Therapeutic Advances in Psychopharmacology最新文献

{"title":"History repeating: guidelines to address common problems in psychedelic science.","authors":"Michiel van Elk, Eiko I Fried","doi":"10.1177/20451253231198466","DOIUrl":"10.1177/20451253231198466","url":null,"abstract":"<p><p>Research in the last decade has expressed considerable optimism about the clinical potential of psychedelics for the treatment of mental disorders. This optimism is reflected in an increase in research papers, investments by pharmaceutical companies, patents, media coverage, as well as political and legislative changes. However, psychedelic science is facing serious challenges that threaten the validity of core findings and raise doubt regarding clinical efficacy and safety. In this paper, we introduce the 10 most pressing challenges, grouped into easy, moderate, and hard problems. We show how these problems threaten internal validity (treatment effects are due to factors unrelated to the treatment), external validity (lack of generalizability), construct validity (unclear working mechanism), or statistical conclusion validity (conclusions do not follow from the data and methods). These problems tend to co-occur in psychedelic studies, limiting conclusions that can be drawn about the safety and efficacy of psychedelic therapy. We provide a roadmap for tackling these challenges and share a checklist that researchers, journalists, funders, policymakers, and other stakeholders can use to assess the quality of psychedelic science. Addressing today's problems is necessary to find out whether the optimism regarding the therapeutic potential of psychedelics has been warranted and to avoid history repeating itself.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/b5/10.1177_20451253231198466.PMC10521293.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41155023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Managing medical and psychiatric multimorbidity in older patients.","authors":"David M Carlson, Brandon C Yarns","doi":"10.1177/20451253231195274","DOIUrl":"10.1177/20451253231195274","url":null,"abstract":"<p><p>Aging increases susceptibility both to psychiatric and medical disorders through a variety of processes ranging from biochemical to pharmacologic to societal. Interactions between aging-related brain changes, emotional and psychological symptoms, and social factors contribute to multimorbidity - the presence of two or more chronic conditions in an individual - which requires a more patient-centered, holistic approach than used in traditional single-disease treatment guidelines. Optimal treatment of older adults with psychiatric and medical multimorbidity necessitates an appreciation and understanding of the links between biological, psychological, and social factors - including trauma and racism - that underlie physical and psychiatric multimorbidity in older adults, all of which are the topic of this review.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ed/ea/10.1177_20451253231195274.PMC10469275.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10357819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semaglutide for the treatment of antipsychotic-associated weight gain in patients not responding to metformin - a case series.","authors":"Femin Prasad, Riddhita De, Vittal Korann, Araba F Chintoh, Gary Remington, Bjørn H Ebdrup, Dan Siskind, Filip Krag Knop, Tina Vilsbøll, Anders Fink-Jensen, Margaret K Hahn, Sri Mahavir Agarwal","doi":"10.1177/20451253231165169","DOIUrl":"10.1177/20451253231165169","url":null,"abstract":"<p><p>Metformin is the currently accepted first-line treatment for antipsychotic-associated weight gain (AAWG). However, not all patients benefit from metformin. Glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown promise in the management of obesity in the general population, with preliminary evidence supporting efficacy in AAWG. Semaglutide is a weekly injectable GLP-1RA which received recent approval for obesity management and noted superiority over other GLP-1RAs. This study explored the efficacy and tolerability of semaglutide in AAWG among individuals with severe mental illness. A retrospective chart review of patients treated with semaglutide in the Metabolic Clinic at the Center for Addiction and Mental Health (CAMH) between 2019 and 2021 was conducted. Patients failing a trial of metformin (<5% weight loss or continuing to meet criteria for metabolic syndrome) after 3 months at the maximum tolerated dose (1500-2000 mg/day) were initiated on semaglutide up to 2 mg/week. The primary outcome measure was a change in weight at 3, 6, and 12 months. Twelve patients on