Anticonvulsants

Background
Vitamin B12 deficiency is common in the elderly population and can cause severe complications. The use of certain medication has in previous studies been associated with vitamin B12 deficiency in the general population. To identify elderly patients at risk for vitamin B12 deficiency due to medication use, we evaluated the association between medication use and vitamin B12 deficiency in the elderly population.

Methods
Hospitalized geriatric patients 65 years of age or over with a serum vitamin B12 measurement within one week of the admittance date were included. Patients were classified as either B12 normal (258–635 pmol/L) or B12 deficient (< 148 pmol/L). Upon hospital admission patients’ medication use was verified. The association between vitamin B12 deficiency and the use of antacid, antiepileptic, antidiabetic, lipid lowering and other medication was evaluated by univariate and multivariate analyses.

Results
Of the 7132 patients included in the study, 532 (7.5%) had vitamin B12 deficiency and 3433 (48.1%) patients had normal vitamin B12 concentrations. Metformin use was significantly and independently (adjusted OR 2.5; 95% CI 1.7–3.6) associated with a dose-dependent higher risk of vitamin B12 deficiency. The use of other medication evaluated in this study was not associated with vitamin B12 deficiency.

Conclusions
Metformin use is significantly associated with vitamin B12 deficiency in the elderly, and this risk rises with higher metformin doses. Monitoring and timely start of vitamin B12 supplementation along with the lowest possible metformin dose are essential to prevent complications.

Author/s:

Monique P H Tillemans, Thijs J Giezen, Toine C G Egberts, Kees J Kalisvaart

Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society

Bethie Seay — Tue, 30 Nov 2021 06:00:00 +0000

Date Added:

November 30, 2021

Journal/Publication:

Epilepsy Currents

Publication Date:

January 1, 2016

Issue:

Volume:

Pages:

48-61

Type:

Meta-analyses, Reviews, and Guidelines

DOI (1):

10.5698/1535-7597-16.1.48

PMID (1):

26900382

MeSH

Respiratory Insufficiency

Algorithms

Randomized Controlled Trials as Topic

I thought I would place this guideline for treatment of status epilepticus in the RPR library as a reference. It might also be worth posting the recommended doses and routes of administration of the recommended benzos and assuring that one of them is available if needed.

View

CONTEXT: The optimal pharmacologic treatment for early convulsive status epilepticus is unclear. OBJECTIVE: To analyze efficacy, tolerability and safety data for anticonvulsant treatment of children and adults with convulsive status epilepticus and use this analysis to develop an evidence-based treatment algorithm. DATA SOURCES: Structured literature review using MEDLINE, Embase, Current Contents, and Cochrane library supplemented with article reference lists. STUDY SELECTION: Randomized controlled trials of anticonvulsant treatment for seizures lasting longer than 5 minutes. DATA EXTRACTION: Individual studies were rated using predefined criteria and these results were used to form recommendations, conclusions, and an evidence-based treatment algorithm. RESULTS: A total of 38 randomized controlled trials were identified, rated and contributed to the assessment. Only four trials were considered to have class I evidence of efficacy. Two studies were rated as class II and the remaining 32 were judged to have class III evidence. In adults with convulsive status epilepticus, intramuscular midazolam, intravenous lorazepam, intravenous diazepam and intravenous phenobarbital are established as efficacious as initial therapy (Level A). Intramuscular midazolam has superior effectiveness compared to intravenous lorazepam in adults with convulsive status epilepticus without established intravenous access (Level A). In children, intravenous lorazepam and intravenous diazepam are established as efficacious at stopping seizures lasting at least 5 minutes (Level A) while rectal diazepam, intramuscular midazolam, intranasal midazolam, and buccal midazolam are probably effective (Level B). No significant difference in effectiveness has been demonstrated between intravenous lorazepam and intravenous diazepam in adults or children with convulsive status epilepticus (Level A). Respiratory and cardiac symptoms are the most commonly encountered treatment-emergent adverse events associated with intravenous anticonvulsant drug administration in adults with convulsive status epilepticus (Level A). The rate of respiratory depression in patients with convulsive status epilepticus treated with benzodiazepines is lower than in patients with convulsive status epilepticus treated with placebo indicating that respiratory problems are an important consequence of untreated convulsive status epilepticus (Level A). When both are available, fosphenytoin is preferred over phenytoin based on tolerability but phenytoin is an acceptable alternative (Level A). In adults, compared to the first therapy, the second therapy is less effective while the third therapy is substantially less effective (Level A). In children, the second therapy appears less effective and there are no data about third therapy efficacy (Level C). The evidence was synthesized into a treatment algorithm. CONCLUSIONS: Despite the paucity of well-designed randomized controlled trials, practical conclusions and an integrated treatment algorithm for the treatment of convulsive status epilepticus across the age spectrum (infants through adults) can be constructed. Multicenter, multinational efforts are needed to design, conduct and analyze additional randomized controlled trials that can answer the many outstanding clinically relevant questions identified in this guideline.

Author/s:

Glauser, T., Shinnar, S., Gloss, D., Alldredge, B., Arya, R., Bainbridge, J., Bare, M., Bleck, T., Dodson, W. E., Garrity, L., Jagoda, A., Lowenstein, D., Pellock, J., Riviello, J., Sloan, E., Treiman, D. M.

