 Subjects -> PHARMACY AND PHARMACOLOGY (Total: 575 journals)
| A B C D E F G H I J K L M N O P Q R S T U V W X Y Z | | The end of the list has been reached or no journals were found for your choice. |
|
|
- Implementing gradual, hyperbolic tapering of long-acting injectable
antipsychotics by prolonging the inter-dose interval: an in silico
modelling study
Authors: James R. O’Neill, David M. Taylor, Mark A. Horowitz
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Gradual, hyperbolic tapering has been proposed as a method to reduce the risk of withdrawal effects and potential relapse of an underlying condition by minimising disruption of existing equilibria. We applied hyperbolic tapering principles in silico to long-acting aripiprazole to generate regimens for withdrawal in clinical practice. We derived thresholds for taper rates using existing studies and consensus. Using pharmacokinetic data for aripiprazole long-acting injectable antipsychotic (ALAI), we conducted in silico modelling to examine the impact of abrupt cessation of long-acting injectable antipsychotic (LAI) medication and the effect of prolonging inter-dose interval on plasma aripiprazole levels and consequent D2 occupancy. We also modelled transitions from LAI medication to oral medication. Regimens were designed to afford a rate of reduction between 5 and 12.5 percentage points of D2 occupancy per month. Abrupt discontinuation of ALAI was shown to lead to a maximal D2 occupancy reduction of 16.8 percentage points per month; prolongation of the inter-dose interval of ALAI produced a slower reduction. Specifically, hyperbolic tapering was afforded by prolongation of a 400 mg ALAI inter-dose interval from 4 to 7 weeks, before reducing the dose to 300 mg ALAI. This could then be administered at up to 4-week (for 6% maximal D2 occupancy change), 6-week (9% change) or 7-week (11% change) intervals. Switching to oral medication – 5, 2.5 and 1.25 mg for the three regimens, respectively – is required for ALAI to complete full cessation to prevent too rapid a reduction in D2 occupancy. Oral medication should probably be maintained at a consistent dose for 3–6 months before further reductions to account for residual LAI being concurrently eliminated. Hyperbolic dose tapering is possible with ALAI through prolongation of the inter-dose interval and may reduce the risk of relapse compared to abrupt discontinuation of LAI medication.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-09-13T12:42:31Z
DOI: 10.1177/20451253231198463
Issue No: Vol. 13 (2023)
- The past, present and future of anticholinergic drugs
Authors: David Healy
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
In current medical practice, it is difficult to find any reports claiming that drugs that are primarily anticholinergic or those that have significant anticholinergic effects have any therapeutic benefits. These drugs fell into disrepute within the mental health field from the mid-1960s onwards, and their supposed problems extended to elsewhere in medicine after that. There is considerable evidence that this disrepute stemmed more from marketing copy rather than from hard clinical trial data. Many apparent reviews appear to repeat prior claims rather than present substantial or new evidence. This article offers a perspective rather than a systematic review as there is little evidence other than claims to review. The aim is to challenge the conventional narrative that anticholinergic effects are uniquely hazardous by pointing to the uncertain basis for claims about the harms of anticholinergic drugs, antimuscarinic drugs in particular, ending with pointers to recent research that, if realized, might underpin important possible future benefits.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-09-09T05:44:32Z
DOI: 10.1177/20451253231176375
Issue No: Vol. 13 (2023)
- Anticholinergic action is rarely a good thing
Authors: Delia Bishara
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
The evidence for the risks associated with anticholinergic agents has grown considerably in the last two decades. Not only are they associated with causing peripheral side effects such as dry mouth, blurred vision and constipation, but they can also cause central effects such as cognitive impairment; and more recently, they have consistently been linked with an increased risk of dementia and death in older people. This paper reviews the evidence for the associations of anticholinergic agents and the risk of dementia and increased mortality in dementia.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-09-09T05:43:32Z
DOI: 10.1177/20451253231195264
Issue No: Vol. 13 (2023)
- Preventing and treating delirium in clinical settings for older adults
Authors: Morgan Faeder, Elizabeth Hale, Daniel Hedayati, Alex Israel, Darcy Moschenross, Melanie Peterson, Ryan Peterson, Mariel Piechowicz, Jonathan Punzi, Priya Gopalan
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Delirium is a serious consequence of many acute or worsening chronic medical conditions, a side effect of medications, and a precipitant of worsening functional and cognitive status in older adults. It is a syndrome characterized by fluctuations in cognition and impaired attention that develops over a short period of time in response to an underlying medical condition, a substance (prescribed, over the counter, or recreational), or substance withdrawal and can be multi-factorial. We present a narrative review of the literature on nonpharmacologic and pharmacologic approaches to prevention and treatment of delirium with a focus on older adults as a vulnerable population. Older adult patients are most at risk due to decreasing physiologic reserves, with delirium rates of up to 80% in critical care settings. Presentation of delirium can be hyperactive, hypoactive, or mixed, making identification and study challenging