-
ClinicoEconomics and Outcomes Research... 2024Patients with Parkinson's disease psychosis (PDP) treated with pimavanserin (PIM) versus other atypical antipsychotics (AAPs) including quetiapine (QUE) may have...
Analysis of Medicare Patients Treated with Pimavanserin versus Other Atypical Antipsychotics: A Cost-Offset Model Evaluating Skilled Nursing Facility Stays and Long-Term Care Admissions in Parkinson's Disease Psychosis.
BACKGROUND
Patients with Parkinson's disease psychosis (PDP) treated with pimavanserin (PIM) versus other atypical antipsychotics (AAPs) including quetiapine (QUE) may have health-care cost savings due to fewer skilled nursing facility-stays (SNF-stays) and long-term care admissions (LTCA).
METHODS
A decision analytic model was developed using the 2019 Medicare Patient Driven Payment Model (PDPM) to estimate SNF-stays and LTCA associated per-patient- per-year (PPPY) facility and rehabilitation costs among patients that initiated PIM vs QUE or vs other-AAPs (i.e, quetiapine, risperidone, olanzapine, aripiprazole). Model inputs were derived for: (i) annual SNF-stay and LTCA rates from an analysis of Medicare beneficiaries with PDP, and (ii) annual mean rehabilitation and resident care-stay costs from PDPM case-mix adjusted value-based payment rates for 5 rehabilitation components (ie, physical-therapy, occupational-therapy, nursing, speech-language pathology, non-therapy ancillary), and an additional variable-per-diem for room/board services. PPPY costs were estimated from (i) SNF-stay and (ii) LTCA rates multiplied by annual mean costs of stay in 2022 USD. Probabilistic sensitivity analysis (PSA) was performed using 1000 Monte Carlo simulations.
RESULTS
Overall SNF-stay rates of 20.2%, 31.4%, and 31.7%, and LTCA rates of 23.2%, 33.8%, 34.6% were observed for PIM, QUE, and other-AAPs, respectively. Based on annual mean costs, PPPY SNF-stay rehabilitation and resident related costs for PIM ($41,808) vs QUE ($65,172) or vs other-AAPs ($65,664), resulted in $23,364 and $23,856 PPPY cost savings, respectively. Similarly, PPPY LTCA rehabilitation and resident related costs for PIM ($47,957) vs QUE ($70,091) or vs other-AAPs ($71,566) resulted in $22,134 and $23,609 PPPY cost-savings for PIM, respectively. PSA suggested PIM would provide cost-savings vs QUE or other-AAPs in >99% of iterations.
CONCLUSION
In this analysis, PIM demonstrated nearly 36% and 32% lower PPPY SNF-stays and LTCA costs, respectively, vs QUE or other-AAPs. Research examining additional cost-offsets (i.e., fewer falls/fractures) associated with SNF-stay or LTCA may be needed.
PubMed: 38495124
DOI: 10.2147/CEOR.S452162 -
Journal of Psychopharmacology (Oxford,... Apr 2024Prescribing drugs for psychosis (antipsychotics) is challenging due to high rates of poor treatment outcomes, which are in part explained by an individual's genetics....
BACKGROUND
Prescribing drugs for psychosis (antipsychotics) is challenging due to high rates of poor treatment outcomes, which are in part explained by an individual's genetics. Pharmacogenomic (PGx) testing can help clinicians tailor the choice or dose of psychosis drugs to an individual's genetics, particularly psychosis drugs with known variable response due to CYP2D6 gene variants ('CYP2D6-PGx antipsychotics').
AIMS
This study aims to investigate differences between demographic groups prescribed 'CYP2D6-PGx antipsychotics' and estimate the proportion of patients eligible for PGx testing based on current pharmacogenomics guidance.
METHODS
A cross-sectional study took place extracting data from 243 patients' medical records to explore psychosis drug prescribing, including drug transitions. Demographic data such as age, sex, ethnicity, and clinical sub-team were collected and summarised. Descriptive statistics explored the proportion of 'CYP2D6-PGx antipsychotic' prescribing and the nature of transitions. We used logistic regression analysis to investigate associations between demographic variables and prescription of 'CYP2D6-PGx antipsychotic' versus 'non-CYP2D6-PGx antipsychotic'.
