Therapeutic Advances in Psychopharmacology最新文献

{"title":"Agomelatine for the treatment of generalized anxiety disorder: focus on its distinctive mechanism of action.","authors":"Mark J Millan","doi":"10.1177/20451253221105128","DOIUrl":"https://doi.org/10.1177/20451253221105128","url":null,"abstract":"<p><p>Generalized anxiety disorder (GAD), the most frequently diagnosed form of anxiety, is usually treated by cognitive-behavioural approaches or medication; in particular, benzodiazepines (acutely) and serotonin or serotonin/noradrenaline reuptake inhibitors (long term). Efficacy, compliance, and acceptability are, however, far from ideal, reinforcing interest in alternative options. Agomelatine, clinically employed in the treatment of major depression, expresses anxiolytic properties in rodents and was effective in the treatment of GAD (including severely ill patients) in several double-blind, short-term (12 weeks) and relapse-prevention (6 months) studies. At active doses, the incidence of adverse effects was no higher than for placebo. Agomelatine possesses a unique binding profile, behaving as a melatonin (MT₁/MT₂) receptor agonist and 5-HT_2C receptor antagonist, yet recognizing neither monoamine transporters nor GABA_A receptors. Extensive evidence supports a role for 5-HT_2C receptors in the induction of anxious states, and their blockade likely plays a primary role in mediating the anxiolytic actions of agomelatine, including populations in the amygdala and bed nucleus of stria terminalis, as well as the hippocampus. Recruitment of MT receptors in the suprachiasmatic nucleus, thalamic reticular nucleus, and hippocampus appears to fulfil a complimentary role. Downstream of 5-HT_2C and MT receptors, modulation of stress-sensitive glutamatergic circuits and altered release of the anxiogenic neuropeptides, corticotrophin-releasing factor, and vasopressin, may be implicated in the actions of agomelatine. To summarize, agomelatine exerts its anxiolytic actions by mechanisms clearly distinct from those of other agents currently employed for the management of GAD.</p><p><strong>Plain language summary: </strong><b>How agomelatine helps in the treatment of anxiety disorders</b>.</p><p><strong>Introduction: </strong>• Anxiety disorders have a significant negative impact on quality of life.• The most common type of anxiety disorder, called generalized anxiety disorder (GAD), is associated with nervousness and excessive worry.• These symptoms can lead to additional symptoms like tiredness, sleeplessness, irritability, and poor attention.• GAD is generally treated through either cognitive-behavioural therapy or medication. However, widely used drugs like benzodiazepines and serotonin reuptake inhibitors have adverse effects.• Agomelatine, a well-established antidepressant drug, has shown anxiety-lowering ('anxiolytic') properties in rats and has been shown to effectively treat GAD with minimal side effects.• However, exactly how it acts on the brain to manage GAD is not yet clear.• Thus, this review aims to shed light on agomelatine's mechanism of action in treating GAD.</p><p><strong>Methods: </strong>• The authors reviewed studies on how agomelatine treats anxiety in animals.• They also ","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40487819","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":"Effects of antipsychotics on heart rate in treatment of schizophrenia: a systematic review and meta-analysis.","authors":"Maximilian Huhn,&nbsp;Thomas Arndt,&nbsp;Johannes Schneider-Thoma,&nbsp;Stefan Leucht","doi":"10.1177/20451253221097261","DOIUrl":"https://doi.org/10.1177/20451253221097261","url":null,"abstract":"<p><strong>Background: </strong>Antipsychotics are the treatment of choice in the therapy of schizophrenia. These drugs can be associated with changes in heart rate, but this question has never been examined systematically.</p><p><strong>Objective: </strong>We aimed to analyse changes in heart rate during treatment with antipsychotics using the frequency of tachycardia and bradycardia events.</p><p><strong>Design: </strong>For this systematic review and meta-analysis, we included all randomized controlled trials for the acute treatment of schizophrenia comparing antipsychotics head-to-head or with placebo.</p><p><strong>Data sources and methods: </strong>We searched Embase, MEDLINE, PsycINFO, PubMed, BIOSIS, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform and ClinicalTrials.gov (last search June 2021). Two authors independently selected studies and extracted data. We conducted pairwise meta-analyses using a random-effects model. Outcomes were tachycardia and bradycardia events.