Antiepileptics

by David Rosenblum November,18

Antiepileptics

Classification

Barbiturate	Phenobarbitone
Deoxybarbiturate	Primidone
Hydantoin	Phenytoin Fosphenytoin
Iminostilbene	CarbamazepineOxcarbazepine
Succinimide	Ethosuximide
Aliphatic carboxylic acid	Valproic acid (sodium valproate)Divalproex
Benzodiazepines	Clonazepam Diazepam Lorazepam Clobazam
Phenyltriazine	Lamotrigine
Cyclic GABA analogue	Gabapentin Pregabalin
Newer drugs	Topiramate Zonisamide Levetiracetam Vigabatrin Tiagabine Lacosamide

Phenobarbitone

Enhancement of GABA_A receptor medited synaptic inhibition appears to be most important mechanism
Higher anticonvulsant: hypnotic ratio of phenobarbitone is due to minimal effect on Ca²⁺ channels and glutamate release.
It has a wide spectrum of anticonvulsant property – it raises seizure threshold as well as limits spread and suppresses kindled seizures
A mean intravenous or intramuscular loading dose of 15 mg/kg of phenobarbitone safely achieved therapeutic levels within 2 hours of injection and high therapeutic levels weremaintained with a dose of 6 mg/kg a day. ⁽¹⁾
In infants with asphyxia, prophylactic phenobarbitol does not reduce the incidence of seizures, HIE and mortality. ⁽²⁾
Parenteral phenobarbitone is an integral part of the management of status epilepticus in resource poor counteries (RPC). It is highly effective at cntrolling seizures. Withdrawal of this drug is likely to have a devastating effect on the outcome of status epilepticus in RPCs. ⁽³⁾
Phenobarbitone potentiates the effect of ethyl alcohol in human behaviour. ⁽⁴⁾
Activated charcoal seems to be as efefctive as forced alkaline diuresis, hemodialysis and hemoperfusion for removal of phenobarbitone following overdosage. ⁽⁵⁾
Phenobarbital is more selective than pentobarbital in increasing motor cortical thresholds. ⁽⁶⁾
Phenobarbitoen is an alternative to beta -adrenoreceptor antagonists in treating essential tremor. ⁽⁷⁾
Phenobarbital is still the most cost effective pharmacological treatment for epilepsy. It helps to close the gap in low and middle income counteries during its second century of clinical use. ⁽⁸⁾
Phenobarbital is safe and effective as a large community based intervention for epilepsy care. ⁽⁹⁾
Phenobarbitone induce the metabolism of acetaminophen. ⁽¹⁰⁾
Phenobarbitone is efefctiv, well tolerated AED and donot have cognitive impairment. There is variable and distinct improvement in cognition and psychosocial functioning and is effective in seizure control. ⁽¹¹⁾
Has slow oral absorption and a long plasma t ½ (80-120 hours).
It is metabolized in liver and excreted unchanged in urine
Steady state is reached after 2-3 weeks and single daily dose can be used for maintenance
Side effects include:
Osteomalacia
Megaloblastic anemia
Rashes
Mental confusion in older people
Hyperactivity in children
Impairment of learning and memory
Dimunition of intelligence
Behavioural abnormalities
Sedation
It induces drug reaction with eosinophillia and systemic symptoms (DRESS). ⁽¹²⁾

Uses:
Generalized tonic clonic seizures (GTC)
Simple partial seizures (SP)
Complex partial seizures (CP)

