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Journal of Intensive Care Medicine Dec 2023Patients experiencing significant agitation or perceptual disturbances related to delirium in an intensive care setting may benefit from short-term treatment with an... (Review)
Review
BACKGROUND
Patients experiencing significant agitation or perceptual disturbances related to delirium in an intensive care setting may benefit from short-term treatment with an antipsychotic medication. Some antipsychotic medications may prolong the QTc interval, which increases the risk of potentially fatal ventricular arrhythmias. In this targeted review, we describe the evidence regarding the relationships between antipsychotic medications and QTc prolongation and practical methods for monitoring the QTc interval and mitigating arrhythmia risk.
METHODS
Searches of PubMed and Cochrane Library were performed to identify studies, published before February 2023, investigating the relationships between antipsychotic medications and QTc prolongation or arrhythmias.
RESULTS
Most antipsychotic medications commonly used for the management of delirium symptoms (eg, intravenous haloperidol, olanzapine, quetiapine) cause a moderate degree of QTc prolongation. Among other antipsychotics, those most likely to cause QTc prolongation are iloperidone and ziprasidone, while aripiprazole and lurasidone appear to have minimal risk for QTc prolongation. Genetic vulnerabilities, female sex, older age, pre-existing cardiovascular disease, electrolyte abnormalities, and non-psychiatric medications also increase the risk of QTc prolongation. For individuals at risk of QTc prolongation, it is essential to measure the QTc interval accurately and consistently and consider medication adjustments if needed.
CONCLUSIONS
Antipsychotic medications are one of many risk factors for QTc prolongation. When managing agitation related to delirium, it is imperative to assess an individual patient's risk for QTc prolongation and to choose a medication and monitoring strategy commensurate to the risks. In intensive care settings, we recommend regular ECG monitoring, using a linear regression formula to correct for heart rate. If substantial QTc prolongation (eg, QTc > 500 msec) is present, a change in pharmacologic treatment can be considered, though a particular medication may still be warranted if the risks of discontinuation (eg, extreme agitation, removal of invasive monitoring devices) outweigh the risks of arrhythmias.
AIMS
This review aims to summarize the current literature on relationships between antipsychotic medications and QTc prolongation and to make practical clinical recommendations towards the approach of antipsychotic medication use for the management of delirium-related agitation and perceptual disturbances in intensive care settings.
PubMed: 38130132
DOI: 10.1177/08850666231222470 -
Journal of Affective Disorders Jan 2024To explore the effect of escitalopram combined with aripiprazole on cognitive function in patients with major depressive disorder (MDD), and to evaluate the clinical... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of aripiprazole on promoting cognitive function and enhancing clinical efficacy in patients with first-episode depression on escitalopram: A randomized controlled trial.
OBJECTIVES
To explore the effect of escitalopram combined with aripiprazole on cognitive function in patients with major depressive disorder (MDD), and to evaluate the clinical efficacy of the combination therapy.
METHOD
A total of 70 patients with first-episode MDD were randomly divided into the study group or the control group, receiving escitalopram combined with aripiprazole (5 mg/day) or escitalopram monotherapy respectively for 8 weeks. The severity of illness was assessed by using the Hamilton Rating Scale for Depression (HAMD) at baseline, at the end of 4 and 8 week, and cognitive function was assessed by using the THINC integrated tool (THINC-it), the Wisconsin Card Sorting Test (WCST), and the Continuous Performance Test (CPT). Rating Scale for Extrapyramidal Side Effects (RSESE) was applied to assess adverse reactions.
RESULTS
The average HAMD-17 and HAMA scores decreased over time in both the control and the study groups, but the reductions were not statistically different between two groups with the passage of time. In WCST, total number of response (TR) of the study group decreased relative to the baseline at the end of the eighth week, but the control group did not significantly change during whole eight weeks. Perseverative errors (PE) in the control group eventually decreased at the end of Week 8 compared to that at Week 4, but in the study group, it was a continuous trend of decrease. In CPT, the decrease of leakage responses (LR) in the study group was higher than that of the control group in 2-digit number, and LR of the control group was higher than that of the study group at the end of Week 8 in 4-digit number. The downtrend of LR in 4-digit number kept for the whole period in study group, while in the control group, the LR did not decrease significantly until the end of Week 8 compared to that at baseline.
