Phonophoresis
Number: 0210
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses phonophoresis.
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Experimental, Investigational, or Unproven
The use of phonophoresis is considered experimental, investigational, or unproven for all indications, including any of the following (not an all-inclusive list), because the effectiveness of this approach has not been established:
- Adhesive capsulitis
- Carpal tunnel syndrome
- Chronic non-bacterial prostatitis
- Chronic obstructive pulmonary disease
- Chronic rhinosinusitis
- Chronic wound management
- Epicondylalgia (lateral epicondylitis)
- Iliotibial band syndrome
- Knee osteoarthritis / knee pain
- Low back pain
- Medial tibial stress syndrome
- Myositis ossificans
- Neck pain
- Patellofemoral pain syndrome
- Post-surgical scar of carpal tunnel release (Contractubex phonophoresis)
- Rotator cuff tendinopathy
- Serous otitis media
- Shoulder impingement syndrome (subacromial impingement syndrome)
- Sinusitis
- Temporomandibular joint disorders
- Trapezio-metacarpal joint arthritis
- Traumatic muscle injury
- Tuberculous lymphadenitis
- Upper trapezius latent myofascial trigger point
- Venous and diabetic ulcers (bee venom phonophoresis).
Note: Phonophoresis has been used to enhance the absorption of analgesics and anti-inflammatory agents. Controlled clinical trials, however, have failed to demonstrate that phonophoresis increases the rate or extent of absorption of these agents.
Background
Phonophoresis, also known as sonophoresis, has been claimed to enhance the percutaneous absorption of certain pharmacological agents such as anti-inflammatory steroids and local anesthetics from intact skin into the underlying subcutaneous structures by ultrasound, therefore improving their effectiveness. This procedure is commonly used in physical therapy practices. The procedure generally utilizes an ultrasound apparatus that generates frequencies of 0.7 to 1.1 MHz. The ultrasound intensities employed usually range from 0.0 to 3.0 Watts per cm2. Both continuous-mode as well as pulse-mode applications were utilized, and most treatments lasted from 5 to 8 mins, with the exception of treatments of larger areas (greater than 36 cm2) requiring more than 8 mins. The exact mechanism enabling drugs to be propelled into the subcutaneous structures is still unclear.
Phonophoresis has been suggested by early studies to enhance the absorption of analgesics and anti-inflammatory agents. More recent, better-controlled studies have consistently failed to demonstrate that phonophoresis increases the rate of absorption or the extent of absorption over placebo. Several reviews stated that more research is needed to ascertain optimal techniques and conditions for safe and efficacious utilization of physical modalities including phonophoresis; and there is a need for additional research to establish clinical effectiveness and determine optimal treatment parameters for the physical agents (e.g., phonophoresis) used most frequently to alleviate pain in hand therapy.
In a randomized study (n = 60) comparing the effectiveness of ibuprofen phonophoresis with conventional ultrasound therapy in patients with knee osteoarthritis, Kozanoglu et al (2003) found that ibuprofen phonophoresis was not superior to conventional ultrasound.
Ellis et al (2007) stated that Iliotibial band friction syndrome (ITBFS) is a common injury of the lateral aspect of the knee particularly in runners, cyclists and endurance sports. A number of investigators suggested that ITBFS responds well to conservative treatment, however, much of this notion appears anecdotal and is not supported by available evidence. These researchers performed a systematic review of the literature on the conservative treatment of ITBFS. With respect to the management of ITBFS, 4 randomized controlled trials were identified. The interventions examined included the use of non-steroidal anti-inflammatory drugs, deep friction massage, phonophoresis versus immobilization and corticosteroid injection. This review highlighted both the paucity in quality and quantity of research regarding the conservative treatment of ITBFS. There seems limited evidence to suggest that the conservative treatments that have been studied offer any significant benefit in the management of ITBFS. The authors noted that future research will need to re-examine those conservative therapies, which have already been examined, along with others, and will need to be of sufficient quality to enable accurate clinical judgements to be made regarding their use.
- treatment parameters to be followed in physical therapy,
- appropriate dosage forms of drugs to ensure propagation of ultrasound waves,
- principles of homoeostasis and other physiological processes that play a decisive role in achieving the biological and therapeutic effects of ultrasound therapy, and
- indications and contraindications to this kind of treatment. The dearth of objective research methods and reliable scientific verification does not allow unambiguous determination of the effectiveness of phonophoresis.
Jewell et al (2009) examined if physical therapy interventions predicted meaningful short-term improvement in 4 measures of physical health, pain, and function for patients diagnosed with adhesive capsulitis. Data were examined from 2,370 patients (mean age of 55.3 years, SD = 12.4; 65% females, 35% males) classified into ICD-9 code 726.0 who had completed an episode of outpatient physical therapy. Principal components factor analysis was used to define intervention categories from specific treatments applied during the episode of care. A nested logistic regression model was used to identify intervention categories that predicted a 50% or greater change in Physical Component Summary-12 (PCS-12), physical function (PF), bodily pain (BP), and hybrid function (HF) scores. None of the patients achieved a 50% or greater improvement in PCS-12 scores. Improvement in BP scores was more likely in patients who received joint mobility interventions (odds ratio [OR] = 1.35, 95% confidence interval [CI]: 1.10 to 1.65). Improvement in HF scores was more likely in patients who received exercise interventions (OR = 1.50, 95% CI: 1.03 to 2.17). Use of iontophoresis, phonophoresis, ultrasound, or massage reduced the likelihood of improvement in these 3 outcome measures by 19% to 3 2%. The authors concluded that these results are consistent with findings from randomized clinical trials that demonstrated the effectiveness of joint mobilization and exercise for patients with adhesive capsulitis. However, ultrasound, massage, iontophoresis, and phonophoresis reduced the likelihood of a favorable outcome, which suggests that use of these modalities should be discouraged.
An UpToDate review on “Rotator cuff tendinopathy” (Simons and Kruse, 2014) lists electrical stimulation, iontophoresis, laser, phonophoresis, and therapeutic ultrasound as adjunct therapies. Moreover, it states that “No clear evidence exists to support the use of the modalities listed here and we do not routinely use them in the care of our patients”.
Jain et al (2010) hypothesized that transdermal steroid delivery would yield short-term improvements for trapezio-metacarpal (TM) joint arthritis, although these improvements would not persist at later follow-up (3 or 6 months). A total of 84 consecutive TM joints in 62 patients presenting to an orthopedic hand surgeon were randomized to receive either steroid delivery by iontophoresis or phonophoresis or placebo delivery via iontophoresis or phonophoresis. The researchers and patients were blinded as to the treatment assignment. Patients were evaluated before treatment and at 3 follow-up appointments. Subjects were assessed via the Michigan Hand Outcomes Questionnaire, Short Form 12, analog pain score, and provocative and strength testing. The subjects' study group, gender, and arthritic grade were statistically analyzed versus patient-reported and physician-assessed data over the different time points. Following subject recruitment, 17 joints discontinued the study due to joint discomfort, electing for other treatments. Approximately 50% of the 67 subject joints opted for alternative treatment after the first or second follow-up; 34 subject joints completed all follow-up time points. There was no significant predictive relationship between the independent variables and their ability to predict the 9 dependent measures of pain, strength, and well-being. There were trends for the pain to decrease over time, although the trends were not uniform between the different pain metrics and groups. The strength for both iontophoresis groups tended to increase over time, whereas the phonophoresis groups tended to decline. The authors concluded that although there were some trends in the follow-up data, the overall lack of significant differences in the data suggested that transdermal steroid delivery might not be helpful in providing short- or long-term relief of arthritic symptoms.
- 1.5 W/cm, 100% duty cycle with lidocaine for 5 mins (short);
- 1.5 W/cm, 50% duty cycle with lidocaine for 10 mins (long);
- no ultrasound for 10 mins with lidocaine gel (lidocaine sham); and
- no ultrasound for 10 mins with ultrasound gel (true sham).
Skin sensation was measured for analysis. The main outcome measures were Semmes-Weinstein Monofilament (SWM) scores, with higher scores indicating less sensitivity. There was a significant time main effect for SWM scores (p < 0.001). Baseline SWM scores were the lowest (3.00 +/- 0.53; p ≤ 0.006) and post-SWM scores (0 mins) were the highest (3.63 +/- .44; p < 0.001), indicating an anesthetic effect at this time. The authors concluded that neither the long nor the short treatment decreased skin sensation compared with sham conditions. All interventions resulted in decreased skin sensation when comparing baseline SWM scores to all post-treatment scores. Phonophoresis with lidocaine did not result in an enhanced anaesthetic effect on human subjects.
Gurney et al (2011) noted that phonophoresis has been a mainstay in physical therapy. The most common drug used in phonophoresis is hydrocortisone acetate (HA). A number of studies have been done examining phonophoresis in the delivery of HA through the skin to underlying tissues; however, a study has never been done examining the absorption of HA using phonophoresis on human connective tissue. In a randomized controlled study, these researchers examined if phonophoresis will facilitate the transmission of HA in human connective tissue. A total of 21 patients undergoing anterior cruciate ligament reconstruction surgery were randomly assigned to either a sham or true phonophoresis treatment group. The latter group received 6 minutes of 10% HA ultrasound at a point consistent with the gastrocnemius slip of the semitendinosis tendon (treatment site). The sham group received 6 minutes of 10% HA ultrasound to the same area, but the ultrasound was not turned on. The slip and a sample of the distal attachment of the tendon (control) were removed. Samples were analyzed for HA levels. Although the mean and median levels of HA found at the treatment site were greater than those of the control site (means, 34.1 versus 22.9 parts per billion; medians, 7 versus 0 parts per billion), the levels of HA found at the treatment site were not significantly greater than those at the control site (p = 0.15). There were no statistically significant differences between the true and sham phonophoresis groups in HA levels (p = 0.80) nor in age, sex, or skin thickness. The authors concluded that phonophoresis does not appear to facilitate the absorption of HA in connective tissue when compared with simple absorption (sham). Thus, the, use of phonophoresis should be re-considered in inflammatory conditions.
