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Psychotherapy and Psychosomatics 2020Studies on psychotropic medications decrease, discontinuation, or switch have uncovered withdrawal syndromes. The present overview aimed at analyzing the literature to... (Review)
Review
Studies on psychotropic medications decrease, discontinuation, or switch have uncovered withdrawal syndromes. The present overview aimed at analyzing the literature to illustrate withdrawal after decrease, discontinuation, or switch of psychotropic medications based on the drug class (i.e., benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonists, antidepressants, ketamine, antipsychotics, lithium, mood stabilizers) according to the diagnostic criteria of Chouinard and Chouinard [Psychother Psychosom. 2015;84(2):63-71], which encompass new withdrawal symptoms, rebound symptoms, and persistent post-withdrawal disorders. All these drugs may induce withdrawal syndromes and rebound upon discontinuation, even with slow tapering. However, only selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, and antipsychotics were consistently also associated with persistent post-withdrawal disorders and potential high severity of symptoms, including alterations of clinical course, whereas the distress associated with benzodiazepines discontinuation appears to be short-lived. As a result, the common belief that benzodiazepines should be substituted by medications that cause less dependence such as antidepressants and antipsychotics runs counter the available literature. Ketamine, and probably its derivatives, may be classified as at high risk for dependence and addiction. Because of the lag phase that has taken place between the introduction of a drug into the market and the description of withdrawal symptoms, caution is needed with the use of newer antidepressants and antipsychotics. Within medication classes, alprazolam, lorazepam, triazolam, paroxetine, venlafaxine, fluphenazine, perphenazine, clozapine, and quetiapine are more likely to induce withdrawal. The likelihood of withdrawal manifestations that may be severe and persistent should thus be taken into account in clinical practice and also in children and adolescents.
Topics: Humans; Mental Disorders; Psychotropic Drugs; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome
PubMed: 32259826
DOI: 10.1159/000506868 -
Journal of Clinical Sleep Medicine :... Sep 2021This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of central disorders of hypersomnolence in adults... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of central disorders of hypersomnolence in adults and children. The review focuses on prescription medications with U.S. Food & Drug Administration approval and nonpharmacologic interventions studied for the treatment of symptoms caused by central disorders of hypersomnolence.
METHODS
The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine to perform a systematic review. Randomized controlled trials and observational studies addressing pharmacological and nonpharmacological interventions for central disorders of hypersomnolence were identified. Statistical analyses were performed to determine the clinical significance of all outcomes. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to assess the evidence for the purpose of making specific treatment recommendations.
RESULTS
The literature search identified 678 studies; 144 met the inclusion criteria and 108 provided data suitable for statistical analyses. Evidence for the following interventions is presented: armodafinil, clarithromycin, clomipramine, dextroamphetamine, flumazenil, intravenous immune globulin (IVIG), light therapy, lithium, l-carnitine, liraglutide, methylphenidate, methylprednisolone, modafinil, naps, pitolisant, selegiline, sodium oxybate, solriamfetol, and triazolam. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations.
CITATION
Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. 2021;17(9):1895-1945.
Topics: Adult; Child; Disorders of Excessive Somnolence; GRADE Approach; Humans; Modafinil; Sleep; Sodium Oxybate; United States
PubMed: 34743790
DOI: 10.5664/jcsm.9326 -
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 -
Frontiers in Psychiatry 2023Benzodiazepines (BZs) are prescribed as anxiolytics, but their use is limited by side effects including abuse liability and daytime drowsiness. Neuroactive steroids are...
INTRODUCTION
Benzodiazepines (BZs) are prescribed as anxiolytics, but their use is limited by side effects including abuse liability and daytime drowsiness. Neuroactive steroids are compounds that, like BZs, modulate the effects of GABA at the GABA receptor. In a previous study, combinations of the BZ triazolam and neuroactive steroid pregnanolone produced supra-additive (i.e., greater than expected effects based on the drugs alone) anxiolytic effects but infra-additive (i.e., lower than expected effects based on the drugs alone) reinforcing effects in male rhesus monkeys, suggestive of an improved therapeutic window.
METHODS
Female rhesus monkeys (=4) self-administered triazolam, pregnanolone, and triazolam-pregnanolone combinations intravenously under a progressive-ratio schedule. In order to assess characteristic sedative-motor effects of BZ-neuroactive steroid combinations, female rhesus monkeys (n=4) were administered triazolam, pregnanolone, and triazolam-pregnanolone combinations. Trained observers, blinded to condition, scored the occurrence of species-typical and drug-induced behaviors.
