Dosing of valproate in an elderly population with dementia: Evaluation of discontinuations and dose reductions

2012 ◽  
Vol 1 (11) ◽  
pp. 274-276
Author(s):  
Jonathan G. Leung ◽  
Sandra Mullen
Keyword(s):  
Elderly Patients ◽  
Dose Reduction ◽  
Psychiatric Hospitalization ◽  
Psychological Symptoms ◽  
Functional Decline ◽  
Total Daily Dose ◽  
Maximum Daily Dose ◽  
Daily Dose ◽  
Record Review ◽  
Initial Starting

It is estimated that more than half of elderly patients with dementia will develop some degree of behavioral and psychological symptoms of dementia (BPSD). BPSD is associated with significant morbidity, rapid functional decline, and psychiatric hospitalization, and there are currently no medications approved by the Food and Drug Administration (FDA) for its treatment. One treatment option that has been evaluated is the antiepileptic drug valproate. This retrospective medical record review evaluated the tolerability of valproate in elderly patients with dementia. A total of 62 patients met inclusion criteria for this review, which sought to determine whether there was an association either between the initial valproate dose and discontinuation or dose reduction (DCDR) or the maximum valproate dose achieved and DCDR. Both the total daily dose and total daily dose in mg/kg were assessed. For both the maximum daily dose (OR 1.0; 95% CI 0.99, 1.01) and maximum daily mg/kg dose (OR =1.15; 95% CI 0.92, 1.49) there was also no association with DCDR. There was no associated risk of DCDR when evaluating initial daily doses (OR: 1.0; 95% CI: 0.99 – 1.01). However, an association between DCDR and initial daily mg/kg dose was found (OR: 1.92; 95% CI: 1.11–4.02). For both the initial dose and initial mg/kg dose model, African Americans were associated with the need for DCDR (OR 20.75; 95% CI: 1.77–660). Results from this study suggest that higher initial starting doses based on weight may lead to higher rates of side effects necessitating a discontinuation or dose reduction; however, large trials are needed to confirm these results.

Behavioral and psychological symptoms in elderly patients with dementia

2016 ◽  
Vol 108 ◽  
pp. 110
Author(s):  
Jorge J. Llibre-Guerra ◽  
Juan J. Llibre-Rodriguez ◽  
Milagros A. Guerra-Hernández ◽  
Juan C. Llibre-Guerra ◽  
Ana M. Rodriguez-Salgado ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Psychological Symptoms ◽  
Behavioral And Psychological Symptoms

scholarly journals Cognitive decline, functional dependency and sociodemographic characteristics in elderly patients with bone fractures

2015 ◽  
Vol 5 (2) ◽  
pp. 221-232
Author(s):  
Ana R. Ortega ◽  
Mª José Calero
Keyword(s):  
Elderly Patients ◽  
Cognitive Decline ◽  
Bone Fractures ◽  
Functional Decline ◽  
The Elderly ◽  
Structured Interview ◽  
Demographic Variables ◽  
Cognitive Status ◽  
Functional Dependency ◽  
Functional Gain

The objective of this paper was to study the evolution of cognitive status and of functional dependency in patients over 65 and how these relate to different demographic variables. The sample consisted of 259 elderly people admitted to the Hospital Neurotraumatológico in Jaen (Spain) with a diagnosis of bone fracture. Sociodemographic data was obtained through a semi-structured interview. Furthermore, the following tests were also administered: Barthel Index, Lawton and Brody’s Scale, Phototest, and Informant Questionnaire on Cognitive Decline in the Elderly. According to the results of this study, elderly patients show increased dependency during hospitalization and a mild recovery at discharge, but without regaining their dependency values prior to hospitalization. There is a differential incidence of functional decline as a function of gender, where women have significantly lower functional dependency at home than men and they do not decline as much as men do from their status prior to hospitalization. Also, we have encountered significant inverse relations between the different levels of dependency and cognitive status, and the age of the elderly patient. Moreover, married patients experienced greater functional gain than did the widowed patients, regardless of gender.

Mania with Bupropion: A Dose-Related Phenomenon?