Lake and Wofford (2011) determined the effectiveness of therapeutic modalities for the treatment of patients with patella-femoral pain syndrome (PFPS). In May and August 2010, Medline was searched using the following databases: PubMed, CINAHL, Web of Science Citation Index, Science Direct, ProQuest Nursing & Allied Health, and Your Journals@OVID. Selected studies were randomized controlled trials that used a therapeutic modality to treat patients with PFPS. The review included articles with all outcome measures relevant for the PFPS patient: knee extension and flexion strength (isokinetic and isometric), patella-femoral pain assessment during activities of daily life, functional tests (e.g., squats), Kujala patella-femoral score, and electromyographic (EMG) recording from knee flexors and extensors and quadriceps femoris cross-sectional areas. Authors conducted independent quality appraisals of studies using the PEDro Scale and a system designed for analysis of studies on interventions for patella-femoral pain. A total of 12 studies met criteria: 1 on the effects of cold and ultrasound together, ice alone, iontophoresis, and phonophoresis; 3, neuromuscular electrical stimulation; 4, EMG biofeedback; 3, electrical stimulation for control of pain; and 1, laser. Most studies were of low-to-moderate quality. Some reported that therapeutic modalities, when combined with other treatments, may be of some benefit for pain management or other symptoms. There was no consistent evidence of any beneficial effect when a therapeutic modality was used alone. Studies did not consistently provide added benefit to conventional physical therapy in the treatment of PFPS. The authors concluded that none of the therapeutic modalities reviewed has sound scientific justification for the treatment of PFPS when used alone.
An UpToDate review on “Patellofemoral pain syndrome” (O’Connor and Mulvaney, 2014) states that “There is no empiric evidence to support the use of ultrasound, iontophoresis, phonophoresis, or electrical stimulation in the treatment of PFPS”.
Bakhtiary et al (2013) compared the effectiveness of iontophoresis and phonophoresis of dexamethasone sodium phosphate (Dex-P) treatment for mild-to-moderate carpal tunnel syndrome (CTS). A total of 52 hands in 34 consecutive patients with mild-to-moderate CTS confirmed by EMG were allocated randomly into 2 groups. One group received iontophoresis of 0.4% Dex-P and the other group received phonophoresis of 0.4% Dex-P. Phonophoresis (using ultrasound 1 MHz, 5-cm probe, 1.0 W/cm, pulse 1:4, 5 mins/session) and iontophoresis (using galvanic current, negative electrode, 2 mA/min, total dose 40 mA for 20 mins) was applied over the wrist chin for 10 daily treatment sessions (5 sessions/week). Measurements were performed before and after treatment and at follow-up 4 weeks later, and included pain assessment by visual analog scale, electroneurographic measurement (motor and sensory latency, motor and sensory action potential amplitude), and pinch and grip strength. Improvement was significantly more pronounced in the phonophoresis group than in the iontophoresis group for motor latency [mean difference 0.8 m/s; 95% CI: 0.5 to 1.1], motor action potential amplitude (4.1 mV; 95% CI: 3.0 to 5.2), finger pinch strength (31.6 N; 95% CI: 15.9 to 47.3), hand grip strength (27.1 N; 95% CI: 13.5 to 40.5), and pain relief (2.1 points on a 10-point scale; 95% CI: 1.3 to 2.9). Effects were sustained in the follow-up period. The authors concluded that phonophoresis of Dex-P treatment was more effective than iontophoresis of Dex-P for treatment of CTS. Moreover, they stated that further investigation is needed to examine the combination therapy effects of these treatments with other conservative treatments in CTS patients.
In a case report, Ansari et al (2013) described the results of a novel treatment, erythromycin phonophoresis, in a woman with chronic rhino-sinusitis (CRS). A 31-year old woman with a 7-month history of CRS refractory to conventional medical management was treated with erythromycin phonophoresis to both maxillary sinuses. Individual sinus symptom severity was assessed and sinus CT scans were obtained both pre-treatment and post-treatment. After treatment, the total sinusitis symptom score improved from 12 to 0 and the CT scan showed almost complete disease resolution. At 5-month follow-up, the patient reported sustained improvement. The authors concluded that erythromycin phonophoresis has potential as an effective treatment for CRS.
Packer et al (2013) stated that the dental anesthesia sonophoresis device (DASD) is a novel device that is intended to reduce the discomfort associated with intra-oral mucosa needle puncture. The DASD produces ultrasonic energy that provides a sonophoretic effect on the oral mucosa, generating micro-channels through the lipids between the keratinized cells that make up the stratum corneum. Once the topical anesthetic has permeated the stratum corneum, it quickly diffuses through the soft tissue, desensitizing the nerve endings and reducing the perception of pain caused by needle penetration. In a pilot study, these researchers evaluated whether topical anesthesia applied using the DASD will reduce the discomfort of the needle puncture when compared to the control device. A split-mouth model, using 50 healthy subjects with puncture site at the maxillary canine vestibule, was used for this study. Subjects received a needle puncture on both sides of the mouth. Prior to the needle puncture, there was randomized application of 5% lidocaine with the DASD and a control device. Subjects rated their discomfort after needle punctures utilizing the visual analog scale pain scoring system. There was no statistically significant difference in the pain perception using the DASD versus the control device.
Winters et al (2013) stated that medial tibial stress syndrome (MTSS) is a common exercise-induced leg injury among athletes and military personnel. Several treatment options have been described in the literature, but it remains unclear which treatment is most effective. The objective of this systematic review was to evaluate the effectiveness of any intervention in the treatment of MTSS. Published or non-published studies, reporting randomized controlled trials (RCTs) or non-RCTs of any treatment in subjects with MTSS were eligible for inclusion. Treatments were assessed for effects on pain, time to recovery or global perceived effect. Computerized bibliographic databases (MEDLINE, CENTRAL, EMBASE, CINAHL, PEDro and SPORTDiscus) and trial registries were searched for relevant reports, from their inception to June 1, 2012. Grey literature was searched for additional relevant reports. The Cochrane Risk of Bias Tool was used to appraise study quality of RCTs whereas the Newcastle Ottawa Scale was used to appraise non-RCTs. The “levels of evidence”, according to the Oxford Centre for Evidence-Based Medicine, addressed the impact of the assessed trials. Two reviewers independently performed the search for articles, study selection, data extraction and appraised methodological quality. A total of 11 trials were included in this systematic review. All RCTs revealed a high-risk of bias (Level 3 of evidence). Both non-RCTs were found to be of poor quality (Level 4 of evidence). Randomized clinical trials, studying the effect of a lower leg brace versus no lower leg brace, and iontophoresis versus phonophoresis, were pooled using a fixed-effects model. No significant differences were found for lower leg braces (standardized mean difference [SMD] -0.06; 95% CI: -0.44 to 0.32, p = 0.76), or iontophoresis (SMD 0.09; 95% CI: -0.50 to 0.68, p = 0.76). Iontophoresis, phonophoresis, ice massage, ultrasound therapy, periosteal pecking and extracorporeal shockwave therapy (ESWT) could be effective in treating MTSS when compared with control (Level 3 to 4 of evidence). Low-energy laser treatment, stretching and strengthening exercises, sports compression stockings, lower leg braces and pulsed electromagnetic fields have not been proven to be effective in treating MTSS (level 3 of evidence). The authors concluded that none of the studies was sufficiently free from methodological bias to recommend any of the treatments investigated. Of those examined, ESWT appeared to have the most promise.
An UpToDate review on “Shoulder impingement syndrome” (Simons et al, 2014) lists acupuncture, electrical stimulation, iontophoresis, laser, phonophoresis, and therapeutic ultrasound as adjunct therapies. Moreover, it states that “No clear evidence exists to support the use of the modalities listed here in the treatment of SIS, and we do not routinely use them in the care of our patients”.
An UpToDate review on “Overview of geriatric rehabilitation: Program components and settings for rehabilitation” (Hoenig and Kortebein, 2014) states that “Iontophoresis/Phonophoresis -- These modalities utilize electric current (iontophoresis) or ultrasound energy (phonophoresis) to force a therapeutic medication (e.g., glucocorticoid) into tissues. Both are used to treat soft tissue musculoskeletal injuries. Although evidence is limited, the few randomized controlled trials indicate that these modalities are generally no more effective than placebo”.
Myositis Ossificans
Bagnulo et al (2014) noted that myositis ossificans (MO) is a potential complication of muscle contusion. In a case-series study, these researchers presented the findings of patients who developed traumatic MO (confirmed on diagnostic ultrasound) who participated in a treatment regimen consisting of phonophoresis of acetic acid with ultrasound. In all cases, a trial of phonophoresis therapy significantly decreased patient signs, symptoms and the size of the calcification on diagnostic ultrasound in most at a 4-week post-diagnosis mark. The authors concluded that due to the potential damage to the muscle and its function that surgical excision carries, safe and effective conservative treatments for MO are crucial. They also stated that “Research on conservative care is necessary for chiropractors and other manual therapists to appropriately manage patients with MO. Proving to be effective in this case and the paucity of literature on conservative treatment, this area needs to be investigated … Acetic acid phonophoresis deserves more attention in the literature. For conclusive information about conservative care, studies must investigate long-term effects of conservative care in a randomized trial with a clinically significant number of participants”. These findings need to be validated by well-designed studies.
