution Main Indication(s) Rationale Parameters

Acetic Acid

Calcific tendinitis (myositis ossificans)

Acetate believed to increase solubility of calcium deposits in tendons (and other soft tissues)

2 - 5% aqueous solution
NEGATIVE pole

Calcium chloride

Muscle spasm (also hypersensitive peripheral nerves)

Calcium thought to stabilise excitable membranes, appears to decrease excitability threshold in peripheral nerves and skeletal muscle

2 - 5% aqueous solution
NEGATIVE pole

Dexamethasone

Inflammation

(synthetic) anti inflammatory

4mg/mL aqueous solution
NEGATIVE pole

Hydrocortisone

Inflammation

Steroid based anti inflammatory

0.5% ointment POSITIVE pole (Rothstein et al)

Hydrocortisone, prednisone

Inflammation

Steroid based anti inflammatory

NEGATIVE pole (Belanger)

Iodine

Adhesive capsulitis
Other soft tissue adhesive presentations
Infection (microbial)

Iodine acts as a broad spectrum antibiotic. Its actions in relation to adhesive presentations appear not to be fully understood

5 - 10% solution (some use ointment)
NEGATIVE pole

Lidocaine

Soft tissue pain
Inflammation

Local anaesthetic effects (blocks peripheral nerve activity).
May stimulate healing

4 - 5% solution (ointment)
POSITIVE pole

Magnesium sulphate (sulfate)

Muscle spasm
Myositis

Thought that 'relaxing' effect is achieved by decreased excitability of muscle membrane and reduced activity at neuromuscular junction

2% aqueous solution (ointment)
POSITIVE pole

Hyaluronidase

Oedema (local)
Subacute and Chronic stages

Increases permeability in connective tissues thus allowing dispersion of accumulated fluid. Hydrolysation of hyaluronic acid

Delivered after reconstitution with 0.9% sodium chloride (Normasol) to give a 150µg/mL solution
POSITIVE pole

Salicylates

Muscle and Joint pain
Acute and Chronic

Mode of action akin to Asprin - analgesia and anti inflammatory. Inhibits synthesis of prostaglandins

2-3% sodium sallicylate solution
OR
10% trolamine sallicylate ointment
NEGATIVE pole

Tolazoline hydrochloride

Ulcers (open wounds)

Stimulates local blood flow
Stimulates tissue healing (thought to be via inhibition of local vascular smooth muscle contraction)

2% aqueous solution
POSITIVE pole

Zinc Oxide

Open wounds - ulcers
Some dermatological conditions

Antiseptic effects related to the zinc.
May stimulate healing

20% ointment
POSITIVE pole

Tap Water

Hyperhydrosis
(illustrations below)

Suppresses sweating in palms, soles of feet, axilla through ?keratin plug formation in ducts

Equal time with POSITIVE and NEGATIVE polarity - use 2 x hand baths. Reverse polarity 1/2 way through treatment (typically 30 minutes : 15+15)

Tap water Iontophoresis Tap water Iontophoresis Tap water Iontophoresis
Illustration of tap water iontophoresis for (palmar) hyperhydrosis

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References

Reviews and Background Reading

Belanger, A.-Y. (2010). Therapuetic Electrophysical Agents: Evidence Behind Practice. Philadelphia, Lippincott Williams and Wilkins.

Bolin, D. and M. Goforth (2004). "Electric delivery: generally well tolerated by patients, iontophoresis has many uses for the rehab clinician." Rehab Management: The Interdisciplinary Journal of Rehabilitation 17(10): 18-21.

Gangarosa, L. P. et al (1995). "Iontophoresis for enhancing penetration of dermatologic and antiviral drugs." J Dermatol 22(11): 865-875.

Kalia, Y. N. et al (2004). "Iontophoretic drug delivery." Adv Drug Deliv Rev 56(5): 619-658.

Rothstein, J. M. et al (1998). The Rehabilitation Specialist's Handbook. Philadelphia, F A Davis.

Warden, G. D. (2007). "Electrical safety in iontophoresis." Rehab Management: The Interdisciplinary Journal of Rehabilitation 20(2): 22-23.

