Nonpharmacological Interventions in the Management of Xerostomia: A Review on Topical Treatments, Alternative Medicine, and Innovative Therapies
Abstract
1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Study Selection
2.3. Study Quality Assessment
2.4. Flow of Article Selection
3. Results
3.1. Topical Therapies
3.1.1. Saliva Substitutes
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- Salivary substitutes in radiation-induced xerostomia
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- Salivary substitutes in drug-induced xerostomia
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- Salivary substitutes in xerostomia suffered in elderly
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- Salivary substitutes in xerostomia suffered in Sjögren’s syndrome
3.1.2. Salivary Stimulants
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- Salivary stimulants in radiation-induced xerostomia
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- Salivary stimulants in drug-induced xerostomia
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- Salivary stimulants in elderly-induced xerostomia
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- Salivary stimulants in xerostomia in Sjögren’s syndrome patients
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- Salivary stimulants in xerostomia due to unspecified causes
3.2. Traditional and Complementary Medicine
3.2.1. Traditional Medicinal Herbs
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- Medicinal herbs in radiation-induced xerostomia
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- Medicinal herbs in drug-induced xerostomia
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- Medicinal Herbs in xerostomia in elderly
3.2.2. Acupuncture
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- Acupuncture in chemotherapy and radiotherapy-induced xerostomia
3.3. Innovative Therapies in the Treatment of Xerostomia
3.3.1. Electrostimulation
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- Electrostimulation in radiation-induced xerostomia
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- Electrostimulation in xerostomia suffered in Sjögren’s syndrome
3.3.2. Photobiomodulation
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- Photobiomodulation in chemotherapy and radiotherapy-induced xerostomia
3.3.3. Hyperbaric Therapy
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- Hyperbaric therapy in radiation-induced xerostomia
3.3.4. Stem Cell Therapy
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- Stem cell therapy in radiation-induced xerostomia
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- Stem cell therapy in xerostomia suffered in Sjögren’s syndrome
3.3.5. Gene Therapy
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- Gene therapy in radiation-induced xerostomia
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Ref. | Experimental Preparation | Main Component and Vector | Sample Characteristics | Study Design | Time Treatment | Daily Applications | Time Points Assessment | Results |
---|---|---|---|---|---|---|---|---|
Navarro-Morante et al. 2017 [27] | Surat® vs. control | Lycopene-enriched virgin olive oil as a spray | 60 patients with drug-induced xerostomia | RCT | 12 weeks | Four times per day (1.5 mL) | Baseline vs. 12 weeks | A significant improvement (p < 0.05) and quality of life (p = 0.001); |
Nuchit et al. 2020 [29] | OMJ vs. control | Carboxymethylcellulose, glycerol, and xanthan gum as a gel | 73 HNC patients with radiation-induced xerostomia | RCT | 2 months | Six times per day (1–2 teaspoon) | Baseline vs. 1, 2 months | A significant improvement (p < 0.0001) |
Barbe et al. 2018 [31] | GUM Hydral vs. control | Betaine, taurine, and hyaluronic acid as a mouth rinse and gel | 40 patients with drug-induced xerostomia | RCT | 4 weeks | Mouthrinse two times per day (15 mL); gel five time per day (1–2 cm) | Baseline vs. 4 weeks | A significant improvement (p < 0.05) |
Kvalheim et al. 2019 [32] | Glycerol preparation vs. controls | Glycerol solution as an oral moisturizer | 30 patients with drug-induced xerostomia | RCT | 3 days | Once per day | Baseline vs. immediately after, and 2 h after the application | A significant improvement (p < 0.001) |
