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- Dose-response analysis of aripiprazole in patients with schizophrenia in
Taiwan
Authors: Yun Tien, Hsiang-Ping Huang, Ding-Lieh Liao, Shang-Chien Huang
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Background:Aripiprazole is a third-generation antipsychotic agent with acceptable efficacy and a good safety profile. Previous studies have indicated the therapeutic serum concentration of aripiprazole to be 100 to 350 ng/ml; however, most of these studies examined a Western population. Patients with schizophrenia from Tungs’ Taichung MetroHarbor Hospital in central Taiwan were recruited to analyze the dose–response relationship of aripiprazole in the Chinese population.Objective:We aimed to investigate whether a serum concentration of aripiprazole higher than the current suggested range leads to higher response rates.Design:A prospective cohort study was designed to investigate the response rates in different studied cohorts grouped by serum concentration of aripiprazole.Data Sources and Methods:Data of 64 patients who presented to a single medical center in central Taiwan and who received therapeutic drug monitoring (TDM) were obtained. Serum concentrations of aripiprazole were correlated with the clinical response of patients by using the Clinical Global Impressions (CGI) scores.Results:The mean concentration of aripiprazole was 432.1 ± 275.1 ng/ml in the study cohort. Among the much-improved patients, the mean serum concentration of aripiprazole was 494 ± 273 ng/ml (25th–75th percentiles 264–666 ng/ml), which was higher than the current recommended therapeutic target of 100–350 ng/ml for aripiprazole. The response rate in the severe group (baseline CGI score of 6 or 7) was significantly higher than in the moderate group (baseline CGI score of 4 or 5; 86.7% versus 55.9%, p = 0.007).Conclusion:A significantly higher response rate was observed in the study cohort with serum aripiprazole concentrations over 300 ng/ml. Therefore, dosing higher than the current recommended range may potentially improve the treatment efficacy in the Chinese population. Because the serum concentration varies among patients due to multiple intrinsic and extrinsic factors, TDM, especially in outpatients, is recommended if the clinical response is limited.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-07-30T11:09:26Z
DOI: 10.1177/20451253221113238
Issue No: Vol. 12 (2022)
- Comment on: Treatment strategies for clozapine-induced hypotension: A
systematic review
Authors: Patrick M. Wieruszewski, Erica D. Wittwer, Sarah B. Leung, Jonathan G. Leung
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-07-19T07:34:42Z
DOI: 10.1177/20451253221111682
Issue No: Vol. 12 (2022)
- Olanzapine long-acting injection, discontinuation rates and reasons for
discontinuation: 10 years’ experience at a UK high-secure hospital
Authors: Azizah Attard, John Wakelam, Josephine Broyd, David Taylor, Jonathan Hafferty
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Background:Olanzapine pamoate has been shown to be an effective second-generation long-acting injection. Its popularity has possibly been adversely affected by the rare incidence of post-injection syndrome (PIS) and the associated requirement to monitor for 3 h after each injection.Objective:This study aimed to collect and present data on the use of olanzapine long-acting injection (OLAI) over a 10-year period in a high-security forensic hospital in South East England.Design:This was a non-interventional retrospective study collecting information from anonymised electronic patient and prescription records. As per hospital Trust guidelines, patient consent to access of hospital records was presumed unless explicitly withdrawn.Method:All patients prescribed OLAI between the years 2009 and 2019 were identified. Data collected included date that OLAI was started, stopped, dose range, side effects and concomitant medication.Results:Of 88 patients who were started OLAI, 45 (51%) continued at month 24. At 60 months, 22 of 70 (31%) patients for whom data were available continued with OLAI. Over 60% of continuers were on higher than recommended doses. Of almost 5000 injections administered, there was 1 episode of PIS.Conclusion:OLAI is an effective treatment for schizophrenia and schizoaffective disorder, especially when used in patients have been able to tolerate the drug and were stabilised on it for 24 months. In over half the patients who continued OLAI, the doses were higher than that recommended by the manufacturer. The incidence of PIS in this study was very low in comparison with other studies.Registration code:2049
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-07-19T06:41:35Z
DOI: 10.1177/20451253221113093
Issue No: Vol. 12 (2022)
- Exercise interventions to reduce anxiety in mid-life and late-life anxiety
disorders and subthreshold anxiety disorder: a systematic review
Authors: Terence W.H. Chong, Scherazad Kootar, Helen Wilding, Sarah Berriman, Eleanor Curran, Kay L. Cox, Alex Bahar-Fuchs, Ruth Peters, Kaarin J. Anstey, Christina Bryant, Nicola T. Lautenschlager