RESULTS
In contrast to our previous study with males, triazolam-pregnanolone combinations had primarily supra-additive reinforcing effects in three monkeys but infra-additive reinforcing effects in one monkey. Scores for deep sedation (i.e., defined as atypical loose-limbed posture, eyes closed, does not respond to external stimuli) and observable ataxia (any slip, trip, fall, or loss of balance) were significantly increased by both triazolam and pregnanolone. When combined, triazolam-pregnanolone combinations had supra-additive effects for inducing deep sedation, whereas observable ataxia was attenuated, likely due to the occurrence of robust sedative effects.
DISCUSSION
These results suggest that significant sex differences exist in self-administration of BZ-neuroactive steroid combinations, with females likely to show enhanced sensitivity to reinforcing effects compared with males. Moreover, supra-additive sedative effects occurred for females, demonstrating a higher likelihood of this adverse effect when these drug classes are combined.
PubMed: 37252149
DOI: 10.3389/fpsyt.2023.1142531 -
Frontiers in Neuroscience 2022Insomnia is a stress-related sleep disorder, may favor a state of allostatic overload impairing brain neuroplasticity, stress immune and endocrine pathways, and may... (Review)
Review
INTRODUCTION
Insomnia is a stress-related sleep disorder, may favor a state of allostatic overload impairing brain neuroplasticity, stress immune and endocrine pathways, and may contribute to mental and physical disorders. In this framework, assessing and targeting insomnia is of importance.
AIM
Since maladaptive neuroplasticity and allostatic overload are hypothesized to be related to GABAergic alterations, compounds targeting GABA may play a key role. Accordingly, the aim of this review was to discuss the effect of GABA receptor agonists, short-medium acting hypnotic benzodiazepines and the so called Z-drugs, at a molecular level.
METHOD
Literature searches were done according to PRISMA guidelines. Several combinations of terms were used such as "hypnotic benzodiazepines" or "brotizolam," or "lormetazepam" or "temazepam" or "triazolam" or "zolpidem" or "zopiclone" or "zaleplon" or "eszopiclone" and "insomnia" and "effects on sleep" and "effect on brain plasticity" and "effect on stress system". Given the complexity and heterogeneity of existing literature, we ended up with a narrative review.
RESULTS
Among short-medium acting compounds, triazolam has been the most studied and may regulate the stress system at central and peripheral levels. Among Z-drugs eszopiclone may regulate the stress system. Some compounds may produce more "physiological" sleep such as brotizolam, triazolam, and eszopiclone and probably may not impair sleep processes and related neural plasticity. In particular, triazolam, eszopiclone, and zaleplon studied in animal models did not alter neuroplasticity.
CONCLUSION
Current models of insomnia may lead us to revise the way in which we use hypnotic compounds in clinical practice. Specifically, compounds should target sleep processes, the stress system, and sustain neural plasticity. In this framework, among the short/medium acting hypnotic benzodiazepines, triazolam has been the most studied compound while among the Z-drugs eszopiclone has demonstrated interesting effects. Both offer potential new insight for treating insomnia.
PubMed: 35968380
DOI: 10.3389/fnins.2022.893015 -
The Cochrane Database of Systematic... Feb 2023The term central sleep apnoea (CSA) encompasses diverse clinical situations where a dysfunctional drive to breathe leads to recurrent respiratory events, namely apnoea... (Review)
Review
BACKGROUND
The term central sleep apnoea (CSA) encompasses diverse clinical situations where a dysfunctional drive to breathe leads to recurrent respiratory events, namely apnoea (complete absence of ventilation) and hypopnoea sleep (insufficient ventilation) during sleep. Studies have demonstrated that CSA responds to some extent to pharmacological agents with distinct mechanisms, such as sleep stabilisation and respiratory stimulation. Some therapies for CSA are associated with improved quality of life, although the evidence on this association is uncertain. Moreover, treatment of CSA with non-invasive positive pressure ventilation is not always effective or safe and may result in a residual apnoea-hypopnoea index.
OBJECTIVES
To evaluate the benefits and harms of pharmacological treatment compared with active or inactive controls for central sleep apnoea in adults.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 30 August 2022.