</p><p><strong>Results: </strong>We found 469 trials meeting the inclusion criteria. Seventy-seven studies with 16,907 participants provided data on tachycardia or bradycardia events. We found no significant differences between antipsychotics and placebo or between antipsychotics for bradycardia events based on sparse data. Antipsychotics had a higher risk for tachycardia events compared with placebo [<i>N</i> = 37, <i>n</i> = 7827, risk ratio (RR) = 1.83, 95% confidence interval (CI) = 1.40-2.41], with large differences between the individual substances (iloperidone RR = 14.05, chlorpromazine RR = 4.84, loxapine RR = 4.52, risperidone RR = 3.38, quetiapine RR = 2.64, paliperidone RR = 1.65). Some head-to-head comparisons were also significantly different: olanzapine <i>versus</i> haloperidol RR = 2.87, chlorpromazine <i>versus</i> thiothixene RR = 2.92, quetiapine <i>versus</i> lurasidone RR = 3.22, risperidone <i>versus</i> aripiprazole RR = 4.37, iloperidone <i>versus</i> ziprasidone RR = 4.65).</p><p><strong>Conclusion: </strong>Many studies do not report data for cardiac outcomes, but the available evidence indicates that treatment with antipsychotics raises the risk for tachycardia. Therefore, especially patients with cardiac risk factors should be monitored closely during antipsychotic treatment.</p><p><strong>Registration: </strong>PROSPERO: CRD42014014919.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/68/99/10.1177_20451253221097261.PMC9237927.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40573548","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":"Estimation of cardiac QTc intervals in people prescribed antipsychotics: a comparison of correction factors.","authors":"Teodora Andric,&nbsp;Karl Winckel,&nbsp;Timothy David Tanzer,&nbsp;Samantha Hollingworth,&nbsp;Lesley Smith,&nbsp;Katherine Isoardi,&nbsp;Olivier Tan,&nbsp;Dan Siskind","doi":"10.1177/20451253221104947","DOIUrl":"https://doi.org/10.1177/20451253221104947","url":null,"abstract":"<p><strong>Background: </strong>A prolonged electrocardiogram (ECG) QT interval is associated with cardiac events and increased mortality. Antipsychotics can prolong the QT interval. The QT interval requires correction (QTc) for heart rate using a formula or QT-nomogram. The QT and QTc can be calculated automatically by the ECG machine or manually; however, machine-measured QT(c) intervals may be inaccurate.</p><p><strong>Objective: </strong>We aimed to investigate the mean QTc and proportion of prolonged QTc intervals in people taking antipsychotic medicines.</p><p><strong>Methods: </strong>We conducted an observational retrospective chart review and data analysis of all consecutive patients taking antipsychotics, with an ECG record, admitted to the psychiatric unit of a large tertiary hospital in Brisbane, Australia, between 1 January 2017 and 30 January 2019. We investigated the mean QTc of people taking antipsychotics to determine differences using (a) machine <i>versus</i> manual QT interval measurement and (b) QTc correction formulae (Bazett, Fridericia, Framingham, Hodges and Rautaharju) and the QT-nomogram. We also determined the number of people with a prolonged QTc using different methods and compared rates of prolonged QTc with antipsychotic monotherapy and polypharmacy.</p><p><strong>Results: </strong>Of 920 included people, the mean (±SD) machine-measured, Bazett-corrected QT interval (recorded from the ECG) was 435 ms (±27), significantly longer (<i>p</i> < 0.001) than the mean manually measured corrected QT intervals with Fridericia 394 ms (±24), Framingham 395 ms (±22), Hodges 398 ms (±22) and Rautaharju 400 ms (±24) formulae. There were significantly more people with a prolonged QTc using machine-measured QT and the Bazett formula (12.0%, 110/920) when compared with manually measured QT and the Fridericia formula (2.2%, 20/920) or QT-nomogram (0.7%, 6/920). Rates of QTc prolongation did not differ between people taking antipsychotic polypharmacy compared with monotherapy.</p><p><strong>Conclusion: </strong>Machine-measured QTc using the Bazett formula overestimates the QTc interval length and number of people with a prolonged QTc, compared with other formulae and the QT-nomogram. We recommend manually measuring the QT and correcting with the Fridericia formula or QT-nomogram prior to modifying antipsychotic therapies.