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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and the Chinese Electronic Journal Database (Qikan.cqvip.com) were searched for published/unpublished RCTs of antipsychotic-induced sialorrhea (any definition) in adults, up to 06/12/2023.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 -
Pharmaceutics Jun 2022This systematic review summarizes the impact of pharmacogenetics on the effect and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressants when used... (Review)
Review
BACKGROUND
This systematic review summarizes the impact of pharmacogenetics on the effect and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressants when used for pain treatment.
METHODS
A systematic literature search was performed according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines regarding the human in vivo efficacy and safety of NSAIDs and antidepressants in pain treatment that take pharmacogenetic parameters into consideration. Studies were collected from PubMed, Scopus, and Web of Science up to the cutoff date 18 October 2021.
RESULTS
Twenty-five articles out of the 6547 initially detected publications were identified. Relevant medication-gene interactions were noted for drug safety. Interactions important for pain management were detected for (1) ibuprofen/; (2) celecoxib/; (3) piroxicam/, ; (4) diclofenac/, , , ; (5) meloxicam/; (6) aspirin/, , and ; (7) amitriptyline/ and ; (8) imipramine/; (9) nortriptyline/, , ; and (10) escitalopram/, , and .
CONCLUSIONS
Overall, a lack of well powered human in vivo studies assessing the pharmacogenetics in pain patients treated with NSAIDs or antidepressants is noted. Studies indicate a higher risk for partly severe side effects for the poor metabolizers and NSAIDs. Further in vivo studies are needed to consolidate the relevant polymorphisms in NSAID safety as well as in the efficacy of NSAIDs and antidepressants in pain management.
PubMed: 35745763
DOI: 10.3390/pharmaceutics14061190 -
Rheumatology (Oxford, England) Dec 2008The objective of this study was to assess the efficacy and safety of amitriptyline as a treatment of FM. A comprehensive computerized search in Medline (Pubmed), EMBASE... (Review)
Review
The objective of this study was to assess the efficacy and safety of amitriptyline as a treatment of FM. A comprehensive computerized search in Medline (Pubmed), EMBASE and The Cochrane Library was performed. Randomized controlled trials (RCTs) comparing amitriptyline vs placebo in adult patients suffering from FM were identified, the methodological quality was assessed and the results of the main outcomes were evaluated. Ten RCTs were identified. Large clinical variability and statistical heterogeneity precluded quantitative meta-analysis. Overall, the study quality was moderate to high. Amitriptyline 25 mg/day (six RCTs) demonstrated a therapeutic response compared with placebo in the domains of pain, sleep, fatigue and overall patient and investigator impression. This benefit was generally seen at 6-8 weeks of treatment but no effect was noted at 12 weeks. Amitriptyline 50 mg/day (four RCTs) did not demonstrate a therapeutic effect compared with placebo. Neither dose of amitriptyline had an effect on tender points count. No clear statements on adverse events with amitriptyline can be made due to inconsistencies in data among the studies. A definitive clinical recommendation regarding the efficacy of amitriptyline for FM symptoms cannot be made. There is some evidence to support the short-term efficacy of amitriptyline 25 mg/day in FM. There is no evidence to support the efficacy of amitriptyline at higher doses or for periods >8 weeks. More stringent RCTs with longer follow-up periods are required to determine the long-term efficacy and safety of the amitriptyline and define its role in the multidisciplinary management of FM.
Topics: Adult; Amitriptyline; Antidepressive Agents, Tricyclic; Female; Fibromyalgia; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome
PubMed: 18697829
DOI: 10.1093/rheumatology/ken317 -
Neurogastroenterology and Motility Jan 2022Irritable bowel syndrome (IBS) is a highly prevalent and economically burdensome condition; and pain is often the most unpleasant, disruptive, and difficult-to-treat... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Irritable bowel syndrome (IBS) is a highly prevalent and economically burdensome condition; and pain is often the most unpleasant, disruptive, and difficult-to-treat symptom. Visceral hypersensitivity is a common feature driving pain in IBS, suggesting that neuropathic mechanisms may be implicated. We conducted a systematic review of available evidence to examine the role of anti-neuropathic medicines in the management of pain in IBS.
