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The Cochrane Database of Systematic... 2001The main pharmacological approach for the treatment of Alzheimer's disease (AD) has been based on the use of agents potentiating cholinergic transmission, particularly... (Review)
Review
BACKGROUND
The main pharmacological approach for the treatment of Alzheimer's disease (AD) has been based on the use of agents potentiating cholinergic transmission, particularly by inhibiting acetylcholinesterase (AChE), the enzyme that destroys acetylcholine after it has been secreted into the synaptic clefts. Physostigmine is an AChE inhibitor originally extracted from calabar beans. It is licensed in many countries as an agent for reversing the effect of drugs and poisons causing the anticholinergic syndrome. Studies conducted more than 20 years ago suggested that physostigmine could improve memory in people with or without dementia. Investigation of this property has been limited by the very short half-life of physostigmine. Various forms of administering the drug have been tried to overcome this problem, most recently a controlled-release (CR) oral formulation, and a skin patch. It has been proposed as a potential drug for the symptomatic treatment of AD.
OBJECTIVES
To determine whether there is evidence of beneficial effects for the use of physostigmine in Alzheimer's disease. To assess the incidence and severity of adverse effects.
SEARCH STRATEGY
The Cochrane Controlled Trials Register was searched using the following terms: 'physostigmine', 'physostigmine salicylate', 'Synapton' and 'Antilirium' in accordance with the Cochrane Dementia and Cognitive Improvement Group's search strategy. The pharmaceutical company was contacted.
SELECTION CRITERIA
All relevant unconfounded, double-blind, randomized, placebo-controlled trials in which physostigmine was administered for more than one day to patients with dementia of Alzheimer type. Trials in which the allocation to the treatment was not randomized, or in which the allocation to the treatment was not concealed were excluded.
DATA COLLECTION AND ANALYSIS
Data were extracted independently by two reviewers (JMC & JB), pooled where appropriate and possible, and the weighted or standardized mean differences or Peto odds ratios (95% CI) were estimated. Where possible, intention-to-treat analysis was used.
MAIN RESULTS
Fifteen studies were included using four different methods of administration of physostigmine. Four studies, involving 29 people in total, used intravenous infusion; seven, involving 131 people, used a conventional oral form; four, involving 1456 participants, used a controlled-release oral form, and one study of 181 people used a verum skin patch. There are no usable results from the intravenous infusion trials, and the few results from the conventional oral form showed no benefit of physostigmine compared with placebo. The results from two of the four studies of the controlled-release physostigmine apply only to a group of patients identified as responders in a pre-randomization titration period. The best dose physostigmine (mean 25mg/day) was associated with a 1.75 point improvement on ADAS-Cog score (mean difference -1.75, 95% confidence interval -2.90, -0.60 on an intention-to-treat basis) and a 0.26 point improvement on the CGIC score (treated as a continuous scale) (mean difference -0.26, 95% confidence interval 0.06, 0.46 on an intention-to-treat basis) compared with placebo at 6 weeks. There were statistically significantly higher numbers of patients from the physostigmine group withdrawing from the trial (22/183 vs 2/183)(OR 5.92, 95% confidence limits 2.59, 13.54) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, flatulence or sweating compared with placebo at 6 weeks. The best dose physostigmine (mean 27mg/day) was associated with a 2.0 point improvement on ADAS-Cog score (mean difference -2.02, 95% confidence interval -3.59, -0.45 on an intention to treat basis) compared with placebo at 12 weeks. There were statistically significantly higher numbers of patients from the physostigmine group withdrawing from the trial due to adverse events (13/83 vs 5/93)(OR 3.05, 95% confidence limits 1.15, 8.07) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, tremor, asthenia or sweating compared with placebo at 12 weeks. When no attempt was made to identify responders and all relevant patients with Alzheimer's disease were randomized, fixed dose physostigmine (mean 33 mg/day) was associated with a statistically significantly higher number withdrawing (234/358 vs 31/117)(OR 4.82, 95% confidence limits 3.17, 7.33), withdrawing due to adverse events (196/358 vs 10/117) (OR 6.54, 95%confidence limits 4.29, 9.95) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, dyspepsia, sweating, asthenia, dyspnoea or abnormal dreaming compared with placebo at 24 weeks. The results from the study of the verum patch physostigmine show that the double dose (delivering mean dose 12mg/day) was associated with statistically significantly higher numbers suffering at least one adverse event of vomiting, nausea or abdominal cramps compared with placebo at 24 weeks, but placebo was associated with statistically significantly greater numbers of gastrointestinal complaints at 24 weeks compared with single-dose physostigmine.