Paterson et al. 2019 [33] | Visco-ease TM vs. control | Lamellar Body Mimetic (multi-lipid system) as an oral spray | 43 HNC patients with radiation-induced xerostomia | RCT | 6 weeks | At least two times per day (unspecified dose) | Baseline vs. 1, 2, 3, 4, 5, 6 weeks | No significant difference (p = 0.90). |
Kerr et al. 2010 [43] | OraMoist vs. control | Carbomer homopolymer and triglycerides as a mucoadhesive disk | 27 patients with non-homogeneous xerostomia | RCT | 1 week | One disk three times per day | Baseline vs. 1, 2, 3 weeks | A significant improvement (p < 0.005) and UWS (p < 0.001) |
Salom et al. 2015 [44] | Novasial vs. control | Ovalbumin and other egg derivatives as a liquid saliva substitute | 210 patients with non-homogeneous xerostomia | RCT | 2 weeks | Four times per day (5 mL) | Baseline vs. 2 weeks | A significant improvement (p < 0.0001) |
Apperley et al. 2017 [45] | RBO Alfa One™ vs. control | Rice bran oil and soy lecithin emulsion as a spray | 40 HNC patients with radiation-induced xerostomia | RCT | 1 week | At least four times per day (50 mL) | Baseline vs. 1 week | A significant improvement (p = 0.02) |
Lòpez-Pintor et al. 2018 [46] | Xerostom vs. control | Olive oil, betaine as a mouth rinse, and toothpaste | 28 patients with Sjögren’s syndrome-induced xerostomia | RCT | 4 weeks | Three times per day (7 mL mouthrinse + 0.5 g toothpaste) | Baseline vs. 4 weeks | A significant improvement (p < 0.05) and quality of life (p = 0.04) |
Marimuthu et al. 2021 [47] | Oral7®mouthwash vs. control | Lactoperoxidase, lysozyme, glucose oxidase, and lactoferrin as a mouth rinse | 94 HNC patients with radiation-induced xerostomia | RCT | 4 weeks | Three times per day (2 puffs) | Baseline vs. 4 weeks | A significant improvement (p < 0.0001) |
Lung 2021 [48] | Biotène Spray vs. control | Glycerin, carboxymethylcellulose (CMC), as spray | 25 patients with non-homogenous xerostomia | RCT | Single dose | Once per session (3 puffs) | Baseline vs. every 15 min up to 2 h | No significant improvement (p = 0.88) |
Martìn 2017 [49] | Xerostom (no control) | Olive oil, betaine, as toothpaste, mouthwash, gel, and spray | 40 HNC patients with radiation-induced xerostomia | RCT | 2 weeks | Toothpaste: 3 times daily; spray: ≥8 times daily; mouthwash and gel as needed | Baseline vs. after 2 weeks | A significant improvement (p < 0.05) |
Ref. | Experimental Preparation | Main Component and Vector | Sample Characteristics | Study Design | Time Treatment | Daily Applications | Time Points Assessment | Results |
---|---|---|---|---|---|---|---|---|
Marìn 2021 [55] | Xeros Dentaid spray vs. control | Malic acid (1%) as a spray | 51 patients with drug-induced xerostomia | RCT | 2 weeks | Up to 8 times per day | Baseline vs. after 2 weeks | No significant improvement between interventions (p > 0.05) |
Femiano et al. 2011 [56] | Citric acid preparation vs. control | Citric acid (3%) as a mouth rinse | 54 patients with drug-induced xerostomia | RCT | 30 days | Four times per day (5 mL) | 15 min and 1 h after | A significant improvement in dry mouth symptoms (p = 0.0047) |
Gomez-Moreno 2013 [57] | Xeros Dentaid spray© vs. control | Malic acid (1%) as a spray | 45 patients with drug-induced xerostomia | RCT | 2 weeks | On demand, up to a maximum of eight applications per day | Baseline vs. 2 weeks | A significant improvement in dry mouth symptoms, UWS and SWS (p < 0.05) |
Niklander et al. 2018 [58] | Xeros Dentaid Spray vs. control | Malic acid (1%) as a spray | 70 patients with drug-induced xerostomia | RCT | 2 weeks | On demand, up to a maximum of eight applications per day | Baseline vs. 2 weeks | A significant improvement (p < 0.001) |
Kaae et al. 2020 [59] | Saliva stimulant vs. control | Chew gum (unspecified component) | 91 HNC patients with radiation-induced xerostomia | RCT | 1 month | Five minutes for five times per day | Baseline vs. 1 month | A significant improvement (p = 0.05) |
da Mata et al. 2019 [60] | Xeros® System vs. control | Malic acid (4.33%) as lozenges | 110 patients with Sjogren’s syndrome-induced dry mouth | RCT | 2 weeks | Four times per day | Baseline vs. 15, 30, 45 days | A significant improvement (p < 0.05). |
