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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 Pharmacotherapy Jun 2020Chronic insomnia, whether it is primary or in combination with another medical or psychiatric disorder, is a prevalent condition associated with significant morbidity,... (Review)
Review
INTRODUCTION
Chronic insomnia, whether it is primary or in combination with another medical or psychiatric disorder, is a prevalent condition associated with significant morbidity, reduced productivity, increased risk of accidents, and poor quality of life. Pharmacologic and behavioral treatments have equivalent efficacy with each having its own advantages and limitations.
AREAS COVERED
The purpose of this perspective is to delineate the limitations encountered in implementing cognitive behavioral therapy (CBT) and to review the pharmacological treatments designed to target the different phenotypes of insomnia. The discussions address how to choose the optimal medication or combination thereof based on patients' characteristics, available medications, and the presence of comorbid conditions. Selective nonbenzodiazepine sedative 'Z-drug' hypnotics, melatonin receptor agonist-ramelteon, and low-dose doxepin are the agents of choice for treatment of primary and comorbid insomnia.
EXPERT OPINION
A pharmacological intervention should be offered if cognitive behavioral therapy for insomnia is not available or has failed to achieve its goals. Increasing evidence of the significant adverse consequences of long-term benzodiazepines should limit the prescription of these agents to specific conditions. Testing novel dosing regimens with a combination of hypnotic classes augmented with CBT deserve further investigation.
Topics: Cognitive Behavioral Therapy; Humans; Quality of Life; Sleep Initiation and Maintenance Disorders
PubMed: 32202451
DOI: 10.1080/14656566.2020.1743265 -
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 -
Arquivos de Neuro-psiquiatria May 2022Although, insomnia is one of the most common diseases that health professionals face in their practice, it receives little attention in medical training. Diagnosis is...
Although, insomnia is one of the most common diseases that health professionals face in their practice, it receives little attention in medical training. Diagnosis is based on a careful history taking, and physicians must be aware of the diagnostic criteria. Insomnia should not be considered a symptom, but a comorbid condition. Although cognitive behavioral therapy (CBT) has been the mainstay treatment for insomnia for many years, it is usually regarded as a novel therapeutic strategy, both because of scarcity of qualified psychologists and of limited knowledge about insomnia among physicians. GABA receptor acting drugs are being abandoned in the treatment of insomnia because of abuse and dependence potential and accident risk. Two main current therapeutic options with the best scientific evidence are the tricyclic antidepressant, doxepin, and a new melatoninergic receptor agonist, ramelteon. Newer drugs to treat insomnia are in the pipeline. Hypocretine blocking agents will be marketed in the near future.
Topics: Cognitive Behavioral Therapy; Humans; Sleep Initiation and Maintenance Disorders
PubMed: 35976314
DOI: 10.1590/0004-282X-ANP-2022-S124 -
Journal of Clinical Sleep Medicine :... May 2020Pediatric insomnia is a widespread problem and especially difficult to manage in children with neurodevelopmental disorders. There are currently no US Food and Drug...
STUDY OBJECTIVES
Pediatric insomnia is a widespread problem and especially difficult to manage in children with neurodevelopmental disorders. There are currently no US Food and Drug Administration-approved medications to use once first-line therapy fails. The objective of this study was to evaluate the efficacy and tolerability of doxepin in pediatric patients.
METHODS
This is a retrospective single-center chart review of children and adolescents (2-17 years of age) whose sleep failed to improve with behavioral intervention and melatonin who were then trialed on doxepin. Treatment was initiated at a median starting dose of 2 mg and slowly escalated to a median maintenance dose of 10 mg. Improvement in sleep was recorded using a 4-point Likert scale reported by parents on follow-up visits.
RESULTS
A total of 29 patients were included in the analysis. Mean follow-up duration was 6.5 ± 3.5 months. Of 29 patients, 4 (13.8%) patients discontinued doxepin because of lack of efficacy or side effects. Eight (27.6%) patients showed significant improvement of their insomnia, 8 (27.6%) showed moderate improvement, 10 (34.5%) showed mild improvement, and 3 (10.3%) showed minimal to no improvement on treatment with doxepin (P < .05) Only 2 patients (6.9%) experienced adverse effects in the form of behavioral side effects (aggression) and enuresis.