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b0/bb/10.1177_20451253221104947.PMC9210090.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40391772","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":"Clozapine blood level assessment using a point-of-care device: feasibility and reliability.","authors":"Shiri Kamhi-Nesher,&nbsp;Sharon Taub,&nbsp;Shikma Halimi,&nbsp;Maria Frenkel,&nbsp;Mahmud Azam,&nbsp;Gil Bormant,&nbsp;Helena Isakov,&nbsp;Dikla Radzinsky,&nbsp;Abraham Weizman,&nbsp;Amir Krivoy","doi":"10.1177/20451253221094435","DOIUrl":"https://doi.org/10.1177/20451253221094435","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic drug monitoring (TDM) is useful to assess clozapine adherence and optimize treatment. However, analysis of venous blood levels by liquid chromatography tandem mass spectrometry (LC-MS/MS) is often logistically complicated and process time is prolonged.</p><p><strong>Objective: </strong>To assess the feasibility and reliability of a new point-of-care device, (MyCare™ Insite), using capillary blood for clozapine therapeutic monitoring.</p><p><strong>Methods: </strong>Matched venous and capillary blood samples were collected from patients treated with clozapine on a stable dose. Samples were analyzed by LC-MS/MS and MyCare Insite Clozapine Test. Clozapine plasma levels were compared between methods using linear regression model. Both patients and treatment team completed questionnaires about the feasibility of blood sampling.</p><p><strong>Results: </strong>Of the total sample (44 patients, 61% males, mean age 43 ± 12 years), mean daily clozapine dose was 293 ± 134 mg/day. Linear regression model demonstrated high correlation with <i>R</i> ² = 0.83 (<i>p</i> < 0.0001) and mean difference of 26 ± 162 ng/ml. More than 60% of the patients found the clozapine TDM to be important. Most of the participants (58%) favored the capillary sampling and 11% claimed that testing method would affect their adherence to TDM. Moreover, a larger portion (72%) strongly preferred to be tested at the office rather than at the lab.</p><p><strong>Conclusions: </strong>The point-of-care device offers an accessible and satisfactory measurement of clozapine blood levels. Both patients and healthcare providers reported preference for capillary sampling as well as for the in-office TDM procedure. The immediate results provided by the device can facilitate rapid and informed clinical decisions and therefore improve clozapine treatment outcomes.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ba/d0/10.1177_20451253221094435.PMC9201354.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40026066","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":"The clinical effectiveness and cost effectiveness of clozapine for inpatients with severe borderline personality disorder (CALMED study): a randomised placebo-controlled trial.","authors":"Mike J Crawford, Verity C Leeson, Rachel Evans, Barbara Barrett, Aisling McQuaid, Jack Cheshire, Rahil Sanatinia, Gary Lamph, Piyal Sen, Katina Anagnostakis, Louise Millard, Inti Qurashi, Fintan Larkin, Nusrat Husain, Paul Moran, Thomas R E Barnes, Carol Paton, Zoe Hoare, Marco Picchioni, Simon Gibbon","doi":"10.1177/20451253221090832","DOIUrl":"10.1177/20451253221090832","url":null,"abstract":"<p><strong>Background: </strong>Data from case series suggest that clozapine may benefit inpatients with borderline personality disorder (BPD), but randomised trials have not been conducted.</p><p><strong>Methods: </strong>Multicentre, double-blind, placebo-controlled trial. We aimed to recruit 222 inpatients with severe BPD aged 18 or over, who had failed to respond to other antipsychotic medications. We randomly allocated participants on a 1:1 ratio to receive up to 400 mg of clozapine per day or an inert placebo using a remote web-based randomisation service. The primary outcome was total score on the Zanarini Rating scale for Borderline Personality Disorder (ZAN-BPD) at 6 months. Secondary outcomes included self-harm, aggression, resource use and costs, side effects and adverse events. We used a modified intention to treat analysis (mITT) restricted to those who took one or more dose of trial medication, using a general linear model fitted at 6 months adjusted for baseline score, allocation group and site.