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Background:Anxiety disorders are highly prevalent and cause significant distress, disability, and cost. Medication adverse effects and interactions increase in mid-life and late-life, highlighting the need for effective non-pharmacological interventions.Objectives:We aimed to evaluate the extent of evidence supporting exercise interventions for anxiety and subthreshold anxiety disorders in mid-life and late-life.Design:Systematic review.Data Sources and Methods:We searched MEDLINE, PsycINFO, Embase, Emcare, Ovid Nursing, CINAHL Plus, Cochrane Library, Health Collection, Humanities & Social Sciences Collection, and https://clinicaltrials.gov databases for trials published January 1994–May 2019. Randomised controlled trials of exercise interventions involving aerobic exercise or resistance training for adults aged 40 years and above with anxiety or subthreshold anxiety disorders in residential or health settings were identified. The primary outcome was change in anxiety. We excluded trials including participants aged below 40 years, participants with diagnosis of separation anxiety, selective mutism, obsessive-compulsive disorder, acute stress disorder and post-traumatic stress disorder, and head-to-head comparisons of interventions. Trial quality was assessed using the Cochrane Risk of Bias Tool and evidence synthesised in narrative form.Results:Four trials totalling 132 participants met inclusion criteria, although some had methodological limitations. Interventions included a home-based resistance training intervention, supervised group-based aerobic intervention, Tai Chi intervention, and supervised group-based aerobic and strength intervention. Three trials included late-life participants and the fourth mid-life. Three trials demonstrated greater reductions in anxiety in the intervention group compared with control. The fourth trial showed pre–post reductions in anxiety in both groups, with between-group difference not reaching statistical significance.Conclusion:There is limited supportive evidence suggesting that exercise interventions have potential to be effective, feasible and safe non-pharmacological interventions for anxiety and subthreshold anxiety disorders in mid-life and late-life. The heterogeneity, limited number and high risk of bias of some trials meant that we were not able to conduct a meta-analysis. Tailoring of interventions may improve uptake and reduce dropout. The paucity of research in this area with only four included trials demonstrates the urgent need for future and larger trials to provide proof of concept, data about effective types and doses of exercise interventions, and guidance to community, clinical, and public health services.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-07-07T10:33:31Z
DOI: 10.1177/20451253221104958
Issue No: Vol. 12 (2022)
- Vortioxetine as adjunctive therapy in the treatment of schizophrenia
Authors: Sofia Redaelli, Lilla Porffy, Ebenezer Oloyede, Olubanke Dzahini, Gabriella Lewis, Maria Lobo, Eromona Whiskey, Sukhi S. Shergill
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Background:The evidence for safe and effective interventions to treat the negative and cognitive symptoms of schizophrenia is lacking.Objectives:Vortioxetine is a novel antidepressant that has been used as adjunctive therapy for the treatment of psychosis; however, its effectiveness in clinical practice is relatively unknown. In this study, we aimed to determine the potential clinical effectiveness and safety and tolerability of vortioxetine in psychosis.Design:This is a non-interventional, retrospective study on the add-on use of vortioxetine in a group of people with schizophrenia-spectrum disorders in a large UK NHS mental health trust.Methods:Clinical effectiveness of vortioxetine was retrospectively assessed through the Clinical Global Impression – Severity (CGI-S) scale at 3 months. Safety and tolerability were evaluated through treatment discontinuation rates at 3, 6, and 12 months, and clinical reasons were evaluated at the primary endpoint of 3 months.Results:Data were available for 40 subjects with a diagnosis of schizophrenia or schizoaffective disorder–prescribed vortioxetine treatment; 30 (75%) remained on treatment at 3 months. At CGI-S assessment, 15 of the 35 evaluated subjects reported at least a 1-point improvement, from 5 at baseline to 4 after 3 months of treatment. Twenty-six (65%) remained on treatment at 1-year follow-up. The main reasons for those discontinuing treatment were inadequate response (10%) and manic switch (7.5%), while one subject refused treatment. Tolerability to treatment was good, and 36 subjects (90%) reported no adverse events specific to vortioxetine treatment.Conclusion:Schizophrenia is a complex illness, and there is insufficient treatment response in many individuals. A significant proportion of whom may require adjunctive treatments depending on the nature of the residual symptoms. Vortioxetine could be a potentially safe and effective option in such people, but further controlled studies are required.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-07-06T06:25:39Z
DOI: 10.1177/20451253221110014
Issue No: Vol. 12 (2022)
- Agomelatine for the treatment of generalized anxiety disorder: focus on
its distinctive mechanism of action
Authors: Mark J. Millan
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
