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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and websites of regulatory agencies from database inception to Nov 25, 2021, to identify published and unpublished randomised controlled trials.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 -
JAMA Oct 2016Nausea and vomiting affects approximately 85% of pregnant women. The most severe form, hyperemesis gravidarum, affects up to 3% of women and can have significant adverse... (Review)
Review
IMPORTANCE
Nausea and vomiting affects approximately 85% of pregnant women. The most severe form, hyperemesis gravidarum, affects up to 3% of women and can have significant adverse physical and psychological sequelae.
OBJECTIVE
To summarize current evidence on effective treatments for nausea and vomiting in pregnancy and hyperemesis gravidarum.
EVIDENCE REVIEW
Databases were searched to June 8, 2016. Relevant websites and bibliographies were also searched. Titles and abstracts were assessed independently by 2 reviewers. Results were narratively synthesized; planned meta-analysis was not possible because of heterogeneity and incomplete reporting of findings.
FINDINGS
Seventy-eight studies (n = 8930 participants) were included: 67 randomized clinical trials (RCTs) and 11 nonrandomized studies. Evidence from 35 RCTs at low risk of bias indicated that ginger, vitamin B6, antihistamines, metoclopramide (for mild symptoms), pyridoxine-doxylamine, and ondansetron (for moderate symptoms) were associated with improved symptoms compared with placebo. One RCT (n = 86) reported greater improvements in moderate symptoms following psychotherapy (change in Rhodes score [range, 0 {no symptoms} to 40 {worst possible symptoms}], 18.76 [SD, 5.48] to 7.06 [SD, 5.79] for intervention vs 19.18 [SD, 5.63] to 12.81 [SD, 6.88] for comparator [P < .001]). For moderate-severe symptoms, 1 RCT (n = 60) suggested that pyridoxine-doxylamine combination taken preemptively reduced risk of recurrence of moderate-severe symptoms compared with treatment once symptoms begin (15.4% vs 39.1% [P < .04]). One RCT (n = 83) found that ondansetron was associated with lower nausea scores on day 4 than metoclopramide (mean visual analog scale [VAS] score, 4.1 [SD, 2.9] for ondansetron vs 5.7 [SD, 2.3] for metoclopramide [P = .023]) but not episodes of emesis (5.0 [SD, 3.1] vs 3.3 [SD, 3], respectively [P = .013]). Although there was no difference in trend in nausea scores over the 14-day study period, trend in vomiting scores was better in the ondansetron group (P = .042). One RCT (n = 159) found no difference between metoclopramide and promethazine after 24 hours (episodes of vomiting, 1 [IQR, 0-5] for metoclopramide vs 2 [IQR, 0-3] for promethazine [P = .81], VAS [0-10 scale] for nausea, 2 [IQR, 1-5] vs 2 [IQR, 1-4], respectively [P = .99]). Three RCTs compared corticosteroids with placebo or promethazine or metoclopramide in women with severe symptoms. Improvements were seen in all corticosteroid groups, but only a significant difference between corticosteroids vs metoclopramide was reported (emesis reduction, 40.9% vs 16.5% at day 2; 71.6% vs 51.2% at day 3; 95.8% vs 76.6% at day 7 [n = 40, P < .001]). For other interventions, evidence was limited.
CONCLUSIONS AND RELEVANCE
For mild symptoms of nausea and emesis of pregnancy, ginger, pyridoxine, antihistamines, and metoclopramide were associated with greater benefit than placebo. For moderate symptoms, pyridoxine-doxylamine, promethazine, and metoclopramide were associated with greater benefit than placebo. Ondansetron was associated with improvement for a range of symptom severity. Corticosteroids may be associated with benefit in severe cases. Overall the quality of evidence was low.