CONCLUSION
Escitalopram combined with a low-dose of aripiprazole, and escitalopram monotherapy could both enhance cognitive function of MDD patients, while the improvements of combination therapy might happen relatively earlier. The combined use of escitalopram and aripiprazole might be more beneficial to the domains of executive function (EF) and continuous attention compared to escitalopram monotherapy. There was no significant differences between two treatment options in alleviating depressive and anxiety symptoms.
Topics: Humans; Aripiprazole; Escitalopram; Antidepressive Agents; Depressive Disorder, Major; Depression; Treatment Outcome; Cognition; Citalopram; Double-Blind Method
PubMed: 37827257
DOI: 10.1016/j.jad.2023.10.038 -
International Journal of Psychiatry in... Mar 2024Anhedonia is a common symptom of depression, but is also a negative symptom of schizophrenia. The purpose of this study was to examine the effects of vortioxetine on... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Anhedonia is a common symptom of depression, but is also a negative symptom of schizophrenia. The purpose of this study was to examine the effects of vortioxetine on anhedonia in patients with schizophrenia.
METHODS
A total of 120 patients with schizophrenia in remission who met inclusion criteria were randomized 1:1 by the envelope method into intervention and control groups. All participants in both groups were divided into three subgroups based on the antipsychotic therapy they were receiving (olanzapine, risperidone, or aripiprazole). Vortioxetine was administered to those in the intervention group at a fixed dose of 10 mg per day. The Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), and Chapman Scale for Social and Physical Anhedonia (CSPA) were administered. The study lasted 12 weeks. Participants were assessed twice: At baseline and at the end of the study. Six participants dropped out, with 114 completing the trial.
FINDINGS
Vortioxetine treatment had a significant effect on level of physical anhedonia. The treatment interaction was also statistically significant, but with a relatively small effect (F = 3.17, < .05; η2 = .061). Vortioxetine treatment had a particularly strong effect on the level of social anhedonia. The interaction between the treatment and the type of antipsychotics was also statistically significant with a small effect (F = 5.04, < 0. 01; η2 = .091).
CONCLUSION
The combination of olanzapine and vortioxetine was found to be the best option to reduce symptoms of social and physical anhedonia in these patients with remitted schizophrenia.
Topics: Humans; Schizophrenia; Olanzapine; Anhedonia; Vortioxetine; Antipsychotic Agents; Benzodiazepines
PubMed: 37647498
DOI: 10.1177/00912174231199925 -
Expert Opinion on Pharmacotherapy 2023Agitation is commonly encountered in people with bipolar disorder, particularly when experiencing a manic episode. The number of approved pharmacological agents to... (Review)
Review
INTRODUCTION
Agitation is commonly encountered in people with bipolar disorder, particularly when experiencing a manic episode. The number of approved pharmacological agents to manage acute episodes of agitation in this population is limited.
AREAS COVERED
A search was conducted using the US National Library of Medicine PubMed.gov resource for English-language papers of clinical trials and reviews/meta-analyses, using the text words 'bipolar disorder' AND 'agitation,' as well as any papers with both two text words in the title, without any date restrictions.
EXPERT OPINION
Existing pharmacologic options approved by regulatory authorities for the treatment of acute episodes of agitation associated with bipolar disorder have similar degrees of efficacy but differ in their tolerability profiles and ease of use, giving clinicians an opportunity to individualize treatment. The goal is to treat mild-moderate agitation before it evolves into severe agitation, encouraging noninvasive pharmacologic treatment options. Inhaled loxapine and sublingual dexmedetomidine are newer options with rapid onset of action and may be preferable for patients willing to cooperate with treatment.
Topics: Humans; Bipolar Disorder; Antipsychotic Agents; Psychomotor Agitation; Loxapine; Administration, Inhalation
PubMed: 37581475
DOI: 10.1080/14656566.2023.2248893 -
Towards precision medicine of long-acting aripiprazole through population pharmacokinetic modelling.Psychiatry Research Mar 2024Population pharmacokinetic (popPK) models constitute a valuable tool for characterizing the pharmacokinetic properties of once-monthly long-acting injectable...