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-HT2C receptor antagonist, yet recognizing neither monoamine transporters nor GABAA receptors. Extensive evidence supports a role for 5-HT2C 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-HT2C 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.Plain Language SummaryHow agomelatine helps in the treatment of anxiety disordersIntroduction:• 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.Methods:• The authors reviewed studies on how agomelatine treats anxiety in animals.• They also looked at clinical studies on the effects of agomelatine in people with GAD.Results:• The study showed that agomelatine ‘blocks’ a receptor in nerve cells, which plays a role in causing anxiety, called the 5-HT2C receptor.• Blocking this receptor, especially in specific brain regions such as nerve cells of the amygdala, bed nucleus of stria terminalis, and hippocampus, produced the anxiety reduction seen during agomelatine treatment.• Agomelatine also activates the melatonin (MT) receptor, which is known to keep anxiety in check, promote sleep, and maintain the sleep cycle.• Agomelatine should thus tackle sleep disturbances commonly seen in patients with GAD.• Beyond 5-HT2C and MT receptors, signalling molecules in nerve cells that are known to be involved in anxiety disorders (called ‘neurotransmitters’ and ‘neuropeptides’) are also affected by agomelatine.Conclusion:• Agomelatine’s anxiolytic effects are caused by mechanisms that are distinct from those of other medications currently used to treat GAD.• This explains its therapeutic success and minimal adverse side effects.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-06-30T10:48:10Z
DOI: 10.1177/20451253221105128
Issue No: Vol. 12 (2022)
- Effects of antipsychotics on heart rate in treatment of schizophrenia: a
systematic review and meta-analysis
Authors: Maximilian Huhn, Thomas Arndt, Johannes Schneider-Thoma, Stefan Leucht
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Background: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.Objective:We aimed to analyse changes in heart rate during treatment with antipsychotics using the frequency of tachycardia and bradycardia events.Design: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.Data Sources and Methods: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.Results: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 [N = 37, n = 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 versus haloperidol RR = 2.87, chlorpromazine versus thiothixene RR = 2.92, quetiapine versus lurasidone RR = 3.22, risperidone versus aripiprazole RR = 4.37, iloperidone versus ziprasidone RR = 4.65).Conclusion: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.Registration:PROSPERO: CRD42014014919
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-06-24T09:46:56Z
DOI: 10.1177/20451253221097261
Issue No: Vol. 12 (2022)
- Duration of prior psychotic illness and clozapine response: a
retrospective observational study using electronic health records
Authors: Rowena Jones, Rachel Upthegrove, Malcolm J. Price, Megan Pritchard, Joht Singh Chandan, Sophie Legge, James H. MacCabe
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Background:Clozapine is the gold-standard medication for treatment-resistant schizophrenia (TRS) yet its initiation is often delayed.Objective:To examine whether earlier initiation of clozapine in TRS is associated with lower Clinical Global Impression – Severity (CGI-S) scores at 2 years.Methods:This was a retrospective cohort study from electronic health records of patients with first adequate trial of clozapine at the South London and Maudsley mental health service between 1 January 2007 and 31 December 2016. Dates of illness onset and clozapine commencement were manually extracted from anonymised case notes. CGI-S scores were rated blind to illness duration. Ordinal logistic regression was used to describe the association between illness duration at baseline and CGI-S outcome score at 2 years, following adjustment for CGI-S start score and other key covariates.Results:Among the 401 patients included, there was an association between illness duration and CGI-S outcome score with a 4% increase in the odds of a higher (worse) outcome CGI-S score per year of illness [adjusted odds ratio (AOR) = 1.04; 95% confidence interval (CI): 1.01–1.06]. The association between illness duration and clozapine response was most marked at less than 4 years illness duration. There were too few clozapine initiations within the first 2 years of illness to draw any conclusions about early clozapine initiation.Conclusion:Initiation of clozapine within 2–4 years of psychotic illness onset offers the best outcome for TRS, but the advantage, if any, of earlier initiation is unclear from these data.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-06-20T01:49:47Z
DOI: 10.1177/20451253221103353
Issue No: Vol. 12 (2022)
- Estimation of cardiac QTc intervals in people prescribed antipsychotics: a
comparison of correction factors
Authors: Teodora Andric, Karl Winckel, Timothy David Tanzer, Samantha Hollingworth, Lesley Smith, Katherine Isoardi, Olivier Tan, Dan Siskind
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Background: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.Objective:We aimed to investigate the mean QTc and proportion of prolonged QTc intervals in people taking antipsychotic medicines.Methods: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 versus 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.Results:Of 920 included people, the mean (±SD) machine-measured, Bazett-corrected QT interval (recorded from the ECG) was 435 ms (±27), significantly longer (p
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-06-17T06:17:33Z
DOI: 10.1177/20451253221104947
Issue No: Vol. 12 (2022)
- Clozapine blood level assessment using a point-of-care device: feasibility
and reliability
Authors: Shiri Kamhi-Nesher, Sharon Taub, Shikma Halimi, Maria Frenkel, Mahmud Azam, Gil Bormant, Helena Isakov, Dikla Radzinsky, Abraham Weizman, Amir Krivoy