REVIEWERS' CONCLUSIONS
The evidence of effectiveness of physostigmine for the symptomatic treatment of Alzheimer's disease is limited. Even in a controlled release formulation designed to overcome the short half-life, physostigmine showed no convincing benefit and adverse effects remained common leading to a high rate of withdrawal.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Humans; Physostigmine; Randomized Controlled Trials as Topic
PubMed: 11405996
DOI: 10.1002/14651858.CD001499 -
The Cochrane Database of Systematic... Feb 2017Glaucoma is the international leading cause of irreversible blindness. Intraocular pressure (IOP) is the only currently known modifiable risk factor; it can be reduced... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Glaucoma is the international leading cause of irreversible blindness. Intraocular pressure (IOP) is the only currently known modifiable risk factor; it can be reduced by medications, incisional surgery, or laser trabeculoplasty (LTP). LTP reduces IOP by 25% to 30% from baseline, but early acute IOP elevation after LTP is a common adverse effect. Most of these IOP elevations are transient, but temporarily elevated IOP may cause further optic nerve damage, worsening of glaucoma requiring additional therapy, and permanent vision loss. Antihypertensive prophylaxis with medications such as acetazolamide, apraclonidine, brimonidine, dipivefrin, pilocarpine, and timolol have been recommended to blunt and treat the postoperative IOP spike and associated pain and discomfort. Conversely, other researchers have observed that early postoperative IOP rise happens regardless of whether people receive perioperative glaucoma medications. It is unclear whether perioperative administration of antiglaucoma medications may be helpful in preventing or reducing the occurrence of postoperative IOP elevation.
OBJECTIVES
To assess the effectiveness of medications administered perioperatively to prevent temporarily increased intraocular pressure (IOP) after laser trabeculoplasty (LTP) in people with open-angle glaucoma (OAG).
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 11), MEDLINE Ovid (1946 to 18 November 2016), Embase.com (1947 to 18 November 2016), PubMed (1948 to 18 November 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 18 November 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com); last searched 17 September 2013, ClinicalTrials.gov (www.clinicaltrials.gov); searched 18 November 2016 and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 18 November 2016. We did not use any date or language restrictions.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in which participants with OAG received LTP. We included trials which compared any antiglaucoma medication with no medication, one type of antiglaucoma medication compared with another type of antiglaucoma medication, or different timings of medication.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened records retrieved by the database searches, assessed the risk of bias, and abstracted data. We graded the certainty of the evidence using GRADE.
MAIN RESULTS
We included 22 trials that analyzed 2112 participants and identified no ongoing trials. We performed several comparisons of outcomes: one comparison of any antiglaucoma medication versus no medication or placebo, three comparisons of one antiglaucoma medication versus a different antiglaucoma mediation, and one comparison of antiglaucoma medication given before LTP to the same antiglaucoma medication given after LTP. Only one of the included trials used selective laser trabeculoplasty (SLT); the remaining trials used argon laser trabeculoplasty (ALT). Risk of bias issues were primarily in detection bias, reporting bias, and other potential bias due to studies funded by industry. Two potentially relevant studies are awaiting classification due to needing translation.In the comparison of any medication versus no medication/placebo, there was moderate-certainty evidence that the medication group had a lower risk of IOP increase of 10 mmHg or greater within two hours compared with the no medication/placebo group (risk ratio (RR) 0.05, 95% confidence interval (CI) 0.01 to 