as patients with hypoactive delirium are less likely to come to attention in an inpatient or long-term care setting. Studies of delirium focus on prevention and treatment with nonpharmacological or medication interventions, with the preponderance of evidence favoring multi-component nonpharmacological approaches to prevention as the most effective. Though use of antipsychotic medication in delirium is common, existing evidence does not support routine use, showing no clear benefit in clinically significant outcome measures and with evidence of harm in some studies. We therefore suggest that antipsychotics be used to treat agitation, psychosis, and distress associated with delirium at the lowest effective doses and shortest possible duration and not be considered a treatment of delirium itself. Future studies may clarify the use of other agents, such as melatonin and melatonin receptor agonists, alpha-2 receptor agonists, and anti-epileptics.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-09-09T05:38:22Z
DOI: 10.1177/20451253231198462
Issue No: Vol. 13 (2023)
- Antipsychotics and structural brain changes: could treatment adherence
explain the discrepant findings'
Authors: Robin Emsley
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Progressive structural brain changes are well documented in schizophrenia and have been linked to both illness progression and the extent of antipsychotic treatment exposure. Literature reporting longitudinal changes in brain structure in individuals with schizophrenia is selectively reviewed to assess the roles of illness, antipsychotic treatment, adherence and other factors in the genesis of these changes. This narrative review considers literature investigating longitudinal changes in brain structure in individuals with schizophrenia. The review focusses on structural changes in the cortex, basal ganglia and white matter. It also examines effects of medication non-adherence and relapse on the clinical course of the illness and on structural brain changes. Studies investigating structural magnetic resonance imaging changes in patients treated with long-acting injectable antipsychotics are reviewed. Temporal changes in brain structure in schizophrenia can be divided into those that are associated with antipsychotic treatment and those that are not. Changes associated with treatment include increases in basal ganglia and white matter volumes. Relapse episodes may be a critical factor in illness progression and brain volume reductions. Medication adherence may be an important factor that could explain the findings that brain volume reductions are associated with poor treatment response, higher intensity of antipsychotic treatment exposure and more time spent in relapse. Improved adherence via long-acting injectable antipsychotics and adherence focussed psychosocial interventions could maximize protective effects of antipsychotics against illness progression.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-09-09T05:27:53Z
DOI: 10.1177/20451253231195258
Issue No: Vol. 13 (2023)
- Managing medical and psychiatric multimorbidity in older patients
Authors: David M. Carlson, Brandon C. Yarns
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Aging increases susceptibility both to psychiatric and medical disorders through a variety of processes ranging from biochemical to pharmacologic to societal. Interactions between aging-related brain changes, emotional and psychological symptoms, and social factors contribute to multimorbidity – the presence of two or more chronic conditions in an individual – which requires a more patient-centered, holistic approach than used in traditional single-disease treatment guidelines. Optimal treatment of older adults with psychiatric and medical multimorbidity necessitates an appreciation and understanding of the links between biological, psychological, and social factors – including trauma and racism – that underlie physical and psychiatric multimorbidity in older adults, all of which are the topic of this review.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-08-30T09:04:44Z
DOI: 10.1177/20451253231195274
Issue No: Vol. 13 (2023)
- Altered whole-brain resting-state functional connectivity and brain
network topology in typhoon-related post-traumatic stress disorder
Authors: Hui Juan Chen, Jun Ke, Jie Qiu, Qiang Xu, Yuan Zhong, Guang Ming Lu, Yanglei Wu, Rongfeng Qi, Feng Chen
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Background:Altered resting-state functional connectivity has been found in patients with post-traumatic stress disorder (PTSD). However, the alteration of resting-state functional connectivity at whole-brain level in typhoon-traumatized individuals with PTSD remains largely unknown.Objectives:To investigate changes in whole-brain resting-state functional connectivity and brain network topology in typhoon-traumatized subjects with and without PTSD.Design:Cross-sectional study.Methods:Twenty-seven patients with typhoon-related PTSD, 33 trauma-exposed controls (TEC), and 30 healthy controls (HC) underwent resting-state functional MRI scanning. The whole brain resting-state functional connectivity network was constructed based on the automated anatomical labeling atlas. The graph theory method was used to analyze the topological properties of the large-scale resting-state functional connectivity network. Whole-brain resting-state functional connectivity and the topological network property were compared by analyzing the variance.Results:There was no significant difference in the area under the curve of γ, λ, σ, global efficiency, and local efficiency among the three groups. The PTSD group showed increased dorsal cingulate cortex (dACC) resting-state functional connectivity with the postcentral gyrus (PoCG) and paracentral lobe and increased nodal betweenness centrality in the precuneus relative to both control groups. Compared with the PTSD and HC groups, the TEC group showed increased resting-state functional connectivity between the hippocampus and PoCG and increased connectivity strength in the putamen. In addition, compared with the HC group, both the PTSD and TEC groups showed increased connectivity strength and nodal efficiency in the insula.Conclusion:Aberrant resting-state functional connectivity and topology were found in all trauma-exposed individuals. These findings broaden our knowledge of the neuropathological mechanisms of PTSD.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-06-17T12:11:13Z