Topics: Acupuncture; Adrenal Cortex Hormones; Antiemetics; Doxylamine; Female; Zingiber officinale; Histamine Antagonists; Humans; Hyperemesis Gravidarum; Nausea; Ondansetron; Phytotherapy; Pregnancy; Pregnancy Complications; Psychotherapy; Pyridoxine; Randomized Controlled Trials as Topic; Vitamin B Complex; Vomiting
PubMed: 27701665
DOI: 10.1001/jama.2016.14337 -
Health Technology Assessment... Oct 2016Nausea and vomiting in pregnancy (NVP) affects up to 85% of all women during pregnancy, but for the majority self-management suffices. For the remainder, symptoms are... (Review)
Review
BACKGROUND
Nausea and vomiting in pregnancy (NVP) affects up to 85% of all women during pregnancy, but for the majority self-management suffices. For the remainder, symptoms are more severe and the most severe form of NVP - hyperemesis gravidarum (HG) - affects 0.3-1.0% of pregnant women. There is no widely accepted point at which NVP becomes HG.
OBJECTIVES
This study aimed to determine the relative clinical effectiveness and cost-effectiveness of treatments for NVP and HG.
DATA SOURCES
MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, PsycINFO, Commonwealth Agricultural Bureaux (CAB) Abstracts, Latin American and Caribbean Health Sciences Literature, Allied and Complementary Medicine Database, British Nursing Index, Science Citation Index, Social Sciences Citation Index, Scopus, Conference Proceedings Index, NHS Economic Evaluation Database, Health Economic Evaluations Database, China National Knowledge Infrastructure, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects were searched from inception to September 2014. References from studies and literature reviews identified were also examined. was hand-searched, as were websites of relevant organisations. Costs came from NHS sources.
REVIEW METHODS
A systematic review of randomised and non-randomised controlled trials (RCTs) for effectiveness, and population-based case series for adverse events and fetal outcomes. Treatments: vitamins B6 and B12, ginger, acupressure/acupuncture, hypnotherapy, antiemetics, dopamine antagonists, 5-hydroxytryptamine receptor antagonists, intravenous (i.v.) fluids, corticosteroids, enteral and parenteral feeding or other novel treatment. Two reviewers extracted data and quality assessed studies. Results were narratively synthesised; planned meta-analysis was not possible due to heterogeneity and incomplete reporting. A simple economic evaluation considered the implied values of treatments.
RESULTS
Seventy-three studies (75 reports) met the inclusion criteria. For RCTs, 33 and 11 studies had a low and high risk of bias respectively. For the remainder ( = 20) it was unclear. The non-randomised studies ( = 9) were low quality. There were 33 separate comparators. The most common were acupressure versus placebo ( = 12); steroid versus usual treatment ( = 7); ginger versus placebo ( = 6); ginger versus vitamin B6 ( = 6); and vitamin B6 versus placebo ( = 4). There was evidence that ginger, antihistamines, metoclopramide (mild disease) and vitamin B6 (mild to severe disease) are better than placebo. Diclectin [Duchesnay Inc.; doxylamine succinate (10 mg) plus pyridoxine hydrochloride (10 mg) slow release tablet] is more effective than placebo and ondansetron is more effective at reducing nausea than pyridoxine plus doxylamine. Diclectin before symptoms of NVP begin for women at high risk of severe NVP recurrence reduces risk of moderate/severe NVP compared with taking Diclectin once symptoms begin. Promethazine is as, and ondansetron is more, effective than metoclopramide for severe NVP/HG. I.v. fluids help correct dehydration and improve symptoms. Dextrose saline may be more effective at reducing nausea than normal saline. Transdermal clonidine patches may be effective for severe HG. Enteral feeding is effective but extreme method treatment for very severe symptoms. Day case management for moderate/severe symptoms is feasible, acceptable and as effective as inpatient care. For all other interventions and comparisons, evidence is unclear. The economic analysis was limited by lack of effectiveness data, but comparison of costs between treatments highlights the implications of different choices.
LIMITATIONS
The main limitations were the quantity and quality of the data available.
CONCLUSION
There was evidence of some improvement in symptoms for some treatments, but these data may not be transferable across disease severities. Methodologically sound and larger trials of the main therapies considered within the UK NHS are needed.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42013006642.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Antiemetics; Clinical Trials as Topic; Complementary Therapies; Cost-Benefit Analysis; Female; Fluid Therapy; Humans; Hyperemesis Gravidarum; Nausea; Pregnancy
PubMed: 27731292
DOI: 10.3310/hta20740 -
Journal of Obstetrics and Gynaecology :... Jan 2020To assess the efficacy alternative medicine in the treatment of nausea and vomiting of pregnancy (NVP), three major databases of PubMed, Cochrane Library and Scopus were...