CONCLUSIONS
Results of our studies suggest that low-dose doxepin is both effective and well tolerated in pediatric patients with insomnia.
Topics: Adolescent; Child; Doxepin; Humans; Melatonin; Retrospective Studies; Sleep; Sleep Initiation and Maintenance Disorders
PubMed: 32029069
DOI: 10.5664/jcsm.8338 -
Analytical Chemistry Apr 2024In this work, the concept of magnetic particle spray mass spectrometry (MPS-MS) is reported for the first time. Magnetic sorbent particles are used to extract the...
In this work, the concept of magnetic particle spray mass spectrometry (MPS-MS) is reported for the first time. Magnetic sorbent particles are used to extract the analytes from a liquid sample. The particles are magnetically attracted to the tip of a magnetic probe that is positioned at the entrance of the mass spectrometer. A solvent is dispensed on the particles, and a high voltage promotes the formation of the Taylor cone around the particles agglomerate. Analytes are desorbed by the solvent, ionized, and analyzed by mass spectrometry. MPS-MS is totally in consonance with the green chemistry principle. A minimal consumption of sample (100 μL), solvent (34 μL), and magnetic sorbent (500 μg) is needed per analysis for an excellent performance of MPS-MS in terms of sensitivity and selectivity. The determination of amitriptyline, citalopram, clomipramine, chlorpromazine, doxepin, haloperidol, nortriptyline, and venlafaxine in human plasma samples using magnetic restricted-access carbon nanotubes was carried out as a proof of principle. Limits of quantification of 10 μg L and correlation coefficients higher than 0.98 were obtained for all of the analytes. Limits of detection ranged from 0.43 to 2.82 μg L. Precision (as relative standard deviation) and accuracies (as relative error) ranged from 3.6 to 23.6%, as well as -12.8 to 18.7%, respectively. MPS-MS opens a new line of developments in the association of sample preparation with ambient ionization. New sorbents, device configurations, and physical and chemical conditions can also be analyzed for the analysis of many other analytes in different samples.
PubMed: 38551631
DOI: 10.1021/acs.analchem.3c05680 -
The Medical Letter on Drugs and... Jul 2022
Topics: Humans; Hypnotics and Sedatives; Imidazoles; Pyrrolidines; Sleep Initiation and Maintenance Disorders
PubMed: 35802843
DOI: No ID Found -
Systematic Reviews Nov 2019This review aimed to assess the existing evidence regarding the clinical effectiveness and safety of pharmacological and non-pharmacological interventions in adults with... (Review)
Review
BACKGROUND
This review aimed to assess the existing evidence regarding the clinical effectiveness and safety of pharmacological and non-pharmacological interventions in adults with insomnia and identify where research or policy development is needed.
METHODS
MEDLINE, Embase, PsycINFO, The Cochrane Library, and PubMed were searched from inception until June 14, 2017, along with relevant gray literature sites. Two reviewers independently screened titles/abstracts and full-text articles, and a single reviewer with an independent verifier completed charting, data abstraction, and quality appraisal.
RESULTS
A total of 64 systematic reviews (35 with meta-analysis) were included after screening 5024 titles and abstracts and 525 full-text articles. Eight of the included reviews were rated as high quality using the Assessment of Multiple Systematic Reviews 2 (AMSTAR2) tool, and over half of the included articles (n = 40) were rated as low or critically low quality. Consistent evidence of effectiveness across multiple outcomes based on more than one high- or moderate quality review with meta-analysis was found for zolpidem, suvorexant, doxepin, melatonin, and cognitive behavioral therapy (CBT), and evidence of effectiveness across multiple outcomes based on one high-quality review with meta-analysis was found for temazepam, triazolam, zopiclone, trazodone, and behavioral interventions. These interventions were mostly evaluated in the short term (< 16 weeks), and there was very little harms data available for the pharmacological interventions making it difficult to evaluate their risk-benefit ratio.
