Anti-epileptics

DR. ALTAF QADIR KHAN

PROFESSOR OF PSYCHIATRY
PGMI/LAHORE GENERAL HOSPITAL, LAHORE
Mood Stabilizers
Anti-epileptics
Bromide
Phenobarbitone
Phenytoin
Valproic acid
Carbamazepine
Lamotrigine
Levetracetam
Topiramate
Gabapentin
Pregabalin
Antiepileptics
Carbamazepine (Tegral)
Na Valproate (Epival)
Lamotrigine (Lamictal)
Levetracitam (Lyrica)
Topiramate (Topamax)
Na channels
Neurones fire at high frequencies during seizures

Action potential generation is dependent on Na+ channels

Na+ channel blockers reduce high frequency firing without

affecting physiological firing
Ca channels
Absence seizures are caused by oscillations between thalamus
and cortex that are generated in thalamus by T-type (transient)
Ca2+ currents

Ethosuximide is a specific blocker of T-type currents and is

highly effective in treating absence seizures
K channels
K+ channels have important inhibitory control over neuronal
firing in CNS – repolarize membrane to end action potentials

K+ channels agonists would decrease hyperexcitability in brain

So far the only drug with known actions on K+ channels is Na

valproate
 GABA
GABA
Barbiturates
Benzodiazepines
Gabapentin
Levetiracetam
Tiagabine
Topiramate
Valproate
Vigabatrin

Na++
Na Ca2+2+
Ca
Carbamazepine
Ethosuximide
Lamotrigine
Levetiracetam
Oxcarbazepine
Pregabalin
Phenytoin
Valproate
Topiramate
Valproate
Phenobarbital
Partial seizures, effective in neonates
Second-line drug in adults
Modulator of GABA A receptor
Half life 50 – 120 hours
Adverse effects: CNS sedation (excitement) skin rashes
Tolerance and physical dependence possible
Interactions: CNS depression with benzodiazepines
Phenytoin
First line drug for partial seizures
Inhibits Na+ channels
Half life 22 – 36 hours
Adverse affects: CNS sedation, drowsiness, ataxia, confusion,
insomnia, nystagmus, gum hyperplasia, hirsutism
Interactions: carbamazepine decreases and diazepam
increases plasma levels
Benzodiazepines
Diazepam and clonazepam
Status epilepticus
GABA A receptors
Half life: 20 – 40 hours
Adverse effects: CNS sedative, tolerance, dependence
paradoxical hyper-excitability in children
Drug interactions: enhance the action of other CNS
depressants
Carbamazepine (Tegral)
First line agent for acute mania and mania prophylaxis
Indicated for rapid cyclers and mixed patients
Carbamazepine
First-line drug for partial seizures
Inhibits Na+ channels
Half life: CNS sedation. Agranulocytosis and aplastic anemia in
elderly patients, rare but very serious adverse side effect. Mild
transient leukopenia in 10% (usually disappears in first 4
months)
Can exacerbate some generalized seizures
Drug interactions: stimulates the metabolism of other drugs
and stimulates its own metabolism (this may require increase
in dose)
.
Before med is started: baseline liver function tests, CBC and an
EKG
Monitoring: Steady state achieved after 5 days -check 12 hours
after last dose and repeat CBC and LFTs
Goal: Target levels 4-12mcg/ml
Need to check level and adjust dosing after around a month
because induces own metabolism
Carbamazepine side effects
Rash- most common SE seen
Nausea, vomiting, diarrhea, transaminitis
Sedation, dizziness, ataxia, confusion
AV conduction delays
Aplastic anemia and agranulocytosis (<0.002%)
Water retention due to vasopressin-like effect which can result
in hyponatremia
Drug-drug interactions
Valproate
First-line for generalized seizures, partial seizures
Enhances GABA transmission, blocks Na+ channels, activates
K+ channels
Half life: 6 – 16 hours
Adverse effects: CNS depressant , anorexia nausea, vomiting
hair loss, weight gain, elevation of liver enzymes.
Hepatotoxicity is rare but severe
Drug Interactions: may potentiate CNS depressants
Steven-Johnson syndrome
Valproic acid (Epival)
Valproic acid is as effective as Lithium in mania prophylaxis but
is not as effective in depression prophylaxis
Factors predicting a positive response:
Rapid cycling patients (females>males)
Comorbid substance issues
Mixed patients
Comorbid anxiety disorders
Better tolerated than Lithium
Valproic acid
Before med is started: baseline liver function tests (LFT),
pregnancy test and CBC
Start folic acid supplement in women
Monitoring: Steady state achieved after 4-5 days -check 12
hours after last dose and repeat CBC and Liver Function Tests
Goal: target level is between 50-125
Ethosuximide
Absence seizures
Blocks T-type Ca++ currents in thalamus
Half life: 40 hours
Adverse effects: gastric distress – pain, nausea, vomiting.
Transient fatigue, dizziness, headache
Drug interactions: Valproate inhibits its metabolism
Lamotrigine
Effective against generalized seizures
Mono-therapy for refractory partial seizures
Add-on therapy
Inhibition of Na+ channels, glutamate release , may inhibit Ca+
+ channels
Half life: 24 hours
Adverse effects: CNS sedative (less), Dermatitis
Drug interactions: Valproate increases its level, Carbamazepine
decreases its level
Lamotrigine ( Lamictal)
Indications similar to other anticonvulsants
Also used for neuropathic/chronic pain
Before med is started: baseline liver function tests
Initiation/titration: start with 25 mg daily X 2 weeks then
increase to 50mg X 2 weeks then increase to 100mg- faster
titration has a higher incidence of serious rash
If the patient stops the med for 5 days or more have to start at
25mg again
Levetiracetam
Add-on therapy for partial seizures
Binds to synaptic vesicle protein SV2A, may regulate
neurotransmitter release
Half life: 6 – 8 hours
Adverse effects: CNS depressant
Drug interactions: minimal
Topiramate
Effective as monotherapy for partial or generalized seizures
Add-on for refractory partial or generalized seizures
Blockade of Na+ channels, increases frequency of GABA A
channel openings, may interfere glutamate binding
Half life: 20 – 30 hours
Adverse effects: CNS sedative
Drug interactions: some drugs
Antipsychotics as mood
stabilizers
Antipsychotics as mood
stabilizers
Olanzapine