2000 ◽  
Vol 34 (5) ◽  
pp. 619-621 ◽  
Author(s):  
Jessica L Goren ◽  
Gary M Levin
Keyword(s):  
Affective Disorder ◽  
Bipolar Depression ◽  
Bipolar Affective Disorder ◽  
Antidepressant Drug ◽  
Manic Episode ◽  
Total Daily Dose ◽  
High Dose ◽  
Related Phenomenon ◽  
Increased Risk ◽  
Daily Dose

OBJECTIVE: To report a case in which bipolar depression was resistant to usual therapies, requiring dosages of bupropion >450 mg/d and to review the literature on mania associated with bupropion and propose a potential theory of a dose-related threshold associated with bupropion and mania. CASE SUMMARY: A 44-year-old white man with a 25-year history of bipolar affective disorder presented with depression resistant to usual therapies. Bupropion therapy was initiated and the dosage was titrated to 600 mg/d. After exceeding the maximum recommended daily dose (450 mg/d), he experienced a manic episode attrib uted to high-dose bupropion. DISCUSSION: Due to increased risk of seizures, current prescribing guidelines state that the total daily dose of bupropion is not to exceed 450 mg/d. Since bupropion is the agent least likely to cause a manic switch in bipolar disorder, this agent seemed a logical choice to treat the patient's depression. Due to a lack of response, the bupropion dosage was titrated to a maximum of 600 mg/d. Since the patient did not switch into mania until the dosage exceeded 450 mg/d, we speculate that this adverse reaction is a dose-related phenomenon. Scientific literature supports this theory. CONCLUSIONS: A switch into mania is a potential risk associated with antidepressant drug use in bipolar affective disorder. Bupropion is believed to be associated with a decreased risk compared with other antidepressant therapies. However, our case report as well as others support the theory that this decreased risk may be due to dosages not exceeding the recommended daily dose (450 mg/d). Doses of bupropion >450 mg/d should be used with caution in depressed patients with bipolar affective disorder.

A Grave Case of Morphia and Cocaine Habit [Considérations sur un cas grave de morphi-cocaïnomanie]. (Prog. Méd., May 12th, 1900.) Sollier, P

1901 ◽  
Vol 47 (198) ◽  
pp. 603-603
Author(s):  
W. C. Sullivan
Keyword(s):  
Subcutaneous Tissue ◽  
Abdominal Region ◽  
Maximum Daily Dose ◽  
Daily Dose

The patient was a medical man, æt. 40; the morphia habit dated back ten years, the maximum daily dose being 3 grammes; the cocaine habit was more recent. When the case came under Sollier's treatment the intoxication was profound; the patient was emaciated; there was diffuse induration of the subcutaneous tissue, and there were numerous ulcers in the abdominal region where the patient injected the drugs; the urine contained albumen, and severe uræmic symptoms had appeared; the hæmoglobin was reduced to 4·5 per cent., and was shown by the spectroscope to be very imperfectly oxidised. The author specially indicates this blood-state, as he considers that the symptoms of collapse on the withdrawal of morphia are due to asphyxia.

scholarly journals Melatonin for prevention of postoperative delirium after lower limb fracture surgery in elderly patients (DELIRLESS): study protocol for a multicentre randomised controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e053908
Author(s):  
Stéphanie Sigaut ◽  
Camille Couffignal ◽  
Marina Esposito-Farèse ◽  
Vincent Degos ◽  
Serge Molliex ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Lower Limb ◽  
Postoperative Delirium ◽  
Controlled Trial ◽  
Functional Decline ◽  
Assessment Method ◽  
Phase Iii ◽  
Double Blind ◽  
Prolonged Length ◽  
Surgery In Elderly

IntroductionPostoperative delirium (POD) is one of the most frequent complication after surgery in elderly patients, and is associated with increased morbidity and mortality, prolonged length of stay, cognitive and functional decline leading to loss of autonomy, and important additional healthcare costs. Perioperative inflammatory stress is a key element in POD genesis. Melatonin exhibits antioxidative and immune-modulatory proprieties that are promising concerning delirium prevention, but in perioperative context literature are scarce and conflicting. We hypothesise that perioperative melatonin can reduce the incidence of POD.Methods and analysisThe DELIRLESS trial is a prospective, national multicentric, phase III, superiority, comparative randomised (1:1) double-blind clinical trial. Among patients aged 70 or older, hospitalised and scheduled for surgery of a severe fracture of a lower limb, 718 will be randomly allocated to receive either melatonin 4 mg per os or placebo, every night from anaesthesiologist preoperative consultation and up to 5 days after surgery. The primary outcome is POD incidence measured by either the French validated translation of the Confusion Assessment Method (CAM) score for patients hospitalised in surgery, or CAM-ICU score for patients hospitalised in ICU (Intensive Care Unit). Daily delirium assessment will take place during 10 days after surgery, or until the end of hospital stay if it is shorter. POD cumulative incidence function will be compared at day 10 between the two randomised arms in a competing risks framework, using the Fine and Grey model with death as a competing risk of delirium.Ethics and disseminationThe DELIRLESS trial has been approved by an independent ethics committee the Comité de Protection des Personnes (CPP) Sud-Est (ref CPP2020-18-99 2019-003210-14) for all study centres. Participant recruitment begins in December 2020. Results will be published in international peer-reviewed medical journals.Trial registration numberNCT04335968, first posted 7 April 2020.Protocol version identifierN°3–0, 3 May 2021.