DOI: 10.1177/20451253231175302
Issue No: Vol. 13 (2023)
- The psychedelic afterglow phenomenon: a systematic review of subacute
effects of classic serotonergic psychedelics
Authors: Ricarda Evens, Marianna Elisa Schmidt, Tomislav Majić, Timo Torsten Schmidt
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Background:Classic serotonergic psychedelics have anecdotally been reported to show a characteristic pattern of subacute effects that persist after the acute effects of the substance have subsided. These transient effects, sometimes labeled as the ‘psychedelic afterglow’, have been suggested to be associated with enhanced effectiveness of psychotherapeutic interventions in the subacute period.Objectives:This systematic review provides an overview of subacute effects of psychedelics.Methods:Electronic databases (MEDLINE, Web of Science Core Collection) were searched for studies that assessed the effects of psychedelics (LSD, psilocybin, DMT, 5-MeO-DMT, mescaline, or ayahuasca) on psychological outcome measures and subacute adverse effects in human adults between 1950 and August 2021, occurring between 1 day and 1 month after drug use.Results:Forty-eight studies including a total number of 1,774 participants were eligible for review. Taken together, the following subacute effects were observed: reductions in different psychopathological symptoms; increases in wellbeing, mood, mindfulness, social measures, spirituality, and positive behavioral changes; mixed changes in personality/values/attitudes, and creativity/flexibility. Subacute adverse effects comprised a wide range of complaints, including headaches, sleep disturbances, and individual cases of increased psychological distress.Discussion:Results support narrative reports of a subacute psychedelic ‘afterglow’ phenomenon comprising potentially beneficial changes in the perception of self, others, and the environment. Subacute adverse events were mild to severe, and no serious adverse events were reported. Many studies, however, lacked a standardized assessment of adverse effects. Future studies are needed to investigate the role of possible moderator variables and to reveal if and how positive effects from the subacute window may consolidate into long-term mental health benefits.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-05-30T06:52:41Z
DOI: 10.1177/20451253231172254
Issue No: Vol. 13 (2023)
- Safety and tolerability of intramuscular and sublingual ketamine for
psychiatric treatment in the Roots To Thrive ketamine-assisted therapy
program: a retrospective chart review
Authors: Vivian W.L. Tsang, Brendan Tao, Shannon Dames, Zach Walsh, Pam Kryskow
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Background:In the last few years, ketamine is becoming increasingly common in the treatment of mental health conditions, but there is a lack of safety data informing intramuscular and sublingual dosing in a community-focused group psychotherapy setting. The Roots To Thrive ketamine-assisted therapy (RTT-KaT) program is a unique 12-week RTT-KaT program with 12 community of practice (a form of group therapy) sessions and three ketamine medicine sessions.Objectives:This study reports on adverse effects of intramuscular and sublingual ketamine dosing in a community group psychotherapy setting among 128 participants across four cohorts.Design:Retrospective chart review.Methods:A chart review of the RTT-KaT Program was performed retrospectively on four cohorts (n = 128) that participated in 448 sessions running between September 2020 and December 2021. Baseline characteristics and adverse events were captured including medication administration before, during, and after RTT-KaT sessions. Analyses by session and by individual were conducted. Chi-square test with Yates’ continuity correction was used to assess side effects in subgroups from ketamine administration.Results:RTT-KaT was well tolerated with none of the 128 participants dropping out of the program. Primarily, of the 448 sessions, 49.16% had elevated blood pressures post-KaT session by session. In terms of other adverse effects, 12.05% of participant-sessions experienced nausea, 2.52% had an episode of vomiting, 3.35% had a headache, and seven participant-sessions experienced dizziness. Analysis by individual revealed congruent findings.Conclusion:These findings suggest good safety and tolerability for RTT-KaT among individuals seeking treatment for mental health issues. The majority of participants did not experience adverse reactions and the adverse events that were recorded involved transient symptoms that were resolved with rest and/or medications. The group therapy model described provides a comprehensive approach and presents a promising model for operating a KaT program in a community setting.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-05-25T10:50:39Z
DOI: 10.1177/20451253231171512
Issue No: Vol. 13 (2023)
- High-dose olanzapine in treatment-resistant schizophrenia: a systematic
review
Authors: Louisa Gannon, John Reynolds, Martin Mahon, Fiona Gaughran, John Lally
