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Lancet (London, England) Jul 2022Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently used worldwide. We aimed to estimate the comparative effectiveness of pharmacological treatments for the acute and long-term treatment of adults with insomnia disorder.
METHODS
In this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, PsycINFO, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and websites of regulatory agencies from database inception to Nov 25, 2021, to identify published and unpublished randomised controlled trials. We included studies comparing pharmacological treatments or placebo as monotherapy for the treatment of adults (≥18 year) with insomnia disorder. We assessed the certainty of evidence using the confidence in network meta-analysis (CINeMA) framework. Primary outcomes were efficacy (ie, quality of sleep measured by any self-rated scale), treatment discontinuation for any reason and due to side-effects specifically, and safety (ie, number of patients with at least one adverse event) both for acute and long-term treatment. We estimated summary standardised mean differences (SMDs) and odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with Open Science Framework, https://doi.org/10.17605/OSF.IO/PU4QJ.
FINDINGS
We included 170 trials (36 interventions and 47 950 participants) in the systematic review and 154 double-blind, randomised controlled trials (30 interventions and 44 089 participants) were eligible for the network meta-analysis. In terms of acute treatment, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more efficacious than placebo (SMD range: 0·36-0·83 [CINeMA estimates of certainty: high to moderate]). Benzodiazepines, eszopiclone, zolpidem, and zopiclone were more efficacious than melatonin, ramelteon, and zaleplon (SMD 0·27-0·71 [moderate to very low]). Intermediate-acting benzodiazepines, long-acting benzodiazepines, and eszopiclone had fewer discontinuations due to any cause than ramelteon (OR 0·72 [95% CI 0·52-0·99; moderate], 0·70 [0·51-0·95; moderate] and 0·71 [0·52-0·98; moderate], respectively). Zopiclone and zolpidem caused more dropouts due to adverse events than did placebo (zopiclone: OR 2·00 [95% CI 1·28-3·13; very low]; zolpidem: 1·79 [1·25-2·50; moderate]); and zopiclone caused more dropouts than did eszopiclone (OR 1·82 [95% CI 1·01-3·33; low]), daridorexant (3·45 [1·41-8·33; low), and suvorexant (3·13 [1·47-6·67; low]). For the number of individuals with side-effects at study endpoint, benzodiazepines, eszopiclone, zolpidem, and zopiclone were worse than placebo, doxepin, seltorexant, and zaleplon (OR range 1·27-2·78 [high to very low]). For long-term treatment, eszopiclone and lemborexant were more effective than placebo (eszopiclone: SMD 0·63 [95% CI 0·36-0·90; very low]; lemborexant: 0·41 [0·04-0·78; very low]) and eszopiclone was more effective than ramelteon (0.63 [0·16-1·10; very low]) and zolpidem (0·60 [0·00-1·20; very low]). Compared with ramelteon, eszopiclone and zolpidem had a lower rate of all-cause discontinuations (eszopiclone: OR 0·43 [95% CI 0·20-0·93; very low]; zolpidem: 0·43 [0·19-0·95; very low]); however, zolpidem was associated with a higher number of dropouts due to side-effects than placebo (OR 2·00 [95% CI 1·11-3·70; very low]).
INTERPRETATION
Overall, eszopiclone and lemborexant had a favorable profile, but eszopiclone might cause substantial adverse events and safety data on lemborexant were inconclusive. Doxepin, seltorexant, and zaleplon were well tolerated, but data on efficacy and other important outcomes were scarce and do not allow firm conclusions. Many licensed drugs (including benzodiazepines, daridorexant, suvorexant, and trazodone) can be effective in the acute treatment of insomnia but are associated with poor tolerability, or information about long-term effects is not available. Melatonin, ramelteon, and non-licensed drugs did not show overall material benefits. These results should serve evidence-based clinical practice.
FUNDING
UK National Institute for Health Research Oxford Health Biomedical Research Centre.
Topics: Adult; Benzodiazepines; Doxepin; Eszopiclone; Humans; Melatonin; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Zolpidem
PubMed: 35843245
DOI: 10.1016/S0140-6736(22)00878-9 -
Drugs May 2023Pharmacological treatment is common in practice and widely used for the management of insomnia. However, evidence comparing the relative effectiveness, safety, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pharmacological treatment is common in practice and widely used for the management of insomnia. However, evidence comparing the relative effectiveness, safety, and certainty of evidence among drug classes and individual drugs for insomnia are still lacking. This study aimed to determine the relative effectiveness, safety, and tolerability of drugs for insomnia.