An UpToDate review on “Quadriceps muscle and tendon injuries” (Von Fange, 2016) does not mention phonophoresis as a management tool for MO.
Tuberculous Lymphadenitis
Chen et al (2016) stated that electro-phonophoresis (EP) has been used in various clinical fields. These researchers evaluated the skin permeability of isoniazid (INH) and rifampicin (RIF) in patients with tuberculous lymphadenitis with the aid of EP to validate the clinical applications of this transdermal delivery system for the treatment of superficial extra-pulmonary tuberculosis. Isoniazid and RIF solutions were delivered transdermally, with or without EP, in the surrounding tissue of the lesion for 30 minutes. Local pyogenic fluids or necrotic tissue samples from the infection sites in patients were collected at 1 hour after dosing. Drug concentrations in samples were evaluated by high performance liquid chromatography. The median INH and RIF intra-lesional concentrations were 0.365 (interquartile range [IQR] 0.185 to 1.775) μg/ml and 1.231 (IQR 0.304 to 1.836) μg/ml in oral group; 2.964 (IQR 0.193 to 7.325) μg/ml and 2.646 (IQR 1.211 to 3.753) μg/ml in INH- and RIF-transdermal plus EP group. Drug concentrations in the local sites of patients receiving INH or RIF through EP transdermal delivery were statistically higher than those observed in patients only taking INH and RIF orally. However, this enhancement was not observed in the transdermal delivery of INH or RIF without EP in contrast to the oral administrations of drugs. The authors concluded that EP can effectively enhance the skin permeability of INH and RIF in patients with tuberculous lymphadenitis. The increase in drug concentrations in the lesions could help eradication of the germs; shorten the treatment course and increase the cure rate of patients with tuberculous lymphadenitis. These finding need to be validated by well-designed studies to show that EP would improve health outcomes in patients with tuberculous lymphadenitis.
An UpToDate review on “Tuberculous lymphadenitis” (Spelman, 2016) does not mention phonophoresis as a management tool.
Knee Pain
In a double blinded, randomized clinical trial, Nakhostin-Roohi et al (2016) evaluated the effects of virgin olive oil phonophoresis on female athletes' anterior knee pain (AKP). A total of 93 female athletes suffering from AKP voluntarily participated in this study. Patients were randomly assigned into olive oil (n = 31), piroxicam (n = 31) or base gel phonophoresis (n = 31) groups. At the baseline visit, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was filled by subjects who were then treated with olive oil, piroxicam or pure phonophoresis for 12 sessions. After 6 and 12 sessions of physiotherapy, subjects filled the questionnaire again. Main outcomes were significant improvement in pain, stiffness, physical function, and total WOMAC scores. Although, there was a significant reduction in symptoms of AKP at the end of the therapy in all groups (p < 0.05), but in olive oil group, this improvement was seen after 6 sessions of treatment (p < 0.001). A significant difference between olive oil group and piroxicam and/or phonophoresis group was observed after 6 sessions of therapy (p < 0.05). The authors concluded that it could be proposed that phonophoresis with virgin olive oil is as effective as piroxicam gel on lowering WOMAC scores of AKP in female athletes and also has several beneficial properties including faster effect and shorter duration of therapy. The exact mechanism of beneficial action of virgin olive oil on AKP is unclear and requires further studies.
Chronic Non-Bacterial Prostatitis
Tantawy and colleagues (2018) noted that a significant number of men who are younger than 50 years visit urologists for interminable prostatitis. These investigators examined the effect of pumpkin seed oil (PSO) phonophoresis on chronic non-bacterial prostatitis (CNBP). A total of 60 patients with CNBP were randomly assigned to 3 groups: Group A patients were treated with PSO using phonophoresis; Group B patients underwent trans-perineal continuous low-intensity ultrasound (LIUS); and Group C patients underwent placebo LIUS. All 3 groups received their corresponding treatments daily for up to 3 weeks. The NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), residual urine determined by urodynamic measurements, and flow rate were used to analyze study outcomes. The white blood cell (WBC) count in the prostatic secretion was determined. Comparisons of the intra-group mean values of all measurements in Groups A and B before and after the end of the treatment showed a significant improvement in residual urine, flow rate, WBC count, and NIH-CPSI (p < 0.05), whereas no significant change was found in Group C (p > 0.05). Between-group comparisons of all variables showed a significant difference was found after intervention (p < 0.05). Post-intervention comparisons between Groups A and B showed a significant difference in all measurements, except for WBC, in favor of Group A. Comparing the changes between Groups A and C, a significant difference was found in all measurements (p < 0.05). Furthermore, all parameters differed significantly when comparing Groups B and C (p < 0.05). The authors concluded that the findings of this study demonstrated that PSO phonophoresis could produce a significant effect in the management of CNBP and thus could be considered a safe, non-invasive method for the treatment of CNBP. Moreover, these researchers stated that future investigations should examine the use of other different herbal sources that can be presented to the body by using different modes of LIUS by phonophoresis. The outcome measures of the present study were limited to the use of some urodynamic parameters, such as urinary flow rate and residual urine, WBCs, and NIH-CPSI, which were insufficient measures to strongly support the use of the treatment protocol; thus, further studies should be conducted along with the measurement of prostate weight, inflammatory markers in prostatic secretions (tumor necrotic factor [TNF] and interleukin-6 [IL-6] or interleukin-1 beta (IL-1B), nuclear factor-kappaB (NF-kB)), and dihydrotestosterone levels.
Chronic Rhinosinusitis
Griffin and colleagues (2018) noted that the use of alternative medicine in chronic rhinosinusitis (CRS) continues to increase in popularity, for the most part without meeting the burden of being based on sound clinical evidence. New and emerging treatments, both natural and developed, are numerous, and it remains a challenge for otolaryngologists as well as general practitioners to keep up-to-date with these therapies and their efficacy. In a systematic review, these investigators discussed a number of alternative therapies for CRS, their proposed physiologic mechanisms, and evidence supporting their use. This analysis was based on their review of the English-language literature on alternative therapies for CRS (they did not include any therapies that are already recommended by accepted professional bodies). Data collection was performed using the PubMed database (not restricted to Medline due to the nature of the subject matter), the Cochrane databases, and bibliography searches. These researchers found that while many of the alternative therapies they reviewed might have a firm basis in science, they lack any clinical evidence to support their use specifically for CRS. Some emerging therapies, such as therapeutic ultrasonography and phonophoresis, showed some promise, based on a growing body of positive evidence. In addition, the use of baby shampoo, thyme honey, and bromelain additives to saline lavage in CRS are all supported by clinical evidence, as is Sinupret, an oral preparation that contains echinacea. The authors concluded that higher levels of evidence gleaned from large, well-designed, prospective, RCTs are needed before any of these therapies can be recommended.
Low Back Pain
In a prospective, double-blind, randomized clinical study, Altan and colleagues (2019) examined the effect of phonophoresis with the combination of non-steroidal anti-inflammatory drugs (NSAID's) and myorelaxant versus routine ultrasound (US) treatment with non-therapeutic gel on the patients with acute low back pain (LBP). A total of 60 patients with acute LBP were randomly assigned into 2 groups. In Group 1 (n = 30) US was applied using diclofenac plus thiocolchicoside gel for 10 mins and for a total of 10 sessions. In Group 2 (n = 30) the same US protocol was applied with the same setting and timing with Group 1 using US gel that did not contain any pharmaceutical ingredient. Evaluation parameters were visual numeric scale (VNS), Oswestry Disability Index (ODI), and Shober test. Comparison of the results obtained from the 2 groups before treatment and at 2nd (W2) and 6th weeks (W6) post-treatment showed significant improvement in all parameters in both groups (p < 0.05). Comparison of the groups showed significantly superior improvement in Group 1 for ODI while there was no difference in other parameters at W2. At W6, there was significantly superior improvement in all parameters (p < 0.05) except for Shober test in Group 1. The authors concluded that these findings showed that phonophoresis was superior than conventional US therapy at short-term in the treatment of patients with acute LBP. The relatively small sample sizes (n = 30 in each group) and the short-term follow-up (6 weeks) were the main drawbacks of this trial. These researchers suggested that further studies with larger patient groups are needed for better understanding of the effects of phonophoresis in acute and chronic LBP.
Upper Trapezius Latent Myofascial Trigger Point
Tabatabaiee and associates (2019) stated that latent myofascial trigger point (LMTP) is a small hypersensitive area in skeletal muscles that becomes painful under compression or stimulation; and LMTPs are relevant for various musculoskeletal disorders. Although several treatments have been introduced to treat LMTP, the most efficient one is yet to be found. These researchers compared the effectiveness of pressure release, phonophoresis of betamethasone and dry needling in treating upper trapezius LMTP. A total of 60 subjects (mean ± SD age of 23.6 ± 2.1 years), with at least 1 LMTP in the upper trapezius muscle, participated in this study. Subjects were randomly divided into 3 groups (pressure release, phonophoresis with betamethasone and dry needling groups) for 2 weeks. Pain intensity, pain pressure threshold and active cervical range of motion (ROM) were assessed. Significant pain decrease, active cervical ROM and pain pressure threshold increase were observed in the 3 groups (p < 0.001). The dry needling and phonophoresis groups reported more significant improvement compared to the pressure release group (p < 0.001). There was no difference between the dry needling and phonophoresis groups. The authors concluded that considering the significant, positive effects of all 3 methods, dry needling and phonophoresis appeared to be more effective than pressure release in treating upper trapezius LMTP. This was a relatively small study (a total of 60 subjects), and no follow-up data were provided. These preliminary findings need to be validated by well-designed studies.