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Background:Treatment-resistant schizophrenia (TRS) affects approximately 30% of people with schizophrenia. Clozapine is the gold standard treatment for TRS but is not always suitable, with a proportion of individuals intolerant of side effects or unable to engage in necessary blood monitoring. Given the profound impact TRS can have on those affected, alternative pharmacological approaches to care are needed.Objectives:To review the literature on the efficacy and tolerability of high-dose olanzapine (>20 mg daily) in adults with TRS.Design:This is a systematic review.Data Sources and Methods:We searched for eligible trials published prior to April 2022 in PubMed/MEDLINE, Scopus and Google Scholar. Ten studies met the inclusion criteria [five randomised controlled trials (RCTs), one randomised crossover trial and four open label studies]. Data were extracted for predefined primary outcomes (efficacy, tolerability).Results:Compared with standard treatment, high-dose olanzapine was non-inferior in four RCTs, three of which used clozapine as the comparator. Clozapine was superior to high-dose olanzapine in a double-blind crossover trial. Open-label studies demonstrated tentative evidence in support of high-dose olanzapine use. It was better tolerated than clozapine and chlorpromazine in two respective RCTs, and was generally well tolerated in open-label studies.Conclusion:This evidence suggests high-dose olanzapine is superior for TRS when compared with other commonly used first- and second-generation antipsychotics, including haloperidol and risperidone. In comparison with clozapine, the data are encouraging for the use of high-dose olanzapine where clozapine use is problematic, but larger, better designed trials are needed to assess the comparative efficacy of both treatments. There is insufficient evidence to consider high-dose olanzapine equivalent to clozapine when clozapine is not contraindicated. Overall, high-dose olanzapine was well tolerated, with no serious side effects.Registration:This systematic review was preregistered with PROSPERO [CRD42022312817].
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-05-11T07:03:21Z
DOI: 10.1177/20451253231168788
Issue No: Vol. 13 (2023)
- Outcomes of hyperbolic tapering of antidepressants
Authors: Jim van Os, Peter C. Groot
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Background:In patients attempting to discontinue their antidepressant medication, there have been no prospective studies on patterns of withdrawal as a function of the rate of antidepressant reduction during the tapering trajectory, and moderators thereof.Objective:To investigate withdrawal as a function of gradual dose reduction.Design:Prospective cohort study.Methods:The sampling frame consisted of 3956 individuals in the Netherlands who received an antidepressant tapering strip between 19 May 2019 and 22 March 2022 in routine clinical practice. Of these, 608 patients, majorly with previous unsuccessful attempts to stop, provided daily ratings of withdrawal in the context of reducing their antidepressant medications (mostly venlafaxine or paroxetine), using hyperbolic tapering strips offering daily tiny reductions in dose.Results:Withdrawal in daily-step hyperbolic tapering trajectories was limited, and inverse to the rate of taper. Female sex, younger age, presence of one or more risk factors and faster rate of reduction over shorter tapering trajectories were associated with more withdrawal and differential course over time. Thus, sex and age differences were less marked early in the course of the trajectory, whereas differences associated with risk factors and shorter trajectories tended to peak early in the trajectory. There was evidence that tapering in weekly larger steps (mean per-week dose reduction: 33.4% of previous dose), in comparison with daily tiny steps (mean per-day dose reduction: 4.5% of previous dose or 25.3% per week), was associated with more withdrawal in trajectories of 1, 2 or 3 months, particularly for paroxetine and the group of other (non-paroxetine, non-venlafaxine) antidepressants.Conclusion:Antidepressant hyperbolic tapering is associated with limited, rate-dependent withdrawal that is inverse to the rate of taper. The demonstration of multiple demographic, risk and complex temporal moderators in time series of withdrawal data indicates that antidepressant tapering in clinical practice requires a personalised process of shared decision making over the entire course of the tapering period.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-05-10T05:57:03Z
DOI: 10.1177/20451253231171518
Issue No: Vol. 13 (2023)
- Semaglutide for the treatment of antipsychotic-associated weight gain in
patients not responding to metformin – a case series
Authors: Femin Prasad, Riddhita De, Vittal Korann, Araba F. Chintoh, Gary Remington, Bjørn H. Ebdrup, Dan Siskind, Filip Krag Knop, Tina Vilsbøll, Anders Fink-Jensen, Margaret K. Hahn, Sri Mahavir Agarwal
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Metformin is the currently accepted first-line treatment for antipsychotic-associated weight gain (AAWG). However, not all patients benefit from metformin. Glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown promise in the management of obesity in the general population, with preliminary evidence supporting efficacy in AAWG. Semaglutide is a weekly injectable GLP-1RA which received recent approval for obesity management and noted superiority over other GLP-1RAs. This study explored the efficacy and tolerability of semaglutide in AAWG among individuals with severe mental illness. A retrospective chart review of patients treated with semaglutide in the Metabolic Clinic at the Center for Addiction and Mental Health (CAMH) between 2019 and 2021 was conducted. Patients failing a trial of metformin (
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-04-19T10:00:49Z
DOI: 10.1177/20451253231165169
Issue No: Vol. 13 (2023)
- Long-acting injectable antipsychotics for the treatment of bipolar