CONCLUSIONS
Assuming non-pharmacological interventions are preferable from a safety perspective CBT can be considered an effective first-line therapy for adults with insomnia followed by other behavioral interventions. Short courses of pharmacological interventions can be supplements to CBT or behavioral therapy; however, no evidence regarding the appropriate duration of pharmacological therapy is available from these reviews.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42017072527.
Topics: Antidepressive Agents; Antipsychotic Agents; Azepines; Benzodiazepines; Cognitive Behavioral Therapy; Comparative Effectiveness Research; Humans; Hypnotics and Sedatives; Melatonin; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders; Systematic Reviews as Topic; Triazoles; Zolpidem
PubMed: 31730011
DOI: 10.1186/s13643-019-1163-9 -
Journal of the American Board of Family... Jan 2024Existing guidelines for primary care clinicians (PCCs) on the detection and management of perinatal depression (PD) contain important gaps. This review aims to provide... (Review)
Review
INTRODUCTION
Existing guidelines for primary care clinicians (PCCs) on the detection and management of perinatal depression (PD) contain important gaps. This review aims to provide PCCs with a summary of clinically relevant evidence in the field.
METHODS
A narrative literature review was conducted by searching PubMed and PsycINFO for articles published between 2010 to 2023. Guidelines, systematic reviews, clinical trials, and/or observational studies were all examined.
RESULTS
Screening with the Edinburgh Postnatal Depression Scale or Patient Health Questionnaire-9 followed by a diagnostic evaluation for major depressive disorder in probable cases can enhance PD detection. At-risk individuals and mild to moderate PD should be referred for cognitive behavioral therapy or interpersonal psychotherapy when available. Selective serotonin reuptake inhibitors should be used for moderate to severe PD, with sertraline, escitalopram, or citalopram being preferred first. Using paroxetine or clomipramine in pregnancy, and fluoxetine or doxepin during lactation is generally not preferred. Gestational antidepressant use is associated with a small increase in risk of reduced gestational age at birth, low birth weight, and lower APGAR scores, though whether these links are causal is unclear. Sertraline and paroxetine have the lowest rate of adverse events during lactation. Consequences of untreated PD can include maternal and offspring mortality, perinatal complications, poor maternal-infant attachment, child morbidity and maltreatment, less breastfeeding, and offspring developmental problems.
CONCLUSIONS
These clinically relevant data can support the delivery of high-quality care by PCCs. Risks and benefits of PD treatments and the consequences of untreated PD should be discussed with patients to support informed decision making.
Topics: Pregnancy; Infant, Newborn; Female; Child; Humans; Paroxetine; Sertraline; Depression; Depressive Disorder, Major; Primary Health Care
PubMed: 37704392
DOI: 10.3122/jabfm.2023.230061R1 -
Expert Review of Neurotherapeutics May 2020: Fatigue and apathy are two key non-motor symptoms in Parkinson's disease (PD), with documented negative impact on Quality of life (QoL) and a frequent burden for... (Review)
Review
: Fatigue and apathy are two key non-motor symptoms in Parkinson's disease (PD), with documented negative impact on Quality of life (QoL) and a frequent burden for caregivers.: In this review, the authors comment on the latest pathophysiology, clinical phenomenology, the most frequently used scales for fatigue and apathy in PD with a focus on available therapeutic strategies.:The identification of fatigue and apathy in PD is mainly hampered by the lack of a clear consensus on these subjective symptoms. The pathophysiological processes remain unclear, and the large variation in prevalence is likely due to the heterogeneous PD populations and the lack of an enriched cohort of people with fatigue and/or apathy as main symptoms. Treatment strategies, and especially level 1 evidence for specific treatments for fatigue and apathy in PD, remain scarce. The best evidence to date is doxepin, rasagiline and levodopa infusion therapy (for fatigue), and rivastigmine (for apathy). Further efforts should be made to properly identify these two major symptoms in PD, to correctly detect those who may benefit most from tailored personalized interventions.
Topics: Apathy; Fatigue; Humans; Parkinson Disease
PubMed: 32290717
DOI: 10.1080/14737175.2020.1752669