Primidone

A deoxybarbiturate, converted by liver into phenobarbitone and phenylethyl malonamide (PEMA)
T ½ of primidone is 6-14 hours
Primidone is effective in reducing essential tremor in hand and head, its effective is comparable to that of propanolol. ⁽¹³⁾
Primidone is an effective agent in the treatment of essential tremor. ⁽¹⁴⁾
Primidone is a very effective drug in focal seizures and is the drug of choice for psychomotor seizures. It is relatively more effective on first and second day of the treatment while there is a sharp increase in the effectiveness of diphenylhydantoin on the fifth treatment day. ⁽¹⁵⁾
Primidone possesse independent anticonvulsant activity and is more potent than phenobarbital with respect to maximal electroshock. Primidone and phenobarbital are more effective anticonvulsant than phenylethylmelonamide.⁽¹⁶⁾
Primidone kinetics is influenced by concurrent antiepileptic drugs and by the duration of primidone therapy. ⁽¹⁷⁾
Primidone is effective in suppressing ventricular arrhythmias and shortening of QT interval in patients with seizures, ventricular fibrillation and syncope. ⁽¹⁸⁾
About 1/3^rd of primidone is excreted unchanged in urine
Dose to dose, primidone is less potent, but anti epileptic efficacy is similar to phenobarbitone
Adverse effects are:
Adverse effect similar to phenobarbitone
Anemia
Leucopenia
Psychotic reaction
Lymph node enlargement
Uses:
GTCS generalized tonic clonic seizures
Partial epilepsy

Phenytoin (Diphenylhydantoin)

Not a CNS depressant
Toxic dose produces excitement and muscular rigidity
Abolition of tonic phase of maximal electroshock seizures, with no effect on or prolongation of clonic phase
It limits the spread of seizure activity
Threshold for PTZ convulsions is not raised
Tonic clonic epilepsy is suppressed but paroxysmal focal EEG discharge and aura persists
Phenytoin is appropriate for the treatment of sone seizures seen in the ED, it is associated with significant adverse effects. Trials are ongoing regarding the use of other anticonvulsants in the treatment of status epilepticus. ⁽¹⁹⁾
On increasing the dose of phenytoin in chronic epileptics receiving phenytoin and either phenobarbitone or primidone, there was no effect on minor seizures but major seizures were abolished or reduced. Serum concentration of phenobarbitone also raised. ⁽²⁰⁾
Phenytoin appears to be a useful topical agent in promoting healing of diabetic foot ulcers. ⁽²¹⁾
Marked phenytoin toxicity occurs in critically ill patients associated with hypoalbuminemia causing gradual decrease in the level of consciousness and cerebellar signs. It can be detected only by direct measurement of free phenytoin levels. ⁽²²⁾
Phenytoin has a protective effect in vivo on spinal cord axons, preventing their degeneration, maintaining their ability to conduct action potentials and improving clinical status in a model of neuroinflammation. ⁽²³⁾
There is worsening of seizures following phenytoin discontinuation which reflects loss of therapeutic drug effect rather than a true abstinence phenomenon. ⁽²⁴⁾
When taking phenytoin with food, product switches may result in either side effects or loss of seizure control. ⁽²⁵⁾
Even though phanytoin is classified as both an anticonvulsant and an antiarrhythmic, its sodium channel kinetics and various studies have shown that phenytoin is unlikely to produce cardiac arrhythmias even in setting of severe toxicity. ⁽²⁶⁾
Mechanism of action
It has stabilizing influence on neuronal membrane – prevents repetitive detonation of normal brain cells during depolarization shift that occurs in epileptic patients
It prolongs the inactivated state of voltage sensitive neuronal Na⁺ channel
Higher toxic concentration cause reduction in Ca2+ influx, inhibition of glutamate and facilitation of GABA responses
Pharmacokinetics
Absorption by oral route is slow
It is widely distributed in the body and is 80-90% bound to plasma protein
Phenytoin is metabolized in liver by hydroxylation involving CYP2C9 and 2C19 as well as glucoronide conjugation
Kinetics of metabolism is capacity limited; changes from first order to zero order over the therapeutic range
The t ½ (12-24 hours at therapeutic level), progressively increases (up to 60 hours) when plasma concentration rises above 10 mcg/ ml
Adverse effects:
At therapeutic levels
Gum hypertrophy
Hirsutism, coarsening of facial features, acne
Hypersensitivity reaction – rashes, DLE, lymphadenopathy, neutropenia
Megaloblastic anemia
Osteomalacia
It can inhibit insulin release and cause hyperglycemia
Used during pregnancy, causes fetal hydantoin syndrome: hypoplastic phalanges, cleft palate, hare lip, microcephaly
At high plasma level:
Cerebellar and vestibular manifestations: ataxia, vertigo, diplopia, nystagmus
Drowsiness, behavioural alterations, mental confusion, hallucinations, disorientation and rigidity
Epigastric pain, nausea and vomiting
Local vascular injury
Fall in BP and cardiac arrhythmias occur on iv injection
Drug interactions
Phenobarbitone inhibits phenytoin metabolism
Carbamazepine and phenytoin induce each other’s metabolism
Valproate displaces protein bound phenytoin and decreases its metabolism
Valproic acid displace phenytoin from plasma binding sites, enhancing the systemic clearance of the drug and inhibit its metabolism thereby increasing the concentration of free drug in the serum. ⁽²⁷⁾
Chloramphenicol, isoniazid, cimetidine and warfarin inhibit phenytoin metaboilism
Phenytoin inhibit warfarin metabolism
Phenytoin increases degradation of steroids
A number of acidic drugs displace it from protein binding sites
Uses:
Generalized tonic clonic seizures, simple and complex partial seizures
Status epilepticus
Trigeminal neuralgia