0.20). This trend favoring medication continued between two and 24 hours, but the evidence was of low and very low-certainty for an IOP increase of 5 mmHg or greater (RR 0.17, 95% CI 0.09 to 0.31) and 10 mmHg or greater (RR 0.22, 95% CI 0.11 to 0.42). Medication was favored over placebo/no medication with moderate-certainty in reducing IOP from the pre-LTP measurements for both within two hours and between two and 24 hours. At two hours, the mean difference (MD) in IOP between the medication group and the placebo/no medication group was -7.43 mmHg (95% CI -10.60 to -4.27); at between two and 24 hours, the medication group had a mean reduction in IOP of 5.32 mmHg more than the mean change in the placebo/no medication group (95% CI -7.37 to -3.28). Conjunctival blanching was an ocular adverse effect that was more common when brimonidine was given perioperatively compared with placebo in three studies.In our comparison of brimonidine versus apraclonidine, neither medication resulted in a lower risk of increased IOP of 5 mmHg or greater two hours of surgery; however, we were very uncertain about the estimate. There may be a greater mean decrease in IOP within two hours after LTP. We were unable to perform any meta-analyses for other review outcomes for this comparison.In our comparison of apraclonidine versus pilocarpine, we had insufficient data to perform meta-analyses to estimate effects on either of the primary outcomes. There was moderate-certainty evidence that neither medication was favored based on the mean change in IOP measurements from pre-LTP to two hours after surgery.In the comparison of medication given before LTP versus the same medication given after LTP, we had insufficient data for meta-analysis of IOP increase within two hours. For the risk of IOP increase of 5 mmHg or greater and 10 mmHg or greater at time points between two and 24 hours, there was no advantage of medication administration before or after LTP regarding the proportion of participants with an IOP spike (5 mmHg or greater: RR 0.82, 95% CI 0.25 to 2.63; 10 mmHg or greater: RR 1.55, 95% CI 0.19 to 12.43). For an IOP increase of 10 mmHg or greater, we had very low-certainty in the estimate, it would likely change with data from new studies.
AUTHORS' CONCLUSIONS
Perioperative medications are superior to no medication or placebo to prevent IOP spikes during the first two hours and up to 24 hours after LTP, but some medications can cause temporary conjunctival blanching, a short-term cosmetic effect. Overall, perioperative treatment was well tolerated and safe. Alpha-2 agonists are useful in helping to prevent IOP increases after LTP, but it is unclear whether one medication in this class of drugs is better than another. There was no notable difference between apraclonidine and pilocarpine in the outcomes we were able to assess. Future research should include participants who have been using these antiglaucoma medications for daily treatment of glaucoma before LTP was performed.
Topics: Adrenergic alpha-2 Receptor Agonists; Antihypertensive Agents; Brimonidine Tartrate; Clonidine; Conjunctiva; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Pilocarpine; Postoperative Complications; Randomized Controlled Trials as Topic; Trabeculectomy
PubMed: 28231380
DOI: 10.1002/14651858.CD010746.pub2 -
The Cochrane Database of Systematic... Jul 2017Salivary gland dysfunction is an 'umbrella' term for the presence of either xerostomia (subjective sensation of dryness), or salivary gland hypofunction (reduction in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Salivary gland dysfunction is an 'umbrella' term for the presence of either xerostomia (subjective sensation of dryness), or salivary gland hypofunction (reduction in saliva production). It is a predictable side effect of radiotherapy to the head and neck region, and is associated with a significant impairment of quality of life. A wide range of pharmacological interventions, with varying mechanisms of action, have been used for the prevention of radiation-induced salivary gland dysfunction.
OBJECTIVES
To assess the effects of pharmacological interventions for the prevention of radiation-induced salivary gland dysfunction.