Carpal Tunnel Syndrome
In a double-blind RCT, Boonhong and Thienkul (2020) examined the effects of phonophoresis of piroxicam (PH-P) and phonophoresis of dexamethasone sodium phosphate (PH-Dex) on mild-to-moderate CTS, and compared each of them with the control group of non-drug US therapy. Patients with clinical signs and symptoms of CTS underwent an electrophysiological study to confirm the diagnosis of CTS and severity grading; 33 patients, 50 hands (52% of the patients had bilateral CTS, n = 17) with mild-to-moderate CTS were randomly allocated into 3 study groups: PH-P, PH-Dex, or US. All 3 groups received 10 sessions of 1-MHz frequency, 1.0 w/cm2 intensity US wave with stroking technique, continuous mode, at the palm side of the hand over the carpal tunnel area -- 10 mins/session, 2 to 3 times per week for 4 weeks, for a total of 10 sessions. During each session, subjects received 15 cm3 of study gel according to the study groups. The PH-P group received 0.5% piroxicam gel mixture (equivalence of 20 mg of piroxicam); the PH-Dex group received 0.4% dexamethasone sodium phosphate gel mixture (equivalence 60 mg of dexamethasone); and the US group received non-drug gel. Boston Carpal Tunnel Questionnaire for symptom severity (BCTQ SYMPT), Boston Carpal Tunnel Questionnaire for functional status (BCTQ FUNCT) and electrophysiological parameters of the median nerve including distal sensory latency (DSL) and distal motor latency (DML) were evaluated before the 1st treatment and after the last treatment. After treatment, all treatment groups (PH-P, PH-Dex, and US) showed significant improvements of the BCTQ SYMPT (p < 0.001, -0.74 ± 0.73 [-1.12 to -0.37], -0.91 ± 0.96 [-1.41 to -0.42], and - 0.68 ± 0.71 [-1.05 to -0.30], respectively) and the BCTQ FUNCT (p < 0.001, -0.68 ± 0.89 [-1.14 to -0.22], -0.74 ± 0.84 [-1.17 to -0.30], and - 0.80 ± 0.80 [-1.22 to -0.37], respectively). For the BCTQ SYMPT, only the PH-Dex showed an improvement score above MCID at 0.8 level [-0.91 ± 0.96]. The improvement of BCTQ FUNCT score of all groups was above Minimal Clinically Important Difference (MCID) at 0.5 level (-0.68 ± 0.89, -0.74 ± 0.84 and - 0.80 ± 0.80, respectively). The DSL was decreased in all groups but the changes were not statistically significant (p = 0.70, -0.11 ± 0.34 [-0.28 to 0.06], -0.09 ± 0.32 [-0.26 to 0.07], and - 0.14 ± 0.29 [-0.29 to 0.02], respectively). The DML showed decrease only in PH-DEX and the US group but it was not statistically significant (p = 0.68, 0.05 ± 0.44 [-0.17 to 0.27], -0.09 ± 0.51[-0.34 to 0.17], and - 0.27 ± 0.49 [-0.53 to 0.01], respectively). All measured outcomes were not statistically different in between-group-comparison of BCTQ SYMPT, BCTQ FUNCT, DSL, and DML (p = 0.58, p = 0.79, p = 0.20 and p = 0.39, respectively). However, there was a clinically significant difference of the improvement of BCTQ SYMPT in between-group comparison; only the PH-DEX was above the MCID level, while the PH-P and US were not. The authors concluded that neither non-drug US nor phonophoresis treatments (PH-P and PH-Dex) were effective to improve the DSL and DML in mild-to-moderate CTS. All 3 groups showed significant improvements in clinical symptoms (BCTQ SYMPT) and functional status (BCTQ FUNCT). At 1 MHz frequency and 1.0 w/cm2 intensity of US wave, there was no statistically significant difference between phonophoresis and the non-drug US. Level of Evidence = I.
Knee Osteoarthritis
In a systematic review and meta-analysis, Wu and colleagues (2019) examined the safety and effectiveness of therapeutic US with sham US on pain relief and functional improvement in patients with knee osteoarthritis (OA). As phonophoresis is a unique therapeutic US, these researchers also compared the effects of phonophoresis with conventional non-drug US. PubMed, Embase, and the Cochrane Library were systematically searched for RCTs from inception up to June 2019; RCTs comparing therapeutic US with sham US in knee OA patients were included. Phonophoresis in the experimental and control groups were compared through conventional US, and corresponding trials were also included; 2 reviewers independently identified eligible studies and extracted data. Risk of bias assessments and therapeutic US safety assessments were also performed. A total of 15 studies including 3 phonophoresis-related studies with 1,074 patients were included. Meta-analyses demonstrated that therapeutic US significantly relieved pain (p < 0.00001) and reduced the WOMAC physical function score (p = 0.03). In addition, therapeutic US increased the active ROM (p < 0.00001) and reduced the Lequesne index (p < 0.00001). Subgroup analysis of phonophoresis US showed significant differences on the visual analogue scale (VAS; p = 0.009), but no significant differences on WOMAC pain subscales (p = 0.10), and total WOMAC scores were observed (p = 0.30). There was no evidence to suggest that US was an unsafe treatment. The authors concluded that therapeutic US is a safe treatment to relieve pain and improve physical function in patients with knee OA. However, phonophoresis did not produce additional benefits to functional improvement, but may relieve pain compared to conventional non-drug US.
In a double-blind RCT, Pinkaew and colleagues (2020) examined the effects of treatment with Phyllanthus amarus (P. amarus) nanoparticle gel applied by phonophoresis (PP) and US therapy (UT) in patients with symptomatic knee OA. Patients with knee OA (n = 40; mean age ± SD, 64.30 ± 9.71 years), who had VAS scores for knee pain intensity of 68.00 ± 9.58 (UT group) and 71.00 ± 8.74 (PP group, respectively) before treatment, were randomly allocated into 2 groups. Both groups were treated with an US program in continuous mode, 1.0 W/cm2, 10 mins/session for 10 sessions. Nanoparticles of P. amarus were used in the PP group, whereas a non-drug coupling gel was used in the UT group. The 6-min walk test (6MWT) was carried out to examine functional capacity. The VAS and the 6MWT were evaluated before and after 10 treatment sessions in both groups using a double-blind procedure. VAS and 6-MWT showed significant improvement after treatment in both groups (p < 0.05). The PP group showed more significant effects than the UT group, in terms of both reducing the VAS pain score (p < 0.05) and improving 6MWT (p < 0.05). The authors concluded that PP was suggested as an effective method for the treatment of symptomatic knee OA for reducing pain and improving functional capacity. This was a relatively small study (total of 40 subjects) with no follow-up.
Martin-Vega et al (2022) noted that knee OA is the commonest joint disease. The administration of NSAIDs by phonophoresis is a therapeutic alternative to relieve pain in inflammatory pathologies. In a systematic review and meta-analysis, these investigators examined the effectiveness of the application of NSAIDs by phonophoresis in knee OA. They carried out a review of controlled clinical trials between January and March 2021 in the following databases: Web of Science, Scopus, PubMed, Cinahl, SciELO, and PEDro. The PEDro scale was used to examine the level of evidence of the selected studies. The RevMan 5.4 statistical software was used to obtain the meta-analysis. A total of 8 studies were included, of which 5 were included in the meta-analysis, involving 195 subjects. The NSAIDs used via phonophoresis were ibuprofen, piroxicam, diclofenac sodium, diclofenac diethyl-ammonium, ketoprofen, and methyl salicylate. The overall result for pain showed inconclusive results, but a trend toward significance was found in favor of the phonophoresis group compared to the control group (SMD = -0.92; 95 % CI: -1.87 to 0.02). Favorable results were obtained for physical function (SMD = -1.34; 95 % CI: -2.00 to 0.68). the authors concluded that based on the selected studies, the use of NSAIDs by phonophoresis was effective in relieving the symptoms of knee OA. Moreover, these researchers stated that further investigation is recommended. In particular, future studies are recommended with applications of longer time per session, treatment time, and follow-up in order to observe if the increase of these factors would increase their effectiveness. Other outcomes to consider in future studies are the substance administered, phonophoresis parameters, intervention duration, and measuring instruments.
The authors stated that this review had 2 main drawbacks. First, these findings should be taken with caution due to the limited number of studies included in the meta-analysis. It was not possible to statistically compare all the studies included in the systematic review because different measuring instruments were used. Second, the protocols used by the studies were heterogeneous, including different time measurement and follow-up periods, substances administered, and phonophoresis parameters, making comparisons difficult; thus, it is necessary to perform RCTs unifying protocols regarding the substance administered, phonophoresis parameters, intervention duration, and measuring instruments. This could provide more information on which specific aspects of the intervention might have the greatest impact on outcomes.
In a systematic review and meta-analysis, Yang et al (2022) examined the effect of phonophoresis when various gel types were used. Medline (using PubMed), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were used to identify relevant studies from the date of their inception to June 28, 2021. These investigators included studies that were RCTs, included patients with a diagnosis of knee OA, included treatment with either phonophoresis or therapeutic US with placebo gel, and reported clinical and functional outcomes. Continuous variables were expressed as SMDs with 95 % CIs. Statistical analysis was conducted using RevMan 5.3 software. These researchers initially retrieved 2,176 studies and finally analyzed 9 RCTs including 423 patients. The intervention group significantly out-performed the control group in pain scores with NSAID gel (SMD = - 0.53, 95 % CI: -1.02 to -0.05], I2 = 73 %) and in the WOMAC function score with corticosteroid gel (SMD = - 0.96, 95 % CI: -1.47 to -0.44], I2 = 20 %). The authors concluded that phonophoresis alleviated pain and improved functional performance. Moreover, these researchers stated that because of some limitations of this study, additional high-quality, large-scale RCTs with long follow-up periods are needed to confirm the benefit and long-term effects of this intervention.