To assess the efficacy alternative medicine in the treatment of nausea and vomiting of pregnancy (NVP), three major databases of PubMed, Cochrane Library and Scopus were systematically searched since inception until January 14 2019 to investigate the effects of herbal medicines on NVD. The quality assessment of studies was performed according to Jadad scale. All studies showed that ginger had a positive effect on nausea in pregnant women. Unlike others studies, one study reported that ginger was not beneficial to the treatment of vomiting. Herbal medicines such as matricaria chamomilla, elettaria cardamomum, pomegranate and spearmint syrup, lemon provide safe and effective medical alternatives for treating pregnant women with mild to moderate NVD. The results suggested that ginger were more effective than vitamin B, but at the dose of 35-500 mg ginger, vitamin B6 and ginger had identical effect. However, over a longer treatment period (60 days), vitamin B6 was proved to be more effective than ginger. The same effect was observed in the comparison of quince and vitamin B6 as well as ginger and doxylamine plus pyridoxine. Mentha did not generated a positive effect on nausea and vomiting. However, this finding should be considered in the light of the above limitations.IMPACT STATEMENT Previous systematic reviews have shown the superiority of ginger over the placebo. Lemon, chamomile and Mentha have been found to be more effective than the placebo. This systematic review confirmed the results of previous systematic reviews in a larger sample size. Ginger was more effective than vitamin B, but at the dose of 35-500 mg ginger, vitamin B6 and ginger had identical effect. However, over a longer treatment period (60 days), vitamin B6 was proved to be more effective than ginger. Matricaria chamomilla, elettaria cardamomum, pomegranate and spearmint syrup, lemon and ginger can be recommended to pregnant women for alleviation of NVP.
Topics: Adult; Antiemetics; Complementary Therapies; Female; Zingiber officinale; Humans; Matricaria; Morning Sickness; Phytotherapy; Plant Extracts; Pregnancy; Treatment Outcome; Vitamin B 6; Vitamin B Complex
PubMed: 31215276
DOI: 10.1080/01443615.2019.1587392 -
The Cochrane Database of Systematic... Sep 2015Nausea, retching and vomiting are very commonly experienced by women in early pregnancy. There are considerable physical, social and psychological effects on women who... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nausea, retching and vomiting are very commonly experienced by women in early pregnancy. There are considerable physical, social and psychological effects on women who experience these symptoms. This is an update of a review of interventions for nausea and vomiting in early pregnancy last published in 2014.
OBJECTIVES
To assess the effectiveness and safety of all interventions for nausea, vomiting and retching in early pregnancy, up to 20 weeks' gestation.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, the Cochrane Complementary Medicine Field's Trials Register (19 January 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
All randomised controlled trials of any intervention for nausea, vomiting and retching in early pregnancy. We excluded trials of interventions for hyperemesis gravidarum, which are covered by another Cochrane review. We also excluded quasi-randomised trials and trials using a cross-over design.
DATA COLLECTION AND ANALYSIS
Four review authors, in pairs, reviewed the eligibility of trials and independently evaluated the risk of bias and extracted the data for included trials.
MAIN RESULTS
Forty-one trials involving 5449 women, met the inclusion criteria. These trials covered many interventions, including acupressure, acustimulation, acupuncture, ginger, chamomile, lemon oil, mint oil, vitamin B6 and several antiemetic drugs. There were no included studies of dietary and other lifestyle interventions. Evidence regarding the effectiveness of P6 acupressure, auricular (ear) acupressure and acustimulation of the P6 point was limited. Acupuncture (P6 or traditional) showed no significant benefit to women in pregnancy. The use of ginger products may be helpful to women, but the evidence of effectiveness was limited and not consistent, though three recent studies support ginger over placebo. There was only limited evidence from trials to support the use of pharmacological agents including vitamin B6, Doxylamine-pyridoxoine and other anti-emetic drugs to relieve mild or moderate nausea and vomiting. There was little information on maternal and fetal adverse outcomes and on psychological, social or economic outcomes.We were unable to pool findings from studies for most outcomes due to heterogeneity in study participants, interventions, comparison groups, and outcomes measured or reported. The methodological quality of the included studies was mixed. Risk of bias was low related to performance bias, detection bias and attrition bias for most studies. Selection bias risk was unclear for many studies and almost half of the studies did not fully or clearly report all pre-specified outcomes.