SELECTION CRITERIA
We included parallel and cross-over randomised controlled trials (RCTs) that evaluated any type of pharmacological agent compared with active controls (e.g. other medications) or passive controls (e.g. placebo, no treatment or usual care) in adults with CSA as defined by the International Classification of Sleep Disorders 3rd Edition. We did not exclude studies based on the duration of intervention or follow-up. We excluded studies focusing on CSA due to periodic breathing at high altitudes.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were central apnoea-hypopnoea index (cAHI), cardiovascular mortality and serious adverse events. Our secondary outcomes were quality of sleep, quality of life, daytime sleepiness, AHI, all-cause mortality, time to life-saving cardiovascular intervention, and non-serious adverse events. We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We included four cross-over RCTs and one parallel RCT, involving a total of 68 participants. Mean age ranged from 66 to 71.3 years and most participants were men. Four trials recruited people with CSA associated with heart failure, and one study included people with primary CSA. Types of pharmacological agents were acetazolamide (carbonic anhydrase inhibitor), buspirone (anxiolytic), theophylline (methylxanthine derivative) and triazolam (hypnotic), which were given for between three days and one week. Only the study on buspirone reported a formal evaluation of adverse events. These events were rare and mild. No studies reported serious adverse events, quality of sleep, quality of life, all-cause mortality, or time to life-saving cardiovascular intervention. Carbonic anhydrase inhibitors versus inactive control Results were from two studies of acetazolamide versus placebo (n = 12) and acetazolamide versus no acetazolamide (n = 18) for CSA associated with heart failure. One study reported short-term outcomes and the other reported intermediate-term outcomes. We are uncertain whether carbonic anhydrase inhibitors compared to inactive control reduce cAHI in the short term (mean difference (MD) -26.00 events per hour, 95% CI -43.84 to -8.16; 1 study, 12 participants; very low certainty). Similarly, we are uncertain whether carbonic anhydrase inhibitors compared to inactive control reduce AHI in the short term (MD -23.00 events per hour, 95% CI -37.70 to 8.30; 1 study, 12 participants; very low certainty) or in the intermediate term (MD -6.98 events per hour, 95% CI -10.66 to -3.30; 1 study, 18 participants; very low certainty). The effect of carbonic anhydrase inhibitors on cardiovascular mortality in the intermediate term was also uncertain (odds ratio (OR) 0.21, 95% CI 0.02 to 2.48; 1 study, 18 participants; very low certainty). Anxiolytics versus inactive control Results were based on one study of buspirone versus placebo for CSA associated with heart failure (n = 16). The median difference between groups for cAHI was -5.00 events per hour (IQR -8.00 to -0.50), the median difference for AHI was -6.00 events per hour (IQR -8.80 to -1.80), and the median difference on the Epworth Sleepiness Scale for daytime sleepiness was 0 points (IQR -1.0 to 0.00). Methylxanthine derivatives versus inactive control Results were based on one study of theophylline versus placebo for CSA associated with heart failure (n = 15). We are uncertain whether methylxanthine derivatives compared to inactive control reduce cAHI (MD -20.00 events per hour, 95% CI -32.15 to -7.85; 15 participants; very low certainty) or AHI (MD -19.00 events per hour, 95% CI -30.27 to -7.73; 15 participants; very low certainty). Hypnotics versus inactive control Results were based on one trial of triazolam versus placebo for primary CSA (n = 5). Due to very serious methodological limitations and insufficient reporting of outcome measures, we were unable to draw any conclusions regarding the effects of this intervention.
AUTHORS' CONCLUSIONS
There is insufficient evidence to support the use of pharmacological therapy in the treatment of CSA. Although small studies have reported positive effects of certain agents for CSA associated with heart failure in reducing the number of respiratory events during sleep, we were unable to assess whether this reduction may impact the quality of life of people with CSA, owing to scarce reporting of important clinical outcomes such as sleep quality or subjective impression of daytime sleepiness. Furthermore, the trials mostly had short-term follow-up. There is a need for high-quality trials that evaluate longer-term effects of pharmacological interventions.
Topics: Male; Adult; Humans; Aged; Female; Sleep Apnea, Central; Carbonic Anhydrase Inhibitors; Buspirone; Apnea; Triazolam; Theophylline; Acetazolamide; Heart Failure; Hypnotics and Sedatives; Disorders of Excessive Somnolence
PubMed: 36861808
DOI: 10.1002/14651858.CD012922.pub2