The authors stated that this study had several drawbacks. First, heterogeneity was moderate-to-high for some outcomes, possibly because of varying disease severity, symptom duration, patient characteristics, and treatment protocol. Therefore, additional studies are needed to establish a standardized therapeutic protocol. Second, different gel contents, such as lidocaine or capsaicin, that could be applied in the experimental group were not examined. In addition, only 1 trial focused on herbal gels and was not included in the meta-analysis, although it revealed a positive effect. Future studies should examine the effects of different gel contents. Third, several studies did not mention blinding to therapeutics and the blinding of patients or assessors; thus, some concerns regarding the risk of bias may persist. Fourth, these investigators observed that the pain scores with NSAID gel were affected by the removal of articles when conducting the sensitivity analysis. This might compromise the stability and reliability of the meta-analysis. Fifth, the included studies had short follow-up durations; thus, these investigators could not analyze long-term outcomes. Sixth, the sample sizes in each study and the number of studies included for each outcome were different; therefore, the outcomes should be interpreted with caution.
Temporomandibular Joint Disorders
Ramakrishnan and Aswath (2019) examined the efficacy of phonophoresis in patients with temporomandibular disorders (TMDs). A total of 50 patients diagnosed clinically and radiographically as TMD were randomly assigned into either of the 2 groups: Group A - plain US, and Group B - phonophoresis. Acoustic gel containing no pharmacological agent was applied in the US group, whereas a gel containing aceclofenac was applied in the phonophoresis group. Each group was treated thricely-weekly for 2 weeks. The assessment of pain and inflammation both before and after treatment were carried out using the VAS and C-reactive protein (CRP). Inter-group comparison was performed and analyzed statistically using independent t-test. Intra-group comparison was carried out using paired t-test. A significant difference in VAS scores and CRP levels before and following treatment were observed within both US and phonophoresis groups. No significant difference was observed statistically between US and phonophoresis group. The authors concluded that the findings of this study suggested that although plain US as well as phonophoresis with aceclofenac gel were effective in the management of TMD, phonophoresis was found be slightly superior as evident in VAS scores and CRP levels though not statistically significant.
The authors stated that this study had several drawbacks. The findings reflected the short-term effects of phonophoresis or US therapy; long-term effectiveness has not been examined. They stated that for a more definitive answer on the use of phonophoresis and therapeutic US in TMDs, large RCTs with long-term follow-up is needed.
In a pilot study, Azam et al (2023) examined the effects of a 3-week program consisting of strain/counter-strain technique (SCST), phonophoresis, heat therapy, and stretching exercises on pain and functions in patients with TMD. A total of 7 participants (mean age of 25.85 years) diagnosed with TMD having pain in the temporomandibular joint (TMJ) area with decreased jaw opening were recruited for the study. Treatments consisted of SCST, phonophoresis (US gel mixed with diclofenac gel), heat therapy, and stretching (mouth-opening) exercises, 3 days a week for 3 weeks. SCST was carried out on the masseter, medial, and lateral pterygoid muscles. No control group was present in the study. Paired samples t-test revealed a significant difference in numerical pain rating scale (NPRS) (decreased by 50 %, p < 0.001) and jaw functional limitation scale (JFLS) (reduced by 59.58 %, p < 0.001) scores after 3 weeks of intervention. A large effect size (Cohen d = -3.00 for NPRS and -3.16 for JFLS) was observed for both variables. No correlation (R = 0) was found between the baseline values of NPRS and JFLS. The authors concluded that a 3-week program consisting of SCST, phonophoresis, heat therapy, and stretching exercises was effective in reducing the pain and improving the functions related to TMJ in patients suffering from TMD. Moreover, these researchers stated that a RCT is needed to reach a definite conclusion.
The authors stated that this study had several drawbacks. First, this was a pilot study where a control group could not be created due to the unavailability of a sufficient number of participants; thus, these investigators could not reach a definite conclusion without a RCT with a control group and a larger sample size. Second, the improvements obtained in this trial may be short-lived, and the symptoms may return with the cessation of the treatment intervention; thus, future research should consider a long-term follow-up. Third, the improvements obtained in this pilot study were the cumulative effects of SCST, phonophoresis, heat therapy, and stretching exercises. Further investigations may find isolated effects of SCST, phonophoresis, heat therapy, and stretching exercises.
Traumatic Muscle Injury
Haupenthal and associates (2020) stated that the repair process consists of molecular and cellular events that can be accelerated by specific therapies. These researchers examined the effects of ibuprofen phonophoresis associated with gold nanoparticles (GNPs) in the animal model of traumatic muscle injury. A total of 80 male Wistar rats were divided into 8 groups: Sham; muscle injury (MI); MI + therapeutic pulsed US (TPU); MI + Ibuprofen (IBU); MI + GNPs; MI + TPU+ IBU; MI + TPU + GNPs and MI + TPU + IBU + GNPs. The lesion in the gastrocnemius was performed by a single direct trauma impact on the injured press. Animals were treated with pulsed US and the gel with GNPs and/or IBU. Treatment was applied daily for 5 days and the 1st session was 12 hours after the muscle injury. The gastrocnemius muscle was surgically removed for analyses -- biochemical, histological, and molecular. In the analyzes only the MI + TPU + IBU + GNPs group showed a reduction in TNF-a and IL-1 levels, with a concomitant increase in the levels of anti-inflammatory cytokines. In the analysis of oxidative stress, only the MI + TPU + IBU + GNPs group presented a reversal of the condition when compared to the MI group. In the histological analysis, the MI group presented a large cell infiltrate and a centralized nucleus and only the MI + TPU + IBU + GNPs group showed a structural improvement, also in the pain results the MI + TPU + IBU + GNPs showed a significant difference in comparison to the MI group (p < 0.01). The authors believed that the effects of phonophoresis with anti-inflammatory drugs associated with gold nanoparticles may potentiate the reduction of the inflammatory response and regulate the cellular redox state. These preliminary findings need to be further investigated.
Lateral Epicondylitis
The American College of Occupational and Environmental Medicine’s occupational medicine practice guidelines on “Elbow disorder” (ACOEM, 2012) phonophoresis is not recommended for acute, subacute, or chronic lateral epicondylalgia. Furthermore, the ACOEM guidelines offer no recommendation regarding the use of phonophoresis for acute, subacute, or chronic ulnar neuropathies at the elbow.
In a prospective, parallel-group, randomized-controlled clinical study, Okan and Turk (2020) compared the efficiency of US, mucopolysaccharide polysulfate phonophoresis, ketoprofen phonophoresis and exercise combinations in terms of pain, functionality, disability, and strength in patients with lateral epicondylitis (LE). This trial included a total of 60 patients (42 men, 18 women; mean age of 38.08 years; range of 21 to 50 years) with LE between April 2016 and October 2017. Subjects were equally randomized into 4 groups based on the time of admission to the outpatient clinic. The VAS, painless weight-lifting, the Patient- Rated Tennis Elbow Evaluation (PRTEE), and Quick Disabilities of Arm, Shoulder and Hand (QuickDASH) were used to measure the outcomes. The measurements were carried out at baseline, at the end of 10 daily sessions, and after a 6-week follow-up period. The resting VAS scores in the ketoprofen phonophoresis group and lifted weights in the MPS and ketoprofen phonophoresis groups showed a significant improvement both after 10 days of treatment and at 6-week follow-up visits (p < 0.001). In the QuickDASH model, there was no significant improvement in the control group after 10 days of treatment (p > 0.05); however, a significant improvement was observed after 6 weeks (p < 0.001). Except for these variables, significant improvements were found in all groups for all variables at 6-week follow-up (p < 0.05); however, improvements were similar in all groups (p > 0.05). The authors concluded that based on the findings of this study, for LE patients who were unable to adhere to exercise and splint use and were given a physical treatment plan, inclusion of ketoprofen and MPS phonophoresis in the treatment program may yield additional benefits in their daily living activities, functionality, and working life. Moreover, these researchers stated that further large-scale, long-term, prospective studies are needed to examine the exact effect of integrating MPS phonophoresis to the treatment algorithms or treatment plans for LE.
The authors stated that this study had several drawbacks. Since the subjects in the present study were in the acute phase, an improvement was observed in all groups; therefore, further studies are needed to examine the effect of treatment on patients in the chronic phase. In a study carried out by Bisset and Vicenzino (2015) the patients with less than 3 months of pain, without an accompanying neck or arm pain, and patients whose PRTEE scores were less than 54/100 were considered to have a good prognosis. These patients were reported to benefit from a wait-and-see approach as a result of counseling on their condition, load management including tools and workstation, and self-management within 12 weeks. Another drawback of this study was that there was no control group in the study receiving no treatment. Home-based exercises and splints were given to the control group not to leave the patients untreated. The final drawback was the lack of long-term follow-ups. The follow-up interval was intentionally chosen to determine the differences of the treatment modalities for the acute clinical outcomes in 6 weeks.