Mizuhashi et al. 2021 [61] | Flavored gels vs. control | Japanese apricot extract as a gel | 56 patients with non-homogeneous xerostomia | CT | Not reported | Single application during test session | Baseline, immediately after, and 10, 20, 30 min after | A significant improvement by the Japanese apricot extract gel (p < 0.05). |
Bielfedt et al.2021 [62] | Ipatal Hydro Med vs. control | Gum arabic as pastilles | 26 patients with non-homogeneous xerostomia | RCT | 3 days | Single application during test session | Baseline vs. 3 days | A significant improvement (p = 0.0016) and in SWS (p < 0.0001) |
Bardellini et al. 2019 [63] | Salivaktive® vs. control | Malic acid (1%) as a spray | 28 transplanted patients | RCT | 2 weeks | Four times per day | Baseline vs. 2 weeks | A significant improvement (p < 0.05) |
Ref. | Main Component and Vector | Sample Characteristic | Study Design | Time Treatment | Daily Application | Time Points Assessment | Results |
---|---|---|---|---|---|---|---|
Morales-Bozo et al. 2017 [42] | Matricaria chamomilla and linseed-extract mouthwash vs. conventional saliva substitute | 74 patients with non-homogeneous xerostomia | RCT | 3 weeks | Four times per day (2 mL) | Baseline vs. 8 and 22 days | 74 patients with non-homogeneous xerostomia |
Charalambous et al. 2017 [70] | Thyme honey mouthwash vs. saline | 72 HNC patients with chemoradiation-induced xerostomia | RCT | 4 weeks | Three times per day | Baseline vs. 1, 6 months | A significant improvement in xerostomia severity (p < 0.001), pain (p < 0.001), and dysphagia (p = 0.033) |
Heydarirad et al. 2017 [71] | Alcea digitata and Malva sylvestris oral infusion vs. artificial saliva | 60 HNC patients with radiation-induced xerostomia | RCT | 4 weeks | Three times per day | Baseline vs. 4 weeks | Significant improvement in dry mouth and quality of life in the herbal group (p = 0.017) |
Chamani et al. 2016 [72] | Ginger capsules vs. placebo | 61 patients with radiation therapy- induced xerostomia | RCT | 14 days | Three times per day | Baseline vs. 14 days | Slight improvement in xerostomia (p = 0.057) |
Yu et al. 2016 [73] | Licorice mouthwash vs. water gargle vs. no gargle | 122 hemodialysis patients with xerostomia | RCT | 10 days | Three times per day | Baseline vs. 5, 10 days | Significant increase in UWS with licorice mouthwash and reduction in xerostomia score (p < 0.001) |
Atashi et al. 2018 [74] | Aloe vera-Peppermint moisturizing gels vs. placebo | 80 ICU patients with xerostomia | RCT | 5 days | Two times per day | Baseline vs. 3, 5 days | Significant reduction in mouth dryness and improved oral health (p = 0.0001) |
Pfister et al. 2010 [75] | Acupuncture vs. standard care | 58 HNC patients with radiation therapy-induced xerostomia | RCT | 4 weeks | 30 min (once weekly) | Baseline vs. 1 week | A significant improvement (p = 0.02) |
Braga et al. 2010 [76] | Acupuncture vs. no treatment | 24 HNC patients with radiation therapy-induced xerostomia | RCT | Before and during radiotherapy (5–7 weeks) | 20 min (twice weekly) | After radiotherapy completion | A significant improvement in salivary flow rates (p < 0.001) and reduced xerostomia symptoms (p < 0.05). |
Garcia et al. 2019 [77] | True acupuncture vs. sham acupuncture vs. standard care | 399 HNC patients with radiation therapy-induced xerostomia | RCT | During radiotherapy | 20 min (3 session per week) | Baseline vs. end of radiotherapy vs. 3, 6, and 12 months post-treatment | Significant reduction in xerostomia score for true acupuncture vs. standard care (p = 0.001); no significant difference vs. sham acupuncture (p = 0.06) |
Ref. | Interventions | Sample Characteristic | Study Design | Time Treatment | Daily Application | Time Points Assessment | Results |
---|---|---|---|---|---|---|---|
Alajbeg et al. 2012 [86] | Intraoral Electrostimulation | 94 patients with non-homogeneous xerostomia | RCT | 11 months | 1, 5, or 10 min per session, up to once every hour | Baseline vs. 5, 8, 11 months of dressing | A significant improvement (p < 0.05), and in UWS (p < 0.001), and SWS (p < 0.05). |
Strietzel et al. 2011 [87] | Intraoral electrostimulations vs. placebo | 114 patients with Sjogren’s syndrome-induced dry mouth | RCT | 5 months | 10 min per session (up to 4 times daily) | Baseline vs. 1 month, and 5 months | A significant improvement in dryness severity (p = 0.0001) and UWS (p = 0.01). |