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Background: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.Objective:To assess the feasibility and reliability of a new point-of-care device, (MyCare™ Insite), using capillary blood for clozapine therapeutic monitoring.Methods: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.Results: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 R2 = 0.83 (p
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-06-14T08:57:27Z
DOI: 10.1177/20451253221094435
Issue No: Vol. 12 (2022)
- Treatment strategies for clozapine-induced hypotension: a systematic
review
Authors: Timothy David Tanzer, Thomas Brouard, Samuel Dal Pra, Nicola Warren, Michael Barras, Steve Kisely, Emily Brooks, Dan Siskind
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Background:Clozapine is the most effective medication for treatment–refractory schizophrenia but is associated with significant adverse drug effects, including hypotension and dizziness, which have a negative impact on quality of life and treatment compliance. Available evidence for the management of clozapine-induced hypotension is scant.Objectives:Due to limited guidance on the safety and efficacy of pharmacological treatments for clozapine-induced hypotension, we set out to systematically review and assess the evidence for the management of clozapine-induced hypotension and provide guidance to clinicians, patients, and carers.Design:We undertook a systematic review of the safety and efficacy of interventions for clozapine-induced hypotension given the limited available evidence.Data Sources and Methods:PubMed, Embase, PsycINFO, CINAHL, and the Cochrane trial Registry were searched from inception to November 2021 for literature on the treatment strategies for clozapine-induced hypotension and dizziness using a PROSPERO pre-registered search strategy. For orthostatic hypotension, we developed a management framework to assist in the choice of intervention.Results:We identified nine case studies and four case series describing interventions in 15 patients. Hypotension interventions included temporary clozapine dose reduction, non-pharmacological treatments, and pharmacological treatments. Midodrine, fludrocortisone, moclobemide and Bovril® combination, and etilefrine were associated with improvement in symptoms or reduction in orthostatic hypotension. Angiotensin II, arginine vasopressin, and noradrenaline successfully restored and maintained mean arterial pressure in critical care situations. A paradoxical reaction of severe hypotension was reported with adrenaline use.Conclusion:Orthostatic hypotension is a common side effect during clozapine titration. Following an assessment of the titration schedule, salt and fluid intake, and review of hypertensive and nonselective α1-adrenergic agents, first-line treatment should be a temporary reduction in clozapine dose or non-pharmacological interventions. If orthostatic hypotension persists, fludrocortisone should be trialled with monitoring of potassium levels and sodium and fluid intake. Midodrine may be considered second-line or where fludrocortisone is contraindicated or poorly tolerated. For patients on clozapine with hypotension in critical care settings, the use of adrenaline to maintain mean arterial pressure should be avoided.Registration:PROSPERO (Registration No. CRD42020191530)
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-05-25T06:44:37Z
DOI: 10.1177/20451253221092931
Issue No: Vol. 12 (2022)
- The efficacy of antipsychotics in the treatment of physical aggressive
behavior in patients with dementia in nursing homes
Authors: Sina Nawzad, Wiepke Cahn, Heshu Abdullah-Koolmees
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Patients with dementia often suffer from behavioral changes. A common behavioral change is acute physical aggressive behavior which is the most distressing change. This can lead to harm, which is especially problematic in nursing homes. Despite the serious safety concerns, antipsychotics are often prescribed to combat this problem. This article is aimed to review the evidence of the efficacy of utilizing antipsychotics in acutely treating physical aggressive behavior in patients with dementia in nursing homes. Therefore, a systematic literature search was performed. The results demonstrated that a meta-analysis confirmed statistically significant reduction in physical aggression when risperidone was compared to placebo. However, a randomized controlled trial showed no change in physical aggressive behavior between quetiapine and placebo. More research is needed to fully investigate the benefits of physical aggressive behavior and safety concerns of all the antipsychotics in patients with dementia in nursing homes.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-05-16T07:00:09Z
DOI: 10.1177/20451253221097452
Issue No: Vol. 12 (2022)
- Gut microbiome in schizophrenia and antipsychotic-induced metabolic
alterations: a scoping review
Authors: Raghunath Singh, Nicolette Stogios, Emily Smith, Jiwon Lee, Kateryna Maksyutynsk, Emily Au, David C. Wright, Giada De Palma, Ariel Graff-Guerrero, Philip Gerretsen, Daniel J. Müller, Gary Remington, Margaret Hahn, Sri Mahavir Agarwal
