Psychotherapy: 92b/93b - Epilepsy and Anticonvulsants

• Phenobarbital

• Phenytoin

• Carbamazepine

Ethosuximide

Increased frequency of Cl- channel opening

Effective for myoclonic seizures

Rescue medication for status epilepticus

• Too much excitation
  

  • Ionic: too much inward Na+, Ca2+

  • NeuroT: Too much glutamate, aspartate

• Too little inhibition
  

  • Ionic: too little inward Cl-, outward K+

  • NeuroT: Not enough GABA

Blocks T-type Ca2+ currents in the thalamus

Drug of choice for abscence seizures

Steven-Johnson syndrome

• But broadly, lamotrigine is a good broad-spectrum AED that is safe in pregnancy

Topiramate

Myoclonic = generalized

• Myoclonus
  

  • Brief, shock-like jerk of a muscle or group of muscles

  • Bilateral, synchronous

  • vs. clonus which is repeated rhythmic jerking

  • If several myoclonic jerks occur in rhythmic succession, it is a clonic seizure

• Consciousness NOT impaired

Lamotrigine

But need frequent adjustment in dose b/c serum levels fall in the 3rd trimester

Tonic = generalized

• Symmetric, tonic muscle contraction of extremities

• Tonic flexion of waist and neck

• Lasts 2-20 seconds

• EEG
  

  • Sudden attenuation, generalized polyspike waves

  • (similar to atonic)

Temporal lobe epilepsy

• Automatisms = lip smacking, swallowing, fumbling, picking at clothes

• Mechanism
  

  • Binds to synaptic vescicle protein SV2A to regulate neurotransmitter release

  • Also reduces activity through high-voltage Ca2+ channels

• Use
  

  • Broad spectrum - used as monotherapy or adjunctive

• Side effect
  

  • CNS depression and irritability

3 Hz spike-wave discharges in every channel

Lasts for 3-10 seconds

• Abscence seizures are generalized

• Sudden onset, sudden resolution

• No post-ictal confusion

Inhibits Na+ channels

Tricyclic

Used to treat epilepsy w/predominantly focal seizures

Will worsen abscence seizures

Mesial temporal lobe epilepsy

• Focal seizures evolve into a bilateral, convulsive seizure early on

• Pregnant women
  

  • High risk of neural tube defects

• Neonates
  

  • Hepatic toxicity due to elevated liver enzymes

Gabapentin

Carbamazepine

Pregabalin

Valproate

Blocks Na+ and T-type Ca2+ channels

Blocks carbonic anhydrase (-> side effect = kidney stones)

Used as add-on therapy for partial and generalized seizures

Interferes with GABA uptake

Add-on therapy for focal seizures

Lacks potency for seizure - used off-label for neuropathic pain

Valproate

• Broad spectrum

• Mechanisms:
  

  • Enhances GABA activity

  • Inhibits Na+ current

  • Activates K+, T-type Ca2+ channels

Pregabalin

• Mechanism
  

  • Blocks Na+ channels

  • Increases frequency of GABAA opening

  • Interferes with glutamate binding

• Uses
  

  • Broad specturm (monotherapy or adjunctive for focal or general)

  • Also used for migraine prophylaxis, neuropathic pain, tremor

• Side effects
  

  • Memory and cognitive impairment

  • Appetitie suppression and weight loss

• Atonic

• Tonic

• Clonic

• Tonic-clonic
  

  • Tonic-clonic or myoclonic

• Abscence

Carbamazepine

Need to start at low doses and titrate up (will be inefective if the dose isn't increased!)

• Mechanism

  • Inhibits voltage-gated Ca2+ channels

  • Also reduces the release of some neurotransmitters

• Uses

  • Neuropathic pain

  • Peripheral neuropathy

  • Fibromyalgia

  • Anxiety

• Side effect

  • Appetite increase and weight gain

Valproate

Topiramate

Zonisamide

Oxcarbazepine

Where the seizure starts

• Focal

  • Seizure starts from one side

  • May progress to affect both sides of the brain, resulting in motor activity on both sides of the body (a secondarily generalized seizure)

• Generalized

  • Seizure start from both sides

Lamotrigine

Valproate

Carbamazepine

No post-ictal confusion with abscence seizure

Recurrent (2+) seizures that are not provoked by systemic or acute neurological insults

• This excludes seizures due to metabolic disorders or alcohol or sedative drug withdrawal or

Inhibits rapid firing of Na+ channels

Phenytoin is the most widely used AED

Used extensively to treat status epilepticus

Temporal lobe epilepsy

• Aura may involve epigastric sensation, deja vu, emotional feeling, perceptual distorion, autonomic

Gabapentin

Atonic = generalized

• Sudden loss of postural tone

  • Severe = fall

  • Mild = head or jaw draw

• Consciousness usually impaired

• EEG

  • Sudden diffuse atenuation, generalized polyspike waves

  • Similar to tonic

Topiramate

Blocks Na+ channels

(its basically better carbamazepine; less risk of toxic metabolite buildup)

Used for monotherapy in focal (aka partial) seizures

Note: tends to cause prominent hyponatremia

Tonic-clonic = generalized

• Loss of consciousness

• Post-ictal confusion, lethargy

• Tonic phase

  • Stiffening + fall

  • Ictal cry

• Clonic phase

  • Rhythmic extremity jerking

• Drooling, foaming at the mouth, biting tongue

• Bladder and bowel incontinence

• Agitation

Abscence = generalized

• Sudden onset

• Eye blinks

• Brief automatic mouth or hand movments

• Changes in muscle tone

• No post-ictal confusion

Felbamate

Levetiracetam

Increases duration of GABAA Cl- channel opening

Side effect: may cause CNS depression when combined with alcohol or benzos

Inhibits Na+ channels and glutamate release

• Broad spectrum

  • Monotherapy or or adjunctive for generalized and focal seizures

• Safe in pregnancy!!

  • But serum levels fall in 3rd trimester, needs adjustment

Feared side effect = Steven-Johnson syndrome

Abscence

• Preceded by aura

  • Often a weird taste in the mouth

• Focal seizures with impaired consciousness with automatisms

  • Lip smacking, swallowing, fumbling, picking at clothes

Often cannot be medically controlled; opt for anteromesial temporal lobectomy

Tramadol (an analgesic)

Venlafaxine (an SNRI antidepressant)