RESULTS
Two-thirds (164) of patients had been prescribed a 'CYP2D6-PGx antipsychotic' (aripiprazole, risperidone, haloperidol or zuclopenthixol). Over a fifth (23%) of patients would have met the suggested criteria for PGx testing, following two psychosis drug trials. There were no statistically significant differences between age, sex, or ethnicity in the likelihood of being prescribed a 'CYP2D6-PGx antipsychotic'.
CONCLUSIONS
This study demonstrated high rates of prescribing 'CYP2D6-PGx-antipsychotics' in an EIP cohort, providing a rationale for further exploration of how PGx testing can be implemented in EIP services to personalise the prescribing of drugs for psychosis.
Topics: Humans; Antipsychotic Agents; Pharmacogenetics; Cytochrome P-450 CYP2D6; Cross-Sectional Studies; Psychotic Disorders; Psychoses, Substance-Induced
PubMed: 38494658
DOI: 10.1177/02698811241238283 -
European Neuropsychopharmacology : the... Jun 2024Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment... (Meta-Analysis)
Meta-Analysis Review
Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment of schizophrenia. We conducted a systematic review and frequentist network meta-analysis of randomized-controlled trials (RCTs), focusing on adult patients in the acute phase of schizophrenia. Interventions were risperidone, paliperidone, aripiprazole, olanzapine, and placebo, administered either orally or as LAI. We synthesized data on overall symptoms, complemented by 17 other efficacy and tolerability outcomes. Confidence in the evidence was assessed with the Confidence-in-Network-Meta-Analysis-framework (CINeMA). We included 115 RCTs with 25,550 participants. All drugs were significantly more efficacious than placebo with the following standardized mean differences and their 95 % confidence intervals: olanzapine LAI -0.66 [-1.00; -0.33], risperidone LAI -0.59[-0.73;-0.46], olanzapine oral -0.55[-0.62;-0.48], aripiprazole LAI -0.54[-0.71; -0.37], risperidone oral -0.48[-0.55;-0.41], paliperidone oral -0.47[-0.58;-0.37], paliperidone LAI -0.45[-0.57;-0.33], aripiprazole oral -0.40[-0.50; -0.31]. There were no significant efficacy differences between LAIs and oral formulations. Sensitivity analyses of the primary outcome overall symptoms largely confirmed these findings. Moreover, some side effects were less frequent under LAIs than under their oral counterparts. Confidence in the evidence was moderate for most comparisons. LAIs are efficacious for acute schizophrenia and may have some benefits compared to oral formulations in terms of side effects. These findings assist clinicians with insights to weigh the risks and benefits between oral and injectable agents when treating patients in the acute phase.
Topics: Humans; Antipsychotic Agents; Administration, Oral; Schizophrenia; Delayed-Action Preparations; Network Meta-Analysis; Randomized Controlled Trials as Topic; Injections; Treatment Outcome
PubMed: 38490016
DOI: 10.1016/j.euroneuro.2024.03.003 -
Neuropsychiatric Disease and Treatment 2024Olanzapine has already been used to treat schizophrenia patients; however, the initial dosage recommendation when multiple drugs are used in combination, remains...
OBJECTIVE
Olanzapine has already been used to treat schizophrenia patients; however, the initial dosage recommendation when multiple drugs are used in combination, remains unclear. The purpose of this study was to explore the drug-drug interaction (DDI) of multiple drugs combined with olanzapine and to recommend the optimal administration of olanzapine in schizophrenia patients.
METHODS
In this study, we obtained olanzapine concentrations from therapeutic drug monitoring (TDM) database. In addition, related medical information, such as physiological, biochemical indexes, and concomitant drugs was acquired using medical log. Sixty-five schizophrenia patients were enrollmented for analysis using population pharmacokinetic model by means of nonlinear mixed effect (NONMEM).
RESULTS
Weight and combined use of aripiprazole significantly affected olanzapine clearance. Without aripiprazole, for once-daily olanzapine administration dosages, 0.6, 0.5 mg/kg/day were recommended for 40-70, and 70-100 kg schizophrenia patients, respectively; for twice-daily olanzapine administration dosages, 0.6, 0.5 mg/kg/day were recommended for 40-60, and 60-100 kg schizophrenia patients, respectively. With aripiprazole, for once-daily olanzapine administration dosages, 0.4, 0.3 mg/kg/day were recommended for 40-53, and 53-100 kg schizophrenia patients, respectively; for twice-daily olanzapine administration dosages, 0.4 mg/kg/day was recommended for 40-100 kg schizophrenia patients, respectively.