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Schizophrenia (SCZ) is a severe mental disorder with high morbidity and lifetime disability rates. Patients with SCZ have a higher risk of developing metabolic comorbidities such as obesity and diabetes mellitus, leading to increased mortality. Antipsychotics (APs), which are the mainstay in the treatment of SCZ, increase the risk of these metabolic perturbations. Despite extensive research, the mechanism underlying SCZ pathophysiology and associated metabolic comorbidities remains unclear. In recent years, gut microbiota (GMB) has been regarded as a ‘chamber of secrets’, particularly in the context of severe mental illnesses such as SCZ, depression, and bipolar disorder. In this scoping review, we aimed to investigate the underlying role of GMB in the pathophysiology of SCZ and metabolic alterations associated with APs. Furthermore, we also explored the therapeutic benefits of prebiotic and probiotic formulations in managing SCZ and AP-induced metabolic alterations. A systematic literature search yielded 46 studies from both preclinical and clinical settings that met inclusion criteria for qualitative synthesis. Preliminary evidence from preclinical and clinical studies indicates that GMB composition changes are associated with SCZ pathogenesis and AP-induced metabolic perturbations. Fecal microbiota transplantation from SCZ patients to mice has been shown to induce SCZ-like behavioral phenotypes, further supporting the plausible role of GMB in SCZ pathogenesis. This scoping review recapitulates the preclinical and clinical evidence suggesting the role of GMB in SCZ symptomatology and metabolic adverse effects associated with APs. Moreover, this scoping review also discusses the therapeutic potentials of prebiotic/probiotic formulations in improving SCZ symptoms and attenuating metabolic alterations related to APs.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-05-16T06:58:48Z
DOI: 10.1177/20451253221096525
Issue No: Vol. 12 (2022)
- Risperidone-induced neuroleptic malignant syndrome: a case report
Authors: Ling Deng, Zhi-Xin Qiu, Mao-Yun Wang
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Neuroleptic malignant syndrome (NMS) is a rare illness that results from reactions to antipsychotics. However, the diagnosis of NMS is challenging due to its atypical clinical presentation and unclear pathogenesis. We report the case of a patient with NMS induced by irregular use of antipsychotics, especially risperidone (RSP). He had typical hyperthermia, muscle rigidity and rhabdomyolysis, which led to renal impairment. We carefully analysed the mechanism by which NMS occurred in this patient. An interesting aspect of the case is the synergistic involvement of risperidone, antidepressants, opioids and stress. Because of these complex predisposing factors, it is difficult to completely rule out the diagnosis of malignant hyperthermia (MH). In addition, the rare phenomenon of elevated lipase and amylase was observed in this patient.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-05-14T08:40:12Z
DOI: 10.1177/20451253221094960
Issue No: Vol. 12 (2022)
- Population pharmacokinetic model and limited sampling strategy for
clozapine using plasma and dried blood spot samples
Authors: Lisanne M. Geers, Dan Cohen, Laura M. Wehkamp, Hans J. van Wattum, Jos G.W. Kosterink, Anton J.M. Loonen, Daan J. Touw
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Background:To improve efficacy, therapeutic drug monitoring is often used in clozapine therapy. Trough level monitoring is regular, but trough levels provide limited information about the pharmacokinetics of clozapine and exposure in time. The area under the concentration time curve (AUC) is generally valued as better marker of drug exposure in time but calculating AUC needs multiple sampling. An alternative approach is a limited sampling scheme in combination with a population pharmacokinetic model meant for Bayesian forecasting. Furthermore, multiple venepunctions can be a burden for the patient, whereas collecting samples by means of dried blood spot (DBS) sampling can facilitate AUC-monitoring, making it more patient friendly.Objective:Development of a population pharmacokinetic model and limited sampling strategy for estimating AUC0-12h (a twice-daily dosage regimen) and AUC0-24h (a once-daily dosage regimen) of clozapine, using a combination of results from venepunctions and DBS sampling.Method:From 15 schizophrenia patients, plasma and DBS samples were obtained before administration and 2, 4, 6, and 8 h after clozapine intake. MwPharm® pharmacokinetic software was used to parameterize a population pharmacokinetic model and calculate limited sampling schemes.Results:A three-point sampling strategy with samples at 2, 6, and 8 h after clozapine intake gave the best estimation of the clozapine AUC0-12h and at 4, 10, and 11 h for the AUC0-24h. For clinical practice, however, a two-point sampling strategy with sampling points at 2 and 6 h was sufficient to estimate AUC0-12h and at 4 and 11 h for AUC0-24h.Conclusion:A pharmacokinetic model with a two–time point limited sampling strategy meant for Bayesian forecasting using DBS sampling gives a better prediction of the clozapine exposure in time, expressed as AUC, compared to trough level monitoring. This limited sampling strategy might therefore provide a more accurate prediction of effectiveness and occurrence of side effects compared to trough level monitoring. The use of DBS samples also makes the collection of clozapine samples easier and wider applicable.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-05-02T02:24:19Z
DOI: 10.1177/20451253211065857
Issue No: Vol. 12 (2022)
- 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