Population pharmacokinetic (popPK) models constitute a valuable tool for characterizing the pharmacokinetic properties of once-monthly long-acting injectable aripiprazole (LAI aripiprazole) and quantifying the sources of variability in drug exposure. Our aim is to develop a popPK model of both aripiprazole and its metabolite dehydro-aripiprazole in patients treated with LAI aripiprazole, and to personalize the dosing regimen of aripiprazole across different sub-groups of patients. This is a prospective study investigating the pharmacokinetics of LAI aripiprazole. A total of 93 patients were included, 21 for model development and 71 for external model evaluation. A one-compartment model with linear absorption and elimination adequately described both aripiprazole and dehydro-aripiprazole concentrations. The weight of the patients has been shown to be the factor that most influences the absorption. However, the metabolizing phenotype for CYP2D6 and the concomitant treatment with strong inhibitors of this cytochrome have been shown to be the covariates that most influence total drug exposure. This is the first popPK model developed for LAI aripiprazole that includes aripiprazole and its main active metabolite, dehydroaripiprazole. It provides a personalized dosage recommendation that maximizes the probability of achieving optimal therapeutic concentrations and minimizes the difficulties associated with trial-and-error therapeutic strategies carried out in clinical practice.
Topics: Humans; Aripiprazole; Antipsychotic Agents; Precision Medicine; Prospective Studies; Cytochrome P-450 CYP2D6
PubMed: 38245977
DOI: 10.1016/j.psychres.2024.115721 -
Progress in Neuro-psychopharmacology &... Dec 2023Dopamine type 2 receptors (DRs) constitute the main molecular target in the pharmacotherapy of schizophrenia. However, the second and third generation of antipsychotics...
Dopamine type 2 receptors (DRs) constitute the main molecular target in the pharmacotherapy of schizophrenia. However, the second and third generation of antipsychotics comprises multi-target ligands, also binding serotonin type 3 receptors (5-HTRs) and other receptor classes as well. Here, we examined two experimental compounds (marked compound K1697 and K1700) from the group of 1,4-di-substituted aromatic piperazines, previously described in the study of Juza et al., 2021, and compared them with the chosen reference antipsychotic, aripiprazole. Their efficacy against schizophrenia-like behavior was tested in two different models of psychosis in the rat, induced by acute administration of either amphetamine (1.5 mg/kg) or dizocilpine (0.1 mg/kg), reflecting the dopaminergic and glutamatergic hypotheses of schizophrenia. The two models exhibited broadly similar behavioral manifestations: hyperlocomotion, disrupted social behavior and impaired prepulse inhibition of the startle response. However, they differed in their treatment responses as hyperlocomotion and prepulse inhibition deficit in the dizocilpine model were resistant to antipsychotic treatment, unlike the amphetamine model. One of the experimental compounds, K1700, ameliorated all the observed schizophrenia-like behaviors in the amphetamine model with an efficacy comparable to or greater than aripiprazole. Whereas social impairments caused by dizocilpine were strongly suppressed by aripiprazole, K1700 was less efficient. Taken together, K1700 showed antipsychotic properties comparable to those of aripiprazole, although the efficacy of the two drugs differed in specific domains of behavior and was also model-dependent. Our present results highlight the differences in these two schizophrenia models and their responsiveness to pharmacotherapy, and confirm compound K1700 as a promising drug candidate.
Topics: Male; Animals; Rats; Rats, Wistar; Dopamine; Glutamic Acid; Disease Models, Animal; Aripiprazole; Receptors, Serotonin, 5-HT3; Piperazines; Antipsychotic Agents; Schizophrenia; Receptors, Dopamine D2; Dopamine D2 Receptor Antagonists; Amphetamine; Dizocilpine Maleate
PubMed: 37379895
DOI: 10.1016/j.pnpbp.2023.110819 -
The FEBS Journal Dec 2023Preclinical and clinical studies have shown that the antipsychotic drug aripiprazole and the antioxidant N-acetylcysteine have unique biological properties. The aim of...
Treatment with aripiprazole and N-acetylcysteine affects anaerobic cysteine metabolism in the hippocampus and reverses schizophrenia-like behavior in the neurodevelopmental rat model of schizophrenia.