disorder: evidence from mirror-image studies
Authors: Francesco Bartoli, Daniele Cavaleri, Christian Nasti, Dario Palpella, Pierluca Guzzi, Ilaria Riboldi, Cristina Crocamo, Sofia Pappa, Giuseppe Carrà
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Clinical trials and real-world data have shown that long-acting injectable antipsychotics (LAIs) might be an effective therapeutic option also for people with bipolar disorder (BD). However, complementing evidence from mirror-image studies investigating LAIs in BD is scattered and has not been systematically evaluated so far. We thus performed a review of observational mirror-image studies testing the effectiveness of LAI treatment on clinical outcomes in people with BD. Embase, MEDLINE, and PsycInfo electronic databases were systematically searched (via Ovid) up to November 2022. We included six mirror-image studies that compared relevant clinical outcomes between the 12-months after (post-treatment period) and the 12-months before (pre-treatment period) the initiation of a LAI treatment in adults with BD. We found that LAI treatment is associated with a significant reduction in days spent in hospital and number of hospitalizations. Moreover, LAI treatment seems to be associated with a significant decrease in the proportion of individuals with at least one hospital admission, even though data on this outcome were reported by just two studies. In addition, studies consistently estimated a significant reduction of hypo-/manic relapses after LAI treatment initiation, while the effect of LAIs for depressive episodes is less clear. Finally, LAI treatment initiation was associated with a lower number of emergency department visits in the year after LAI initiation. The findings of this review seem to suggest that the use of LAIs is an effective strategy to improve major clinical outcomes in people with BD. Nonetheless, additional research, based on standardized assessments of prevalent polarity and relapses, is needed to identify the clinical characteristics of individuals with BD who are most likely to benefit from a LAI treatment.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-03-25T12:37:45Z
DOI: 10.1177/20451253231163682
Issue No: Vol. 13 (2023)
- Second to none: rationale, timing, and clinical management of clozapine
use in schizophrenia
Authors: Mishal Qubad, Robert A. Bittner
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Despite its enduring relevance as the single most effective and important evidence-based treatment for schizophrenia, underutilization of clozapine remains considerable. To a substantial degree, this is attributable to a reluctance of psychiatrists to offer clozapine due to its relatively large side-effect burden and the complexity of its use. This underscores the necessity for continued education regarding both the vital nature and the intricacies of clozapine treatment. This narrative review summarizes all clinically relevant areas of evidence, which support clozapine’s wide-ranging superior efficacy – for treatment-resistant schizophrenia (TRS) and beyond – and make its safe use eminently feasible. Converging evidence indicates that TRS constitutes a distinct albeit heterogeneous subgroup of schizophrenias primarily responsive to clozapine. Most importantly, the predominantly early onset of treatment resistance and the considerable decline in response rates associated with its delayed initiation make clozapine an essential treatment option throughout the course of illness, beginning with the first psychotic episode. To maximize patients’ benefits, systematic early recognition efforts based on stringent use of TRS criteria, a timely offer of clozapine, thorough side-effect screening and management as well as consistent use of therapeutic drug monitoring and established augmentation strategies for suboptimal responders are crucial. To minimize permanent all-cause discontinuation, re-challenges after neutropenia or myocarditis should be considered. Owing to clozapine’s unique efficacy, comorbid conditions including substance use and most somatic disorders should not dissuade but rather encourage clinicians to consider clozapine. Moreover, treatment decisions need to be informed by the late onset of clozapine’s full effects, which for reduced suicidality and mortality rates may not even be readily apparent. Overall, the singular extent of its efficacy combined with the high level of patient satisfaction continues to distinguish clozapine from all other available antipsychotics.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-03-25T12:35:16Z
DOI: 10.1177/20451253231158152
Issue No: Vol. 13 (2023)
- The role of flumazenil in generalised anxiety disorder: a pilot
naturalistic open-label study with a focus on treatment resistance
Authors: Alexander T Gallo, Stephen Addis, Vlad Martyn, Hishani Ramanathan, Grace K Wilkerson, Kellie S Bennett, Sean D Hood, Hans Stampfer, Gary K Hulse
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Background:Anxiety disorders are highly prevalent and chronic disorders with treatment resistance to current pharmacotherapies occurring in approximately one in three patients. It has been postulated that flumazenil (FMZ) is efficacious in the management of anxiety disorders via the removal of α4β2δ gamma-aminobutyric acid A receptors.Objective:To assess the safety and feasibility of continuous low-dose FMZ infusions for the management of generalised anxiety disorder (GAD) and collect preliminary efficacy data.Design:Uncontrolled, open-label pilot study.Method:Participants had a primary diagnosis of generalised anxiety disorder (GAD) and received two consecutive subcutaneous continuous low-dose FMZ infusions. Each infusion contained 16 mg of FMZ and was delivered over 96 ± 19.2 h. The total dose of FMZ delivered was 32 mg over approximately 8 days. Sodium valproate was given to participants at risk