Neck Pain
In a systematic review, Dorji and colleagues (2022) examined the effectiveness of US/phonophoresis as an adjuvant to exercise or manual therapy for the improvement of patient-centered outcomes in adults with non-specific neck pain (NSNP). A total of 7 electronic databases were systematically searched up to September 2020. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to judge the quality of evidence (QoE). A total of 6 studies involving 249 participants were included. The QoE was very low GRADE. Phonophoresis with capsaicin plus exercise improved pain at immediate post-treatment (mean difference [MD]: -3.30 [-4.05 to -2.55]) but not with diclofenac sodium plus exercise as compared to exercise. Continuous US (CUS) plus exercise improved pain and pressure pain threshold (PPT) at immediate post-treatment (pain: MD: -3.42 [-4.08 to -2.7]); (PPT: MD: 0.91 [0.68 to 1.14]) and at intermediate-term as compared to exercise. Continuous US or high power pain threshold (HPPT) US plus manual therapy and exercise showed no benefit for pain reduction (MD: -0.75 [-2.08 to 0.58]) did not improve function/disability (MD: -1.05 [-4.27 to 2.17]) at immediate or short-term as compared to manual therapy and exercise. The authors concluded that due to high risk of bias, inconsistency, and indirectness, the QoE was very low in support of benefit of adding US or phonophoresis to exercise or manual therapy for pain reduction or improvement in function/disability for those with sub-acute and chronic myofascial-associated neck pain. However, the confidence in the findings was very low and conclusions were likely to change as more evidences emerges. These researchers stated that clinicians using US therapy as an adjuvant intervention for management of chronic myofascial-associated neck pain should carefully consider the available evidence on US, including the benefits and costs involved.
The authors stated that a main drawback of this review was the inclusion of a small number of studies with high risk of bias. The QoE was examined using the GRADE approach with results indicating very low-quality evidence. The strength of evidence was down-graded mainly due to the high risk of bias, inconsistency and overall impression. The critical methodological limitations included a small number of included studies that were largely of unclear or high risk of selection bias, lack of blinding, small sample size and lack of long-term follow-up. Selection bias was apparent, as all the included studies were rated as “unclear” or “high risk” for selection bias. All of the studies inadequately described the methods of randomization or allocation concealment except for 1, which reported adequately on allocation concealment. Other drawbacks were inclusion of studies published in only English and inability to carry out meta-analysis mainly due to the small number of studies and high clinical and statistical heterogeneity.
In a randomized clinical trial, Taheri and colleagues (2021) examined the effects of using extra-corporeal shock wave therapy (ECSWT) and phonophoresis therapy on pain and neck disability in patients with neck myofascial pain syndrome (MPS). A total of 40 eligible patients were randomly divided into 2 groups of ECSWT (received 3sessions of ECSWT, once-weekly for 3 weeks) and phonophoresis (received US using hydrocortisone gel 1 % over the trigger point on trapezius muscle, 3 times a week for 3 weeks). Patients in both groups received the same stretching exercise program and drug regimen during the intervention. Pain and NDI scores in both groups were significantly improved at the end of the treatment and 4 weeks later. At the end of the treatment, the pain score was similar between the groups. Four weeks after the treatment, the pain score in the ECSWT group was significantly lower than in the phonophoresis group (p = 0.030). The NDI score was not significantly different between the groups at the end of the treatment. However, 4 weeks after the treatment, the NDI score was significantly lower in the ECSWT group than in the phonophoresis group (p = 0.032). The trend of changes in the pain and NDI scores was not significantly different between the groups. The authors concluded that both phonophoresis and ECSWT groups effectively decreased pain and neck disability in patients with MPS, with the superiority of ECSWT with a more lasting effect for a month after the end of the treatment. Moreover, these researchers stated that further studies may elucidate the effects of ECSWT and phonophoresis in MPS treatment.
The authors stated that this study had several drawbacks. First, the trained stretching exercise program was home-based, and during the follow-up period, the patients were not questioned regarding the duration of the exercises and compliance with this program. Second, these researchers did not have control groups for the studied treatments, sham ECSWT, and conventional US therapy, which could be useful in clarifying the exact effect of adding the studied treatments to the stretching exercise programs and drug regimens.
Chronic Obstructive Pulmonary Disease
Shen and colleagues (2021) stated that chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by coughing, the production of excess sputum, and dyspnea. Patients with excessively thick sputum may have frequent attacks or develop more serious disease. The guidelines recommend airway clearance for patients with excessive sputum who are hospitalized with COPD. The active cycle of breathing technique is the most common non-pharmacological airway clearance technique used by physiotherapists; however, the effectiveness of the technique is not always guaranteed. Active cycle of breathing techniques requires the initial dilution of the sputum, usually by inhalation drugs, which may have limited effects. Recent studies have found that phonophoresis decreases inflammation, suggesting the potential of the combined usage of active cycle of breathing techniques and phonophoresis. These researchers examined the safety and effectiveness of combining active cycle of breathing technique and phonophoresis in treating patients with COPD. They propose a single-blind RCT using 75 hospitalized patients diagnosed with COPD with excessive sputum production. Subjects will be divided into 3 groups. The intervention group will receive active cycle of breathing techniques combined with phonophoresis. The 2 comparison groups will be treated with active cycle of breathing techniques and phonophoresis, respectively. The program will be implemented daily for 1 week. The primary outcomes will be changes in sputum viscosity and production, lung function, and pulse oximetry. Secondary outcomes include the assessment of COPD and anxiety, measured by the COPD Assessment Test scale and the Anxiety Inventory for Respiratory Disease, respectively; self-satisfaction; the degree of co-operation; and the length of hospital stay. All outcome measures, with the exception of sputum production and additional secondary outcomes, will be assessed at the commencement of the study and after 1 week's intervention. Analysis of variance will be used to examine differences between the groups, and a p-value of less than 0.05 (2-tailed) will be considered statistically significant. The authors concluded that this study introduced a combination of active cycle of breathing techniques and phonophoresis to examine the impact of these interventions on patients hospitalized with COPD. If this combined intervention is shown to be effective, it may prove to be a better treatment for patients with COPD.
The authors stated that there are limitations to their research. First, this is a single-center study; thus, it is unclear if the findings are generalizable to other locations and clinical settings. Second, as the study is of relatively short duration, no data will be available beyond 1 week and longer-term effectiveness will not be able to be evaluated.
Chronic Wound Management
Ead et al (2022) stated that US technology has therapeutic properties that could be harnessed to enhance topical drug delivery in a process known as phonophoresis. The literature on this method of drug delivery is currently sparse and scattered. In a mini review, these investigators examined in-vivo and in-vitro controlled studies as well as studies detailing the mechanism of action in phonophoresis to gain a clearer picture of the treatment modality and explore its use in chronic wound management. The authors concluded that phonophoresis has the potential to assist the current therapeutic modalities against bacterial biofilms in chronic wounds. These researchers stated that while more research is needed to confirm the appropriate indications for its use and effectiveness, the available evidence shows promise. These investigators stated that more research is needed to clarify the US parameters that are critical for maximizing local diffusion of topically applied drugs with phonophoresis; and how to measure and control the local versus systemic effects of phonophoresis.
Serous Otitis Media
Krotov and Krotov (2022) examined the effectiveness of US regional lymphotropic therapy in the treatment of protracted forms of serous otitis media (SOM). The study included 75 patients (102 cases of diseased ears) with SOM. Subjects underwent repeated outpatient courses of conservative treatment for 1 to 3 months; however, all subjects exhibited symptoms of the disease. In the department of otorhinolaryngology, each subject with protracted forms of SOM was administered a course of US regional lymphotropic therapy. The criteria of the treatment results were subjective and objective data of a special examination, which included: the presence of relevant complaints, otoscopy, determination of the levels of perception of live speech, indicators of air and bone sound conduction, tonal threshold audiometry, tympanometry characterizing the dynamics of hearing, the airiness of the tympanic cavity, the functioning of the auditory tubes. The examination was carried out before and after treatment. Confirmation of the effectiveness of US regional lymphotropic therapy in protracted forms of SOM was the restoration in 52 % of patients of whispering and in 68 % of patients of colloquial speech to socially adequate values; a decrease in the level of sound perception thresholds at all frequencies by air conduction; an increase in tonal hearing; a complete restoration of the airiness of the tympanic cavity in 57 % of patients (type A tympanogram). The authors concluded that a new method of treating patients with protracted forms of SOM has been developed and clinically justified by the combined use of low-frequency US and medications with lymphotropic effect. Phonophoresis was one of the key words of this study. This was a relatively small, single-center study with no follow-up information. These preliminary findings need to be validated by well-designed studies.
Furthermore, an UpToDate review on “Otitis media with effusion (serous otitis media) in children: Management” (Pelton and Marom, 2022) does not mention phonophoresis / ultrasound as a management / therapeutic option.
