Table 1.
Randomized, double-blind, placebo-controlled studies evaluating the clinical efficacy of oral pilocarpine in improving salivary gland flow and relieving symptoms of xerostomia caused by either radiation therapy of the head and neck or salivary gland dysfunction.
| Reference | Year of Publishment | Number of Patients | Diagnosis | Administrated Dose of Pilocarpine and Duration | Outcome/Results |
|---|---|---|---|---|---|
| Fox et al. [42] | 1986 | 6 | Inflammatory exocrinopathy. | 5.0 mg once a day (o.d) for 2 days. | Reduction in oral dryness and increased salivation in all patients. |
| Creenspan et al. [43] | 1987 | 12 | Radiation-induced xerostomia. | 5.0 or 7.5 mg three times a day (t.i.d) or four times a day (q.i.d) for 90 days. | 75% of the patients treated with pilocarpine experienced significant improvement of the mean stimulated whole salivary and parotid salivary flow rate. |
| Schuller et al. [44] | 1989 | 14 | Radiation-induced xerostomia. |
3.0 mg t.i.d | 60% of the patients treated with pilocarpine presented increased whole salivary flow rate after 6 weeks. |
| Fox et al. [45] | 1991 | 39 | Sjögren’s syndrome (21 patients), radiation-induced xerostomia (12 patients), idiopathic salivary gland dysfunction (6 patients). |
5.0 mg t.i.d for 5 months. | ~68% of the patients treated with pilocarpine (i.e., 21/31) presented significantly increased salivary flow. Moreover, 27/31 participants reported a subjective amelioration in oral dryness feeling, as well as in the processes of speaking, chewing and swallowing. |
| LeVeque et al. [46] | 1993 | 156 | Radiation-induced xerostomia. | 2.5 mg t.i.d increased up to 10 mg t.i.d for 12 weeks. | Pilocarpine significantly ameliorated overall global assessments as compared to placebo. |
| Valdez et al. [47] | 1993 | 9 | Radiation-induced xerostomia. | 5.0 mg q.i.d for 3 months. | A lower frequency of oral symptoms during treatment was reported in the pilocarpine-treated group, as compared to the placebo-treated group. |
| Johnson et al. [48] | 1993 | 207 | Radiation-induced xerostomia. | 5.0 mg or 10.0 mg tablets t.i.d for 12 weeks. | 44 and 46% of patients treated with 5 and 10 mg, respectively, claimed that their feeling of oral dryness was improved. Moreover, 31 and 37% of patients treated with 5 and 10 mg, respectively, referred improved mouth and tongue comfort. |
| Rieke et al. [49] | 1995 | 369 | Radiation-induced xerostomia. | 5.0 mg or 10.0 mg tablets t.i.d for 12 weeks. | Statistically significant improvements in salivary flow in pilocarpine treatment groups. |
| Zimmerman et al. [50] | 1997 | 44 | Radiation-induced xerostomia. | 5.0 mg q.i.d for 18 months. | Oral pilocarpine usage during and 3 months thereafter radiotherapy, appeared to have contributed to a significantly less subjective xerostomia, as compared to patients excluded from pilocarpine treatment. |
| Vivino et al. [51] | 1999 | 373 | Primary or secondary Sjögren’s syndrome. | 2.5 mg or 5.0 mg q.i.d for 12 weeks. | Patients administrated with 5 mg pilocarpine 4 times daily reported a decent tolerance, as well as an important improvement in dry mouth symptoms. |
| Horiot et al. [52] | 2000 | 145 | Radiation-induced xerostomia. | 5.0 mg t.i.d for 12 weeks. | 97 patients (~67%) mentioned a significant alleviation of xerostomia’s symptoms at 12 weeks. 38 patients (26%) stopped treatment because of acute intolerance (sweating, nausea, vomiting) or no response. |
| Mateos et al. [53] | 2001 | 49 | Radiation-induced xerostomia. | 5.0 mg t.i.d (started the day before radiation treatment and continued throughout the first year of follow-up). | The differencies between patients treated with pilocarpine and those receiving placebo was not statistically significant. |
| Haddad et al. [54] | 2002 | 39 | Radiation-induced xerostomia. | 5.0 mg t.i.d (started with radiation and continued until 3 months after the end of radiotherapy. | As compared to placebo, pilocarpine administrated at radiotherapy was capable of resulting in a remarkable alleviation of xerostomia. |
| Warde et al. [55] | 2002 | 130 | Radiation-induced xerostomia. | 5.0 mg t.i.d (starting from day 1 of the radiation and continuing for 1 month after the end of the treatment). | No therapeutic effect of pilocarpine on radiation-induced xerostomia was pointed out. |
| Fisher et al. [56] (ClinicalTrials.gov ID: NCT00003139) |
2003 | 213 | Radiation-induced xerostomia. | 5.0 mg q.i.d (starting before the radiation treatment until 3 or 6 months after treatment). | Concomitant use of pilocarpine maintained and protected unstimulated salivary flow. |
| Gornitsky et al. [57] | 2004 | 58 | Radiation-induced xerostomia. | 1st study phase: 5.0 mg five times a day (from the first to the last day of radiation treatment) 2nd study phase (post-radiation): 5.0 mg q.i.d. |
Pilocarpine reduced discomfort and pain symptoms as well. An improved global quality of life was reported only at the conclusion of the first study phase. |
| Papas et al. [58] (ClinicalTrials.gov ID: NCT04470479) |
2004 | 256 | Sjögren’s-related xerostomia. | 5.0 mg q.i.d for six weeks and then 7.5 mg q.i.d for the next 6 weeks. | A remarkable relief in dry mouth symptoms was noted at 20 mg/day. |
| Taweechaisupapong et al. [59] | 2006 | 33 | Radiation-induced xerostomia. | 3.0 or 5.0 mg every ten days. | There was statistically significant increase in salivary production in pilocarpine treatment groups vs. placebo. |
| Scarantino et al.[60] (ClinicalTrials.gov ID: NCT00003139) |
2006 | 245 | Radiation-induced xerostomia. | 5.0 mg q.i.d. | The overall results for salivary function at 3 and 6 months demonstrated statistically significant differences in favor of the pilocarpine arm for unstimulated salivary flow. |
| Wu et al. [61] | 2006 | 44 | Sjögren’s syndrome. | 5.0 mg q.i.d for 12 weeks. | Pilocarpine treatment managed a significant amelioration of mouth dryness-related symptoms and saliva production, as compared to placebo. |
| Chitapanarux et al. [62] | 2008 | 33 | Radiation-induced xerostomia. | 5.0 mg t.i.d (starting from the 1st of the radiation and continuing for 3 month after the end of the treatment). | Improvement of xerostomia symptoms was observed, with a mean total subjective xerostomia score improvement at the first 4 weeks of oral pilocarpine treatment. |
| Cifuentes et al. [23] (ClinicalTrials.gov ID: NCT04470479) |
2018 | 72 | Sjögren’s syndrome. | 5.0 mg t.i.d for 12 weeks. | Patients treated with pilocarpine showed a statistically significant improvement in their salivary flow, lachrymal flow, as well as their subjective global assessment, as compared to the patients administrated artificial saliva |