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Molecular Psychiatry Sep 2023Antipsychotic-induced sialorrhea carries a significant burden, but evidence-based treatment guidance is incomplete, warranting network meta-analysis (NMA) of... (Meta-Analysis)
Meta-Analysis
Antipsychotic-induced sialorrhea carries a significant burden, but evidence-based treatment guidance is incomplete, warranting network meta-analysis (NMA) of pharmacological interventions for antipsychotic-related sialorrhea. PubMed Central/PsycInfo/Cochrane Central database/Clinicaltrials.gov/WHO-ICTRP and the Chinese Electronic Journal Database (Qikan.cqvip.com) were searched for published/unpublished RCTs of antipsychotic-induced sialorrhea (any definition) in adults, up to 06/12/2023. We assessed global/local inconsistencies, publication bias, risk of bias (RoB2), and confidence in the evidence, conducting subgroup/sensitivity analyses. Co-primary efficacy outcomes were changes in saliva production (standardized mean difference/SMD) and study-defined response (risk ratios/RRs). The acceptability outcome was all-cause discontinuation (RR). Primary nodes were molecules; the mechanism of action (MoA) was secondary. Thirty-four RCTs entered a systematic review, 33 NMA (n = 1958). All interventions were for clozapine-induced sialorrhea in subjects with mental disorders. Regarding individual agents and response, metoclopramide (RR = 3.11, 95% C.I. = 1.39-6.98), cyproheptadine, (RR = 2.76, 95% C.I. = 2.00-3.82), sulpiride (RR = 2.49, 95% C.I. = 1.65-3.77), propantheline (RR = 2.39, 95% C.I. = 1.97-2.90), diphenhydramine (RR = 2.32, 95% C.I. = 1.88-2.86), benzhexol (RR = 2.32, 95% C.I. = 1.59-3.38), doxepin (RR = 2.30, 95% C.I. = 1.85-2.88), amisulpride (RR = 2.23, 95% C.I. = 1.30-3.81), chlorpheniramine (RR = 2.20, 95% C.I. = 1.67-2.89), amitriptyline (RR = 2.09, 95% C.I. = 1.34-3.26), atropine, (RR = 2.03, 95% C.I. = 1.22-3.38), and astemizole, (RR = 1.70, 95% C.I. = 1.28-2.26) outperformed placebo, but not glycopyrrolate or ipratropium. Across secondary nodes (k = 28, n = 1821), antimuscarinics (RR = 2.26, 95% C.I. = 1.91-2.68), benzamides (RR = 2.23, 95% C.I. = 1.75-3.10), TCAs (RR = 2.23, 95% C.I. = 1.83-2.72), and antihistamines (RR = 2.18, 95% C.I. = 1.83-2.59) outperformed placebo. In head-to-head comparisons, astemizole and ipratropium were outperformed by several interventions. All secondary nodes, except benzamides, outperformed the placebo on the continuous efficacy outcome. For nocturnal sialorrhea, neither benzamides nor atropine outperformed the placebo. Active interventions did not differ significantly from placebo regarding constipation or sleepiness/drowsiness. Low-confidence findings prompt caution in the interpretation of the results. Considering primary nodes' co-primary efficacy outcomes and head-to-head comparisons, efficacy for sialorrhea is most consistent for the following agents, decreasing from metoclopramide through cyproheptadine, sulpiride, propantheline, diphenhydramine, benzhexol, doxepin, amisulpride, chlorpheniramine, to amitriptyline, and atropine (the latter not for nocturnal sialorrhea). Shared decision-making with the patient should guide treatment decisions regarding clozapine-related sialorrhea.
Topics: Adult; Humans; Antipsychotic Agents; Clozapine; Sulpiride; Amisulpride; Sialorrhea; Doxepin; Amitriptyline; Network Meta-Analysis; Propantheline; Trihexyphenidyl; Metoclopramide; Chlorpheniramine; Astemizole; Randomized Controlled Trials as Topic; Cyproheptadine; Diphenhydramine; Ipratropium; Atropine Derivatives
PubMed: 37821573
DOI: 10.1038/s41380-023-02266-x -
The Cochrane Database of Systematic... Jul 2008Clozapine is widely used for people with schizophrenia. Although agranulocytosis, weight gain, and cardiac problems are serious problems associated with its use,... (Review)
Review
BACKGROUND
Clozapine is widely used for people with schizophrenia. Although agranulocytosis, weight gain, and cardiac problems are serious problems associated with its use, hypersalivation, sometimes of a gross and socially unacceptable quantity, is also common (30-80%).
OBJECTIVES
To determine the clinical effects of pharmacological interventions for clozapine-induced hypersalivation.
SEARCH STRATEGY
We searched the Cochrane Schizophrenia Group Trials Register (March 2007), inspected references of all identified studies for further trials, contacted relevant pharmaceutical companies, drug approval agencies and authors of trials.
SELECTION CRITERIA
We included randomised controlled trials comparing pharmacological interventions, at any dose and by any route of administration, for clozapine-induced hypersalivation.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For dichotomous data (homogenous) we calculated relative risk (RR) with 95% confidence intervals (CI) and numbers needed to treat (NNT) on an intention-to-treat basis. We calculated weighted mean difference (WMD) for continuous data.