METHODS
We systematically searched scientific repositories for trials investigating conventional oral, and/or parenteral, pharmaceutical antineuropathic treatments in patients with IBS. We summarized key participant characteristics, outcomes related to pain (primary outcome), and selected secondary outcomes.
KEY RESULTS
We included 13 studies (n = 629 participants): six investigated amitriptyline, three duloxetine, three pregabalin, and one gabapentin. There was considerable methodological and statistical heterogeneity, so we performed a narrative synthesis and limited meta-analysis. Amitriptyline was most extensively studied, though only in diarrhea-predominant patients. In individual trials, amitriptyline, pregabalin and gabapentin generally appeared beneficial for pain outcomes. While duloxetine studies tended to report improvements in pain, all were un-controlled trials with high risk of bias. Meta-analysis of three studies (n = 278) yielded a pooled relative-risk of 0.50 (95%CI 0.38-0.66) for not improving with anti-neuropathic agent vs control. We did not identify any eligible studies investigating the role of parenteral anti-neuropathics.
CONCLUSIONS AND INFERENCES
Anti-neuropathic analgesics may improve pain in IBS, and deserve further, high-quality investigation, potentially considering parenteral administration and agents with minimal gastrointestinal motility effects. Investigation of amitriptyline's efficacy in non-diarrhea-predominant subtypes is currently lacking, and we recommend particular caution for its use in IBS-C.
Topics: Abdominal Pain; Administration, Oral; Analgesics; Humans; Irritable Bowel Syndrome; Treatment Outcome
PubMed: 34755926
DOI: 10.1111/nmo.14289 -
The British Journal of Psychiatry : the... Jan 2011Depression is a common condition that has been frequently treated with psychotropics. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Depression is a common condition that has been frequently treated with psychotropics.
AIMS
To review systematically the evidence of efficacy and acceptability of antidepressant and benzodiazepine treatments for patients with minor depression.
METHOD
A systematic review and meta-analysis of double-blind randomised controlled trials comparing antidepressants or benzodiazepines v. placebo in adults with minor depression. Data were obtained from MEDLINE, CINAHL, EMBASE, PsycInfo, Cochrane Controlled Trials Register and pharmaceutical company websites. Risk of bias was assessed for the generation of the allocation sequence, allocation concealment, masking, incomplete outcome data, and sponsorship bias.
RESULTS
Six studies met inclusion criteria. Three studies compared paroxetine with placebo; fluoxetine, amitriptyline and isocarboxazid were studied in one study each. No studies compared benzodiazepines with placebo. In terms of failures to respond to treatment (6 studies, 234 patients treated with antidepressants and 234 with placebo) no significant difference between antidepressants and placebo was found (relative risk (RR) 0.94, 95% CI 0.81-1.08). In terms of acceptability, data extracted from two studies (93 patients treated with antidepressants and 93 with placebo) showed no statistically significant difference between antidepressants and placebo (RR=1.06, 95% CI 0.65-1.73). There was no statistically significant between-study heterogeneity for any of the reported analyses.
CONCLUSIONS
There is evidence showing there is unlikely to be a clinically important advantage for antidepressants over placebo in individuals with minor depression. For benzodiazepines, no evidence is available, and thus it is not possible to determine their potential therapeutic role in this condition.
Topics: Adolescent; Adult; Antidepressive Agents; Benzodiazepines; Data Interpretation, Statistical; Depression; Double-Blind Method; Female; Humans; Male; Outcome Assessment, Health Care; Placebos; Randomized Controlled Trials as Topic
PubMed: 21200071
DOI: 10.1192/bjp.bp.109.076448 -
European Review For Medical and... May 2024Painful peripheral diabetic neuropathy (PRDN) is a common disabling condition. Pregabalin and amitriptyline are commonly prescribed as the first-line for PPDN despite... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Painful peripheral diabetic neuropathy (PRDN) is a common disabling condition. Pregabalin and amitriptyline are commonly prescribed as the first-line for PPDN despite the contradicting recommendations. There is a need to inform the scientific community regarding first-line pain control among patients with PPDN. This meta-analysis assessed pregabalin and amitriptyline effects on PPDN.