Fosphenytoin

Water soluble prodrug of phenytoin.
Administration of fosphenytoin iv ot im offers a tractical and convenient alternative to iv phenytoin. ⁽²⁸⁾
fosphenytoin can be safely administered thrugh the im route and it also offers advantage over phenytoin for iv administration. The efficacy, safety and pharmacokinetics of fosphenytoin is similar in 5-18 year old children and in young adults. ⁽²⁹⁾
Fosphenytoin is a valuable treatment option for the rapid treatment of status epilepticus. The risk of venous adverse events is lower than with pheytoin when administered at the recommended rate. ⁽³⁰⁾
Administration of iv fosphenytoin causes prolongation of ST segment and the QT interval and merging of P and T waves. These changes may be attributed to inorganic phosphate induced hypocalcemia. ⁽³¹⁾
Both intravenous and intramuscular administration of fosphenytoin is well tolerated, with mild bruising, tenderness, swelling and/or erythema seen at infusion and injection sites in small number of patients. ⁽³²⁾
A single intramuscular injection of fosphenytoin (20 phenytoin equivalents/kg) does not prevent seizures or neurologic dificts in childhood nontraumatic coma. ⁽³³⁾
In a single institution, fosphenytoin administartion is inappropriate almost half the time. Oral phenytoin loading is less expensive and safe. ⁽³⁴⁾
Intramuscular fosphenytoin is rapidly absorbed (therapeutic levels achieved as early as 5-20 min). It is well tolerated in most patients irrespective of injection volume. ⁽³⁵⁾
Fosphenytoin sodium is considered to be useful substitute for phenytoin sodium with almost no associated injection site reactions. ⁽³⁶⁾
In the body, it is rapidly metabolized to phenytoin
On iv injection, only minor vascular complications occurs. It is less damaging to intima
Fosphenytoin can be injected with both saline and glucose

Carbamazepine

It is a first line antiepileptic drug
Carbamazepine modifies maximal electroshock seizures as well as raises threshold to PTZ and electroshock convulsions
It exerts a lithium like therapeutic effect in mania and bipolar mood disorder
It also has antidiuretic action, by enhancing ADH action on renal tubules
Carbamazepine is efficacious in the maintenance treatment of bipolar disorder in naturalistic clinical practice, either as monotherapy or in combination with other medicines. ⁽³⁷⁾
Carbamazepine causes anticonvulsant drug hypersensitivity syndromes which can present with wide spectrum of symptoms like diarrhea, negative t wave, fever, skin rashes etc. ⁽³⁸⁾
Lamotrigrine and carbamazepine has similar effeicacy against partial onset seizures and primary generalized tonic-clonic seizures in newly diagnosed epilepsy. ⁽³⁹⁾
Crabamazepine suppresses methamphetamine induced Fos expression in a regionally specific manner. The nucleus accumbens and the Caudate/ Putamen brain region are involved in the antimanic effects of carbamazepine. ⁽⁴⁰⁾
Haemodilysis is a simple, cheap and good therapeutic option in removing carbamazepine from the circulation in patients with severe carbamazepine overdose. ⁽⁴¹⁾
Pharmacokinetics
Oral absorption is slow and variable because of poor water solubility
It is 75% bound to plasma proteins and metabolized in liver by oxidation to an active metabolite (10-11 epoxy carbamazepine) as well as hydroxylation and conjugation to inactive ones
Plasma t ½ of 20-40 hours but decreases on chronic medication due to autoinduction of metabolism
Multiple epoxides and a cyclic peroxide are involved in the invivo metabolism of carbamazepine in man. ⁽⁴²⁾