scholarly journals 134 Long-Term Deutetrabenazine Treatment Is Associated with Sustained Treatment Response in Tardive Dyskinesia: Results from an Open-Label Extension Study

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 284-285 ◽  
Author(s):  
Robert A. Hauser ◽  
Hadas Barkay ◽  
Hubert H. Fernandez ◽  
Stewart A. Factor ◽  
Joohi Jimenez-Shahed ◽  
...  
Keyword(s):  
Adverse Events ◽  
Percentage Change ◽  
Extension Study ◽  
Total Daily Dose ◽  
Open Label ◽  
Daily Dose ◽  
Open Label Extension ◽  
The Mean ◽  
Over Time

Abstract:Background:In the 12-week ARM-TD and AIM-TD studies evaluating deutetrabenazine for the treatment of tardive dyskinesia (TD), the percentage of patients achieving ≥50% response was higher in the deutetrabenazine-treated group than in the placebo group. These studies also showed low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. The current open-label study evaluated the long-term efficacy and safety of deutetrabenazine in patients with TD.Methods:Patients with TD who completed ARM-TD or AIM-TD could enroll in this open-label, single-arm extension study, titrating up over 6 weeks to a maximum total daily dose of deutetrabenazine 48 mg/day on the basis of dyskinesia control and tolerability. The proportion of Abnormal Involuntary Movement Scale (AIMS; items 1-7) responders was assessed based on response rates for achieving ≥50% improvement from baseline in the open-label extension study. AlMS score was assessed by local site raters for this analysis.Results:343 patients enrolled in the extension study. At Week 54 (n=249; total daily dose [mean ± standard error]: 38.6±0.66 mg), the mean percentage change from baseline in AIMS score was –40%; 48% of patients achieved a ≥50% response and 59% of those had already achieved a ≥50% response at Week 15. Further, 34% of those who had not achieved a ≥50% response at Week 15 achieved a ≥50% response at Week 54. At Week 106 (n=169; total daily dose: 39.6±0.77 mg), the mean percentage change from baseline in AIMS score was –45%; 55% of patients achieved a ≥50% response, 59% of those patients had already achieved a ≥50% response at Week 15, and 41% of those who had not achieved a ≥50% response at Week 15 but who reached Week 106 achieved a ≥50% response. At Week 132 (n=109; total daily dose: 39.7±0.97 mg), the mean percentage change from baseline in AIMS score was –61%; 55% of patients achieved a ≥50% response, 61% of those patients had already achieved a ≥50% response at Week 15, and 43% of those who had not achieved a ≥50% response at Week 15 but who reached Week 132 achieved a ≥50% response. Completer analysis suggests that long-term efficacy was not due to dose increases over time. Treatment with deutetrabenazine was generally well tolerated. There were 623 patient-years of exposure through Week 158, and exposure-adjusted incidence rates (incidence/patient-years) of adverse events of special interest were 0.01 for akathisia and restlessness, 0.07 for somnolence and sedation, 0.04 for parkinsonism, and 0.05 for depression.Conclusions:Patients who received long-term treatment with deutetrabenazine achieved response rates that were indicative of clinically meaningful long-term benefit. Results from this open-label trial suggest the possibility of increasing benefit over time with individual dose titration of deutetrabenazine.Funding Acknowledgements:This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.

Opicapone and Levodopa-Carbidopa Intestinal Gel Infusion: The Way Forward Towards Cost Savings for Healthcare Systems?

2020 ◽  
Vol 10 (4) ◽  
pp. 1535-1539
Author(s):  
Valentina Leta ◽  
Daniel J. van Wamelen ◽  
Anna Sauerbier ◽  
Shelley Jones ◽  
Miriam Parry ◽  
...  
Keyword(s):  
United Kingdom ◽  
Side Effects ◽  
Retrospective Analysis ◽  
Dose Reduction ◽  
Clinical Care ◽  
Cost Savings ◽  
Healthcare Systems ◽  
Methyl Transferase ◽  
The United Kingdom ◽  
Daily Dose