METHODS
In this systematic review and network meta-analysis we systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and ClinicalTrials.gov, from inception to January 10, 2022 to identify randomized controlled trials that compared insomnia drugs with placebo or an active comparator in adults with insomnia. We conducted random-effects frequentist network meta-analyses to summarize the evidence, and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty, categorize interventionsand present the findings.
RESULTS
A total of 148 articles met our eligibility criteria; these included 153 trials which enrolled 46,412 participants and assessed 36 individual drugs from eight drug classes. Compared with placebo, both subjectively and objectively measured total sleep time were significantly improved with non-benzodiazepine (subjective: mean difference [MD] 25.07, 95% confidence interval [CI] 15.49-34.64, low certainty; objective: MD 22.34, 95% CI 7.64-37.05, high certainty), antidepressants (subjective: MD 54.40, 95% CI 34.96-75.83, low certainty; objective: MD 35.64, 95% CI 13.05-58.24, high certainty), and orexin receptor antagonists (subjective: MD 21.62, 95% CI 0.84-42.40, high certainty; objective: MD 31.81, 95% CI 2.66-60.95, high certainty); of which doxepin, almorexant, suvorexant, and lemborexant were among the relatively effective drugs with relatively good tolerability and lower risks of any adverse events (AEs). Both subjectively and objectively measured sleep onset latency were significantly shortened with non-benzodiazepines (subjective: MD - 10.12, 95% CI - 13.84 to - 6.40, moderate certainty; objective: MD - 12.11, 95% CI - 19.31 to - 4.90, moderate certainty) and melatonin receptor agonists (subjective: MD - 7.73, 95% CI - 15.21 to - 0.26, high certainty; objective: MD - 7.04, 95% CI - 12.12 to - 1.95, moderate certainty); in particular, zopiclone was among the most effective drugs with a lower risk of any AEs but worse tolerability. Non-benzodiazepines could significantly decrease both subjective and objective measured wake time after sleep onset (subjective: MD - 16.67, 95% CI - 21.79 to - 11.56, moderate certainty; objective: MD - 13.92, 95% CI - 22.71 to - 5.14, moderate certainty).
CONCLUSIONS
Non-benzodiazepines probably improve total sleep time, sleep onset latency, and wake time after sleep onset. Other insomnia drug classes and individual drugs also showed potential benefits in improving insomnia symptoms. However, the choice of insomnia drugs should be based on the phenotype of insomnia presented, as well as each drug's safety and tolerability. Protocol registration PROSPERO (CRD42019138790).
Topics: Humans; Sleep Initiation and Maintenance Disorders; Network Meta-Analysis; Randomized Controlled Trials as Topic; Antidepressive Agents; Sleep
PubMed: 36947394
DOI: 10.1007/s40265-023-01859-8 -
Acta Odontologica Latinoamericana : AOL Apr 2023Oral mucositis (OM) is a frequent complication in cancer patients who are undergoing chemotherapy or radiotherapy. It manifests as an inflammation of the oral mucosa,...
UNLABELLED
Oral mucositis (OM) is a frequent complication in cancer patients who are undergoing chemotherapy or radiotherapy. It manifests as an inflammation of the oral mucosa, sometimes provoking severe consequences such as eating limitations, difficulty in speaking, and possibly superinfection.
AIM
The aim of this review was to update the evidence published during the last five years on the treatment of oral mucositis induced by radiotherapy and/or chemotherapy in patients with cancer.
MATERIALS AND METHOD
A search was conducted in Pubmed, Scielo and Scopus, using the search terms mucositis, stomatitis, therapy, treatment, oral cancer, oral squamous cell carcinoma, head and neck cancer and head and neck carcinoma, with Mesh terms and free terms, from 2017 to January 2023. The systematic review was conducted in accordance with the PRISMA guidelines.
RESULTS
A total 287 articles were retrieved, of which 86 were selected by title and abstract, and 18 were included after full-text analysis. The most frequently assessed variables were OM severity, pain intensity and healing time. Treatment types were diverse, and included drugs, mouthwashes, medicines based on plant extracts, cryotherapy and low-intensity laser therapies.