</p><p><strong>Results: </strong>The study closed early due to poor recruitment and the impact of the COVID-19 pandemic. Of 29 study participants, 24 (83%) were followed up at 6 months, of whom 21 (72%) were included in the mITT analysis. At 6 months, 11 (73%) participants assigned to clozapine and 6 (43%) of those assigned to placebo were still taking trial medication. Adjusted difference in mean total ZAN-BPD score at 6 months was -3.86 (95% Confidence Intervals = -10.04 to 2.32). There were 14 serious adverse events; 6 in the clozapine arm and 8 in the placebo arm of the trial. There was little difference in the cost of care between groups.</p><p><strong>Interpretation: </strong>We recruited insufficient participants to test the primary hypothesis. The study findings highlight problems in conducting placebo-controlled trials of clozapine and in using clozapine for people with BPD, outside specialist inpatient mental health units.</p><p><strong>Trial registration: </strong>ISRCTN18352058. https://doi.org/10.1186/ISRCTN18352058.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9058570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47815492","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":"Will psilocybin lose its magic in the clinical setting?","authors":"Caroline Hayes, M. Wahba, S. Watson","doi":"10.1177/20451253221090822","DOIUrl":"https://doi.org/10.1177/20451253221090822","url":null,"abstract":"Psilocybin as a novel treatment for depression is garnering a lot of attention from both the mainstream media and the academic community. Although phase 3 trials are only just beginning, we feel that it is important for clinicians to consider what psilocybin-assisted psychotherapy might look like in the clinical setting. In this narrative review article we have considered the difficulties that may arise as psilocybin emerges from the research setting, which may hamper its progress towards becoming a licenced medication. Psilocybin has its own unique challenges: the expectation patients come to dosing with having read overwhelmingly positive media; patient suggestibility under the influence of psilocybin and requirement for specialised therapists to name a few. We have also made some recommendations for measures that should be taken in both the phase 3 trials and with clinicians to try and minimise some of the issues raised. In doing so our hope is that psilocybin will continue towards becoming a licenced medication that suitable patients are able to access with relative ease. Practicing psychiatrists need to have an awareness of the potential pitfalls of psilocybin as they will be responsible for prescribing it in the future.","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46162690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time to rehospitalization in involuntarily hospitalized individuals suffering from schizophrenia discharged on long-acting injectable antipsychotics or oral antipsychotics","authors":"Ching-Hua Lin, H. Chan, Fu-Chiang Wang, Chun-Chi Hsu","doi":"10.1177/20451253221079165","DOIUrl":"https://doi.org/10.1177/20451253221079165","url":null,"abstract":"Background: Involuntarily hospitalized individuals suffering from schizophrenia often have a poorer prognosis after discharge. Objective: This study aimed to analyze time to rehospitalization within 6 months of discharge in involuntarily hospitalized individuals suffering from schizophrenia discharged on long-acting injectable antipsychotics (LAIs) or oral antipsychotics (OAPs). In addition, temporal trends in LAI use at discharge were explored. Methods: Involuntarily hospitalized individuals suffering from schizophrenia discharged from the study hospital between 2006 and 2019 (n = 806) were included in the analysis. Survival analysis was used to compare time to rehospitalization within 6 months of discharge between individuals discharged on LAIs and OAPs, and between first-generation antipsychotic (FGA) LAIs and second-generation antipsychotic (SGA) LAIs. The Cochran–Armitage trend test was used to test whether a temporal trend existed for LAIs use at discharge during the study period. Results: The LAIs group (n = 231) had a significantly lower rate of rehospitalization and a significantly longer time to rehospitalization than the OAPs group (n = 575). Rehospitalization rate and time to rehospitalization were not significantly different between individuals discharged on FGA-LAIs and SGA-LAIs. LAIs use at discharge grew significantly from 16.77% in 2006 to 50.00% in 2019 (Z = 6.81, p < 0.0001). Among all