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Journal of Child Neurology Apr 2019Sleep problems are common in children, especially those with neurodevelopmental disorders, and can lead to consequences in behavior, functioning, and quality of life. We...
Sleep problems are common in children, especially those with neurodevelopmental disorders, and can lead to consequences in behavior, functioning, and quality of life. We systematically reviewed the efficacy and harms of pharmacologic treatments for sleep disorders in children and adolescents. We searched MEDLINE, Cochrane library databases, and PsycINFO through June 2018. We included 22 placebo-controlled randomized controlled trials (1-13 weeks' duration), involving 1758 children (mean age 8.2 years). Single randomized controlled trials of zolpidem and eszopiclone in children with attention-deficit/hyperactivity disorder (ADHD) showed no improvement in sleep or ADHD ratings. Clinical Global Impression Improvement/Severity scores significantly improved with zolpidem ( P = .03 and P = .006, respectively). A single, small randomized controlled trial of diphenhydramine reported small improvements in sleep outcomes (8-10 minutes' better sleep latency and duration) after 1 week. In 19 randomized controlled trials, melatonin significantly improved sleep latency (median 28 minutes; range 11-51 minutes), sleep duration (median 33 minutes; range 14-68 minutes), and wake time after sleep onset (range 12-43 minutes), but not number of awakenings per night (range 0-2.7). Function and behavior improvement varied. Improvement in sleep was greatest in children with autism or other neurodevelopmental disorders, and smaller in adolescents and children with chronic delayed sleep onset. Adverse events were infrequent with melatonin, but more frequent than placebo in children taking eszopiclone or zolpidem. These findings show that melatonin was useful in improving some sleep outcomes in the short term, particularly those with comorbid ASD and neurodevelopmental disorders. Other drugs and outcomes are inadequately studied.
Topics: Adolescent; Child; Humans; Neurodevelopmental Disorders; Randomized Controlled Trials as Topic; Sleep Wake Disorders
PubMed: 30674203
DOI: 10.1177/0883073818821030 -
American Journal of Perinatology Aug 2021Headaches affect 88% of reproductive-aged women. Yet data are limited addressing treatment of headache in pregnancy. While many women experience improvement in...
OBJECTIVE
Headaches affect 88% of reproductive-aged women. Yet data are limited addressing treatment of headache in pregnancy. While many women experience improvement in pregnancy, primary and secondary headaches can develop. Consequently, pregnancy is a time when headache diagnosis can influence maternal and fetal interventions. This study was aimed to summarize existing randomized control trials (RCTs) addressing headache treatment in pregnancy.
STUDY DESIGN
We searched PubMed, CINAHL, EMBASE, ClinicalTrials.gov, Cochrane Library, CINAHL, and SCOPUS from January 1, 1970 through June 31, 2019. Studies were eligible if they were English-language RCTs addressing treatment of headache in pregnancy. Conference abstracts and studies investigating postpartum headache were excluded. Three authors reviewed English-language RCTs addressing treatment of antepartum headache. To be included, all authors agreed each article to meet the following criteria: predefined control group, participants underwent randomization, and treatment of headache occurred in the antepartum period. If inclusion criteria were met no exclusions were made. Our systematic review registration number was CRD42019135874.
RESULTS
A total of 193 studies were reviewed. Of the three that met inclusion criteria all were small, with follow-up designed to measure pain reduction and showed statistical significance.
CONCLUSION
Our systematic review of RCTs evaluating treatment of headache in pregnancy revealed only three studies. This paucity of data limits treatment, puts women at risk for worsening headache disorders, and delays diagnosis placing both the mother and fetus at risk for complications.
Topics: Acupuncture Analgesia; Analgesics; Biofeedback, Psychology; Codeine; Complementary Therapies; Diphenhydramine; Female; Headache; Humans; Metoclopramide; Pain Measurement; Physical Therapy Modalities; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic
PubMed: 32120417
DOI: 10.1055/s-0040-1705180 -
CNS Drugs Mar 2019Clozapine is the most effective medication for treatment-refractory schizophrenia. However, it has a high burden of adverse events, including common adverse events such... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clozapine is the most effective medication for treatment-refractory schizophrenia. However, it has a high burden of adverse events, including common adverse events such as sialorrhea. Sialorrhea can lead to severe physical complications such as aspiration pneumonia, as well as psychological complications including embarrassment and low self-esteem. Compromised adherence and treatment discontinuation can occur due to intolerability. There have been no meta-analyses examining strategies to mitigate clozapine-induced sialorrhea.