PATIENTS AND METHODS
We searched PubMed, MEDLINE, Cochrane Library, EBSCO, and Google Scholar; the terms used were amitriptyline, pregabalin, painful diabetic neuropathy, antidepressant, gabapentinoids, quality of life, and adverse events. Boolean operators like AND, and OR were used. Six hundred and thirty-one studies were retrieved, and 37 full texts were screened. However, only six randomized controlled trials fulfilled the inclusion and exclusion criteria.
RESULTS
No significant statistical differences between amitriptyline and pregabalin regarding pain score and significant pain reduction (odd ratio, -0.82, 95% CI, -2.21-0.58, and odd ratio, 1.16, 95% CI, 0.76-1.76 respectively). Quality of life, total adverse events, and drug discontinuation were not different between the two drugs (odd ratio, 0.89, 95% CI, -2.11-3.89, odd ratio, 0.98, 95% CI, 0.52-1.85, and odd ratio, 0.51, 95% CI, 0.08-3.15, respectively).
CONCLUSIONS
No significant statistical differences between amitriptyline and pregabalin regarding their effects on pain and quality of life. The drugs showed similar total adverse events and drug withdrawal. Further larger real-world studies are needed.
Topics: Pregabalin; Amitriptyline; Humans; Diabetic Neuropathies; Analgesics; Quality of Life
PubMed: 38856135
DOI: 10.26355/eurrev_202405_36296 -
Pain Practice : the Official Journal of... Feb 2014Painful diabetic peripheral neuropathy (pDPN) is prevalent among persons with diabetes and increases over time. Published guidelines recommend a number of medications to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Painful diabetic peripheral neuropathy (pDPN) is prevalent among persons with diabetes and increases over time. Published guidelines recommend a number of medications to treat this condition providing clinicians with a variety of treatment options. This study provides a comprehensive systematic review and meta-analysis of published pharmacologic therapies for pDPN.
METHODS
The published literature was systematically searched to identify randomized, controlled trials of all available pharmacologic treatments for pDPN (recommended or nonrecommended) reporting predefined efficacy and safety outcomes. Bayesian fixed-effect mixed treatment comparison methods were used to assess relative therapeutic efficacy and harms.
RESULTS
Data from 58 studies including 29 interventions and 11,883 patients were analyzed. Pain reduction over that of placebo on the 11-point numeric rating scale ranged from -3.29 for sodium valproate (95% credible interval [CrI] = [-4.21, -2.36]) to 1.67 for Sativex (-0.47, 0.60). Estimates for most treatments were clustered between 0 and -1.5 and were associated with more study data and smaller CrIs. Pregabalin (≥ 300 mg/day) was the most effective on the 100-point visual analog scale (-21.88; [-27.06, -16.68]); topiramate was the least (-3.09; [-3.99, -2.18]). Relative risks (RRs) of 30% pain reduction ranged from 0.78 (Sativex) to 1.84 (lidocaine 5% plaster). Analysis of the RR ratio of these 2 treatments reveals marginal significance for Sativex (3.27; [1.07, 9.81]), indicating the best treatment is only slightly better than the worst. Relative risks of 50% pain reduction ranged from 0.98 (0.56, 1.52) (amitriptyline) to 2.25 (1.51, 3.00) (alpha-lipoic acid). RR ratio for these treatments was not statistically different (3.39; [0.88, 3.34]). Fluoxetine had the lowest risk of adverse events (0.94; [0.62, 1.23]); oxycodone had the highest (1.55; [1.45, 1.64]). Discontinuation RRs were clustered around 0.8 to 1.5, with those on the extreme having greater uncertainty.
CONCLUSIONS
Selecting an appropriate pDPN therapy is key given the large number of available treatments. Comparative results revealed relative equivalence among many of the studied interventions having the largest overall sample sizes and highlight the importance of standardization of methods to effectively assess pain.
Topics: Analgesics; Bayes Theorem; Diabetic Neuropathies; Humans; Neuralgia; Randomized Controlled Trials as Topic
PubMed: 23534696
DOI: 10.1111/papr.12054 -
Rheumatology (Oxford, England) Mar 2011To evaluate and compare the efficacy and acceptability of the antidepressants amitriptyline (AMT), duloxetine (DLX) and milnacipran (MLN) for FM syndrome (FMS). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To evaluate and compare the efficacy and acceptability of the antidepressants amitriptyline (AMT), duloxetine (DLX) and milnacipran (MLN) for FM syndrome (FMS).