weekly semaglutide injections of 0.71 ± 0.47 mg/week were included in the analysis. About 50% were female; the average age was 36.09 ± 13.32 years. At baseline, mean weight was 111.4 ± 31.7 kg, BMI was 36.7 ± 8.2 kg/m², with a mean waist circumference of 118.1 ± 19.3 cm. A weight loss of 4.56 ± 3.15 kg (<i>p</i> < 0.001), 5.16 ± 6.27 kg (<i>p</i> = 0.04) and 8.67 ± 9 kg (<i>p</i> = 0.04) was seen at 3, 6, and 12 months, respectively, after initiation of semaglutide with relatively well-tolerated side-effects. Initial evidence from our real-world clinical setting suggests that semaglutide may be effective in reducing AAWG in patients not responding to metformin. Randomized control trials investigating semaglutide for AAWG are needed to corroborate these findings.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2023-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/73/20/10.1177_20451253231165169.PMC10126648.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9357127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia.","authors":"Mishal Qubad, Robert A Bittner","doi":"10.1177/20451253231158152","DOIUrl":"10.1177/20451253231158152","url":null,"abstract":"<p><p>Despite its enduring relevance as the single most effective and important evidence-based treatment for schizophrenia, underutilization of clozapine remains considerable. To a substantial degree, this is attributable to a reluctance of psychiatrists to offer clozapine due to its relatively large side-effect burden and the complexity of its use. This underscores the necessity for continued education regarding both the vital nature and the intricacies of clozapine treatment. This narrative review summarizes all clinically relevant areas of evidence, which support clozapine's wide-ranging superior efficacy - for treatment-resistant schizophrenia (TRS) and beyond - and make its safe use eminently feasible. Converging evidence indicates that TRS constitutes a distinct albeit heterogeneous subgroup of schizophrenias primarily responsive to clozapine. Most importantly, the predominantly early onset of treatment resistance and the considerable decline in response rates associated with its delayed initiation make clozapine an essential treatment option throughout the course of illness, beginning with the first psychotic episode. To maximize patients' benefits, systematic early recognition efforts based on stringent use of TRS criteria, a timely offer of clozapine, thorough side-effect screening and management as well as consistent use of therapeutic drug monitoring and established augmentation strategies for suboptimal responders are crucial. To minimize permanent all-cause discontinuation, re-challenges after neutropenia or myocarditis should be considered. Owing to clozapine's unique efficacy, comorbid conditions including substance use and most somatic disorders should not dissuade but rather encourage clinicians to consider clozapine. Moreover, treatment decisions need to be informed by the late onset of clozapine's full effects, which for reduced suicidality and mortality rates may not even be readily apparent. Overall, the singular extent of its efficacy combined with the high level of patient satisfaction continues to distinguish clozapine from all other available antipsychotics.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10041648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9219549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Olanzapine for the treatment of ICU delirium: a systematic review and meta-analysis.","authors":"Si Bo Liu, Shan Liu, Kai Gao, Guo Zhi Wu, Guo Zu, Jin Jie Liu","doi":"10.1177/20451253231152113","DOIUrl":"10.1177/20451253231152113","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;As an atypical antipsychotic drug, olanzapine is one of the most commonly used drugs for delirium control. There are no systematic evaluations or meta-analyses of the efficacy and safety of olanzapine for delirium control in critically ill adults.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;In this meta-analysis, we evaluated the efficacy and safety of olanzapine for delirium control in critically ill adults in the intensive care unit (ICU).