METHODS
We systematically searched Chinese and Western research databases for randomised controlled trials examining agents for clozapine-induced sialorrhea. No limit to language or date were applied to the search. Where sufficient data for individual agents was available, pairwise meta-analyses were conducted. Results were provided as risk ratios and number needed to treat. Sensitivity analysis was conducted by study quality. Adverse events were provided as number needed to harm.
RESULTS
19 studies provided data for use in the meta-analysis. Improvement in clozapine-induced sialorrhea was seen in meta-analyses of propantheline (studies = 6, risk ratio [RR] 2.38, 95% confidence interval [CI] 1.52-3.73; number needed to treat [NNT] 3, 95% CI 1.9-2.7), diphenhydramine (studies = 5, RR 3.09, 95% CI 2.36-4.03; NNT 2, 95% CI 1.5-2.0), chlorpheniramine (studies = 2, RR 2.37, 95% CI 1.59-3.55; NNT 3, 95% CI 1.6-3.5), and benzamide derivatives (odds ratio [OR] 6.93, 95% CI 3.03-15.86). When meta-analyses were limited to high-quality studies, all these results remained significant. Single studies of benzhexol, cyproheptadine, doxepin and Kongyan Tang showed promise. Propantheline increased rates of constipation with a number needed to harm (NNH) of 9 (95% CI 4.2-204.1).
CONCLUSION
Clozapine-induced sialorrhea is a potentially serious adverse event. Included studies in this meta-analysis were limited by poor study quality. Diphenhydramine, chlorpheniramine and benzamide derivatives appear to have the best supporting evidence and lowest reported adverse events. Caution should be exercised when using propantheline given its increased risk of constipation.
Topics: Antidepressive Agents; Antipsychotic Agents; Clozapine; Histamine Antagonists; Humans; Medicine, Chinese Traditional; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Salivation; Schizophrenia; Sialorrhea
PubMed: 30758782
DOI: 10.1007/s40263-019-00612-8 -
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 -
The Journal of Emergency Medicine Feb 2021Neuroleptics are commonly prescribed drugs to treat acute conditions (e.g., migraines) in the emergency department, but can cause serious adverse effects. Using... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Neuroleptics are commonly prescribed drugs to treat acute conditions (e.g., migraines) in the emergency department, but can cause serious adverse effects. Using diphenhydramine to prevent these adverse effects is very common but remains controversial.
OBJECTIVE
We performed a systematic review to determine whether prophylactic administration of diphenhydramine reduces the incidence of neuroleptic adverse effects in patients with acute conditions.
METHODS
Medline, Embase, Cochrane, PsycInfo, and Web of Science were searched for randomized controlled trials evaluating any neuroleptic with diphenhydramine vs. the same neuroleptic with any inactive agent. Primary outcome was incidence of any extrapyramidal adverse effect. Secondary outcomes were akathisia, rescue medication, subjective restlessness, neuroleptic malignant syndrome, and sedation. Independent reviewers scanned identified citations, extracted data, and assessed risk of bias. Meta-analysis was performed using random effect models.
RESULTS
Of 1566 identified citations, nine studies (n = 1648 patients) met eligibility criteria. Four studies were specifically designed to compare the incidence of neuroleptic adverse effects with and without co-administration of diphenhydramine. Four studies were at high risk of bias. In primary analysis, diphenhydramine had no effect on the incidence of extrapyramidal symptoms (7 studies, n = 1393, risk ratio [RR] 0.75; 95% confidence interval [CI] 0.44-1.31) or akathisia (5 studies, n = 1094; RR 0.78; 95% CI 0.33-1.82) or any of the secondary outcomes. In subgroup analysis, diphenhydramine was associated with a significant decrease in extrapyramidal adverse effects compared with placebo (4 studies, n = 705; RR 0.61; 95% CI 0.41-0.90). Dosage analysis yielded no further information.
CONCLUSIONS
When compared with placebo, diphenhydramine was associated with a significant reduction of extrapyramidal adverse effects. Overall quality of evidence is low. Further studies are warranted.
Topics: Antipsychotic Agents; Basal Ganglia Diseases; Diphenhydramine; Drug-Related Side Effects and Adverse Reactions; Humans; Psychomotor Agitation
PubMed: 33131965
DOI: 10.1016/j.jemermed.2020.09.031