Adverse effects:
Dose related neurotoxicity- sedation, dizziness, vertigo, diplopia and ataxia
Vomiting and diarrhea
Acute intoxication causes coma, convulsions and cardiovascular collapse
Hypersensitivity reactions: rashes, photosensitivity, hepatitis, lupus like syndrome, agranulocytosis and aplastic anemia
Water retention and hyponatremia occurs in elderly as it enhances ADH action
Carbamazepine is a potentially hepatotoxic drug. Vitamin C has a hepatoprotective activity against carbamazepine induced hepatotoxicity. ⁽⁴³⁾

Interactions:
Carbamazepine can reduce efficacy of haloperidol, oral contraceptives, lamotrigine, valproate and topiramate
Metabolism of carbamazepine is induced by phenobarbitone, phenytoinand vice versa
Erythromycin, fluoxetine, isoniazid inhibit metabolism of carbamazepine
Erythromycin induces carbamazepine toxicity which manifest as drowsiness, lethargy, ataxia, vomiting and nystagmus. More serious adverse effects are heart block and severe liver and kidney failure. ⁽⁴⁴⁾
Simethicone and carbamzepine when taken together may be a cause of carbamazepine toxicity. ⁽⁴⁵⁾

Uses:
Complex partial seizures (CPS)
GTCS (generalized tonic clonic seizures)
SPS (simple partial seizures)
Trigeminal and other neuralgia: carbamazepine is the drug of choice
Manic depressive illnesses and acute mania

Oxcarbamazepine

Newer congener of carbamazepine that is rapidly converted to an active metabolite that is glucoronide conjugated but not oxidized
Risk of hepatotoxicity is lower but that of hyponatremia is more
Indications are same as that of carbamazepine, but it is better tolerated.
Dose to dose, it is 1 ½ times less potent
Oxcarbamzepine induces immunoglobulin deficiency. ⁽⁴⁶⁾
Oxcarbamazepine has a potent antineuralgic properties in the absence of significant side effects and therfore may be useful in the management of intractable trigeminal neuralgia. ⁽⁴⁷⁾
For patients with partial onset seizures, oxcarbamazepine is less likely to be withdrawn. It cannot be assessed whenther oxcarbamazepine is equivalent, superior or inferior to phenytoin in seizure control. ⁽⁴⁸⁾
Oxcarbamazepine can be used in patients with autistic disorder and significant disruptibe behaviors. It has a favorable side effect profile and is available in liquid formulation which is more convenient for autistic patients. ⁽⁴⁹⁾
Acute dyskinesia is a rare adverse efefct of oxcarbamazepine in epilepsy patient with neurobehavioral symptoms. ⁽⁵⁰⁾
Oxcarbamazepine does not suppress cortical spreading depression and thus cannot be used for migraine prophylaxis. ⁽⁵¹⁾
Oxcarbamazepine is a useful adjunct in the treatment of gabapentin resistant complex regional pain syndrome type 1 in children. ⁽⁵²⁾
Superior oblique myokymia is a rare form of nystagmus that causes oscillopsia and blurry vision. oxcarbamazepine can be used to successfully eliminate oscillopsia without serious adverse reaction. ⁽⁵³⁾
Oxcarbamazepine can also induce Steven Johnson syndrome. ⁽⁵⁴⁾