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Data sources and methods: &lt;/strong&gt;From inception to October 2022, 12 electronic databases were searched. We retrieved randomized controlled trials (RCTs) and retrospective cohort studies of critically ill adults with delirium that compared the effects of olanzapine and other interventions, including routine care (no intervention), nonpharmaceutical interventions and pharmaceutical interventions. The main outcome measures were the (a) relief of delirium symptoms and (b) a decrease in delirium duration. Secondary outcomes were ICU and in-hospital mortality, ICU and hospital length of stay, incidence of adverse events, cognitive function, sleep quality, quality of life, mechanical ventilation time, endotracheal intubation rate and delirium recurrence rate. We applied a random effects model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Data from 10 studies (four RCTs and six retrospective cohort studies) involving 7076 patients (2459 in the olanzapine group and 4617 in the control group) were included. Olanzapine did not effectively relieve delirium symptoms (OR = 1.36, 95% CI [0.83, 2.28], &lt;i&gt;p&lt;/i&gt; = 0.21), nor did it shorten the duration of delirium [standardized mean difference (SMD) = 0.02, 95% CI [-1.04, 1.09], &lt;i&gt;p&lt;/i&gt; = 0.97] when compared with other interventions. Pooled data from three studies showed that the use of olanzapine reduced the incidence of hypotension (OR = 0.44, 95% CI [0.20, 0.95], &lt;i&gt;p&lt;/i&gt; = 0.04) compared with other pharmaceuticals. There was no significant difference in other secondary outcomes, including ICU or hospital length of stay, in-hospital mortality, extrapyramidal reactions, QTc interval prolongation, or overall incidence of other adverse reactions. The number of included studies was not sufficient for performing a comparison between olanzapine and no intervention.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Compared with other interventions, olanzapine has no advantage in alleviating delirium symptoms and shortening delirium duration in critically ill adults. However, there is some evidence that the rate of hypotension was lower in patients who received olanzapine than in those who received other pharmaceutical interventions. There was a nonsignificant difference in the length of ICU or hospital stay, in-hospital mortality, and other adverse reactions. This study provides reference data for delirium research and clinical drug intervention strategies in critically ill adults.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Registration: &lt;/strong&gt;Prospective Register of Systematic Reviews (PROSPE","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/51/50/10.1177_20451253231152113.PMC9944192.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9357460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enduring neurological sequelae of benzodiazepine use: an Internet survey.","authors":"Christy Huff, A J Reid Finlayson, D E Foster, Peter R Martin","doi":"10.1177/20451253221145561","DOIUrl":"10.1177/20451253221145561","url":null,"abstract":"<p><strong>Introduction: </strong>Benzodiazepine tapering and cessation has been associated with diverse symptom constellations of varying duration. Although described in the literature decades ago, the mechanistic underpinnings of enduring symptoms that can last months or years have not yet been elucidated.</p><p><strong>Objective: </strong>This secondary analysis of the results from an Internet survey sought to better understand the acute and protracted withdrawal symptoms associated with benzodiazepine use and discontinuation.</p><p><strong>Methods: </strong>An online survey (<i>n</i> = 1207) was used to gather information about benzodiazepine use, including withdrawal syndrome and protracted symptoms.</p><p><strong>Results: </strong>The mean number of withdrawal symptoms reported by a respondent in this survey was 15 out of 23 symptoms. Six percent of respondents reported having all 23 listed symptoms. A cluster of least-frequently reported symptoms (whole-body trembling, hallucinations, seizures) were also the symptoms most frequently reported as lasting only days or weeks, that is, short-duration symptoms. Symptoms of nervousness/anxiety/fear, sleep disturbances, low energy, and difficulty focusing/distractedness were experienced by the majority of respondents (⩾85%) and, along with memory loss, were the symptoms of longest duration. Prolonged symptoms of anxiety and insomnia occurred in many who have discontinued benzodiazepines, including over 50% who were not originally prescribed benzodiazepines for that indication. It remains unclear if these symptoms might be caused by neuroadaptive and/or neurotoxic changes induced by benzodiazepine exposure. In this way, benzodiazepine withdrawal may have acute and long-term symptoms attributable to different underlying mechanisms, which is the case with alcohol withdrawal.</p><p><strong>Conclusions: </strong>These findings tentatively support the notion that symptoms which are acute but transient during benzodiazepine tapering and discontinuation may be distinct in their nature and duration from the enduring symptoms experienced by many benzodiazepine users.