of seizure. The primary outcome was the change in stress and anxiety subscale scores on the Depression Anxiety Stress Scale–21 between baseline, day 8, and day 28.Results:Nine participants with a primary diagnosis of GAD were treated with subcutaneous continuous low-dose FMZ infusions; seven participants met the criteria for treatment resistance. There was a significant decrease in anxiety and stress between baseline and day 8 and baseline and day 28. There was also a significant improvement in subjective sleep quality from baseline to day 28 measured by the Jenkins Sleep Scale. No serious adverse events occurred.Conclusion:This study presents preliminary results for subcutaneous continuous low-dose FMZ’s effectiveness and safety in GAD. The findings suggest that it is a safe, well-tolerated, and feasible treatment option in this group of patients. Future randomised control trials are needed in this field to determine the efficacy of this treatment.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-03-15T01:27:24Z
DOI: 10.1177/20451253231156400
Issue No: Vol. 13 (2023)
- The place of long-acting injectable antipsychotics in the treatment of
schizophrenia
Authors: John M. Kane, Jose M. Rubio
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-03-06T09:34:24Z
DOI: 10.1177/20451253231157219
Issue No: Vol. 13 (2023)
- The potential of ketamine for posttraumatic stress disorder: a review of
clinical evidence
Authors: Anya Ragnhildstveit, Jeremy Roscoe, Lisa C. Bass, Christopher L. Averill, Chadi G. Abdallah, Lynnette A. Averill
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Posttraumatic stress disorder (PTSD) is a devastating condition, for which there are few pharmacological agents, often with a delayed onset of action and poor efficacy. Trauma-focused psychotherapies are further limited by few trained providers and low patient engagement. This frequently results in disease chronicity as well as psychiatric and medical comorbidity, with considerable negative impact on quality of life. As such, off-label interventions are commonly used for PTSD, particularly in chronic refractory cases. Ketamine, an N-methyl-D-aspartate (NDMA) receptor antagonist, has recently been indicated for major depression, exhibiting rapid and robust antidepressant effects. It also shows transdiagnostic potential for an array of psychiatric disorders. Here, we synthesize clinical evidence on ketamine in PTSD, spanning case reports, chart reviews, open-label studies, and randomized trials. Overall, there is high heterogeneity in clinical presentation and pharmacological approach, yet encouraging signals of therapeutic safety, efficacy, and durability. Avenues for future research are discussed.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-03-06T08:42:00Z
DOI: 10.1177/20451253231154125
Issue No: Vol. 13 (2023)
- Olanzapine for the treatment of ICU delirium: a systematic review and
meta-analysis
Authors: Si Bo Liu, Shan Liu, Kai Gao, Guo Zhi Wu, Guo Zu, Jin Jie Liu
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Background:As an atypical antipsychotic drug, olanzapine is one of the most commonly used drugs for delirium control. There are no systematic evaluations or meta-analyses of the efficacy and safety of olanzapine for delirium control in critically ill adults.Objectives:In this meta-analysis, we evaluated the efficacy and safety of olanzapine for delirium control in critically ill adults in the intensive care unit (ICU).Data Sources and Methods:From inception to October 2022, 12 electronic databases were searched. We retrieved randomized controlled trials (RCTs) and retrospective cohort studies of critically ill adults with delirium that compared the effects of olanzapine and other interventions, including routine care (no intervention), nonpharmaceutical interventions and pharmaceutical interventions. The main outcome measures were the (a) relief of delirium symptoms and (b) a decrease in delirium duration. Secondary outcomes were ICU and in-hospital mortality, ICU and hospital length of stay, incidence of adverse events, cognitive function, sleep quality, quality of life, mechanical ventilation time, endotracheal intubation rate and delirium recurrence rate. We applied a random effects model.Results:Data from 10 studies (four RCTs and six retrospective cohort studies) involving 7076 patients (2459 in the olanzapine group and 4617 in the control group) were included. Olanzapine did not effectively relieve delirium symptoms (OR = 1.36, 95% CI [0.83, 2.28], p = 0.21), nor did it shorten the duration of delirium [standardized mean difference (SMD) = 0.02, 95% CI [−1.04, 1.09], p = 0.97] when compared with other interventions. Pooled data from three studies showed that the use of olanzapine reduced the incidence of hypotension (OR = 0.44, 95% CI [0.20, 0.95], p = 0.04) compared with other pharmaceuticals. There was no significant difference in other secondary outcomes, including ICU or hospital length of stay, in-hospital mortality, extrapyramidal reactions, QTc interval prolongation, or overall incidence of other adverse reactions. The number of included studies was not sufficient for performing a comparison between olanzapine and no intervention.Conclusion:Compared with other interventions, olanzapine has no advantage in alleviating delirium symptoms and shortening delirium duration in critically ill adults. However, there is some evidence that the rate of hypotension was lower in patients who received olanzapine than in those who received other pharmaceutical interventions. There was a nonsignificant difference in the length of ICU or hospital stay, in-hospital mortality, and other adverse reactions. This study provides reference data for delirium research and clinical drug intervention strategies in critically ill adults.Registration:Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42021277232).