CONCLUSION
Aripiprazole significantly affected olanzapine clearance, and when schizophrenia patients use aripiprazole, the olanzapine dosages need adjust. Meanwhile, we firstly recommended the optimal initial dosages of olanzapine in schizophrenia patients.
PubMed: 38469209
DOI: 10.2147/NDT.S455183 -
European Review For Medical and... Feb 2024Aripiprazole, risperidone, atomoxetine, and methylphenidate are drugs commonly prescribed for many psychiatric conditions and can be used alone or in combination in...
OBJECTIVE
Aripiprazole, risperidone, atomoxetine, and methylphenidate are drugs commonly prescribed for many psychiatric conditions and can be used alone or in combination in children and adolescents. This study aimed to investigate comparatively the possible genotoxic effects or genoprotective potentials of these drugs on human lymphocytes and HepG2 cells.
MATERIALS AND METHODS
Cytotoxicity analysis was performed with the cell viability test on human lymphocytes and HepG2 cells, and half-maximal inhibitory concentration (IC50) values of the drugs were determined, and three different doses (¼ IC50, ½ IC50, and IC50) were applied for genetic analysis. For the determined doses, cells with and without DNA damage were examined by comet analysis.
RESULTS
In lymphocytes, aripiprazole and risperidone increased DNA damage at moderate and maximum doses, whereas atomoxetine increased DNA damage only at the maximum dose. In HepG2 cells, risperidone reduced DNA damage at all doses, while atomoxetine increased DNA damage at all doses. On the other hand, in the DNA-damaged cells induced by hydrogen peroxide (H2O2), DNA damage decreased at all concentrations of all drugs in both lymphocytes and HepG2 cells.
CONCLUSIONS
As a result, the genotoxicity of the drugs was found to be dose-dependent, and all drugs showed a genoprotective effect on DNA-damaged cells.
Topics: Adolescent; Child; Humans; Antipsychotic Agents; Risperidone; Aripiprazole; Atomoxetine Hydrochloride; Methylphenidate; Hep G2 Cells; Hydrogen Peroxide; DNA Damage; Lymphocytes; DNA
PubMed: 38436168
DOI: 10.26355/eurrev_202402_35456 -
The Journal of Clinical Psychiatry Feb 2024Aripiprazole lauroxil (AL) 1064 mg every 2 months following initiation using the AL NanoCrystal Dispersion formulation (AL) plus 30-mg oral aripiprazole was efficacious... (Comparative Study)
Comparative Study Randomized Controlled Trial
Safety and Tolerability of Starting Aripiprazole Lauroxil With Aripiprazole Lauroxil NanoCrystal Dispersion in 1 Day Followed by Aripiprazole Lauroxil Every 2 Months Using Paliperidone Palmitate Monthly as an Active Control in Patients With Schizophrenia: A Post Hoc Analysis of a Randomized...
Aripiprazole lauroxil (AL) 1064 mg every 2 months following initiation using the AL NanoCrystal Dispersion formulation (AL) plus 30-mg oral aripiprazole was efficacious and well tolerated in a 25-week, randomized, double-blind phase 3 trial in adults with acute schizophrenia. This post hoc analysis further characterized the safety of AL 1064 mg administered every 2 months and that of active control paliperidone palmitate (PP) 156 mg monthly based on occurrence, timing, and severity of adverse events (AEs) associated with antipsychotic medications. This study was conducted between November 2017 and March 2019. AL or PP was initiated during an inpatient stay of ≥ 2 weeks with transition to outpatient treatment thereafter. Rates of AEs of clinical interest, including injection site reactions (ISRs), motor AEs, sedation, hypotension, prolactin level increase, weight gain, and suicidal ideation/behavior, were summarized through weeks 4, 9, and 25 for each treatment. Of 200 patients who received ≥ 1 dose of study treatment, 99 (49.5%) completed the study (AL, 57%; PP, 43%). Mean (SD) baseline Positive and Negative Syndrome Scale total scores were 94.1 (9.04) and 94.6 (8.41) in the AL and PP treatment groups, respectively. AEs were reported by 69/99 (70%) patients administered AL and 72/101 (71%) administered PP; most AEs were mild or moderate in severity. ISRs (AL, 18.2%; PP, 26.7%) occurred primarily on days 1 and 8. All akathisia/restlessness AEs (AL, 10.1%; PP, 11.9%) occurred during the first 4 weeks; <10% of patients (either treatment) experienced hypotension, sedation, or suicidal ideation/behavior events. Weight gain of ≥ 7% from baseline occurred in 9.3% of AL- and 23.8% of PP-treated patients. Median prolactin concentrations changed by -4.60 and -3.55 ng/mL among AL-treated males and females, respectively, and did not exceed 2 times normal levels in any AL-treated patients. In PP-treated patients, changes were 21.20 and 80.40 ng/mL and concentrations exceeded 2 times normal in 38% and 88% of males and females, respectively. No new early- or late-emerging safety concerns were observed through 25 weeks of treatment with AL 1064 mg every 2 months following initiation using AL plus 30-mg oral aripiprazole. Results were consistent with known safety profiles of AL and PP and support the safety of AL 1064 mg every 2 months initiated using AL plus 30-mg oral aripiprazole. ClinicalTrials.gov identifier: NCT03345979.