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 14 September 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library (searched 14 September 2016); MEDLINE Ovid (1946 to 14 September 2016); Embase Ovid (1980 to 14 September 2016); CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 14 September 2016); LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; 1982 to 14 September 2016); Zetoc Conference Proceedings (1993 to 14 September 2016); and OpenGrey (1997 to 14 September 2016). We searched the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA
We included randomised controlled trials, irrespective of their language of publication or publication status. Trials included participants of all ages, ethnic origin and gender, scheduled to receive radiotherapy on its own or in addition to chemotherapy to the head and neck region. Participants could be outpatients or inpatients. We included trials comparing any pharmacological agent regimen, prescribed prophylactically for salivary gland dysfunction prior to or during radiotherapy, with placebo, no intervention or an alternative pharmacological intervention. Comparisons of radiation techniques were excluded.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 39 studies that randomised 3520 participants; the number of participants analysed varied by outcome and time point. The studies were ordered into 14 separate comparisons with meta-analysis only being possible in three of those.We found low-quality evidence to show that amifostine, when compared to a placebo or no treatment control, might reduce the risk of moderate to severe xerostomia (grade 2 or higher on a 0 to 4 scale) at the end of radiotherapy (risk ratio (RR) 0.35, 95% confidence interval (CI) 0.19 to 0.67; P = 0.001, 3 studies, 119 participants), and up to three months after radiotherapy (RR 0.66, 95% CI 0.48 to 0.92; P = 0.01, 5 studies, 687 participants), but there is insufficient evidence that the effect is sustained up to 12 months after radiotherapy (RR 0.70, 95% CI 0.40 to 1.23; P = 0.21, 7 studies, 682 participants). We found very low-quality evidence that amifostine increased unstimulated salivary flow rate up to 12 months after radiotherapy, both in terms of mg of saliva per 5 minutes (mean difference (MD) 0.32, 95% CI 0.09 to 0.55; P = 0.006, 1 study, 27 participants), and incidence of producing greater than 0.1 g of saliva over 5 minutes (RR 1.45, 95% CI 1.13 to 1.86; P = 0.004, 1 study, 175 participants). However, there was insufficient evidence to show a difference when looking at stimulated salivary flow rates. There was insufficient (very low-quality) evidence to show that amifostine compromised the effects of cancer treatment when looking at survival measures. There was some very low-quality evidence of a small benefit for amifostine in terms of quality of life (10-point scale) at 12 months after radiotherapy (MD 0.70, 95% CI 0.20 to 1.20; P = 0.006, 1 study, 180 participants), but insufficient evidence at the end of and up to three months postradiotherapy. A further study showed no evidence of a difference at 6, 12, 18 and 24 months postradiotherapy. There was low-quality evidence that amifostine is associated with increases in: vomiting (RR 4.90, 95% CI 2.87 to 8.38; P < 0.00001, 5 studies, 601 participants); hypotension (RR 9.20, 95% CI 2.84 to 29.83; P = 0.0002, 3 studies, 376 participants); nausea (RR 2.60, 95% CI 1.81 to 3.74; P < 0.00001, 4 studies, 556 participants); and allergic response (RR 7.51, 95% CI 1.40 to 40.39; P = 0.02, 3 studies, 524 participants).We found insufficient evidence (that was of very low quality) to determine whether or not pilocarpine performed better or worse than a placebo or no treatment control for the outcomes: xerostomia, salivary flow rate, survival, and quality of life. There was some low-quality evidence that pilocarpine was associated with an increase in sweating (RR 2.98, 95% CI 1.43 to 6.22; P = 0.004, 5 studies, 389 participants).We found insufficient evidence to determine whether or not palifermin performed better or worse than placebo for: xerostomia (low quality); survival (moderate quality); and any adverse effects.There was also insufficient evidence to determine the effects of the following interventions: biperiden plus pilocarpine, Chinese medicines, bethanechol, artificial saliva, selenium, antiseptic mouthrinse, antimicrobial lozenge, polaprezinc, azulene rinse, and Venalot Depot (coumarin plus troxerutin).
AUTHORS' CONCLUSIONS
There is some low-quality evidence to suggest that amifostine prevents the feeling of dry mouth in people receiving radiotherapy to the head and neck (with or without chemotherapy) in the short- (end of radiotherapy) to medium-term (three months postradiotherapy). However, it is less clear whether or not this effect is sustained to 12 months postradiotherapy. The benefits of amifostine should be weighed against its high cost and side effects. There was insufficient evidence to show that any other intervention is beneficial.
Topics: Amifostine; Drugs, Chinese Herbal; Female; Fibroblast Growth Factor 7; Humans; Male; Pilocarpine; Quality of Life; Radiation-Protective Agents; Radiotherapy; Randomized Controlled Trials as Topic; Saliva, Artificial; Salivary Gland Diseases; Salivary Glands; Salivation; Xerostomia
PubMed: 28759701
DOI: 10.1002/14651858.CD012744 -
The Cochrane Database of Systematic... Sep 2012Open angle glaucoma (OAG) is a common cause of blindness. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Open angle glaucoma (OAG) is a common cause of blindness.