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6f/01/10.1177_20451253221145561.PMC9905027.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9240662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticholinergic action is rarely a good thing.","authors":"Delia Bishara","doi":"10.1177/20451253231195264","DOIUrl":"https://doi.org/10.1177/20451253231195264","url":null,"abstract":"<p><p>The evidence for the risks associated with anticholinergic agents has grown considerably in the last two decades. Not only are they associated with causing peripheral side effects such as dry mouth, blurred vision and constipation, but they can also cause central effects such as cognitive impairment; and more recently, they have consistently been linked with an increased risk of dementia and death in older people. This paper reviews the evidence for the associations of anticholinergic agents and the risk of dementia and increased mortality in dementia.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c6/0b/10.1177_20451253231195264.PMC10493059.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10239721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventing and treating delirium in clinical settings for older adults.","authors":"Morgan Faeder,&nbsp;Elizabeth Hale,&nbsp;Daniel Hedayati,&nbsp;Alex Israel,&nbsp;Darcy Moschenross,&nbsp;Melanie Peterson,&nbsp;Ryan Peterson,&nbsp;Mariel Piechowicz,&nbsp;Jonathan Punzi,&nbsp;Priya Gopalan","doi":"10.1177/20451253231198462","DOIUrl":"https://doi.org/10.1177/20451253231198462","url":null,"abstract":"<p><p>Delirium is a serious consequence of many acute or worsening chronic medical conditions, a side effect of medications, and a precipitant of worsening functional and cognitive status in older adults. It is a syndrome characterized by fluctuations in cognition and impaired attention that develops over a short period of time in response to an underlying medical condition, a substance (prescribed, over the counter, or recreational), or substance withdrawal and can be multi-factorial. We present a narrative review of the literature on nonpharmacologic and pharmacologic approaches to prevention and treatment of delirium with a focus on older adults as a vulnerable population. Older adult patients are most at risk due to decreasing physiologic reserves, with delirium rates of up to 80% in critical care settings. Presentation of delirium can be hyperactive, hypoactive, or mixed, making identification and study challenging as patients with hypoactive delirium are less likely to come to attention in an inpatient or long-term care setting. Studies of delirium focus on prevention and treatment with nonpharmacological or medication interventions, with the preponderance of evidence favoring multi-component nonpharmacological approaches to prevention as the most effective. Though use of antipsychotic medication in delirium is common, existing evidence does not support routine use, showing no clear benefit in clinically significant outcome measures and with evidence of harm in some studies. We therefore suggest that antipsychotics be used to treat agitation, psychosis, and distress associated with delirium at the lowest effective doses and shortest possible duration and not be considered a treatment of delirium itself. Future studies may clarify the use of other agents, such as melatonin and melatonin receptor agonists, alpha-2 receptor agonists, and anti-epileptics.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/65/10/10.1177_20451253231198462.PMC10493062.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10244540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketamine and esketamine in suicidal thoughts and behaviors: a systematic review.","authors":"Fabrice Jollant,&nbsp;Romain Colle,&nbsp;Thi Mai Loan Nguyen,&nbsp;Emmanuelle Corruble,&nbsp;Alain M Gardier,&nbsp;Martin Walter,&nbsp;Mocrane Abbar,&nbsp;Gerd Wagner","doi":"10.1177/20451253231151327","DOIUrl":"https://doi.org/10.1177/20451253231151327","url":null,"abstract":"<p><strong>Background: </strong>More than 2% of the general population experience suicidal ideas each year and a large number of them will attempt suicide. Evidence-based therapeutic options to manage suicidal crisis are currently limited.</p><p><strong>Objectives: </strong>The aim of this study was to overview the findings on the use of ketamine and esketamine for the treatment of suicidal ideas and acts.</p><p><strong>Design: </strong>Systematic review.