Ethosuximide

The most prominent action is antagonism of PTZ induced clonic seizures at doses which produces no discernable action
It raises seizure threshold but does not modify maximal electroshock seizures or inhibit kindling
Clinically effective only in absence seizures
Primary action is exerted on thalamocortical system which is involved in generation of absence seizures
It selectively suppresses T current without affecting other types of Ca²⁺ or Na⁺ currents
It does not potentiate GABA at therapeutic concentrations
Slowly but completely absorbed, not protein bound, evenly distributed in the body.
It is metabolized in liver by hydroxylation and glucoronidation and excreted in urine – about ¼ in unchanged form
Plasma t ½ averages 48 hours in adults and 32 hours in children
Adverse effects:
Gastrointestinal intolerance
Tiredness
Mood changes
Agitation
Headache, drowsiness and inability to concentrate
Hypersensitivity reaction like rashes, DLE and blood dyscrasias
The only indication of ethosuximide is absence seizures
Ethosuximide is used in the treatment of absence (petit mal) seizures. ⁽⁵⁵⁾
There is ethosuximide induced conversion of of typical childhood absence seizures to rolandic spikes. ⁽⁵⁶⁾
Ethosuximide compensate damage caused by seizure attacks and other neuronal loss disorders. ⁽⁵⁷⁾
Granulopenia and thrombocytopenia occurs after ethosuximide. ⁽⁵⁸⁾
In human adult and infant plasma, the monohydroxyethosuximides are present in larger quantities than the unchanged drug. Four monohydroxymetabolites of ethosuximide are identified in urine of man. ⁽⁵⁹⁾
Ethosuximide may be useful pharmacological agent for alcohol withdrawal and treatment of resulting seizures. ⁽⁶⁰⁾
Age does not alter the plasma level of ethosuximide. The plasma level increases more rapidly in females than males. Intake of methylphenobarbitone and not phenytoin, phenobarbitone, primidone and carbamazepine alter the relationship between plasma ethosuximide level and ethosuximide dose. ⁽⁶¹⁾
Ethosuximide and Gabapentin significantly attenuates nonconvulsive seizures in a dose related manner and may help to improve patient outcome from brain ischemia induced seizure activity. ⁽⁶²⁾

Valproic acid (Sodium Valproate)