MAIN RESULTS
Of the 15 trials identified, 14 were conducted in China and 14 in hospitals. The quality of reporting was poor with no studies clearly describing allocation concealment and much data were missing or unusable. All results are vulnerable to considerable bias. Most frequently the primary outcome was the diameter of the wet patch on the pillow. Antimuscarinics (astemizole, diphenhydramine, propantheline, doxepin) were the most commonly evaluated drugs. For the outcome of 'no clinically important improvement' astemizole and diphenhydramine were more effective than placebo (astemizole: n=97, 2 RCTs, RR 0.61 CI 0.47 to 0.81 NNT 3 CI 2 to 5; diphenhydramine: n=131, 2 RCTs, RR 0.43 CI 0.31 to 0.58, NNT 2 CI 1.5 to 2.5), but the doses of astemizole used were those that can cause toxicity. Data involving propantheline were heterogeneous (I2= 86.6%), but both studies showed benefit over placebo. Adverse effects were poorly recorded. Of the other interventions, oryzanol (rice bran oil and rice embryo oil extract) showed benefit over the antimuscarinic doxepin in terms of 'no clinically important change' (n=104, 1 RCT, RR 0.45 CI 0.27 to 0.75, NNT 4 CI 2 to 7). The Chinese medicine suo quo wan (comprises spicebush root, Chinese yam and bitter cardamom) showed benefit over doxepin (n=70, 1 RCT, RR 'no clinically important change' 0.31 CI 0.16 to 0.59, NNT 3 CI 1.5 to 3.7).
AUTHORS' CONCLUSIONS
There are currently insufficient data to confidently inform clinical practice. The limitations of these studies are plentiful and the risk of bias is high. These trials, however, are invaluable guides for current and future study design. Well conducted randomised trials are possible. Some may be underway. Current practice outside of well designed randomised trials should be clearly justified.
Topics: Antipsychotic Agents; Clozapine; Drugs, Chinese Herbal; Muscarinic Antagonists; Phenylpropionates; Randomized Controlled Trials as Topic; Sialorrhea
PubMed: 18646130
DOI: 10.1002/14651858.CD005579.pub2 -
BMJ Clinical Evidence Apr 2007Seasonal allergic rhinitis is found throughout the world. Epidemiological evidence suggests that there is considerable geographical variation in its prevalence. Symptoms... (Review)
Review
INTRODUCTION
Seasonal allergic rhinitis is found throughout the world. Epidemiological evidence suggests that there is considerable geographical variation in its prevalence. Symptoms are caused by an IgE mediated type 1 hypersensitivity reaction to air-borne allergens such as pollen or fungal spores, and may also cause eye, respiratory, and systemic problems.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for seasonal allergic rhinitis in adolescents and adults? We searched: Medline, Embase, The Cochrane Library and other important databases up to September 2005 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 165 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: astemizole, intranasal azelastine, intranasal corticosteroids, intranasal ipratropium bromide, intranasal levocabastine, oral antihistamines, oral decongestants, oral leukotriene receptor antagonists, pseudoephedrine, systemic corticosteroids, terfenadine.
Topics: Geography; MEDLINE; Rhinitis, Allergic, Seasonal; United States; United States Food and Drug Administration
PubMed: 19454070
DOI: No ID Found -
Revista Alergia Mexico (Tecamachalco,... 2005To compare astemizole with other first or second generation antihistaminics in the treatment of allergic rhinitis or urticaria. (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To compare astemizole with other first or second generation antihistaminics in the treatment of allergic rhinitis or urticaria.
DESIGN
Systematic revision of clinical, controlled and randomized tests.
MATERIAL AND METHODS
36 controlled, randomized, clinical, double or simple blind tests were made in 6,446 patients; 4,513 of them were assigned to astemizole and 1,933 to other first or second generation antihistaminics. Analyzed outcomes: Rate of global success; global scoring improvement of rhinitis; ocular, nasal or pharingeal pruritus; watering; nasal obstruction; sneeze; urticaria; cutaneous response to histamine; time to get a satisfactory improvent; frequency of sedation and headache.
RESULTS
In connection to global success there were significant differences in favor of astemizole (OR 6.72, CI95% 5.36 to 8.41, p 0.0001); alike global scoring improvement of rhinitis (SMD -0.82, CI95% -1.70 to 0.06, p 0.04); rhinorrhea (SMD of -0.70, CI95% -1.47 to -0.03, p 0.02); nasal, pharingeal or ocular pruritus (SMD -0.64, CI95% -1.63 to 0.35, p 0.03); urticaria (SMD of -3.53, CI95% -4.11 to -2.94, p 0.0001), and reduction of cutaneous response to histamine (SMD -2.02, CI95% -2.47 to -1.57, p 0.0001). Differences for watering, nasal obstruction or sneeze were not observed. Finally, the safety area was analyzed considering the existence of sedation and headache; it was demonstrated less sedation (OR 0.23, CI95% 0.18 to 0.30, p 0.0001) and less headache (OR 0.58, CI95% 0.40 to 0.85, p 0.005) in the group treated with astemizole.
CONCLUSIONS
The available evidence shows a therapeutic superiority of astemizole versus other antihistaminics in relation to the percentage of global success and the global scoring improvement of rhinitis, rhinorrhea, pruritus in general, urticaria symptoms and of the reduction of response to histamine, with a smaller frequency of headache or sedation.
Topics: Adult; Anti-Allergic Agents; Astemizole; Child; Histamine H1 Antagonists; Humans; Odds Ratio; Prospective Studies; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome; Urticaria
PubMed: 16158785
DOI: No ID Found