OBJECTIVES
To assess the effects of medication compared with initial surgery in adults with OAG.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2012), EMBASE (January 1980 to August 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to August 2012), Biosciences Information Service (BIOSIS) (January 1969 to August 2012), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to August 2012), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), Zetoc, the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 1 August 2012. The National Research Register (NRR) was last searched in 2007 after which the database was archived. We also checked the reference lists of articles and contacted researchers in the field.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing medications with surgery in adults with OAG.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data. We contacted study authors for missing information.
MAIN RESULTS
Four trials involving 888 participants with previously untreated OAG were included. Surgery was Scheie's procedure in one trial and trabeculectomy in three trials. In three trials, primary medication was usually pilocarpine, in one trial it was a beta-blocker.The most recent trial included participants with on average mild OAG. At five years, the risk of progressive visual field loss, based on a three unit change of a composite visual field score, was not significantly different according to initial medication or initial trabeculectomy (odds ratio (OR) 0.74, 95% confidence interval (CI) 0.54 to 1.01). In an analysis based on mean difference (MD) as a single index of visual field loss, the between treatment group difference in MD was -0.20 decibel (dB) (95% CI -1.31 to 0.91). For a subgroup with more severe glaucoma (MD -10 dB), findings from an exploratory analysis suggest that initial trabeculectomy was associated with marginally less visual field loss at five years than initial medication, (mean difference 0.74 dB (95% CI -0.00 to 1.48). Initial trabeculectomy was associated with lower average intraocular pressure (IOP) (mean difference 2.20 mmHg (95% CI 1.63 to 2.77) but more eye symptoms than medication (P = 0.0053). Beyond five years, visual acuity did not differ according to initial treatment (OR 1.48, 95% CI 0.58 to 3.81).From three trials in more severe OAG, there is some evidence that medication was associated with more progressive visual field loss and 3 to 8 mmHg less IOP lowering than surgery. In the longer-term (two trials) the risk of failure of the randomised treatment was greater with medication than trabeculectomy (OR 3.90, 95% CI 1.60 to 9.53; hazard ratio (HR) 7.27, 95% CI 2.23 to 25.71). Medications and surgery have evolved since these trials were undertaken.In three trials the risk of developing cataract was higher with trabeculectomy (OR 2.69, 95% CI 1.64 to 4.42). Evidence from one trial suggests that, beyond five years, the risk of needing cataract surgery did not differ according to initial treatment policy (OR 0.63, 95% CI 0.15 to 2.62).Methodological weaknesses were identified in all the trials.
AUTHORS' CONCLUSIONS
Primary surgery lowers IOP more than primary medication but is associated with more eye discomfort. One trial suggests that visual field restriction at five years is not significantly different whether initial treatment is medication or trabeculectomy. There is some evidence from two small trials in more severe OAG, that initial medication (pilocarpine, now rarely used as first line medication) is associated with more glaucoma progression than surgery. Beyond five years, there is no evidence of a difference in the need for cataract surgery according to initial treatment.The clinical and cost-effectiveness of contemporary medication (prostaglandin analogues, alpha2-agonists and topical carbonic anhydrase inhibitors) compared with primary surgery is not known.Further RCTs of current medical treatments compared with surgery are required, particularly for people with severe glaucoma and in black ethnic groups. Outcomes should include those reported by patients. Economic evaluations are required to inform treatment policy.
Topics: Aged; Glaucoma, Open-Angle; Humans; Middle Aged; Pilocarpine; Randomized Controlled Trials as Topic; Trabeculectomy; Vision Disorders
PubMed: 22972069
DOI: 10.1002/14651858.CD004399.pub3 -
Dental Clinics of North America Oct 2002The results of the present systematic review of randomized controlled trials published in peer-reviewed journals demonstrate the presence of a wide variety of biases and... (Meta-Analysis)
Meta-Analysis Review
The results of the present systematic review of randomized controlled trials published in peer-reviewed journals demonstrate the presence of a wide variety of biases and the weakness of the existing literature of xerostomia treatment. The report of statistically significant efficacy on an outcome measure is only meaningful in the setting of a well-controlled, appropriately designed clinical trial. This points to the importance of evaluating the quality of the clinical trial closely when deciding if study results are applicable to a specific patient population. Future studies in the management of xerostomia will require an increased effort on the part of investigators to eliminate easily recognized flaws during the planning stages of a clinical trial. Minimizing bias in clinical studies will allow for easier interpretation and comparisons of different studies. Better clinical trial design is vital to provide maximal confidence in the efficacy of xerostomia interventions.