Viscusi, E. R. and T. A. Witkowski (2005). "Iontophoresis: the process behind noninvasive drug delivery." Regional Anesthesia and Pain Medicine 30(3): 292-294. 

Examples of Iontophoresis Research Publications (there are over 5000 references relating to this subject - this is a SMALL smaple!)

Baskurt, F. et al (2003). "Comparison of effects of phonophoresis and iontophoresis of naproxen in the treatment of lateral epicondylitis." Clin Rehabil 17(1): 96-100.

Ciccone, C. D. (2003). "Does acetic acid iontophoresis accelerate the resorption of calcium deposits in calcific tendinitis of the shoulder?" Phys Ther 83(1): 68-74 

Gokoglu, F. et al (2005). "Evaluation of iontophoresis and local corticosteroid injection in the treatment of carpal tunnel syndrome." Am J Phys Med Rehabil 84(2): 92-96.

Gulick, D. T. et al (2000). "Effects of acetic acid iontophoresis on heel spur reabsorption." Phys-Ther-Case-Rep. 3(2): 64-70.

Gurney, A. B. and D. C. Wascher (2008). "Absorption of dexamethasone sodium phosphate in human connective tissue using iontophoresis." Am J Sports Med 36(4): 753-759.

Hamann, H. et al (2006). "Effectiveness of iontophoresis of anti-inflammatory medications in the treatment of common musculoskeletal inflammatory conditions: a systematic review." Physical Therapy Reviews 11(3): 190-194.

Hartrick, C. T. et al (2006). "Fentanyl iontophoretic transdermal system for acute-pain management after orthopedic surgery: a comparative study with morphine intravenous patient-controlled analgesia." Reg Anesth Pain Med 31(6): 546-554.

Neeter, C. et al. (2003). "Iontophoresis with or without dexamethazone in the treatment of acute Achilles tendon pain." Scand-J-Med-Sci-Sports. 13(6): 376-382.       

Japour, C. J. et al (1999). "Management of heel pain syndrome with acetic acid iontophoresis." J-Am-Podiatr-Med-Assoc 89(5): 251-257.

Nirschl, R. P. et al (2003). "Iontophoretic administration of dexamethasone sodium phosphate for acute epicondylitis: a randomized, double-blind, placebo-controlled study." American Journal of Sports Medicine 31(2): 189-195.

Osborne, H. R. and G. T. Allison (2006). "Treatment of plantar fasciitis by LowDye taping and iontophoresis: short term results of a double blinded, randomised, placebo controlled clinical trial of dexamethasone and acetic acid. " British Journal of Sports Medicine 40(6): 545-549.

Jaffer, U. and A. Cameron (2006). "Hyperhidrosis: current management." British Journal of Hospital Medicine 67(2): 82-84.

O'Keeffe, J. (2006). "No sweat! Hyperhidrosis -- an overview." Chiropody Review 63(3): 4-5.

Riedl, C. R. et al (2000). "Iontophoresis for treatment of Peyronie's disease." J Urol 163(1): 95-99.

Wallace, M. S. et al (2001). "Topical delivery of lidocaine in healthy volunteers by electroporation, electroincorporation, or iontophoresis: an evaluation of skin anesthesia." Regional Anesthesia and Pain Medicine 26(3): 229-238 

Yarrobino, T. E. et al (2006). "Lidocaine iontophoresis mediates analgesia in lateral epicondylalgia treatment." Physiother-Res-Int. 11(3): 152-160.

Zempsky, W. T. et al (2004). "Evaluation of a low-dose lidocaine iontophoresis system for topical anesthesia in adults and children: a randomized, controlled trial." Clinical Therapeutics 26(7): 1110-1119.

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Resources

Courses

Courses

A wide range of Electrotherapy Courses are delivered throughout the UK, Europe and Worldwide with varying content, aims and duration.

Books

Books

Current books on Electrotherapy with brief descriptions and links to Amazon pages for purchase.

FAQs: Prof. Tim Watson

FAQs: Prof. Tim Watson

Some common answers to the most frequently asked questions on Electrotherapy, particularly in the area of Contraindications.