AUTHORS' CONCLUSIONS
Given the high prevalence of nausea and vomiting in early pregnancy, women and health professionals need clear guidance about effective and safe interventions, based on systematically reviewed evidence. There is a lack of high-quality evidence to support any particular intervention. This is not the same as saying that the interventions studied are ineffective, but that there is insufficient strong evidence for any one intervention. The difficulties in interpreting and pooling the results of the studies included in this review highlight the need for specific, consistent and clearly justified outcomes and approaches to measurement in research studies.
Topics: Acupuncture Therapy; Antiemetics; Female; Zingiber officinale; Humans; Morning Sickness; Nausea; Phytotherapy; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin B 6; Vitamin B Complex; Vomiting
PubMed: 26348534
DOI: 10.1002/14651858.CD007575.pub4 -
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 -
Expert Opinion on Drug Safety Dec 2014Approximately 10 - 15% of women reportedly take an antihistamine during pregnancy for the relief of nausea and vomiting, allergy and asthma symptoms, or indigestion.... (Review)
Review
INTRODUCTION
Approximately 10 - 15% of women reportedly take an antihistamine during pregnancy for the relief of nausea and vomiting, allergy and asthma symptoms, or indigestion. Antihistamines include histamine H1-receptor and H2-receptor antagonists.
AREAS COVERED
This is a systematic evaluation of the peer-reviewed epidemiologic literature published through February 2014 on the association between prenatal exposure to antihistamines and birth defects. Papers addressing histamine H1- or H2-receptor antagonists are included. Papers addressing pyridoxine plus doxylamine (Bendectin in the United States, Debendox in the United Kingdom, Diclectin in Canada, Lenotan and Merbental in other countries) prior to the year 2001 were excluded post hoc because of several previously published meta-analyses and commentaries on this medication.
EXPERT OPINION
The literature on the safety of antihistamine use during pregnancy with respect to birth defects is generally reassuring though the positive findings from a few large studies warrant corroboration in other populations. The findings in the literature are considered in light of three critical methodological issues: i) selection of appropriate study population; ii) ascertainment of antihistamine exposures; and iii) ascertainment of birth defect outcomes. Selected antihistamines have been very well studied (e.g., loratadine); others, especially H2-receptor antagonists, require additional study before an assessment of safety with respect to birth defect risk could be made.
Topics: Congenital Abnormalities; Female; Histamine Antagonists; Humans; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 25307228
DOI: 10.1517/14740338.2014.970164 -
American Journal of Perinatology Sep 2014Antihistamines are commonly used to treat nausea and vomiting of pregnancy (NVP). We re-analyzed the 24 primary studies cited in a 1997 meta-analysis that concluded... (Meta-Analysis)
Meta-Analysis
Antihistamines are commonly used to treat nausea and vomiting of pregnancy (NVP). We re-analyzed the 24 primary studies cited in a 1997 meta-analysis that concluded antihistamine use for NVP was safe as they had been studied in more than 200,000 participating women and the pooled odds ratio for congenital malformations was 0.76 (95% confidence interval [CI]: 0.60-0.94). Our analysis of this meta-analysis showed that 139,414 women were included in 22 original studies involving antihistamines, 129,108 of which were in studies involving doxylamine. In these studies, 23,485 women were exposed to antihistamines, 14,624 of which were exposed to doxylamine. The summary relative risk (cohort studies) and odds ratio (case-control studies) for congenital malformations from antihistamine exposure were 1.09 (95% CI: 1.01-1.18) and 1.04 (95% CI: 0.91-1.19), and for doxylamine exposure, the summary relative risk and odds ratio were 0.94 (95% CI: 0.80-1.10) and 1.07 (95% CI: 0.93-1.23), respectively. Although not a new systematic review, our re-analysis demonstrates that the safety data for antihistamines, and doxylamine in particular, are based on many fewer than 200,000 participating women and exposures, and that doxylamine use is not associated with a decreased risk of malformations as previously reported.