LAIs, only use of SGA-LAIs at discharge increased significantly (Z = 5.74, p < 0.0001), but not FGA-LAIs. Conclusions: LAIs were superior to OAPs in preventing rehospitalization. However, SGA-LAIs were comparable with FGA-LAIs in reducing rehospitalization risk. Use of LAIs increased significantly in discharged involuntarily hospitalized individuals during the study period, especially SGA-LAIs.","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42693882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical practice guideline recommendations on tapering and discontinuing antidepressants for depression: a systematic review.","authors":"Anders Sørensen,&nbsp;Karsten Juhl Jørgensen,&nbsp;Klaus Munkholm","doi":"10.1177/20451253211067656","DOIUrl":"https://doi.org/10.1177/20451253211067656","url":null,"abstract":"<p><strong>Background: </strong>Tapering and discontinuing antidepressants are important aspects of the management of patients with depression and should therefore be considered in clinical practice guidelines.</p><p><strong>Objectives: </strong>We aimed to assess the extent and content, and appraise the quality, of guidance on tapering and discontinuing antidepressants in major clinical practice guidelines on depression.</p><p><strong>Methods: </strong>Systematic review of clinical practice guidelines on depression issued by national health authorities and major national or international professional organisations in the United Kingdom, the United States, Canada, Australia, Singapore, Ireland and New Zealand (PROSPERO CRD42020220682). We searched PubMed, 14 guideline registries and the websites of relevant organisations (last search 25 May 2021). The clinical practice guidelines were assessed for recommendations and information relevant to tapering and discontinuing antidepressants. The quality of the clinical practice guidelines as they pertained to tapering and discontinuation was assessed using the AGREE II tool.</p><p><strong>Results: </strong>Of the 21 included clinical practice guidelines, 15 (71%) recommended that antidepressants are tapered gradually or slowly, but none provided guidance on dose reductions, how to distinguish withdrawal symptoms from relapse or how to manage withdrawal symptoms. Psychological challenges were not addressed in any clinical practice guideline, and the treatment algorithms and flow charts did not include discontinuation. The quality of the clinical practice guidelines was overall low.</p><p><strong>Conclusion: </strong>Current major clinical practice guidelines provide little support for clinicians wishing to help patients discontinue or taper antidepressants in terms of mitigating and managing withdrawal symptoms. Patients who have deteriorated upon following current guidance on tapering and discontinuing antidepressants thus cannot be concluded to have experienced a relapse. Better guidance requires better randomised trials investigating interventions for discontinuing or tapering antidepressants.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/20/ff/10.1177_20451253211067656.PMC8841913.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39792317","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":"Clinical outcomes following switching antipsychotic treatment due to market withdrawal: a retrospective naturalistic cohort study of pipotiazine palmitate injection (Piportil Depot) discontinuation, subsequent acute care use and effectiveness of medication to which patients switched.","authors":"Rollo J G Sheldon,&nbsp;Marco Pereira,&nbsp;George Aldersley,&nbsp;Tim Sales,&nbsp;Jed Hewitt,&nbsp;Ray Lyon,&nbsp;Richard Whale","doi":"10.1177/20451253211067042","DOIUrl":"https://doi.org/10.1177/20451253211067042","url":null,"abstract":"<p><strong>Introduction: </strong>Pipotiazine palmitate depot injection (Piportil) was withdrawn from the UK marketplace in 2015. Few studies exist on the clinical impact of such market withdrawal. <b>Purpose:</b> We aimed to identify a cohort of patients switching from pipotiazine following this withdrawal and explore factors associated with effectiveness of the medication switched to and subsequent acute service use.</p><p><strong>Methods: </strong>A naturalistic retrospective cohort study was conducted in Sussex, United Kingdom. Those discontinuing pipotiazine solely due to market withdrawal were identified from electronic patient database and manual searching. Multivariate logistic regression analyses and survival analyses were performed to explore associations between available baseline variables and dichotomous all-cause discontinuation of the next prescribed medication and admission to acute mental health services over the subsequent year.