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-02-21T07:03:41Z
DOI: 10.1177/20451253231152113
Issue No: Vol. 13 (2023)
- Serum cytokine variations among inpatients with major depression, bipolar
disorder, and schizophrenia versus healthy controls: a prospective
‘true-to-life’ study
Authors: Antonio Augusto Schmitt Junior, Lucas Primo de Carvalho Alves, Barbara Larissa Padilha, Neusa Sica da Rocha
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Background:There is increasing evidence of the association between chronic low-grade inflammation and severe mental illness (SMI). The objective of our study was to assess serum cytokine levels (SCLs) at admission and discharge in a true-to-life-setting population of inpatients with major depression (MD), bipolar disorder (BD), and schizophrenia (Sz), as well as of healthy controls.Methods:We considered MD, BD, and Sz to be SMIs. We evaluated 206 inpatients [MD, N = 92; BD, N = 26; mania (Ma), N = 44; Sz, N = 44). Generalized estimating equations were used to analyze variations in SCL [interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17] at hospital admission and discharge. Results of 100 healthy controls were compared with those of SMI patients at both time points. We evaluated patients’ improvement during in-hospital treatment in terms of general psychiatric symptoms, global clinical impression, functionality, and manic and depressive symptoms with validated scales.Results:In all, 68.9% of patients completed the study. Overall, SMI inpatients had higher SCL when compared with controls regardless of diagnosis. There was a significant decrease in Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression–Severity Scale (CGI-S) scores, and an increase in Global Assessment of Functioning (GAF) scores for all disorders evaluated (p
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-02-16T01:28:57Z
DOI: 10.1177/20451253221135463
Issue No: Vol. 13 (2023)
- Incidence of hyperthyroidism in patients with bipolar or schizoaffective
disorder with or without lithium: 21-year follow-up from the LiSIE
retrospective cohort study
Authors: Ingrid Lieber, Michael Ott, Robert Lundqvist, Mats Eliasson, Ursula Werneke
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Background:Lithium-associated hyperthyroidism is much rarer than lithium-associated hypothyroidism. Yet, it may be of substantial clinical significance for affected individuals. For instance, lithium-associated hyperthyroidism could destabilise mood, mimic manic episodes and impact physical health. Only few studies have explored incidence rates of lithium-associated hyperthyroidism. Even fewer studies have compared incidence rates according to lithium exposure history.Objectives:To determine the impact of lithium treatment on the incidence rate of hyperthyroidism in patients with bipolar or schizoaffective disorder and assess its aetiology.Design:This study is part of the LiSIE (Lithium – Study into Effects and Side Effects) retrospective cohort study.Methods:Between 1997 and 2017, patients in the Swedish region of Norrbotten with a diagnosis of bipolar or schizoaffective disorder were screened for all episodes of overt hyperthyroidism in form of thyrotoxicosis or thyroiditis. Incidence rates of episodes of hyperthyroidism per 1000 person-years (PY) were compared in relation to lithium exposure; concurrent, previous, or no exposure ever (lithium-naïve patients)Results:In 1562 patients, we identified 16 episodes of hyperthyroidism corresponding to an incidence rate of 0.88 episodes per 1000 PY. Ninety-four percent of episodes had occurred in women. Patients who had concurrently been exposed to lithium, had an incidence rate of 1.35 episodes per 1000 PY. Patients who had previously been exposed to lithium had an incidence rate of 0.79 per 1000 PY. Patients who had never been exposed to lithium had an incidence rate of 0.47 per 1000 PY. There were no significant differences in the risk ratios for patients with concurrent or previous exposure compared with lithium-naïve patients, neither for hyperthyroidism overall, thyrotoxicosis, or thyroiditis.Conclusion:Lithium-associated hyperthyroidism seems uncommon. The risk of hyperthyroidism does not seem significantly higher in patients with current or previous lithium exposure than in lithium-naïve patients.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-02-09T09:39:47Z
DOI: 10.1177/20451253231151514
Issue No: Vol. 13 (2023)
- Ketamine and esketamine in suicidal thoughts and behaviors: a systematic
review
Authors: Fabrice Jollant, Romain Colle, Thi Mai Loan Nguyen, Emmanuelle Corruble, Alain M. Gardier, Martin Walter, Mocrane Abbar, Gerd Wagner