Topics: Antiemetics; Congenital Abnormalities; Doxylamine; Female; Humans; Morning Sickness; Odds Ratio; Pregnancy; Risk
PubMed: 24323370
DOI: 10.1055/s-0033-1358772 -
Journal of Orofacial Pain 2003To carry out a systematic review of the literature in order to assess the pain-relieving effect and safety of pharmacologic interventions in the treatment of chronic... (Review)
Review
AIMS
To carry out a systematic review of the literature in order to assess the pain-relieving effect and safety of pharmacologic interventions in the treatment of chronic temporomandibular disorders (TMD), including rheumatoid arthritis (RA), as well as atypical facial pain (AFP), and burning mouth syndrome (BMS).
METHODS
Study selection was based on randomized clinical trials (RCTs). Inclusion criteria included studies on adult patients (> or = 18 years) with TMD, RA of the temporomandibular joint (TMJ), AFP, or BMS and a pain duration of > 3 months. Data sources included Medline, Cochrane Library, Embase, and Psych Litt.
RESULTS
Eleven studies with a total of 368 patients met the inclusion criteria. Four trials were on TMD patients, 2 on AFP, 1 on BMS, 1 on RA of the TMJ, and 3 on mixed groups of patients with TMD and AFP. Of the latter, amitriptyline was effective in 1 study and benzodiazepine in 2 studies; the effect in 1 of the benzodiazepine studies was improved when ibuprofen was also given. One study showed that intra-articular injection with glucocorticoid relieved the pain of RA of the TMJ. In 1 study, a combination of paracetamol, codeine, and doxylamine was effective in reducing TMD pain. No effective pharmacologic treatment was found for BMS. Only minor adverse effects were reported in the studies.
CONCLUSION
The common use of analgesics in TMD, AFP, and BMS is not supported by scientific evidence. More large RCTs are needed to determine which pharmacologic interventions are effective in TMD, AFP, and BMS.
Topics: Adult; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Burning Mouth Syndrome; Facial Pain; Glucocorticoids; Humans; Randomized Controlled Trials as Topic; Temporomandibular Joint Disorders; Tranquilizing Agents
PubMed: 14737874
DOI: No ID Found -
The Primary Care Companion For CNS... 2015To investigate the level of evidence supporting the use of common over-the-counter (OTC) agents (diphenhydramine, doxylamine, melatonin, and valerian) for occasional...
OBJECTIVE
To investigate the level of evidence supporting the use of common over-the-counter (OTC) agents (diphenhydramine, doxylamine, melatonin, and valerian) for occasional disturbed sleep or insomnia.
DATA SOURCES
A systematic review of the literature was conducted on July 31, 2014, using MEDLINE (PubMed) and the search terms (insomnia OR sleep) AND (over*the*counter OR OTC OR non*prescription OR antihistamine OR doxylamine OR diphenhydramine OR melatonin OR valerian) with the filters English, human, and clinical trials.
STUDY SELECTION
Identified publications (from 2003 to July 31, 2014, following previous published literature reviews) that met the inclusion criteria were selected. The criteria included randomized placebo-controlled clinical studies that utilized overnight objective (polysomnography) or next-day participant-reported sleep-related endpoints and that were conducted in healthy participants with or without occasional disturbed sleep or diagnosed insomnia.
RESULTS
Measures of efficacy and tolerability were summarized for each study individually and grouped according to OTC agent: H1 antagonists or antihistamines (3 studies, diphenhydramine), melatonin (8), and valerian or valerian/hops (7). Of the 3 sleep agents, studies conducted with melatonin, especially prolonged-release formulations in older individuals with diagnosed insomnia, demonstrated the most consistent beneficial effects (vs placebo) on sleep measures, specifically sleep onset and sleep quality, with favorable tolerability. In contrast, the clinical trial data for diphenhydramine, immediate-release melatonin, and valerian suggested limited beneficial effects.
CONCLUSIONS
A review of randomized controlled studies over the past 12 years suggests commonly used OTC sleep-aid agents, especially diphenhydamine and valerian, lack robust clinical evidence supporting efficacy and safety.
PubMed: 27057416
DOI: 10.4088/PCC.15r01798