Topics: Adult; Female; Humans; Male; Antipsychotic Agents; Aripiprazole; Delayed-Action Preparations; Hypotension; Nanoparticles; Noncommunicable Diseases; Paliperidone Palmitate; Prolactin; Schizophrenia; Treatment Outcome; Weight Gain; Double-Blind Method
PubMed: 38416865
DOI: 10.4088/JCP.23m15095 -
Tongue Biting Event in Patients with Sleep-Related Facial Mandibular Myoclonus: A Case Series Study.Nature and Science of Sleep 2024Sleep-related facial mandibular myoclonus (SRFMM) remains rare in clinical practice. The aim of this study was to provide a comprehensive understanding of the...
BACKGROUND
Sleep-related facial mandibular myoclonus (SRFMM) remains rare in clinical practice. The aim of this study was to provide a comprehensive understanding of the electroclinical manner, therapeutic regimen, and prognosis of SRFMM.
METHODS
Twenty-three patients who were diagnosed with SRFMM by clinical manifestation, video-electroencephalography (EEG) and electromyography over bilateral masseter and temporalis muscles were enrolled. Clinical and electrophysiological evaluation as well as follow-up information were recorded and analyzed.
RESULTS
The cohort involved 4 infants and 19 adults with a mean onset age of 43.5 years for SRFMM, among whom 19 were male. Twenty-one patients complained of tongue injuries and disturbed night-time sleep. SRFMM in 4 patients were ascribed to oral aripiprazole, brainstem ischemia and brain trauma. In 62 SRFMM episodes, 93.5% occurred in NREM sleep and 6.5% in REM sleep, and all events were associated with EEG arousals. In 13 patients with or without clonazepam, the motor events gradually disappeared, and the rest turned to be sporadic.
CONCLUSION
SRFMM is a characteristic parasomnia manifested by tongue biting and accompanying facial mandibular myoclonus, leading to disrupted sleep. Besides adults, infants can also experience SRFMM with spontaneous remission. Most patients respond well to clonazepam, eventually with favorable prognosis.
PubMed: 38410526
DOI: 10.2147/NSS.S433628 -
Cureus Jan 2024Background Major depressive disorder (MDD) has many facets including mixed or atypical depression that requires personalized care to improve treatment-related outcomes....