Wong et al. 2015 [88] | ALTENS vs. pilocarpine | 148 HNC patients with radiation therapy-induced xerostomia | RCT | 12 weeks | Twenty minutes per day, (twice weekly) | Baseline vs. 4, 6, 9, 15 months after treatment | No significant difference |
Dalbem Paim et al. 2019 [89] | TENS vs. standard care | 68 HNC patients with radiation therapy-induced xerostomia | RCT | 4 weeks | Twenty minutes per day (twice weekly) | Baseline vs. 1, 3, 6 months after treatment | A significant improvement QoL, and SWS (p < 0.0001) |
Lakshman et al. 2015 [90] | TENS vs. no treatment | 40 HNC patients with radiotherapy-induced xerostomia | RCT | During and after radiotherapy | 5 min per session | Baseline vs. 3, 6 weeks of radiotherapy and 1-month post-radiotherapy | A significant improvement in salivary flow rate (p < 0.001); |
El Mobadder et al. 2019 [91] | Photo-biomodulation | 1 HNC patient with radiation therapy-induced xerostomia | CS | 5 days | Five minutes per day | Baseline vs. 24 h of treatment | A significant improvement (p < 0.05) |
Vidmar et al. 2022 [92] | HBOT vs. no treatment | 18 HNC patients with radiation therapy-induced xerostomia | CT | 20 days | Ninety minutes per day | Baseline vs. 3, 7 days after treatment | A significant improvement (p < 0.01) |
Forner et al. 2022 [93] | HBOT vs. standard care | 97 HNC patients with radiation therapy-induced xerostomia | RCT | 6 weeks (first trial), 2 weeks (second trial) | Ninety minutes per day (five days/week) | Baseline vs. 3-month, 1 year | No significant differences |
Grønhøj et al. 2018 [94] | Mesenchymal stem cells (MSC) vs. placebo | 30 HNC patient with radiation-induced xerostomia | RCT | Single administration | N/A | Baseline vs. 1 month, and 4 months | A significant improvement in UWS (at 1 month, p = 0.048; at 4 months, p = 0.003) and xerostomia symptoms. |
Lynggaard et al. 2022 [95] | Allogeneic adipose tissue-derived MSCs | 10 HNC patient with radiation-induced xerostomia | OL | Single administration | N/A | Baseline vs. day 1, day 5, 1 month, and 4 months | A significant improvement in UWS (p = 0.0009) and SWS (p = 0.017) |
Blitzer et al. 2024 [96] | Autologous IFNγ-stimulated bone marrow MSCs | 6 HNC patient with radiation-induced xerostomia | First-in-human pilot clinical trial | Single administration | N/A | Baseline, 1 month, and 3 months post-injection | Improvement in salivary production (unstimulated saliva: +46% at 3 months) and QoL. |
Jakobsen et al. 2024 [97] | Allogeneic adipose-derived MSCs vs. placebo | 120 HNC patient with radiation-induced xerostomia | RCT | Single administration | N/A | Baseline, 4 months post-injection | A significant UWS increase for MSCs (p = 0.01); no significant difference between groups (p = 0.11). |
Baum et al. 2012 [98] | Adenoviral-mediated aquaporin-1 gene therapy (AdhAQP1) | 11 HNC patient with radiation-induced xerostomia | OL | Single administration | N/A | Baseline vs. days 7, 14, 28, and 42 | Significant improvement in parotid saliva flow (p = 0.032). |
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Sardellitti, L.; Filigheddu, E.; Serralutzu, F.; Bortone, A.; Bandiera, E.; Milia, E. Nonpharmacological Interventions in the Management of Xerostomia: A Review on Topical Treatments, Alternative Medicine, and Innovative Therapies. Oral 2024, 4, 616-638. https://doi.org/10.3390/oral4040048
Sardellitti L, Filigheddu E, Serralutzu F, Bortone A, Bandiera E, Milia E. Nonpharmacological Interventions in the Management of Xerostomia: A Review on Topical Treatments, Alternative Medicine, and Innovative Therapies. Oral. 2024; 4(4):616-638. https://doi.org/10.3390/oral4040048
Chicago/Turabian StyleSardellitti, Luigi, Enrica Filigheddu, Francesca Serralutzu, Antonella Bortone, Egle Bandiera, and Egle Milia. 2024. "Nonpharmacological Interventions in the Management of Xerostomia: A Review on Topical Treatments, Alternative Medicine, and Innovative Therapies" Oral 4, no. 4: 616-638. https://doi.org/10.3390/oral4040048
APA StyleSardellitti, L., Filigheddu, E., Serralutzu, F., Bortone, A., Bandiera, E., & Milia, E. (2024). Nonpharmacological Interventions in the Management of Xerostomia: A Review on Topical Treatments, Alternative Medicine, and Innovative Therapies. Oral, 4(4), 616-638. https://doi.org/10.3390/oral4040048