Preclinical and clinical studies have shown that the antipsychotic drug aripiprazole and the antioxidant N-acetylcysteine have unique biological properties. The aim of the study was to investigate, in a rat model of schizophrenia, the effects of chronic administration of these drugs on schizophrenia-like behaviors and anaerobic cysteine metabolism in the hippocampus (HIP). The schizophrenia-type changes were induced in Sprague-Dawley rats by repeated administration of the glutathione synthesis inhibitor l-butionine-(S,R)-sulfoximine in combination with the dopamine reuptake inhibitor GBR 12909 in the early postnatal period. Adult model rats were chronically treated with aripiprazole (0.3 mg·kg , i.p.) or N-acetylcysteine (30 mg·kg , orally), and their effects on schizophrenia-like behaviors were assessed using the social interaction test and novel object recognition test. In the HIP, the level of anaerobic cysteine metabolites, H S, and bound sulfane sulfur were determined by a fluorescence method, while the expression of H S-synthetizing enzymes: cystathionine β-synthase (CBS) and mercaptopyruvate sulfurtransferase (MST) by western blot. Long-term treatment with aripiprazole or N-acetylcysteine reversed social and cognitive deficits and reduced the exploratory behaviors. In the HIP of 16-day-old model pups, H S levels and MST protein expression were significantly decreased. In adult model rats, H S levels remained unchanged, bound sulfane sulfur significantly increased, and the expression of CBS and MST slightly decreased. The studied drugs significantly reduced the level of bound sulfane sulfur and the expression of tested enzymes. The reduction in bound sulfane sulfur level coincided with the attenuation of exploratory behavior, suggesting that modulation of anaerobic cysteine metabolism in the HIP may have therapeutic potential in schizophrenia.
Topics: Rats; Animals; Acetylcysteine; Cysteine; Aripiprazole; Schizophrenia; Anaerobiosis; Rats, Sprague-Dawley; Sulfur; Hippocampus
PubMed: 37646112
DOI: 10.1111/febs.16944 -
Cureus Nov 2023Many antipsychotic (AP) medications work by reducing dopamine levels. As hyperdopaminergia is known to cause psychosis, antipsychotics work to relieve these symptoms by... (Review)
Review
Many antipsychotic (AP) medications work by reducing dopamine levels. As hyperdopaminergia is known to cause psychosis, antipsychotics work to relieve these symptoms by antagonizing dopamine receptors and lowering dopamine levels. Dopamine is also a known negative modulator of the prolactin pathway, which allows for drug agents like dopamine agonists (DAs) to be incredibly effective in managing tumors that secrete excess prolactin (prolactinomas). While the effects of DAs on prolactinoma size and growth have been studied for decades, the effects of APs on prolactinoma size remain to be seen. We hope to investigate the effects of APs on prolactinomas by conducting a thorough PubMed search, including patients with diagnosed prolactinoma on concurrent AP therapy. Our search led to 27 studies with a total of 32 patients. We identified themes regarding seven antipsychotics: risperidone, haloperidol, amisulpride, thioridazine, aripiprazole, olanzapine, and clozapine. Risperidone, haloperidol, amisulpride, and thioridazine caused a significant increase in prolactin in most cases where they were used, and prolactin decreased after their discontinuation. For example, risperidone discontinuation resulted in a decrease in prolactin levels by an average of 66%, while haloperidol, amisulpride, and thioridazine discontinuation lowered prolactin by an average of 82%, 72%, and 89.7%, respectively. However, there were some exceptions in regard to risperidone, haloperidol, and thioridazine, where prolactin levels were not as severely affected. Aripiprazole, olanzapine, and clozapine all had significant reductions in prolactin levels when patients were switched from another antipsychotic, such as risperidone or haloperidol. The average percent decrease in prolactin when switched to aripiprazole was 67.65%, while it was 54.16% and 68% for olanzapine and clozapine, respectively. The effect of individual antipsychotics on prolactinoma size was difficult to ascertain, as imaging was not obtained (or indicated) after every antipsychotic switch, and many patients were taking dopamine agonists concurrently. Therefore, it would be difficult to ascertain which factor affected size more. Also, some patients received surgery or radiotherapy, which completely negated our ability to make any assertions about the effects of certain pharmacological agents. Although it is difficult to ascertain the role that antipsychotic medications play in the formation of prolactinoma, we have found that the cessation of certain antipsychotic medications may lead to a reduction in prolactin levels and possibly the presence of a measurable prolactinoma.