Topics: Acupuncture Therapy; Bias; Humans; Muscarinic Agonists; Pilocarpine; Radiotherapy; Randomized Controlled Trials as Topic; Reproducibility of Results; Research Design; Saliva, Artificial; Salivary Gland Diseases; Sjogren's Syndrome; Treatment Outcome; Xerostomia
PubMed: 12436835
DOI: 10.1016/s0011-8532(02)00023-x -
The Cochrane Database of Systematic... Jul 2007Salivary gland dysfunction is a predictable side effect of radiotherapy to the head and neck region. Pilocarpine hydrochloride (a choline ester) is licensed in many... (Review)
Review
BACKGROUND
Salivary gland dysfunction is a predictable side effect of radiotherapy to the head and neck region. Pilocarpine hydrochloride (a choline ester) is licensed in many countries for the treatment of radiation-induced salivary gland dysfunction. Other parasympathomimetics have also been used 'off licence' in the treatment of this condition.
OBJECTIVES
To determine the efficacy and tolerability of parasympathomimetic drugs in the treatment of radiation-induced salivary gland dysfunction.
SEARCH STRATEGY
A detailed search strategy was developed for MEDLINE, and adapted for other databases (Cochrane Pain, Palliative and Supportive Care Group Register; Cochrane Oral Health Group Register; The Cochrane Controlled Trials Register; EMBASE; CINAHL; SIGLE; Dissertation Abstracts). The reference lists of identified studies, review articles and radiotherapy textbooks were checked for additional studies. Relevant pharmaceutical companies, clinical investigators, and professional organizations/journals were also contacted about additional studies.
SELECTION CRITERIA
The selection criteria for the review were: 1) randomised controlled trials; 2) patients suffering from radiation-induced salivary gland dysfunction; 3) patients treated with parasympathomimetic drugs; and 4) assessable data available on primary outcome measures.
DATA COLLECTION AND ANALYSIS
The two review authors independently collected data from the full text version of relevant papers including: 1) citation details; 2) patients; 3) interventions; 4) assessments; 5) outcomes (i.e. efficacy, tolerability); and 6) quality issues. We were unable to perform a meta-analysis, due to a lack of appropriate data.
MAIN RESULTS
Only three studies, involving a total of 298 patients, fulfilled the entry criteria for the review. All three studies involved the use of pilocarpine hydrochloride. The data suggest that pilocarpine hydrochloride was more effective than placebo, and at least as effective as artificial saliva in those participants that responded. The response rate was 42 to 51%. The time to response was up to 12 weeks. The side effect rate was high, and side effects were the main reason for withdrawal (six to 15% patients taking 5 mg tds). The side effects were usually the result of generalised parasympathomimetic stimulation (e.g. sweating, headaches, urinary frequency, vasodilatation). Response rates were not dose dependent, but side effect rates were dose dependent.
AUTHORS' CONCLUSIONS
There is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation-induced salivary gland dysfunction. Currently, there is little evidence to support the use of other parasympathomimetic drugs in the treatment of this condition. Available studies suggest approximately half of patients will respond, but side effects to responders can be problematic. Adverse effects are dose dependent therefore it is important to keep dose to 5 mg tds.