</p><p><strong>Results: </strong>Of 205 patients identified as receiving pipotiazine in October 2014, 137 switched from this due to market withdrawal. Over the subsequent year, 31.5% discontinued the medication to which they were switched and 19% required acute care. Drug class switched to (typical depot vs atypical long acting injection (LAI) vs atypical oral) had no significant association with discontinuation. Switch to atypical LAI was significantly associated with acute care in comparison to typical depot. Those with a schizophrenia diagnosis were significantly less likely to discontinue switched medication or to receive acute care in comparison to those with schizoaffective disorder. Women were significantly more likely to discontinue switched medication than men. Of those requiring acute care, only 38% had required this in the previous 2 years.</p><p><strong>Conclusions: </strong>Antipsychotic market withdrawal has demonstrable negative clinical implications and requires careful clinical management. Increased acute care rates in those receiving an atypical LAI versus a typical depot following pipotiazine suggests lower effectiveness or possible withdrawal effects. No significant difference between depots, LAIs and oral medications on discontinuation supports the importance of a collaborative, fully informed approach when deciding next treatment options.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8808037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39756474","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":"Identifying dopamine supersensitivity through a randomized controlled study of switching to aripiprazole from other antipsychotic agents in patients with schizophrenia.","authors":"Chia-Hao Ma,&nbsp;Hung-Yu Chan,&nbsp;Ming H Hsieh,&nbsp;Chen-Chung Liu,&nbsp;Chih-Min Liu,&nbsp;Hai-Gwo Hwu,&nbsp;Ching-Hua Kuo,&nbsp;Wei J Chen,&nbsp;Tzung-Jeng Hwang","doi":"10.1177/20451253211064396","DOIUrl":"https://doi.org/10.1177/20451253211064396","url":null,"abstract":"<p><strong>Background: </strong>Aripiprazole has been reported to worsen psychotic symptoms when switching from other antipsychotics, possibly due to dopamine supersensitivity psychosis.</p><p><strong>Objective: </strong>This study aimed to explore the predictors and possible underlying mechanisms of aripiprazole-related psychotic exacerbation.</p><p><strong>Methods: </strong>We conducted an 8-week, open-label, randomized controlled study from October 2007 to September 2009, assigning patients with a primary diagnosis of schizophrenia or schizoaffective disorder to switch from other antipsychotics to aripiprazole with 2-week dual administration, and then to taper off the original agents in fast (n = 38, within 1 week) or slow (n = 41, within 4 weeks) strategies. Positive and Negative Syndrome Scale (PANSS) was examined at day 0, 7, 14, 28, 56. Aripiprazole-related exacerbation (ARE) was defined positive as a 2-point increase in delusion/hallucination dimension score within 28 days compared with baseline. Baseline demographic, clinical and intervention-related variables were compared between the ARE+ and ARE- groups.</p><p><strong>Results: </strong>Of the 79 randomized patients, 21 fulfilled the criteria of ARE+ , and 46 were classified as ARE-. Fourteen patients in the ARE+ group had worsening psychotic symptoms in the first and second weeks. Compared with the ARE- group, the ARE+ group had a higher baseline chlorpromazine equivalent dose (405.8 ± 225.8 mg vs 268.1 ± 165.4 mg, <i>p</i> = 0.007) and was associated with prescription of first-generation antipsychotics (<i>p</i> = 0.038).</p><p><strong>Conclusions: </strong>A higher dose of original antipsychotics and prescription of first-generation antipsychotics may be associated with a higher risk of ARE. The underlying mechanism might be covert dopamine supersensitivity psychosis. These findings may help to identify high-risk patients and guide appropriate treatment strategies.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, identifier: NCT00545467.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b6/2f/10.1177_20451253211064396.PMC8801645.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39882134","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}