Background Major depressive disorder (MDD) has many facets including mixed or atypical depression that requires personalized care to improve treatment-related outcomes. Second-generation antipsychotics (SGAs) offer complementary mechanisms for clinical roles in difficult-to-treat depression and treatment-resistant depression cases. Aim/objective To further delineate a consensus on the clinical positioning of SGAs for MDD, mixed, or atypical depression, a Knowledge Attitude Perception (KAP)-mediated Delphi Statement was planned. Material/methods A literature review for the definition, diagnosis, and management of MDD, mixed, and atypical depression as treatment-resistant depression (TRD) or difficult-to-treat depression (DTD) was conducted by a steering committee of academic and clinical experts (n=6) while developing a validated KAP questionnaire. Scientific statements as clinical recommendations were evolved using the Delphi methodology before building a clinical expert consensus with an online survey (n=24). Results Twenty-four psychiatrists highlighted DTD to offer a multidimensional approach to assess treatment strategies involving selective serotonin reuptake inhibitors (SSRIs) or SGAs, while ensuring symptom, functional, and quality of life (QoL) domain improvement for improved outcomes and remission rates. MDD cases with anxiety, anhedonia, comorbidities, and risk traits require personalized care with early induction of SGAs for severe cases or symptom persisters with functional impairment. Early augmentation with SGAs including aripiprazole or cariprazine can provide a favorable risk-benefit profile for clinical cases of MDD with or without the antecedent of mixed depression or personality disorder. Conclusion The literature review and KAP responses emphasize the importance of early identification for personalized care strategies with SGAs for DTD. Large-scale real-world evidence needs to evolve with due recognition of different phenotypes as TRD or DTD with partial or functional impairment to understand the impact of appropriate treatment pathways with SGAs.
PubMed: 38406088
DOI: 10.7759/cureus.52878 -
Cureus Jan 2024Stiff-person syndrome (SPS) is an uncommon autoimmune neurological disorder marked by painful muscle stiffness, muscle spasms, and limb weakness. Neurological symptoms...
Stiff-person syndrome (SPS) is an uncommon autoimmune neurological disorder marked by painful muscle stiffness, muscle spasms, and limb weakness. Neurological symptoms in SPS can mimic a psychogenic movement disorder in which symptoms are triggered by sudden movement and emotional distress, which might delay proper treatment. However, psychiatric symptoms are far less common, and there is limited understanding regarding the co-occurrence of psychiatric conditions. Psychiatric symptoms include nonspecific anxiety, agoraphobia, and depression, which can be triggered by sudden movement, noise, or emotional stress. This case report dives into the psychiatric manifestations seen in a patient with SPS. The case report focuses on a 42-year-old female with SPS, migraines, systemic lupus erythematosus, Sjogren's syndrome, and a psychiatric history of anorexia, depression, and anxiety. Her unique presentation underscored the necessity for a multidisciplinary approach to psychiatric care. The patient was evaluated and managed during her admission to the psychiatric unit for unspecified psychosis. Her course included a complicated medical evaluation for cardiovascular and neurologic symptoms and comprehensive psychiatric management. She manifested resistance to specific psychiatric medications and care strategies. She had atypical presentations, like sensory symptoms and left-sided chest pain. She exhibited paranoia and psychosis, which were managed with a combination of pharmacologic treatments, including aripiprazole. Psychotic symptoms were resolved upon discharge, with an emphasis on strict outpatient follow-up. This case report enhances our understanding of the clinical nuances associated with SPS and its intersection with psychiatric symptoms. The objective of this case report is to detail the diagnostic and therapeutic complexities of managing psychosis in a patient with SPS, along with a pre-existing complex medical and psychiatric profile, and to contribute to a deeper understanding of SPS and associated psychiatric conditions and more effective management strategies.
PubMed: 38406022
DOI: 10.7759/cureus.52930 -
BioRxiv : the Preprint Server For... Feb 2024Invasive fungal infections (IFIs) impose an enormous clinical, social, and economic burden on humankind. For many IFIs, ≥ 30% of patients fail therapy with existing...
Invasive fungal infections (IFIs) impose an enormous clinical, social, and economic burden on humankind. For many IFIs, ≥ 30% of patients fail therapy with existing antifungal drugs, including the widely used azole class. We previously identified a collection of 13 approved medications that antagonize azole activity. While gain-of-function mutants resulting in antifungal resistance are often associated with reduced fitness and virulence, it is currently unknown how exposure to azole antagonistic drugs impact physiology, fitness, or virulence. In this study, we examined how exposure to azole antagonists affected phenotype and capacity to cause disease. We discovered that most of the azole antagonists had little impact on fungal growth, morphology, stress tolerance, or gene transcription. However, aripiprazole had a modest impact on hyphal growth and increased cell wall chitin content. It also worsened the outcome of disseminated infections in mice at human equivalent concentrations. This effect was abrogated in immunosuppressed mice, indicating an additional impact of aripiprazole on host immunity. Collectively, these data provide proof-of-principle that unanticipated drug-fungus interactions have the potential to influence the incidence and outcomes of invasive fungal disease.
PubMed: 38405954
DOI: 10.1101/2024.02.13.580133