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Background:Data from case series suggest that clozapine may benefit inpatients with borderline personality disorder (BPD), but randomised trials have not been conducted.Methods: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.Results: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.Interpretation: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.Trial registrationISRCTN18352058. https://doi.org/10.1186/ISRCTN18352058
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-04-30T04:21:08Z
DOI: 10.1177/20451253221090832
Issue No: Vol. 12 (2022)
- Analysis of the clinical characteristics of olanzapine-induced acute
pancreatitis
Authors: Yang He, Weijin Fang, Zuojun Li, Linli Sun, Yulu Zhou, Cuifang Wu, Wei Sun, Chunjiang Wang
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Numerous case reports of acute pancreatitis (AP) induced by olanzapine have been published. Little is, however, known about the clinical features of olanzapine-induced AP. The aim of the study was to explore the clinical characteristics of olanzapine-induced AP. We collected literature on AP cases induced by olanzapine from 1996 to April 2021 for retrospective analysis in Chinese and English. The median time to onset of olanzapine-induced acute pancreatic symptoms was 12 (range = 0.86–216) weeks in 25 patients. The clinical features of AP range from asymptomatic elevation of blood amylase/lipase levels to digestive system symptoms (abdominal pain, vomiting, and nausea) and even death in a small number of patients. Laboratory tests showed varying degrees of elevated serum amylase and lipase levels, along with high blood sugar and high triglyceride levels in some patients. Computed tomography showed acute edematous pancreatitis, acute hemorrhagic pancreatitis, and acute necrotizing pancreatitis in the patients. The patients’ symptoms were completely relieved and high triglyceride levels gradually returned to normal levels after olanzapine was stopped. Some patients with hyperglycemia still needed hypoglycemic therapy. AP is a rare adverse effect of olanzapine. Clinicians should be aware of such complications and monitor pancreatin.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-04-30T04:19:09Z
DOI: 10.1177/20451253221079971
Issue No: Vol. 12 (2022)
- Experiences with benzodiazepine use, tapering, and discontinuation: an
Internet survey
Authors: Alistair J. Reid Finlayson, Jane Macoubrie, Christy Huff, Darren E. Foster, Peter R. Martin
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Background:Over 92 million prescriptions for benzodiazepines are dispensed in the United States annually, yet little is known about the experiences of those taking and discontinuing them.Objective:The aim of this study is to assess the experiences of those taking, tapering, or having discontinued benzodiazepines.Methods:An online survey (n = 1207) elicited information about benzodiazepine use, including long-term use, tapering, discontinuation, and withdrawal symptoms.Results:Symptoms associated with benzodiazepine use, tapering, and discontinuation were numerous and ranged from symptoms such as anxiety, insomnia, and nervousness to digestive problems, irregular heart rhythms, uncontrollable anger, photosensitivity, balance problems, and others. When asked how benzodiazepine symptoms affected their lives, 82.9% reported work problems, 86.3% had problems with social interactions and friendships, and 88.8% had problems with fun, recreation, and hobbies. Suicidal thoughts or attempted suicide was reported by 54.4%, and 46.8% said benzodiazepines caused lost employment. Most of the respondents for whom benzodiazepines were prescribed (76.2%) stated they had not been informed that benzodiazepines were indicated for short-term use only and that discontinuation might be difficult. About a third (31.5%) reported food allergies and/or seasonal allergies that occurred only after benzodiazepine use.Conclusion:The trajectory of those who taper or discontinue benzodiazepines is unpredictable, and many patients experience a range of protracted and severe symptoms, even years after benzodiazepines were completely discontinued. Greater awareness is needed for both prescribers and patients about the potential for a difficult withdrawal from benzodiazepines.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-04-25T07:19:16Z
DOI: 10.1177/20451253221082386
Issue No: Vol. 12 (2022)
- Will psilocybin lose its magic in the clinical setting'
Authors: Caroline Hayes, Mourad Wahba, Stuart Watson
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
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.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-04-23T06:51:01Z
DOI: 10.1177/20451253221090822
Issue No: Vol. 12 (2022)
- Time to rehospitalization in involuntarily hospitalized individuals
suffering from schizophrenia discharged on long-acting injectable
antipsychotics or oral antipsychotics
Authors: Ching-Hua Lin, Hung-Yu Chan, Fu-Chiang Wang, Chun-Chi Hsu
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
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
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-03-23T09:59:40Z
DOI: 10.1177/20451253221079165
Issue No: Vol. 12 (2022)
- Clozapine- and non-clozapine-associated neutropenia in patients with
schizophrenia: a retrospective cohort study
Authors: Claas-Frederik Johannsen, Tonny Studsgaard Petersen, Jimmi Nielsen, Anders Jørgensen, Espen Jimenez-Solem, Anders Fink-Jensen
