What is the best hypnotic for use in the elderly?

Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines (strength of recommendation: B, based on extrapolations of randomized controlled trials). Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep

Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network 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and websites of regulatory agencies from database inception to Nov 25, 2021, to identify published and unpublished randomised controlled trials.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

Orexin Receptor Antagonism, a New Sleep-Enabling Paradigm: A Proof-of-Concept Clinical Trial

Peer reviewe

Association between Zolpidem Use and Glaucoma Risk: A Taiwan Population-Based Case-control Study

[[journaltype]]國外[[incitationindex]]SCI[[ispeerreviewed]]Y[[booktype]]電子版[[countrycodes]]US

Psychopharmacology

Psychopharmacology is the scientific study of the effects drugs have on mood, sensation, thinking, and behavior. Particularly it concerns the use of medications in the treatment of mental disorders. The goal of this chapter is to define the major classes of psychotropic drugs, introducing general pharmacological concepts, explaining the different mechanisms of action and the main clinical applications of the drugs used to treat psychiatric disorders. Psychotropic drugs are commonly categorized according to their major clinical applications: antidepressants, anxiolytics, antipsychotics, and mood stabilizers. However, almost every drug used in psychiatry has multiple therapeutic roles and many clinical applications. For example, SSRIs are considered the first-line pharmacological treatment for several disorders, such as depressive disorders, anxiety disorders, and OCD. Similarly, antipsychotics are indicated as first-choice drugs for psychotic disorders, but many guidelines recommend their use, in combination with mood stabilizers, also in the treatment of acute mania

Gabapentinoid use disorder. Update for clinicians

Gabapentinoids (gabapentin and pregabalin) are versatile drugs, indicated mainly for epilepsy and neuropathic pain, and have long been viewed as agents with little potential for abuse. Burgeoning prescribing patterns and studies indicate that these drugs are increasingly being abused, particularly by polydrug abusers who also abuse opioids. Gabapentinoid abuse is found in less 2% of the general population but may be as high as 15% to 22% among opioid abusers. Other risk factors for gabapentinoid abuse are less clear-cut but include mental health disorders. Gabapentinoids are relatively easy for drug abusers to obtain and many clinicians are not fully aware of their abuse potential. It is thought that gabapentinoids may offer psychoactive effects or enhance the effects of other drugs of abuse. Those who discontinue gabapentinoids abruptly may suffer withdrawal symptoms, but gabapentinoid overdose fatality is rare. Since gabapentinoids are often prescribed off-label to treat psychiatric disorders, these drugs may be dispensed to a particularly vulnerable population. Clinicians must be aware of the potential for Gabapentinoid Use Disorder: Update for Clinicians

ZOLPIDEM IS AN EFFECTIVE OPTION WITH A REDUCED RISK FOR DEPENDENCE IN THE TREATMENT OF INSOMNIA

Insomnia is a highly prevalent sleep disorder that frequently occurs in its acute form and occurs at a rate of approximately 10 per cent in its chronic form in many countries. There is a high prevalence of insomnia in a variety of medical and psychiatric conditions for which insomnia often serves as a risk factor. There are various types of insomnia which are categorized in terms of how it affects sleep it has been shown to negatively affect many physiological, cognitive, and behavioural measures within the body. Recent years have observed that there is sudden increase of various diseases like hypertension, Heart attack, Obesity, Diabetes etc which occurs as a result of insomnia. Hence its impact on financial, social and psychological status of patients and their caregivers cannot be ignored. Thus finding a novel way to tackle these health problems is the need of present times. The most commonly prescribed medications for insomnia are the benzodiazepines (BZP) such as temazepam and diazepam. Although these medications are efficacious, they are associated with tolerance, dependence, residual daytime sedative effects, cognitive and psychomotor impairment, and discontinuation syndromes including rebound insomnia and withdrawal symptoms. For this reason, BZD use should be judicious and is replaced by Zolpidem, a novel non-benzodiazepine hypnotics of Imidazopyridine class that has various advantages over benzodiazepines. Chronic administration of zolpidem produces neither tolerance to its sedative effects nor signs of withdrawal when the drug is discontinued. Also it has little effect on the stages of sleep in normal human subjects. The drug is as effective as benzodiazepines in shortening sleep latency and prolonging total sleep time in patients with insomnia. Tolerance and physical dependence develop only rarely and under unusual circumstances. Keywords: Insomnia, sleep disorder, benzodiazepines, tolerance, dependence, zolpidem, ImidazopyridineÂ

The Effects of Body Weight, Food Intake, Activity, and Anxiety in Female Rats

Zolpidem is a nonbenzodiazepine sedative-hypnotic drug. It is placed in the imidazopyridine class of drugs, which are gamma aminobutyric acis (GABA)-A receptor agonists due to their effect on the alpha-1 GABA-A receptor subunit. The present study focused on differences observed during administration of zolpidem to female rats as compared to a previous study performed on male rats. Female rats receiving zolpidem did not differ significantly from those rats not receiving zolpidem; whereas, male animals were shown to be more affected by zolpidem causing increased food intake, lowered activity levels, increased anxiety, and increased visceral adiposity. Female rats exhibited little change during the withdrawal period compared to the experimental period; while, during the withdrawal period, male rats previously receiving zolpidem quickly returned to levels observed during the habituation period. This suggests that the effects of zolpidem are longer lasting in the female body than in the male body. The differences between male and female rats observed in these experiments may be useful in making dosage recommendations for human patients being administered zolpidem