Topics: Humans; Muscarinic Agonists; Parasympathomimetics; Pilocarpine; Radiation Injuries; Randomized Controlled Trials as Topic; Salivary Glands
PubMed: 17636736
DOI: 10.1002/14651858.CD003782.pub2 -
Immunopharmacology and Immunotoxicology Apr 2019Sjogren's syndrome is an immunologic disorder, characterized by symptoms of dry mouth and dry eyes. Management of xerostomia is more difficult and challenging, various... (Meta-Analysis)
Meta-Analysis
Sjogren's syndrome is an immunologic disorder, characterized by symptoms of dry mouth and dry eyes. Management of xerostomia is more difficult and challenging, various pharmacologic agents have been tried and evaluated in the management of xerostomia in these patients, but the results were inconsistent and variable. Hence, the present study is aimed at evaluation and comparison of different pharmacological agents in the management of xerostomia in patients with Sjogren's syndrome. A meta-analysis of case-control studies was conducted on pharmacological management of xerostomia in patients with Sjogren's Syndrome and the collected data are subjected to exclusion and inclusion criteria and standard mean difference (SMD), ODD's ratio and confidence intervals (95% CI) were calculated by Review Manager software using fixed and random effects model from the data of five studies. Both objective response and subjective response evaluation favored experimental group suggesting an increase in unstimulated salivary flow rate using pharmacological agents. Interferon alpha 150 IU three times daily had a good effect in increasing the unstimulated whole saliva flow rate with SMD 2.72 at 95% CI [2.43, 3.00] < .00001. Cevimeline vs placebo showed good response with ODDS ratio 2.74 at 95% CI [1.58, 4.76] = .0003. Interferon - α 150 IU thrice daily was proven to be effective in increasing salivary flow rate and also has an advantage of disease modification in SS patients attributing to its immunomodulatory action. Cevimeline 30 mg thrice daily also had a considerable therapeutic effect in SS patients compared to Pilocarpine.
Topics: Female; Humans; Interferon-alpha; Male; Pilocarpine; Quinuclidines; Saliva; Sjogren's Syndrome; Thiophenes
PubMed: 30932714
DOI: 10.1080/08923973.2019.1593448 -
Frontiers in Endocrinology 2022Salivary gland dysfunction (e.g., sialadenitis and xerostomia) is the most common complication of radioactive iodine (RAI) therapy for differentiated thyroid cancer...
INTRODUCTION
Salivary gland dysfunction (e.g., sialadenitis and xerostomia) is the most common complication of radioactive iodine (RAI) therapy for differentiated thyroid cancer (DTC). Several methods have been used to reduce/prevent this adverse effect. We aimed to systematically review the effectiveness of non-pharmacological and pharmacological interventions in preventing RAI-induced salivary gland dysfunction in patients with DTC.
METHODS
A systematic review was conducted, according to PRISMA guidelines. The protocol was registered (PROSPERO: CRD42022295229). PubMed, Embase, Scopus, and the Cochrane Library electronic databases were searched from inception to November 2021. Inclusion criteria were randomized controlled trials of DTC patients who were older than 18 years and underwent RAI after thyroidectomy in which at least one studied group received an intervention to prevent salivary gland dysfunction.
RESULTS
Twelve studies (a total of 667 participants) were included. Among DTC patients who were treated with RAI, nonpharmacological treatment such as parotid gland massage and aromatherapy ameliorated salivary gland dysfunction. Antioxidants such as vitamin E and selenium demonstrated radioprotective effects on the salivary gland, while other antioxidants did not show radioprotective benefits. Vitamin C showed no significant effects on preventing salivary gland dysfunction. Amifostine had inconsistent outcomes among studies. Among cholinergic agonists, pilocarpine did not demonstrate the radioprotective effect on parotid glands, while bethanechol lowered salivary gland dysfunction. However, the negative results from pilocarpine may be explained by the strong sialorrheic effect of the Cincinnati regimen in both study arms.
CONCLUSION
Among non-pharmacological and pharmacological methods, parotid gland massage, aromatherapy, vitamin E, selenium, amifostine, and bethanechol may have benefits in minimizing RAI-induced salivary gland dysfunction in patients with DTC. The results are limited by a small number of patients and should be confirmed in future larger randomized controlled trials.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=295229, PROSPERO, identifier CRD42022295229.
Topics: Adenocarcinoma; Amifostine; Bethanechol; Humans; Iodine Radioisotopes; Pilocarpine; Randomized Controlled Trials as Topic; Salivary Glands; Selenium; Thyroid Neoplasms; Vitamin E
PubMed: 36105397
DOI: 10.3389/fendo.2022.960265