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Introduction:The antipsychotic drug clozapine remains underutilized partly because of the risk of life-threatening adverse effects, such as neutropenia. Therefore, an extensive hematological monitoring program was set up to detect neutropenia.Methods:In this retrospective cohort study, we used registry-based data from the Capital Region of Denmark to investigate incidence rates of neutropenia among patients with a diagnosis of schizophrenia or other psychotic disorders and treated with clozapine for the first time. In a within-subject design, we compared rates of neutropenia in time periods where patients were exposed to clozapine versus time periods, where they were not exposed to clozapine. We also investigated whether the lengths of clozapine-associated neutropenia (CAN) were related to discontinuation of clozapine treatment.Results:Data from 520 clozapine users were included. The incidence rate of CAN was 3.2 cases per 100 person-years (95% confidence interval [CI]: 2.1–4.8) throughout the entire study. There was no significant difference in incidence rates of neutropenia during clozapine exposure and non-clozapine exposure, with an incidence rate ratio of 0.7 (95% CI: 0.4–1.3). One episode of severe neutropenia was detected. Episodes of CAN with only one sub-threshold neutrophil count were not associated with higher clozapine discontinuation (26%) than CAN episodes of more than one sub-threshold neutrophil count (28%).Conclusion:In the present study, we could not confirm that clozapine treatment was associated with neutropenia.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-03-05T09:16:35Z
DOI: 10.1177/20451253211072341
Issue No: Vol. 12 (2022)
- Can the use of long-acting injectable antipsychotic preparations be
increased in routine clinical practice and the benefits realised'
Authors: Carol Paton, Chike I. Okocha, Maxine X. Patel
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Background:The use of continuing antipsychotic medication is an established evidence-based strategy for preventing relapse in people with schizophrenia, but medication adherence is known to be suboptimal. Covert non-adherence can be eliminated by the use of long-acting injectable (LAI) formulations. We sought to (1) raise awareness among clinicians of the potential benefits of LAI antipsychotic formulations, (2) increase use of these formulations for the treatment of schizophrenia in routine clinical practice and thereby (3) reduce the number of relapses requiring hospitalisation in patients with schizophrenia under our care.Method:Educational initiatives, promotion of reflective practice and patient-specific reminders were used to prompt increased use of LAI antipsychotic medication for patients with schizophrenia. Data relating to the use of these medications and the number of acute admissions for schizophrenia spectrum disorders (F20-29, ICD-10) over time were extracted from existing clinical information systems.Results:Over the 3-year time frame of our local initiative, the use of LAI antipsychotic preparations increased by 11%, the number of acute admissions for schizophrenia/schizoaffective disorder (F20 and F25) decreased by 26% and the number of acute bed days occupied by patients with these diagnoses decreased by 8%. The number of admissions for other psychosis diagnoses (F21-24 and F28-29) did not show the same pattern of improvement.Conclusion:In our health care organisation, raising clinicians’ awareness of the evidence base relating to the potentially favourable benefit–risk balance for LAI antipsychotic medication compared with oral formulations resulted in more use of the former. There were accompanying reductions in acute admissions and occupied bed days for patients with schizophrenia.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-02-15T08:02:44Z
DOI: 10.1177/20451253211072347
Issue No: Vol. 12 (2022)
- Clinical practice guideline recommendations on tapering and discontinuing
antidepressants for depression: a systematic review
Authors: Anders Sørensen, Karsten Juhl Jørgensen, Klaus Munkholm
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Background:Tapering and discontinuing antidepressants are important aspects of the management of patients with depression and should therefore be considered in clinical practice guidelines.Objectives: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.Methods: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.Results: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.Conclusion: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.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-02-11T10:36:58Z
DOI: 10.1177/20451253211067656
Issue No: Vol. 12 (2022)
- 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, Marco Pereira, George Aldersley, Tim Sales, Jed Hewitt, Ray Lyon, Richard Whale
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Introduction:Pipotiazine palmitate depot injection (Piportil) was withdrawn from the UK marketplace in 2015. Few studies exist on the clinical impact of such market withdrawal. Purpose: 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.Methods: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.Results: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.Conclusions: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.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-01-31T04:40:05Z
DOI: 10.1177/20451253211067042
Issue No: Vol. 12 (2022)
- Clozapine augmentation with cariprazine for negative symptoms: a case
series and literature review