CONCLUSION
Dentoxol mouthwashes, Plantago major extract, thyme honey extract, zinc oxide paste, vitamin B complex combined with GeneTime, and the consumption of L-glutamine are effective in diminishing the severity of OM. Pain intensity was lower with doxepin mouthwashes and diphenhydramine-lidocaine-antacid mouthwashes.
Topics: Humans; Mucositis; Radiotherapy
PubMed: 37314054
DOI: 10.54589/aol.36/1/3 -
CNS Drugs Apr 2022Bipolar disorder (BD) is a chronic relapsing-remitting psychiatric disorder. Sleep and circadian rhythm disturbances persist during acute mood episodes of the disorder... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bipolar disorder (BD) is a chronic relapsing-remitting psychiatric disorder. Sleep and circadian rhythm disturbances persist during acute mood episodes of the disorder and during euthymia. However, the treatment potential of hypnotic agents that might be used to manage sleep disturbance in BD is not well understood. Similarly, melatonin and medications with a melatonin-receptor agonist mechanism of action may have chronotherapeutic potential for treating people with the disorder, but the impact of these substances on sleep and circadian rhythms and core symptoms in BD is unclear.
OBJECTIVE
Our aim was to conduct a systematic review and meta-analysis evaluating the current evidence for hypnotic and melatonin/melatonin-receptor agonist pharmacotherapy for symptoms of sleep disturbance, mania, and depression in patients with BD.
METHODS
AMED, Embase, MEDLINE and PsychINFO databases were searched for studies published in English from the date of inception to 31 October 2021. Studies included in this review were randomised controlled trials (RCTs) and non-controlled/non-randomised studies for BD that examined hypnotic medications selected based on a common pattern of usage for treating insomnia (i.e. chloral, clomethiazole, diphenhydramine, doxepin, doxylamine, promethazine, suvorexant, zaleplon, zolpidem, zopiclone, and eszopiclone) and melatonin and the melatonin-receptor agonist drugs ramelteon and agomelatine. Risk of bias was assessed using the RoB2 and AXIS tools. Pooled effect sizes for RCT outcomes were estimated using random-effects models.
RESULTS
A total of eleven studies (six RCTs and five experimental feasibility studies) involving 1279 participants were included. Each study examined melatonin or melatonin-receptor agonists. No studies of hypnotics were found that fulfilled the review inclusion criteria. Pilot feasibility studies suggested beneficial treatment effects for symptoms of sleep disturbance, depression, and mania. However, the pooled effect of the two available RCT studies assessing sleep quality via Pittsburgh Sleep Quality Index scores was not statistically significant (g = - 0.04 [95% CI - 0.81 to 0.73]) and neither was the pooled effect for depressive symptoms (four studies; g = - 0.10 [95% CI - 0.27 to 0.08]). Some RCT evidence suggests ramelteon might prevent relapse into depression in BD. The largest efficacy signal detected was for manic symptoms (four studies; g = - 0.44 [95% CI - 1.03 to 0.14]) but there was substantial heterogeneity between studies and patient characteristics. In the two RCTs assessing manic symptoms during acute mania, adjunctive melatonin demonstrated superior treatment effects versus placebo.
CONCLUSIONS
There is a paucity of studies examining pharmacological interventions for sleep and circadian rhythm disturbance in BD. Few studies assessed sleep-related symptoms, and none quantitatively examined endogenous melatonin patterns or other circadian rhythms. Melatonin may be a promising candidate for the adjunctive treatment of bipolar mania. However, dose-finding studies and studies with larger sample sizes are needed to confirm its efficacy. We recommend parallel monitoring of sleep and circadian rhythms in future trials. Chronobiology-informed trial designs are needed to improve the quality of future studies.
PROTOCOL REGISTRATION
PROSPERO (CRD42020167528).
Topics: Bipolar Disorder; Humans; Hypnotics and Sedatives; Mania; Melatonin; Sleep; Sleep Wake Disorders
PubMed: 35305257
DOI: 10.1007/s40263-022-00911-7 -
The Cochrane Database of Systematic... Jun 2024Postburn pruritus (itch) is a common and distressing symptom experienced on healing or healed burn or donor site wounds. Topical, systemic, and physical treatments are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postburn pruritus (itch) is a common and distressing symptom experienced on healing or healed burn or donor site wounds. Topical, systemic, and physical treatments are available to control postburn pruritus; however, it remains unclear how effective these are.