PubMed: 38143631
DOI: 10.7759/cureus.49342 -
International Clinical... Jan 2024The development of atypical antipsychotics has evolved to include newer pharmacodynamic properties. Lumateperone, aripiprazole, brexpiprazole, and cariprazine are all... (Review)
Review
The development of atypical antipsychotics has evolved to include newer pharmacodynamic properties. Lumateperone, aripiprazole, brexpiprazole, and cariprazine are all dopamine-2 receptor partial agonists with varying receptor affinities. This review aims to compare the clinical and pharmacodynamic differences among these four atypical antipsychotics, all of which are unique when compared to first- and second-generation antipsychotics. For consideration is further delineating these agents as being third-generation antipsychotics. PubMed searches were conducted to compile preclinical and clinical studies derived from animal models and human subjects. Information gathered included pharmacological mechanisms, clinical efficacy, future-oriented clinical approaches, and adverse effects. Efficacy for the shared indications of these drugs seems comparable. Differences among these drugs lie more in their adverse effect profiles. For example, lumateperone was found to have the lowest rate of weight gain while brexpiprazole was found to have the highest rate of weight gain associated with increased appetite. Aripiprazole had the lowest rates of extrapyramidal symptoms not including akathisia while cariprazine had the highest. All four agents reviewed have a variety of receptor affinities, which likely generates a variety of different adverse effects. This suggests that in any given patient, clinicians may see differential clinical effects.
Topics: Animals; Humans; Antipsychotic Agents; Aripiprazole; Schizophrenia; Dopamine Agonists; Weight Gain
PubMed: 37781859
DOI: 10.1097/YIC.0000000000000510 -
General Hospital Psychiatry 2023Drug use is prevalent in patients with schizophrenia spectrum disorders (SSD) but there is limited knowledge about the influence of drug use on the effectiveness of... (Randomized Controlled Trial)
Randomized Controlled Trial
Does drug use affect the efficacy of amisulpride, aripiprazole and olanzapine in patients with schizophrenia spectrum disorders? Results from a pragmatic, randomised study.
OBJECTIVES
Drug use is prevalent in patients with schizophrenia spectrum disorders (SSD) but there is limited knowledge about the influence of drug use on the effectiveness of antipsychotic medication. This secondary explorative study compared the effectiveness of three antipsychotics in patients with SSD, with and without drug use.
METHODS
The BeSt InTro multi-centre, head to head, rater-blinded randomised study compared amisulpride, aripiprazole and olanzapine over a 1-year follow-up period. All patients (n = 144) were aged ≥18 years and met the ICD-10 criteria for SSD (F20-29). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). The primary outcome was reduction of a PANSS positive subscale score.
RESULTS
At baseline, 38% of all patients reported drug use in the last 6 months before inclusion, with cannabis as the main drug (85%), followed by amphetamine-type stimulants (45%), sedatives (26%), hallucinogens (19%), cocaine (13%), opiates (4%), GHB (4%), solvents (4%), analgesics (4%) and anabolic steroids (2%). The predominant pattern was the use of several drugs. There were no significant overall differences in the PANSS positive subscale score reduction for the three studied antipsychotics among patients either with or without drug use. In the drug use group, older patients treated with amisulpride showed a greater PANSS positive subscale score reduction during the treatment period compared to younger patients.
CONCLUSION
The current study showed that drug use does not appear to affect the overall effectiveness of amisulpride, aripiprazole and olanzapine in patients with SSD. However, amisulpride may be a particularly suitable choice for older patients with drug use.
Topics: Humans; Adolescent; Adult; Olanzapine; Aripiprazole; Antipsychotic Agents; Schizophrenia; Amisulpride; Clozapine; Risperidone; Benzodiazepines; Piperazines; Thiazoles; Treatment Outcome
PubMed: 37269769
DOI: 10.1016/j.genhosppsych.2023.05.003