Authors: Ebenezer Oloyede, Ivana Clark, Shubhra Mace, Eromona Whiskey, David Taylor
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Only about 50% of patients with treatment-resistant schizophrenia respond to clozapine, and many more patients continue to experience ongoing and prominent negative symptoms. These negative symptoms, for which there are limited pharmacological options, may represent the greatest barrier to functional recovery. Cariprazine is a novel antipsychotic drug that is a partial agonist at dopamine D2 and D3 receptors with preferential binding to the D3 receptor, antagonism of 5HT2B receptors, and partial agonism at 5HT1A receptors. Cariprazine is currently licenced for the treatment of schizophrenia in Europe and the United States and has also been approved for bipolar disorder in the United States. There is a limited body of evidence to suggest clinical effectiveness as an augmentation strategy for negative symptoms in those treated with clozapine. In this case series, we present five cases of successful treatment of negative symptoms by clozapine combined with cariprazine in treatment-resistant psychosis.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-01-28T12:21:33Z
DOI: 10.1177/20451253211066642
Issue No: Vol. 12 (2022)
- Brugada syndrome: should we be screening patients before prescribing
psychotropic medication'
Authors: Azizah Attard, Claire Stanniland, Stephen Attard, Andrew Iles, Kim Rajappan
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Brugada syndrome (BrS) presents with a characteristic electrocardiogram (ECG) and is associated with sudden cardiac death. Until now, prolongation of QTc interval and its association with Torsade de Pointe and possible fatal arrhythmia have been the focus of routine baseline ECGs before prescribing psychotropic medication. A semi-systematic literature review was conducted using PubMed. The terms ‘Brugada’, ‘Brugada Syndrome’ AND ‘psychotropic’ ‘antipsychotic’ ‘antidepressant’ ‘mood stabilisers’ ‘clozapine’ ‘Tricyclic Antidepressants’ ‘Lithium’ were searched. From a search that delivered over 200 articles, 82 articles were included. Those that included details around causative medication, doses of medication and where clear timeline on drug cause were included. Where clarification was needed, the manufacturer of the medication was contacted directly. Psychotropic medication can be associated with BrS, Brugada phenocopy or unmasking of BrS, in overdose or in normal doses. Our results include a table summarising a number of psychotropic overdoses that led to BrS unmasking. Routine screening for BrS in patients before prescribing psychotropic medication is a natural extension of the baseline ECG currently routinely done to rule out QTc prolongation. Psychiatrists need to invest in ensuring better skills in interpreting ECGs and work closer with cardiologists in interpreting ECGs.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-01-28T10:16:12Z
DOI: 10.1177/20451253211067017
Issue No: Vol. 12 (2022)
- Advances in pharmacotherapy for postpartum depression: a structured review
of standard-of-care antidepressants and novel neuroactive steroid
antidepressants
Authors: Yardana Kaufman, Sara V. Carlini, Kristina M. Deligiannidis
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Postpartum depression is one of the most common morbidities of childbearing, yet it is underdiagnosed and undertreated with negative consequences for mother and offspring. Despite the widespread use of standard-of-care antidepressants as the mainstay of treatment for postpartum depression, there is limited evidence on their safety and efficacy due to their slow onset of action and suboptimal outcomes. The emergence of gamma-aminobutyric acidergic neuroactive steroids may offer faster response and remission times and improved patient outcomes. This article reviews the evidence base for the efficacy of standard-of-care antidepressants, hormonal therapeutics including progestins and estradiol, and gamma-aminobutyric acidergic neuroactive steroids in the treatment of postpartum depression, as well as the safety of infant exposure to these agents during lactation.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-01-28T10:14:32Z
DOI: 10.1177/20451253211065859
Issue No: Vol. 12 (2022)
- Identifying dopamine supersensitivity through a randomized controlled
study of switching to aripiprazole from other antipsychotic agents in
patients with schizophrenia
Authors: Chia-Hao Ma, Hung-Yu Chan, Ming H. Hsieh, Chen-Chung Liu, Chih-Min Liu, Hai-Gwo Hwu, Ching-Hua Kuo, Wei J. Chen, Tzung-Jeng Hwang
Abstract: Therapeutic Advances in Psychopharmacology, Volume 12, Issue , January-December 2022.
Background:Aripiprazole has been reported to worsen psychotic symptoms when switching from other antipsychotics, possibly due to dopamine supersensitivity psychosis.Objective:This study aimed to explore the predictors and possible underlying mechanisms of aripiprazole-related psychotic exacerbation.Methods: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.Results: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, p = 0.007) and was associated with prescription of first-generation antipsychotics (p = 0.038).Conclusions: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.Trial Registration:ClinicalTrials.gov, identifier: NCT00545467
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2022-01-28T10:12:46Z
DOI: 10.1177/20451253211064396
Issue No: Vol. 12 (2022)
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