Quetiapine
Lithium
Salt
Soft drinks
Lithium batteries
Greek tradition
Therapeutic salt (Cade)
Mood stabilizer
 Lithium
Only medication to reduce suicide rate
Rate of completed suicide in BAD 15%
Effective in long-term prophylaxis of both mania and depressive
episodes in 70+% of BAD I patients
Factors predicting positive response to lithium
Prior long-term response or family member with good
response
Classic pure mania
Mania is followed by depression
Lithium
Dose 400 – 800 mg / day
Serum li level
0.5 – 0.8 mmol/L prophylactic
0.8 – 1.0 mmol/L therapeutic
Toxicity
Hypothyroidism
Cardiac toxicity
Diabetes insipidus
Lithium- how to use it
Before starting :Get baseline creatinine, TSH and CBC. In
women check a pregnancy test- during the first trimester is
associated with Ebstein’s anomaly 1/1000 (20X greater risk
than the general population)
Monitoring: Steady state achieved after 5 days- check 12 hours
after last dose. Once stable check q 3 months and TSH and
creatinine q 6 months.
Goal: blood level between 0.6-1.2
Lithium side effects
Most common are GI distress including reduced appetite,
nausea/vomiting, diarrhea
Thyroid abnormalities
Nonsignificant leukocytosis
Polyuria/polydypsia secondary to ADH antagonism. In a small
number of patients can cause interstitial renal fibrosis.
Hair loss, acne
Reduces seizure threshold, cognitive slowing, intention tremor
Lithium toxicity

Mild- levels 1.5-2.0 see vomiting, diarrhea, ataxia, dizziness,

slurred speech, nystagmus.

Moderate-2.0-2.5 nausea, vomiting, anorexia, blurred vision,

clonic limb movements, convulsions, delirium, syncope

Severe- >2.5 generalized convulsions, oliguria and renal failure