Bee Venom Phonophoresis for the Treatment of Venous and Diabetic Ulcers
Othman et al (2023) noted that chronic venous and diabetic ulcers are difficult to treat; they cause patients prolonged suffering as well as significant healthcare and financial costs. In a single-blind RCT, these investigators examined the effectiveness of bee venom (BV) phonophoresis on the healing of chronic unhealed venous and/or diabetic foot ulcers. They also compared the healing rate of diabetic and venous ulcers. This trial entailed 100 patients (71 men and 29 women; age range of 40 to 60 years) who had chronic unhealed venous leg ulcers of grade-I, grade-II, or diabetic foot ulcers with type II diabetes mellitus (T2DM). Participants were randomly assigned into 4 equal groups of 25: Group A (diabetic foot ulcer study group) and group C (venous ulcer study group) who both received conservative treatment of medical ulcer care and phonophoresis with BV gel, in addition to group B (diabetic foot ulcer control group) and group D (venous ulcer control group) who both received conservative treatment of medical ulcer care and received US sessions only without BV gel. Wound surface area (WSA) and ulcer volume measurement (UVM) were used to evaluate the ulcer healing pre-application (P0), post-6 weeks of treatment (P1), and after 12 weeks of treatment (P2). Furthermore, Ki-67 immunohistochemistry was employed to examine the cell proliferative in the granulation tissue of ulcers pre-application (P0) and after 12 weeks of treatment (P2) for all groups. This study demonstrated a statistical significance improvement (p ≤ 0.0) in the WSA, and UVM with no significant difference between study groups after treatment. Ki-67 immunohistochemistry showed higher post-treatment values in the venous ulcer group in comparison to the diabetic foot ulcer group. The authors concluded that BV provided by phonophoresis was an effective adjuvant treatment in accelerating venous and diabetic foot ulcer healing with higher proliferative effect on venous ulcer. These investigators suggested adding this technique to the chronic ulcer treatment program and conducting follow-up studies for any further improvement.
The authors stated that this study had several drawbacks. First, psychological and cultural concerns might restrict the study's conclusions. Second, these researchers could not achieve double-blinding or confirm if subjects were following both their prescribed diet and correctly taking their medications to control blood glucose. More thorough studies determining the follow-up of different multiple therapeutic periods would be of extreme importance, in addition to diversity in the participants and their implications on the rate of recovery. Third, other kinds of ulcers should be studied in a similar manner. Fourth, with improved data analysis and over a longer length of time than 3 months, more research should be carried out on a larger set of patients. A comparison of various physiotherapeutic modalities and protocols might be done in future studies. Fifth, more studies should be performed using different parameters of US (intensity, frequency, and duration of treatment) or with other physical therapy modalities, such as iontophoresis instead of phonophoresis. Sixth, further investigations are needed to compare the effectiveness of the treatment, after adjusting for factors related to sex and age, as well as different concentrations of BV gel.
Contractubex Phonophoresis for the Management of Post-Surgical Scar of Carpal Tunnel Release
Bokaee et al (2023) noted that Contractubex (Contractubex gel includes 10 % aqueous onion extract, 50 U heparin/g gel, and 1 % allantoin) phonophoresis can be used in clinical setting to manage post-surgical scar after carpal tunnel release. Contractubex phonophoresis supposedly could improve pliability, height, and tenderness of the scar. Scar is one of the most common complications following open release of carpal tunnel. Scars are mentally and physically disturbing, and they can result into itching and pain. Scar following release of carpal tunnel could result in compression of median nerve and failure of surgery. Various treatments have been employed for the management of scar in this setting; and topical drugs are one of these treatments. These researchers stated that phonophoresis of topical drugs could enhance delivery of topical drugs. In this single-case study, the author reported the effect of phonophoresis of Contractubex on post-surgical scar following carpal tunnel release; and result indicated that phonophoresis of Contractubex could be effective in scar management. Moreover, these researchers stated that there are limited studies regarding the impact of Contractubex phonophoresis for scar management following open carpal tunnel release; further investigations in larger sample size are needed.
Shoulder Impingement Syndrome (Subacromial Impingement Syndrome)
In a RCT, Kelle et al (2023) compared the effectiveness of pulsed and continuous modes of therapeutic US for phonophoresis in the treatment of subacromial impingement syndrome (SAIS). Between April 2019 and January 2021, a total of 66 patients with SAIS (17 men, 49 women; mean age of 48.2 ± 8.6 years; range of 19 to 64 years) were included. Subjects were randomized to the phonophoresis with continuous mode group (n = 22), phonophoresis with pulsed mode group (n = 22), and phonophoresis with sham US group (n = 22); 5 g of ibuprofen phonophoresis was applied in 5 sessions/week for 3 weeks for all groups. Primary outcomes were pain intensity as assessed by the VAS and shoulder functions by the short version of QuickDASH. The secondary outcome was the quality of life (QOL) as evaluated by the Nottingham Health Profile (NHP). All subjects were examined at pre-treatment, post-treatment, and at 3 months after the end of the treatment. There was a significant improvement in pain during activity, shoulder function, and QOL after treatment in phonophoresis with continuous and pulsed modes compared to phonophoresis with sham US (p < 0.05). Phonophoresis with continuous mode was superior to other groups in reducing pain at rest (p < 0.05). Changes between pre-treatment and the 3-month follow-up showed a significant improvement in pain during activity and shoulder functions in phonophoresis with continuous and pulsed modes, compared to phonophoresis with sham US (p < 0.05). Phonophoresis with pulsed mode was more effective than the other interventions in improving QOL during the same period (p < 0.05). The authors concluded that they observed a statistically significant difference in the results of the continuous mode for pain at rest and during activity in the early period and pulsed mode for pain during activity and shoulder functions during follow-up. These investigators stated that these findings may provide early clinical improvement, as well as return-to-work and; therefore, less economic loss. Moreover, these researchers stated that further large-scale, long-term, prospective, RCTs are needed to confirm these findings.
The authors stated that this study had several drawbacks. First, the frequency and intensity of therapeutic US were 1 MHz and 1 W/cm2 , respectively. The parameters used were the most frequent in daily practice. The duration of the US treatment was 5 mins. Other frequency and intensity values and treatment durations that are likely to alter treatment outcomes were not tested. Second, ibuprofen was used as the active substance, but another active substance (e.g., dexketoprofen, aceclofenac, betamethasone) that can be used may affect the results. Third, this trial had a relatively short-term follow-up (3 months).
References
The above policy is based on the following references:
- Altan L, Kasapoglu Aksoy M, Kosegil Ozturk E. Efficacy of diclofenac & thiocolchioside gel phonophoresis comparison with ultrasound therapy on acute low back pain; A prospective, double-blind, randomized clinical study. Ultrasonics. 2019;91:201-205.
- American College of Occupational and Environmental Medicine. Elbow disorders. In: Hegmann KT, editor(s). Occupational medicine practice guidelines. Evaluation and management of common health problems and functional recovery in workers. 3rd ed. Elk Grove Village, IL: ACOEM; 2012.
- Ansari NN, Fathali M, Naghdi S, et al. Treatment of chronic rhinosinusitis using erythromycin phonophoresis. Physiother Theory Pract. 2013;29(2):159-165.
- Azam I, Chahal A, Kapoor G, et al. Effects of a program consisting of strain/counterstrain technique, phonophoresis, heat therapy, and stretching in patients with temporomandibular joint dysfunction: A pilot study. Medicine (Baltimore). 2023;102(32):e34569.
- Bagnulo A, Gringmuth R. Treatment of myositis ossificans with acetic acid phonophoresis: A case series. J Can Chiropr Assoc. 2014;58(4):353-360.
- Bakhtiary AH, Fatemi E, Emami M, Malek M. Phonophoresis of dexamethasone sodium phosphate may manage pain and symptoms of patients with carpal tunnel syndrome. Clin J Pain. 2013;29(4):348-353.
- Bare AC, McAnaw MB, Pritchard AE, et al. Phonophoretic delivery of 10% hydrocortisone through the epidermis of humans as determined by serum cortisol concentrations. Phys Ther. 1996;76(7):738-745; discussion 746-749.
- Benson HA, McElnay JC, Harland R. Use of ultrasound to enhance percutaneous absorption of benzydamine. Phys Ther. 1989;69(2):113-118.
- Bisset L, Paungmali A, Vicenzino B, Beller E. A systematic review and meta-analysis of clinical trials on physical interventions for lateral epicondylalgia. Br J Sports Med. 2005;39(7):411-422.
- Bisset LM, Vicenzino B. Physiotherapy management of lateral epicondylalgia. J Physiother. 2015;61(4):174-181.
- Bly NN. The use of ultrasound as an enhancer for transcutaneous drug delivery: Phonophoresis. Phys Ther. 1995;75:539-553.
- Bokaee F. Effect of Contractubex phonophoresis on postsurgical scar of carpal tunnel release: A case report. Clin Case Rep. 2023;12(1):e8389.
- Boonhong J, Thienkul W. Effectiveness of phonophoresis treatment in carpal tunnel syndrome: A randomized double-blind, controlled trial. PM R. 2020;12(1):8-15.
- Boyaci A, Tutoglu A, Boyaci N, et al. Comparison of the efficacy of ketoprofen phonophoresis, ultrasound, and short-wave diathermy in knee osteoarthritis. Rheumatol Int. 2013;33(11):2811-2818.
- Chen S, Qin M, Han Y, et al. Assessment of the efficacy of drug transdermal delivery by electro-phonophoresis in treating tuberculous lymphadenitis. Drug Deliv. 2016;23(5):1588-1593.
- Coates VH, Turkelson CM, Chapell R, et al. and the ECRI Health Technology Assessment Group. Diagnosis and treatment of worker-related musculoskeletal disorders of the upper extremity. Evidence Report/ Technology Assessment No. 62. AHRQ Publication No. 02-E038. Rockville, MD: Agency for Healthcare Research and Quality (AHRQ); December 2002.
- Day P. SonoPrep Ultrasonic Skin Permeation System. Horizon Scanning Report. Australia and New Zealand Horizon Scanning Network. Christchurch, New Zealand: New Zealand Health Technology Assessment; 2005.
- Donovan L, Selkow NM, Rupp K, et al. The anesthetic effect of lidocaine after varying times of phonophoresis. Am J Phys Med Rehabil. 2011;90(12):1056-1063.
- Dorji K, Graham N, Macedo L, et al. The effect of ultrasound or phonophoresis as an adjuvant treatment for non-specific neck pain: Systematic review of randomised controlled trials. Disabil Rehabil. 2022;44(13):2968-2974.