Evidenced-Based Pharmacotherapies for Alcohol Use Disorder

John Bayhi — Thu, 21 May 2020 16:22:32 +0000

Date Added:

May 21, 2020

Journal/Publication:

Mayo Clinic Proceedings

Publisher:

Elsevier Inc / Mayo Foundation for Medical Education and Research

Publication Date:

May 20, 2020

Volume:

Article in Press

URL:

Evidenced-Based Pharmacotherapies for Alcohol Use Disorder

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/j.mayocp.2020.01.030

Keywords

MeSH

Pharmacogenomic Testing

united states food and drug administration

A review of pharmacological approaches to the treatment of alcoholism with some clinical pearls from Mayo physicians. James W. Mold, MD, MPH

Free full text

View

Pathologic alcohol use affects more than 2 billion people and accounts for nearly 6% of all deaths worldwide. There are three medications approved for the treatment of alcohol use disorder by the US Food and Drug Administration (FDA): disulfiram, naltrexone (oral and long-acting injectable), and acamprosate. Of growing interest is the use of anticonvulsants for the treatment of alcohol use disorder, although currently none are FDA approved for this indication. Baclofen, a γ-aminobutyric acid B receptor agonist used for spasticity and pain, received temporary approval for alcohol use disorder in France. Despite effective pharmacotherapies, less than 9% of patients who undergo any form of alcohol use disorder treatment receive pharmacotherapies. Current evidence does not support the use of pharmacogenetic testing for treatment individualization. The objective of this review is to provide knowledge on practice parameters for evidenced-based pharmacologic treatment approaches in patients with alcohol use disorder.

Author/s:

Fairbanks, J, Umbreit, A, Kolla, BP, Karpyak, VM, Schneekloth, TD, Loukianova, LL, Sinha, S

Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study

Brian Desmarais — Thu, 27 Jun 2019 13:04:17 +0000

Date Added:

June 27, 2019

Journal/Publication:

Journal of the American Medical Association Internal Medicine

Publication Date:

June 24, 2019

URL:

Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamainternmed.2019.0677.

Keywords

MeSH

Muscarinic Antagonists

antipsychotic agents

Middle Aged

Anticonvulsants

Confounding Factors (Epidemiology)

Urinary Bladder

cholinergic antagonists

antidepressive agents

I am only posting this article because your patients may ask about it. The research design isn’t very strong, and the association strengths aren’t terribly impressive. The dementia diagnoses weren’t confirmed, and I can’t tell whether patients were still taking the meds, which we know can cause acute cognitive impairment.. James W. Mold, MD, MPH

Commercial full text (fees may apply)

View

IMPORTANCE:

Anticholinergic medicines have short-term cognitive adverse effects, but it is uncertain whether long-term use of these drugs is associated with an increased risk of dementia.

OBJECTIVE:

To assess associations between anticholinergic drug treatments and risk of dementia in persons 55 years or older.

DESIGN, SETTING, AND PARTICIPANTS:

This nested case-control study took place in general practices in England that contributed to the QResearch primary care database. The study evaluated whether exposure to anticholinergic drugs was associated with dementia risk in 58 769 patients with a diagnosis of dementia and 225 574 controls 55 years or older matched by age, sex, general practice, and calendar time. Information on prescriptions for 56 drugs with strong anticholinergic properties was used to calculate measures of cumulative anticholinergic drug exposure. Data were analyzed from May 2016 to June 2018.

EXPOSURES:

The primary exposure was the total standardized daily doses (TSDDs) of anticholinergic drugs prescribed in the 1 to 11 years prior to the date of diagnosis of dementia or equivalent date in matched controls (index date).

MAIN OUTCOMES AND MEASURES:

Odds ratios (ORs) for dementia associated with cumulative exposure to anticholinergic drugs, adjusted for confounding variables.

RESULTS:

Of the entire study population (284 343 case patients and matched controls), 179 365 (63.1%) were women, and the mean (SD) age of the entire population was 82.2 (6.8) years. The adjusted OR for dementia increased from 1.06 (95% CI, 1.03-1.09) in the lowest overall anticholinergic exposure category (total exposure of 1-90 TSDDs) to 1.49 (95% CI, 1.44-1.54) in the highest category (>1095 TSDDs), compared with no anticholinergic drug prescriptions in the 1 to 11 years before the index date. There were significant increases in dementiarisk for the anticholinergic antidepressants (adjusted OR [AOR], 1.29; 95% CI, 1.24-1.34), antiparkinson drugs (AOR, 1.52; 95% CI, 1.16-2.00), antipsychotics (AOR, 1.70; 95% CI, 1.53-1.90), bladder antimuscarinic drugs (AOR, 1.65; 95% CI, 1.56-1.75), and antiepileptic drugs (AOR, 1.39; 95% CI, 1.22-1.57) all for more than 1095 TSDDs. Results were similar when exposures were restricted to exposure windows of 3 to 13 years (AOR, 1.46; 95% CI, 1.41-1.52) and 5 to 20 years (AOR, 1.44; 95% CI, 1.32-1.57) before the index date for more than 1095 TSDDs. Associations were stronger in cases diagnosed before the age of 80 years. The population-attributable fraction associated with total anticholinergic drug exposure during the 1 to 11 years before diagnosis was 10.3%.

CONCLUSIONS AND RELEVANCE:

Exposure to several types of strong anticholinergic drugs is associated with an increased risk ofdementia. These findings highlight the importance of reducing exposure to anticholinergic drugs in middle-aged and older people.

Author/s:

Coupland, C.A.C., Hill, T., Dening, T., Morriss, R., Moore M., Hippisley-Cox J.