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Background:More than 2% of the general population experience suicidal ideas each year and a large number of them will attempt suicide. Evidence-based therapeutic options to manage suicidal crisis are currently limited.Objectives:The aim of this study was to overview the findings on the use of ketamine and esketamine for the treatment of suicidal ideas and acts.Design:Systematic review.Data Sources and methods:PubMed, article references, and Clinicaltrials.gov up to June 30, 2022. Meta-analyses published within the last 2 years were also reviewed.Results:We identified 12 randomized controlled trials with reduction of suicidal ideation as the primary objective and 14 trials as secondary objectives. Intravenous racemic ketamine was superior to control drugs (placebo or midazolam) within the first 72 h, in spite of large placebo effects. Adverse events were minor and transient. In contrast, intranasal esketamine did not differ from placebo in large-scale studies. Limitations, clinical considerations, and opportunities for future research include the following points: large placebo effects when studying suicidal ideation reduction; small concerns about blinding quality due to dissociative effects; no studies on the risk/prevention of suicidal acts and mortality; lack of studies beyond affective disorders; no studies in adolescents and older people; lack of knowledge of long-term side effects, notably liability for abuse; no robust predictive markers; limited understanding of the mechanisms of ketamine on suicidal ideas; need for improved assessment of suicidal ideation in clinical trials; need for studies in outpatient settings, emergency room, and liaison consultation; need for research on ketamine administration; limited knowledge on the positive and negative effects of concomitant treatments.Conclusion:Overall, there is compelling evidence for a favorable short-term benefit-risk balance with intravenous racemic ketamine but not intranasal esketamine. The place of ketamine will have to be defined within a multimodal care strategy for suicidal patients. Caution remains necessary for clinical use, and pharmacovigilance will be essential.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-02-07T12:14:09Z
DOI: 10.1177/20451253231151327
Issue No: Vol. 13 (2023)
- Enduring neurological sequelae of benzodiazepine use: an Internet survey
Authors: Christy Huff, A. J. Reid Finlayson, D. E. Foster, Peter R. Martin
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Introduction:Benzodiazepine tapering and cessation has been associated with diverse symptom constellations of varying duration. Although described in the literature decades ago, the mechanistic underpinnings of enduring symptoms that can last months or years have not yet been elucidated.Objective:This secondary analysis of the results from an Internet survey sought to better understand the acute and protracted withdrawal symptoms associated with benzodiazepine use and discontinuation.Methods:An online survey (n = 1207) was used to gather information about benzodiazepine use, including withdrawal syndrome and protracted symptoms.Results:The mean number of withdrawal symptoms reported by a respondent in this survey was 15 out of 23 symptoms. Six percent of respondents reported having all 23 listed symptoms. A cluster of least-frequently reported symptoms (whole-body trembling, hallucinations, seizures) were also the symptoms most frequently reported as lasting only days or weeks, that is, short-duration symptoms. Symptoms of nervousness/anxiety/fear, sleep disturbances, low energy, and difficulty focusing/distractedness were experienced by the majority of respondents (⩾85%) and, along with memory loss, were the symptoms of longest duration. Prolonged symptoms of anxiety and insomnia occurred in many who have discontinued benzodiazepines, including over 50% who were not originally prescribed benzodiazepines for that indication. It remains unclear if these symptoms might be caused by neuroadaptive and/or neurotoxic changes induced by benzodiazepine exposure. In this way, benzodiazepine withdrawal may have acute and long-term symptoms attributable to different underlying mechanisms, which is the case with alcohol withdrawal.Conclusions:These findings tentatively support the notion that symptoms which are acute but transient during benzodiazepine tapering and discontinuation may be distinct in their nature and duration from the enduring symptoms experienced by many benzodiazepine users.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-02-06T10:07:27Z
DOI: 10.1177/20451253221145561
Issue No: Vol. 13 (2023)
- Tardive dyskinesia: understanding current challenges in diagnosis and
treatment
Authors: David Taylor, Koichiro Watanabe
Abstract: Therapeutic Advances in Psychopharmacology, Volume 13, Issue , January-December 2023.
Citation: Therapeutic Advances in Psychopharmacology
PubDate: 2023-01-30T11:06:32Z
DOI: 10.1177/20451253221144347
Issue No: Vol. 13 (2023)
|
Open Access journal