Combined catechol-O-methyl-transferase-inhibition and Levodopa-Carbidopa intestinal gel (LCIG) infusion has the potential to reduce LCIG daily dose and the costs of this therapy. In this retrospective analysis, we report on Parkinson’s disease (PD) patients on LCIG with concomitant Opicapone. In 11 patients, the introduction of Opicapone led to LCIG daily dose being reduced by 24.8% (p = 0.05) without any significant worsening of dyskinesia. Three patients withdrew from Opicapone due to side effects or inefficacy. LCIG daily dose reduction could lead to cost savings of £142,820.63/year in the United Kingdom while maintaining clinical care.

scholarly journals 158 Long-Term Safety of Deutetrabenazine for the Treatment of Tardive Dyskinesia: Results From an Open-Label, Long-Term Study

CNS Spectrums ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 97-97
Author(s):  
Karen E. Anderson ◽  
Mat D. Davis ◽  
Stewart A. Factor ◽  
Robert A. Hauser ◽  
L. Fredrik Jarskog ◽  
...  
Keyword(s):  
Dose Reduction ◽  
Involuntary Movement ◽  
Incidence Rates ◽  
Extension Study ◽  
Total Daily Dose ◽  
Open Label ◽  
Long Term Study ◽  
Long Term Treatment ◽  
Pharmaceutical Industries

AbstractIntroductionIn the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo, and was generally well tolerated.ObjectiveTo evaluate the long-term safety/tolerability and efficacy of deutetrabenazine in patients with TD. Week 54 open-labelresults are reported in this interim analysis.MethodsPatients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12 mg/day, titrating up to a maximum total daily dose of 48 mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safetymeasures included incidence of adverse events (AEs), serious AEs (SAEs), drug-related AEs, and AEs leading to withdrawal, dose reduction, or dose suspension. This analysis reports results up to Week 54.Results304 patients enrolled in the extension study. There were 215 patient-years of exposure in this analysis, and exposure-adjusted incidence rates (EAIRs) of AEs (incidence/patient-years) were comparable to or lower than those observed with short-term deutetrabenazine treatment and placebo. The frequency of SAEs (EAIR 0.14) was similar to rates observed with short-termplacebo (EAIR 0.33) and deutetrabenazine (EAIR range 0.06–0.33) treatment. AEs leading to study discontinuation (EAIR 0.08), dose reduction (EAIR 0.17), and dose suspension (EAIR 0.09) were uncommon.ConclusionsLong-term treatment with deutetrabenazine was generally safe and well tolerated in patients with TD, and did not result in cumulative toxicity.Presented at: The American Psychiatric Association 2017 Annual Meeting; May 20–24, 2017; San Diego, California, USA.Funding AcknowledgementsThis study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.

scholarly journals Baseline Functional Status and One-year Mortality After Hospital Admission in Elderly Patients: a prospective cohort study

2020 ◽  
Vol 77 (3) ◽  
pp. 143-148
Author(s):  
Victoria Sáenz ◽  
Nicolas Zuljevic ◽  
Cristina Elizondo ◽  
Iñaki Martin Lesende ◽  
Diego Caruso
Keyword(s):  
Cohort Study ◽  
Elderly Patients ◽  
Hospital Admission ◽  
Functional Status ◽  
Prospective Cohort ◽  
Functional Decline ◽  
Long Term Outcomes ◽  
One Year

Introduction: Hospitalization represents a major factor that may precipitate the loss of functional status and the cascade into dependence. The main objective of our study was to determine the effect of functional status measured before hospital admission on survival at one year after hospitalization in elderly patients. Methods: Prospective cohort study of adult patients (over 65 years of age) admitted to either the general ward or intensive Care units (ICU) of a tertiary teaching hospital in Buenos Aires, Argentina. Main exposure was the pre-admission functional status determined by means of the modified “VIDA” questionnaire, which evaluates the instrumental activities of daily living. We used a multivariate Cox proportional hazards model to estimate the effect of prior functional status on time to all-cause death while controlling for measured confounding. Secondarily, we analyzed the effect of post-discharge functional decline on long-term outcomes. Results: 297 patients were included in the present study. 12.8% died during hospitalization and 86 patients (33.2%) died within one year after hospital discharge. Functional status prior to hospital admission, measured by the VIDA questionnaire (e.g., one point increase), was associated with a lower hazard of all-cause mortality during follow-up (Hazard Ratio [HR]: 0.96; 95% Confidence Interval [CI]: 0.94–0.98). Finally, functional decline measured at 15 days after hospital discharge, was associated with higher risk of all-cause death during follow-up (HR: 2.19, 95% CI: 1.09–4.37) Conclusion: Pre-morbid functional status impacts long term outcomes after unplanned hospitalizations in elderly adults. Future studies should confirm these findings and evaluate the potential impact on clinical decision-making.

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