Review of Anticonvulsant Medication Therapy - usi.edu · stroke Metabolic ... DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach, 9th ed. Figure

Review of Anticonvulsant Medications: Traditional and Alternative UsesAndrea Michel, PharmD, CACP

Objectives

Review epidemiology of epilepsy

Classify types of seizures

Discuss non-pharmacologic and pharmacologic treatment options for epilepsy

Outline common adverse reactions and prevalent drug-drug interactions associated with anticonvulsant medications

Highlight important considerations for special patient populations with epilepsy

State appropriate plan for anticonvulsant medication therapy discontinuation

Epilepsy

Definition

Central nervous system disorder in which brain activity becomes abnormal, causing seizures or periods of unusual behavior, sensations, and sometimes loss of awareness

Epilepsy diagnosis requires: History of >2 seizures at least 24 hours apart

OR

1 seizure with significant risk of recurrence (e.g. recent stroke, brain structure abnormality, abnormal electroencephalography (EEG))

Epidemiology

Prevalence in the US 3 Million adults & 470,ooo children

1.2% of population

CDC: Epilepsy Data and Statistics. Accessed 9/2018. https://www.cdc.gov/epilepsy/data/index.html.

Causes

Mechanical – birth injuries, head trauma, tumors, stroke

Metabolic – electrolyte disturbances, hypoglycemia

Genetic Influence – familial neonatal seizures, juvenile myoclonic epilepsy (JME)

Other – fever, infectious disease

Causes

Drugs

Recreational drugs

Carbapenems

Meperidine

Local anesthetics

Metoclopramide

Theophylline

Tricyclic antidepressants

Anticonvulsant therapy: carbamazepine, phenytoin, phenobarbital

Diagnosis

Medical History

Physical and Neurological Exam

Lab tests

Electroencephalogram (EEG)

Magnetic resonance imaging (MRI)

Classification of Seizures

Focal seizure

Focal Seizure

One hemisphere of the brain

Unilateral, asymmetric movements

Associated with an aura

Other terms: simple partial seizure, complex partial seizure, secondarily generalized seizure

Generalized seizure

Generalized seizure

Begins simultaneously in both brain hemispheres

Types of generalized seizures:1. Absence

2. Myoclonic

3. Tonic-clonic

4. Clonic

5. Tonic

6. Atonic

Unknown onset seizure

Unknown seizure

Reserved for seizures that are unwitnessed

Occur while patient is asleep

Observers cannot provide an adequate description

Status epilepticus

Status Epilepticus

Seizure that lasts >20 minutes OR >2 seizures with incomplete recovery of consciousness between episodes

Medical emergency

Up to 20% mortality rate

Treatment of Epilepsy

Treatment

Non-PharmacologicSurgical Procedures

Vagus Nerve Stimulation

Dietary Restrictions

PharmacologicAnticonvulsant medication therapy

Anticonvulsant Therapy

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwipiObHt9bdAhVO6lMKHW4yAKkQjRx6BAgBEAU&url=https://www.consumerreports.org/drugs/avoid-common-medication-errors/&psig=AOvVaw3NsDjUhcpC6F0e5Ts8uaaX&ust=1537974472653611

Treatment algorithm

DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach, 9th ed. Figure 40-1.

First Line Treatment of New-Onset Epilepsy for Patients >13YO

National Institute for Health and Care Excellence (NICE). Epilepsies: Diagnosis and Management.Kanner AM, Ashman E, Gloss D, et al. Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy. Neurology Jul 2018;81:74-81.

Adverse Effects

Kanner AM, Ashman E, Gloss D, et al. Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy. Neurology Jul 2018;81:74-81.

Adverse Effects

Kanner AM, Ashman E, Gloss D, et al. Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I:: Treatment of new-onset epilepsy. Neurology Jul 2018;81:74-81.

Adverse Effects


Drug Selection

Serious adverse effects – rapid discontinuation required Drug reaction with eosinophilia and system

symptoms (DRESS)

Stevens-Johnson syndrome (SJS)

Toxic epidermal necrolysis (TEN)

Drug Selection

Pharmacogenomic Considerations


Drug Selection

Drug Interactions!

Metabolism and Monitoring


Metabolism and Monitoring


Interactions of Non-AEDs

Ryan, M. Neurology: ACCP Updates in Therapeutics 2013: The Pharmacotherapy Review and Recertification Course. Lenexa, KS. 2013: 1-194-195.





Drug Selection

Alternative indications Mood stabilization related to bipolar disorder:

valproate, carbamazepine, and lamotrigine

Neuropathic pain & postherpetic neuralgia: gabapentin and pregabalin

Migraine prophylaxis: valproate and topiramate

Essential tremor: primidone

Trigeminal neuralgia: carbamazepine

Anxiety: phenobarbital

Adjunct Therapy


Adjunct Therapy


Special Populations

Elderly

Pharmacokinetic changes in aging population may affect therapy1. Carbamazepine: Decreased clearance

2. Phenytoin: Decreased protein binding if renal failure or hypoalbuminemic

3. Valproic acid: Decreased protein binding

4. Diazepam: Increased half-life

5. Lamotrigine: Decreased clearance

6. Seizure medications with renal elimination must be adjusted based on CrCl

Women’s Health

Reproductive years:

Match best drug for seizure type

Monotherapy, if possible

Discuss possible decrease in hormonal contraceptive effectiveness if appropriate

Ideal to be seizure free for at least 9 months before pregnancy

Folic acid 1 mg daily

Women’s Health

During pregnancy: Avoid valproic acid monotherapy or polytherapy

during 1st trimester

Avoid use of seizure medication polytherapy throughout complete pregnancy

Avoid use of phenytoin, carbamazepine, and phenobarbital, if possible

Lamotrigine has a lower relative risk of congenital malformations

Treatment discontinuation

Treatment discontinuation

Consider withdrawal of anticonvulsants: Remain seizure-free for 2 or more years

Control obtained with 1 drug

Normal neurologic examination

EEG normalized with seizure medication treatment

No history of seizure relapse after drug withdrawal

Withdraw 1 drug at a time

Taper over several months Common regimen: reduce the dose by 1/3 for 1 month,

reduce by another 1/3 for 1 month, and then stop

Other Considerations

SexualDysfunction

Reported in 30-60% of men and women with epilepsy

Mechanism: Induction of CYP

isoenzymes to increase testosterone metabolism

Increased hepatic synthesis of sex hormone-binding globulin

Induction of aromatase; conversion to testosterone and estradiol

Dysfunction associated with: carbamazepine, phenobarbital, phenytoin, pregabalin, topiramate, zonisamide

Improved functioning with: lamotrigine and oxcarbazepine

Bone Health

Osteopenia and osteoporosis reported in 38-60% in tertiary epilepsy clinics

Increased risk based on treatment duration

Evidence that all seizure medications likely contribute

Treatment: Vitamin D (4000 IU/day for adults and 2000 IU/day for

children)

Suicidality

Twice the risk of suicidal behavior or ideation for patients receiving seizure medications

No difference between type of antiepileptic drug or age group

In 2008, FDA required warning and medication guide for all seizure medications

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwj5vei-sdbdAhUCz1MKHYTeCCAQjRx6BAgBEAU&url=https://www.lutheranhospital.com/bariatric-one-on-one-counseling&psig=AOvVaw3ImCITFrmaLK0EQB2a6ZLF&ust=1537972824382306

Questions?

Documents

Review of Anticonvulsant Medication Therapy - usi.edu · stroke Metabolic ... DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach, 9th ed. Figure