</p><p><strong>Data sources and methods: </strong>PubMed, article references, and Clinicaltrials.gov up to June 30, 2022. Meta-analyses published within the last 2 years were also reviewed.</p><p><strong>Results: </strong>We identified 12 randomized controlled trials with reduction of suicidal ideation as the primary objective and 14 trials as secondary objectives. Intravenous racemic ketamine was superior to control drugs (placebo or midazolam) within the first 72 h, in spite of large placebo effects. Adverse events were minor and transient. In contrast, intranasal esketamine did not differ from placebo in large-scale studies. Limitations, clinical considerations, and opportunities for future research include the following points: large placebo effects when studying suicidal ideation reduction; small concerns about blinding quality due to dissociative effects; no studies on the risk/prevention of suicidal acts and mortality; lack of studies beyond affective disorders; no studies in adolescents and older people; lack of knowledge of long-term side effects, notably liability for abuse; no robust predictive markers; limited understanding of the mechanisms of ketamine on suicidal ideas; need for improved assessment of suicidal ideation in clinical trials; need for studies in outpatient settings, emergency room, and liaison consultation; need for research on ketamine administration; limited knowledge on the positive and negative effects of concomitant treatments.</p><p><strong>Conclusion: </strong>Overall, there is compelling evidence for a favorable short-term benefit-risk balance with intravenous racemic ketamine but not intranasal esketamine. The place of ketamine will have to be defined within a multimodal care strategy for suicidal patients. Caution remains necessary for clinical use, and pharmacovigilance will be essential.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e7/68/10.1177_20451253231151327.PMC9912570.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10712605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of hyperbolic tapering of antidepressants.","authors":"Jim van Os,&nbsp;Peter C Groot","doi":"10.1177/20451253231171518","DOIUrl":"https://doi.org/10.1177/20451253231171518","url":null,"abstract":"<p><strong>Background: </strong>In patients attempting to discontinue their antidepressant medication, there have been no prospective studies on patterns of withdrawal as a function of the rate of antidepressant reduction during the tapering trajectory, and moderators thereof.</p><p><strong>Objective: </strong>To investigate withdrawal as a function of gradual dose reduction.</p><p><strong>Design: </strong>Prospective cohort study.</p><p><strong>Methods: </strong>The sampling frame consisted of 3956 individuals in the Netherlands who received an antidepressant tapering strip between 19 May 2019 and 22 March 2022 in routine clinical practice. Of these, 608 patients, majorly with previous unsuccessful attempts to stop, provided daily ratings of withdrawal in the context of reducing their antidepressant medications (mostly venlafaxine or paroxetine), using hyperbolic tapering strips offering daily tiny reductions in dose.</p><p><strong>Results: </strong>Withdrawal in daily-step hyperbolic tapering trajectories was limited, and inverse to the rate of taper. Female sex, younger age, presence of one or more risk factors and faster rate of reduction over shorter tapering trajectories were associated with more withdrawal and differential course over time. Thus, sex and age differences were less marked early in the course of the trajectory, whereas differences associated with risk factors and shorter trajectories tended to peak early in the trajectory. There was evidence that tapering in weekly larger steps (mean per-week dose reduction: 33.4% of previous dose), in comparison with daily tiny steps (mean per-day dose reduction: 4.5% of previous dose or 25.3% per week), was associated with more withdrawal in trajectories of 1, 2 or 3 months, particularly for paroxetine and the group of other (non-paroxetine, non-venlafaxine) antidepressants.</p><p><strong>Conclusion: </strong>Antidepressant hyperbolic tapering is associated with limited, rate-dependent withdrawal that is inverse to the rate of taper. The demonstration of multiple demographic, risk and complex temporal moderators in time series of withdrawal data indicates that antidepressant tapering in clinical practice requires a personalised process of shared decision making over the entire course of the tapering period.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10185864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9483860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}