METHODS
Cochrane Library, MEDLINE, SCOPUS, www.clinicalstudyresults.org and www.clinicalTrials.gov were searched for randomized pharmacological placebo-controlled trials until 30 May 2010. Outcomes of interest were symptom reduction [pain, fatigue, sleep disturbance and reduced health-related quality of life (HRQOL)] and acceptability (total drop-out rates). We performed a meta-analysis of each drug vs placebo using a random-effects model and adjusted indirect analyses of the three drugs. Methodological quality was assessed by the Cochrane risk of bias tool.
RESULTS
Ten AMT studies (612 patients), four DLX studies (1411 patients) and five MLN studies (4129 patients) met the inclusion criteria. The reported methodological quality of most AMT trials was poor, that of DLX and MLN were high. The three drugs were superior to placebo except DLX for fatigue, MLN for sleep disturbance and AMT for HRQOL. The significant effects of AMT and DLX were small and those of MLN not substantial. In adjusted indirect comparisons, AMT was superior to DLX and MLN in reduction of pain, sleep disturbances, fatigue and limitations of HRQOL. DLX was superior to MLN in reducing pain, sleep disturbances and limitations of HRQOL. MLN was superior to DLX in reducing fatigue. There were no significant differences in acceptability of the three drugs.
CONCLUSIONS
AMT cannot be regarded as the gold standard of FMS therapy with antidepressants because of the methodological limitations of its trials.
Topics: Amitriptyline; Antidepressive Agents; Cyclopropanes; Duloxetine Hydrochloride; Fibromyalgia; Humans; Milnacipran; Thiophenes; Treatment Outcome
PubMed: 21078630
DOI: 10.1093/rheumatology/keq354 -
Clinical and Experimental Allergy :... Mar 2022To determine whether treatment effectiveness can be established for a range of vocal cord dysfunction (VCD) interventions in adolescents and adults. (Review)
Review
OBJECTIVE
To determine whether treatment effectiveness can be established for a range of vocal cord dysfunction (VCD) interventions in adolescents and adults.
DESIGN
A systematic review of the literature and risk of bias appraisal was completed using the Joanna Briggs Institute Critical Appraisal Tools. Data were qualitatively synthesized in the broad intervention groups of glottic airway and respiratory retraining, pharmacological therapies, airway device therapies and psychological therapies.
DATA SOURCES
Nine electronic databases, two clinical trial registries and the grey literature were searched from inception to September 2021 for articles on VCD interventions or equivalent terms.
ELIGIBILITY CRITERIA
Studies were included if they were randomized controlled trials, non-randomized controlled trials, quasi-experimental pre- and post-test studies and within-subject repeated measure designs, participants were 13 years or older, VCD was diagnosed using laryngoscopy or CT larynx, VCD intervention was provided and outcome measures reported on VCD symptoms.
RESULTS
The search yielded no randomized controlled trials. There were 17 quasi-experimental studies that met the eligibility criteria, and these studies reported on glottic airway and respiratory retraining, botulinum toxin injections, inspiratory muscle strength training and amitriptyline; all were associated with VCD symptom reduction. In addition, 2 within-subject repeated measure studies reported inspiratory muscle strength training and respiratory retraining to be effective in reducing symptoms in participants with exertional VCD. The included studies were reported in full-text publications (11) and conference proceedings (8). There was a high risk of bias and low quality of evidence across all intervention areas.
CONCLUSION
Glottic airway and respiratory retraining, botulinum toxin injections, low-dose amitriptyline and inspiratory muscle strength training devices have been associated with symptom reduction in adults and adolescents with vocal cord dysfunction. Limited objective data exist to support the effectiveness of these interventions, and robust controlled trials are needed in this area. Systematic Review Registration: CRD42018092274 (PROSPERO).
Topics: Adolescent; Adult; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Vocal Cord Dysfunction
PubMed: 34699093
DOI: 10.1111/cea.14036