OBJECTIVES
To assess the effects of interventions for treating postburn pruritus in any care setting.
SEARCH METHODS
In September 2022, we searched the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO CINAHL Plus. We also searched clinical trials registries and scanned references of relevant publications to identify eligible trials. There were no restrictions with respect to language, publication date, or study setting.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that enrolled people with postburn pruritus to compare an intervention for postburn pruritus with any other intervention, placebo or sham intervention, or no intervention.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence.
MAIN RESULTS
We included 25 RCTs assessing 21 interventions with 1166 randomised participants. These 21 interventions can be grouped into six categories: neuromodulatory agents (such as doxepin, gabapentin, pregabalin, ondansetron), topical therapies (such as CQ-01 hydrogel, silicone gel, enalapril ointment, Provase moisturiser, beeswax and herbal oil cream), physical modalities (such as massage therapy, therapeutic touch, extracorporeal shock wave therapy, enhanced education about silicone gel sheeting), laser scar revision (pulsed dye laser, pulsed high-intensity laser, fractional CO2 laser), electrical stimulation (transcutaneous electrical nerve stimulation, transcranial direct current stimulation), and other therapies (cetirizine/cimetidine combination, lemon balm tea). Most RCTs were conducted at academic hospitals and were at a high risk of performance, attrition, and detection bias. While 24 out of 25 included studies reported change in burn-related pruritus, secondary outcomes such as cost-effectiveness, pain, patient perception, wound healing, and participant health-related quality of life were not reported or were reported incompletely. Neuromodulatory agents versus antihistamines or placebo There is low-certainty evidence that doxepin cream may reduce burn-related pruritus compared with oral antihistamine (mean difference (MD) -2.60 on a 0 to 10 visual analogue scale (VAS), 95% confidence interval (CI) -3.79 to -1.42; 2 studies, 49 participants). A change of 2 points represents a minimal clinically important difference (MCID). Due to very low-certainty evidence, it is uncertain whether doxepin cream impacts the incidence of somnolence as an adverse event compared to oral antihistamine (risk ratio (RR) 0.64, 95% CI 0.32 to 1.25; 1 study, 24 participants). No data were reported on pain in the included study. There is low-certainty evidence that gabapentin may reduce burn-related pruritus compared with cetirizine (MD -2.40 VAS, 95% CI -4.14 to -0.66; 1 study, 40 participants). A change of 2 points represents a MCID. There is low-certainty evidence that gabapentin reduces the incidence of somnolence compared to cetirizine (RR 0.02, 95% CI 0.00 to 0.38; 1 study, 40 participants). No data were reported on pain in the included study. There is low-certainty evidence that pregabalin may result in a reduction in burn-related pruritus intensity compared with cetirizine with pheniramine maleate (MD -0.80 VAS, 95% CI -1.24 to -0.36; 1 study, 40 participants). A change of 2 points represents a MCID. There is low-certainty evidence that pregabalin reduces the incidence of somnolence compared to cetirizine (RR 0.04, 95% CI 0.00 to 0.69; 1 study, 40 participants). No data were reported on pain in the included study. There is moderate-certainty evidence that ondansetron probably results in a reduction in burn-related pruritus intensity compared with diphenhydramine (MD -0.76 on a 0 to 10 numeric analogue scale (NAS), 95% CI -1.50 to -0.02; 1 study, 38 participants). A change of 2 points represents a MCID. No data were reported on pain and adverse events in the included study. Topical therapies versus relevant comparators There is moderate-certainty evidence that enalapril ointment probably decreases mean burn-related pruritus compared with placebo control (MD -0.70 on a 0 to 4 scoring table for itching, 95% CI -1.04 to -0.36; 1 study, 60 participants). No data were reported on pain and adverse events in the included study. Physical modalities versus relevant comparators Compared with standard care, there is low-certainty evidence that massage may reduce burn-related pruritus (standardised mean difference (SMD) -0.86, 95% CI -1.45 to -0.27; 2 studies, 166 participants) and pain (SMD -1.32, 95% CI -1.66 to -0.98). These SMDs equate to a 4.60-point reduction in pruritus and a 3.74-point reduction in pain on a 10-point VAS. A change of 2 VAS points in itch represents a MCID. No data were reported on adverse events in the included studies. There is low-certainty evidence that extracorporeal shock wave therapy (ESWT) may reduce burn-related pruritus compared with sham stimulation (SMD -1.20, 95% CI -1.65 to -0.75; 2 studies, 91 participants). This equates to a 5.93-point reduction in pruritus on a 22-point 12-item Pruritus Severity Scale. There is low-certainty evidence that ESWT may reduce pain compared with sham stimulation (MD 2.96 on a 0 to 25 pressure pain threshold (PPT), 95% CI 1.76 to 4.16; 1 study, 45 participants). No data were reported on adverse events in the included studies. Laser scar revision versus untreated or placebo controls There is moderate-certainty evidence that pulsed high-intensity laser probably results in a reduction in burn-related pruritus intensity compared with placebo laser (MD -0.51 on a 0 to 1 Itch Severity Scale (ISS), 95% CI -0.64 to -0.38; 1 study, 49 participants). There is moderate-certainty evidence that pulsed high-intensity laser probably reduces pain compared with placebo laser (MD -3.23 VAS, 95% CI -5.41 to -1.05; 1 study, 49 participants). No data were reported on adverse events in the included studies.