- Ead JK, Sharma A, Goransson M, Armstrong DG. Potential utility of ultrasound-enhanced delivery of antibiotics, anti-inflammatory agents, and nutraceuticals: A mini review. Antibiotics (Basel). 2022;11(10):1290.
- Ellis R, Hing W, Reid D. Iliotibial band friction syndrome -- a systematic review. Man Ther. 2007;12(3):200-208.
- Fedorczyk J. The role of physical agents in modulating pain. J Hand Ther. 1997;10(2):110-121.
- Goraj-Szczypiorowska B, Zajac L, Skalska-Izdebska R. Evaluation of factors influencing the quality and efficacy of ultrasound and phonophoresis treatment. Ortop Traumatol Rehabil. 2007;9(5):449-458.
- Griffin AS, Cabot P, Wallwork B, Panizza B. Alternative therapies for chronic rhinosinusitis: A review. Ear Nose Throat J. 2018;97(3):E25-E33.
- Gurney AB, Wascher D, Schenck R, et al. Absorption of hydrocortisone acetate in human connective tissue using phonophoresis. Sports Health. 2011;3(4):346-351.
- Haupenthal DPDS, Dias FM, Zaccaron RP, et al. Effects of phonophoresis with ibuprofen associated with gold nanoparticles in animal model of traumatic muscle injury. Eur J Pharm Sci. 2020;143:105120.
- Hoenig H, Kortebein PM. Overview of geriatric rehabilitation: Program components and settings for rehabilitation. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2014.
- Hoppenrath T, Ciccone CD. Is there evidence that phonophoresis is more effective than ultrasound in treating pain associated with lateral epicondylitis? Phys Ther. 2006;86(1):136-140.
- Huisstede BM, Hoogvliet P, Franke TP, et al. Carpal tunnel syndrome: Effectiveness of physical therapy and electrophysical modalities. An updated systematic review of randomized controlled trials. Arch Phys Med Rehabil. 2018;99(8):1623-1634.
- Jain R, Jain E, Dass AG, et al. Evaluation of transdermal steroids for trapeziometacarpal arthritis. J Hand Surg Am. 2010;35(6):921-927.
- Jewell DV, Riddle DL, Thacker LR. Interventions associated with an increased or decreased likelihood of pain reduction and improved function in patients with adhesive capsulitis: A retrospective cohort study. Phys Ther. 2009;89(5):419-429.
- Kassan DG, Lynch AM, Stiller MJ. Physical enhancement of dermatologic drug delivery: Iontophoresis and phonophoresis. J Am Acad Dermatol. 1996;34(4):657-666.
- Kelle B, Deniz V, Ortac EA. Phonophoresis treatment of subacromial impingement syndrome: Pulsed or continuous: A randomized-controlled clinical trial. Turk J Phys Med Rehabil. 2023;69(2):230-238.
- Klaiman MD, Shrader JA, Danoff JV, et al. Phonophoresis versus ultrasound in the treatment of common musculoskeletal conditions. Med Sci Sports Exerc. 1998;30(9):1349-1355.
- Kozanoglu E, Basaran S, Guzel R, Guler-Uysal F. Short term efficacy of ibuprofen phonophoresis versus continuous ultrasound therapy in knee osteoarthritis. Swiss Med Wkly. 2003;133(23-24):333-338.
- Krotov SY, Krotov YA. Ultrasound regional lymphotropic therapy for protracted forms of serous otitis media. Vestn Otorinolaringol. 2022;87(4):4-8.
- Lake DA, Wofford NH. Effect of therapeutic modalities on patients with patellofemoral pain syndrome: A systematic review. Sports Health. 2011;3(2):182-189.
- Machet L, Boucaud A. Phonophoresis: Efficiency, mechanisms and skin tolerance. Int J Pharm. 2002;243(1-2):1-15.
- Martin-Vega FJ, Lucena-Anton D, Galan-Mercant A, et al. Phonophoresis through nonsteroidal anti-inflammatory drugs for knee osteoarthritis treatment: Systematic review and meta-analysis. Biomedicines. 2022;10(12):3254.
- McElnay JC, Matthews MP, Harland R, McCafferty DF. The effect of ultrasound on the percutaneous absorption of lignocaine. Br J Clin Pharmacol. 1985;20(4):412-424.
- Meidan VM, Michniak BB. Emerging technologies in transdermal therapeutics. Am J Ther. 2004;11(4):312-316.
- Michlovitz SL. Is there a role for ultrasound and electrical stimulation following injury to tendon and nerve? J Hand Ther. 2005;18(2):292-296.
- Nakhostin-Roohi B, Khoshkhahesh F, Bohlooli S. Effect of virgin olive oil versus piroxicam phonophoresis on exercise-induced anterior knee pain. Avicenna J Phytomed. 2016;6(5):535-541.
- Nimgade A, Sullivan M, Goldman R. Physiotherapy, steroid injections, or rest for lateral epicondylosis? What the evidence suggests. Pain Pract. 2005;5(3):203-215.
- O’Connor FG, Mulvaney SW. Patellofemoral pain syndrome. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2014.
- Okan S, Turk AC. Comparing the efficiency of ultrasound, ketoprofen, and mucopolysaccharide polysulfate phonophoresis in the treatment of lateral epicondylitis: A randomized-controlled clinical study. Turk J Phys Med Rehabil. 2020;66(3):307-315.
- Othman EM, Hamada HA, Mohamed GI. Clinical and histopathological responses to bee venom phonophoresis in treating venous and diabetic ulcers: A single-blind randomized controlled trial. Front Med (Lausanne). 2023;10:1085544.
- Packer JL, Krall B, Makki A, Torabinejad M. The effect of sonophoresis on topical anesthesia: A pilot project. Anesth Prog. 2013;60(2):37-41.
- Page MJ, Green S, Kramer S, et al. Electrotherapy modalities for adhesive capsulitis (frozen shoulder). Cochrane Database Syst Rev. 2014;10:CD011324.
- Parrella A, Mundy L. SonoPrep Ultrasonic Skin Permeation system for skin preparation prior to cutaneous penetration. Horizon Scanning Prioritising Summary - Volume 8. Adelaide, SA: Adelaide Health Technology Assessment (AHTA); 2005.
- Pelton SI, Marom T. Otitis media with effusion (serous otitis media) in children: Management. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2022.
- Pinkaew D, Kiattisin K, Wonglangka K, Awoot P. Phonophoresis of phyllanthus amarus nanoparticle gel improves functional capacity in individuals with knee osteoarthritis: A randomized controlled trial. J Bodyw Mov Ther. 2020;24(1):15-18.
- Ramakrishnan SN, Aswath N. Comparative efficacy of analgesic gel phonophoresis and ultrasound in the treatment of temporomandibular joint disorders. Indian J Dent Res. 2019;30(4):512-515.
- Rand SE, Goerlich C, Marchand K, Jablecki N. The physical therapy prescription. Am Fam Physician. 2007;76(11):1661-1666.
- Rao R, Nanda S. Sonophoresis: Recent advancements and future trends. J Pharm Pharmacol. 2009;61(6):689-705.
- Sevier TL, Wilson JK. Treating lateral epicondylitis. Sports Med. 1999;28(5):375-380.
- Shen MD, Guo LR, Li YW, et al. Role of the active cycle of breathing technique combined with phonophoresis for the treatment of patients with chronic obstructive pulmonary disease (COPD): Study protocol for a preliminary randomized controlled trial. Trials. 2021;22(1):228.
- Simons SM, Kruse D, Dixon JB. Shoulder impingement syndrome. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2014.
- Simons SM, Kruse D. Rotator cuff tendinopathy. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2014.
- Spelman D. Tuberculous lymphadenitis. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed January 2016.
- Tabatabaiee A, Ebrahimi-Takamjani I, Ahmadi A, et al. Comparison of pressure release, phonophoresis and dry needling in treatment of latent myofascial trigger point of upper trapezius muscle. J Back Musculoskelet Rehabil. 2019;32(4):587-594.
- Taheri P, Naderi M, Khosravi S. Extracorporeal shock wave therapy versus phonophoresis therapy for neck myofascial pain syndrome: A randomized clinical trial. Anesth Pain Med. 2021;11(2):e112592.
- Tantawy SA, Elgohary HM, Kamel DM. Trans-perineal pumpkin seed oil phonophoresis as an adjunctive treatment for chronic nonbacterial prostatitis. Res Rep Urol. 2018;10:95-101.
- van der Windt DA, van der Heijden GJ, van den Berg SG, et al. Ultrasound therapy for musculoskeletal disorders: A systematic review. Pain. 1999;81(3):257-271.
- Von Fange TJ. Quadriceps muscle and tendon injuries. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed January 2016.
- Vranic E. Sonophoresis-mechanisms and application. Bosn J Basic Med Sci. 2004;4(2):25-32.
- Williams AR. Phonophoresis: An in vivo evaluation using three topical anaesthetic preparations. Ultrasonics. 1990;28(3):137-141.
- Winters M, Eskes M, Weir A, et al. Treatment of medial tibial stress syndrome: A systematic review. Sports Med. 2013;43(12):1315-1333.
- Wu Y, Zhu S, Lv Z, et al. Effects of therapeutic ultrasound for knee osteoarthritis: A systematic review and meta-analysis. Clin Rehabil. 2019;33(12):1863-1875.
- Yang F-A, Chen H-L, Peng C-W, et al. A systematic review and meta-analysis of the effect of phonophoresis on patients with knee osteoarthritis. Sci Rep. 2022;12(1):12877.