AUTHORS' CONCLUSIONS
There is moderate to low-certainty evidence on the effects of 21 interventions. Most studies were small and at a high risk of bias related to blinding and incomplete outcome data. Where there is moderate-certainty evidence, practitioners should consider the applicability of the evidence for their patients.
Topics: Humans; Pruritus; Burns; Randomized Controlled Trials as Topic; Bias; Antipruritics
PubMed: 38837237
DOI: 10.1002/14651858.CD013468.pub2 -
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 -
Sleep May 2021To compare the efficacy and safety of various hypnotics for identifying the best treatments for insomnia in older adults. (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVES
To compare the efficacy and safety of various hypnotics for identifying the best treatments for insomnia in older adults.
METHODS
We searched the EMBASE, PubMed, ClinicalTrials.gov, and ProQuest Dissertations and Theses A&I databases from the inception to September 12, 2020. Only randomized controlled trials comparing hypnotics with either another hypnotic or placebo for insomnia treatment in elderly people were included. Sleep outcomes, including total sleep time, sleep onset latency, wake after sleep onset, sleep efficiency, were derived from polysomnography, valid questionnaires, or sleep diaries.
RESULTS
We identified 24 articles with 5917 older adults. Eszopiclone and low-dose doxepin were ranked the optimal therapy for prolonging objective and subjective total sleep time (26.69 and 28.19 min), respectively, compared to placebo. Zaleplon was the most effective therapy in reducing objective and subjective sleep onset latency (-21.63 and -15.86 min) compared with control. Temazepam was the best treatment for objective and subjective wake after sleep onset (-25.29 and -22.25 min) compared with control. Low-dose doxepin appeared to be the effective treatment for increasing objective sleep efficiency (6.08%) Triazolam showed the higher risk of overall adverse events (odds ratio, 1.96, 95% confidence interval 1.03-3.74) when compared to zaleplon.
CONCLUSIONS
Considering study quality and the potential adverse effects of benzodiazepines and nonbenzodiazepines, low-dose doxepin seems to be the optimal pharmacotherapy for the improvements in total sleep time and sleep efficiency. Future RCTs investigating the treatment effects of hypnotics, particularly low-dose doxepin, on insomnia in older adults are warranted. PROSPERO Registration number: CRD42016046301.
Topics: Aged; Eszopiclone; Humans; Hypnotics and Sedatives; Network Meta-Analysis; Sleep; Sleep Initiation and Maintenance Disorders
PubMed: 33249496
DOI: 10.1093/sleep/zsaa260 -
The effect of smoking on the plasma concentration of tricyclic antidepressants: a systematic review.Acta Neuropsychiatrica Feb 2022Smoking is highly prevalent in the psychiatric population, and hospital admittance usually results in partial or complete smoking cessation. Tobacco use is known to... (Review)
Review
Smoking is highly prevalent in the psychiatric population, and hospital admittance usually results in partial or complete smoking cessation. Tobacco use is known to affect the metabolism of certain psychoactive drugs, but whether smoking influences the plasma concentration of tricyclic antidepressants (TCAs) remains unclear. This article investigates the possible effect of smoking on the plasma concentration of TCAs. A systematic review of the literature available on PubMed and EMBASE as of October 2020 was carried out using PRISMA guidelines. Studies reporting plasma concentrations of any TCA in both a smoking and a non-smoking group were included and compared. Ten eligible studies were identified and included. In the eight studies investigating the effect of smoking on amitriptyline and/or nortriptyline, five studies found no significant effect. Two studies investigating the effect of smoking on imipramine found a significant effect, and one study investigating the effect of smoking on doxepin found no significant effect. The majority of studies included in this review were influenced by small study populations and other methodical issues. The effect of smoking on the plasma concentration of TCAs is still not entirely clear. There is a possibility that smoking affects the distribution of TCA metabolites, but this is probably not of clinical importance.
Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Imipramine; Nortriptyline; Smoking
PubMed: 34497000
DOI: 10.1017/neu.2021.28 -
European Journal of Clinical... Mar 2020Insomnia is highly prevalent in older persons and significantly impacts quality of life, functional abilities, and health status. It is frequently treated with...
PURPOSE
Insomnia is highly prevalent in older persons and significantly impacts quality of life, functional abilities, and health status. It is frequently treated with benzodiazepines or Z-drugs. Due to adverse events, an increased use of alternative sedative medications has been observed in older adults. We aimed to study the efficacy and safety of alternative sedative medications for treating insomnia in older people, excluding benzodiazepines and Z-drugs.
METHODS
We conducted a systematic search of MEDLINE (PubMed), EMBASE, and the Cochrane Central register of Controlled Trials databases. We included randomized controlled trials and prospective and retrospective quasi-experimental studies, conducted in patients older than 65 years, without psychiatric or neurological comorbidities.
RESULTS
The systematic search yielded 9483 articles, of which 24 were included in this review, describing nine different sleep medications in total. No clear beneficial impact on sleep could be demonstrated in studies investigating the impact of melatonin (n = 10), paroxetine (n = 1), diphenhydramine (n = 1), tiagabine (n = 2), and valerian (n = 1). Ramelteon slightly improved sleep latency (n = 4), while doxepin was found to provide a sustained sleep improvement with a safety profile that was comparable to placebo (n = 3). Suvorexant showed an improved sleep maintenance with only mild side effects (n = 1). One study detected increased adverse effects of trazodone after 3 months but did not evaluate the effect on sleep.
CONCLUSIONS
The overall level of evidence was limited, making it difficult to draw robust conclusions. Preliminary evidence points towards suvorexant, doxepin, and possibly ramelteon as effective and safe pharmacological alternatives for treating insomnia in older adults.
Topics: Aged; Benzodiazepines; Humans; Hypnotics and Sedatives; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Retrospective Studies; Sleep; Sleep Initiation and Maintenance Disorders
PubMed: 31838549
DOI: 10.1007/s00228-019-02812-z -
Pain Medicine (Malden, Mass.) Feb 2021Our aim was to give an overview of the effectiveness of adjunctive analgesics in head and neck cancer (HNC) patients receiving (chemo-) radiotherapy.
OBJECTIVE
Our aim was to give an overview of the effectiveness of adjunctive analgesics in head and neck cancer (HNC) patients receiving (chemo-) radiotherapy.
DESIGN
Systematic review.
INTERVENTIONS
This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched for studies concerning "head neck cancer," "adjunctive analgesics," "pain," and "radiotherapy."
OUTCOME MEASURES
Pain outcome, adverse events, and toxicity and other reported outcomes, for example, mucositis, quality of life, depression, etc.
RESULTS
Nine studies were included in our synthesis. Most studies were of low quality and had a high risk of bias on several domains of the Cochrane Collaboration tool. Only two studies comprised high-quality randomized controlled trials in which pregabalin and a doxepin rinse showed their effectiveness for the treatment of neuropathic pain and pain from oral mucositis, respectively, in HNC patients receiving (chemo-) radiotherapy.
CONCLUSIONS
More high-quality trials are necessary to provide clear evidence on the effectiveness of adjunctive analgesics in the treatment of HNC (chemo-) radiation-induced pain.
Topics: Analgesics; Head and Neck Neoplasms; Humans; Pregabalin; Quality of Life; Stomatitis
PubMed: 32219435
DOI: 10.1093/pm/pnaa044