It is a branched chain aliphatic carboxylic acid with broad spectrum anticonvulsant action
More potent in blocking PTZ seizures than in modifying maximal electroshock
At anticonvulsant doses, valproate produce little sedation or other central effects
It is effective in partial seizures and GTCS as well as absence seizures
Valproate facilitates critical period learning in the adult human brain. ⁽⁶³⁾
Sodium valproate is most efficacious in generalized seizure disorders, particularly absence seizures. Drowsiness and gastrointestinal symptoms are most common side effects which are usually minor and transient. ⁽⁶⁴⁾
Maternal use of valproate during pregnancy is associated with significant increase risk of autism spectrum disorder and childhood autism in the offspring even after adjusting maternal epilepsy. ⁽⁶⁵⁾
Intravenous sodium valproate is non-inferior to intravenous phenytoin as the first line treatment in status epilepticus with no significant cardiovascular compromises. ⁽⁶⁶⁾
Sodium valproate or lithium is used as first line treatment in euphoric mania. Sodium valproate is the agent of choice in patients with mixed mania, rapid cycling, comorbid substance use or other associated neurological abnormalities. ⁽⁶⁷⁾
Sodium valproate is a gamma-aminobutyric acid (GABA) transaminase inhibitor and it is suggested that it raises GABA levels in the hypothalamus and ir responsible for the reduction in ACTH secretion. ⁽⁶⁸⁾
The use of valproic acid results in elevated plasma ammonia which may lead to hyperammonemic encephalopathy. ⁽⁶⁹⁾
Intravenous sodium valproate is an effective alternative to diazepam infusion in controlling refractory satus epilepticus in children and is free of respiratory depression and hypotension. ⁽⁷⁰⁾
In mitochondrial disorders, there is a high prevalance of valproate toxicity predicting genomic alterations. ⁽⁷¹⁾
The mood stabilizing effects of valproic acid may be mediated in part by alterations in corticotropin releasing factor neuronal activity. ⁽⁷²⁾
Valprate protect beta-cells of pancreas from palmitate induced apoptosis and ER stress via GSK-3beta inhibition, independent of ATF4/CHOP pathway. ⁽⁷³⁾
Multiple mechanisms:
A phenytoin like frequency dependent prolongation of Na⁺ channel inactivation
Weak accentuation of Ca²⁺ mediated T current (ethosuximide like)
Augmentation of release of inhibitory transmitter GABA by inhibiting its degradation (by GABA transaminase) and also increasing its synthesis from glutamic acid
Pharmacokinetics:
Oral absorption is good
It is 90% bound to plasma proteins; completely metabolized in liver mainly by CYP2C9 and 2C19 and glucuronide conjugation and then excreted in urine
Plasma t ½ is 10-15 hours, but anticonvulsant effects are longer lasting
Adverse effects:
Anorexia
Vomiting, loose motions
Heart burn
Drowsiness, ataxia and tremor
Cognitive and behavioural effects are not prominent
Alopecia, curling of hair
Weight gain
Bleeding tendency
Rashes
Thrombocytopenia
Asymptomatic rise in serum transaminase
Fulminant hepatitis
Used during pregnancy, it causes spina bifida and other neural tube defects
Interactions
Valpraote increases plasma levels of phenobarbitone and lamotrigine
It displaces phenytoin from protein binding site and decreases its metabolism – phenytoin toxicity
It inhibits hydrolysis of active epoxide metabolite of carbamazepine
Concurrent use of clonazepam and valproate is contraindicated because absence status may be precipitated
Fetal abnormalities are more common if valproate and carbamazepine are given concurrently
Uses
Valproate is drug of choice for absence seizures
It is an alternate/ adjuvant drug for GTCS, SPS and CPS
Myoclonic and atonic seizures
Mania and bipolar illness
Also used in panic attacks
Prophylactic efficacy in migraine

Divalproex (Semisodium Valproate)

It is coordination compound of valproic acid with sodium valproate
Oral absorption is slower, but bioavailability is same
Gastric tolerance may be better
Extended release divalproex sodium can be used in the treatment of bipolar disorders. ⁽⁷⁴⁾
Divalproex treatment is associated with accelerated brain volume loss over 1 year and perhaps with greater cognitive impairment. ⁽⁷⁵⁾
Divalproex is an effective prophylactic drug for patients with migraine headache and is generally well tolerated. ⁽⁷⁶⁾
Divalproex sodium is effective and generally well tolerated prophylactic treatment option as monotherapy or in polytherapy for migraine and cluster headache. ⁽⁷⁷⁾

Clonazepam

It is a BZD with prominent anticonvulsant properties; block PTZ at doses which produce mild sedation
Efficacy in modifyomng maximal electroshock seizure is low
It is singularly ineffective in GTCS
Production of generalized seizures by kindling is suppressed, but local after-discharges persist
BZD potentiate GABA induced Cl^– influx to produce sedation.
At large doses, high frequency discharges are inhibited akin to phenytoin
Clonazepam is particularly valuable in epilepsy with associated myoclonus and in photosensitive epilepsy. ⁽⁷⁸⁾
Clonazepam use is associated with pancytopenia, thus patient should be regularly monitored with complete blood count. ⁽⁷⁹⁾
The sleep related painful erection in elderly men can be successfully treated with clonazepam. ⁽⁸⁰⁾
Clonazepam can be used as agonist substitution treatment for benzodiazepine dependence and leads to improvement in clinical situation including cessation of craving, absence of withdrawal symptoms, reduced anxiety, improvements in social functioning and a better cognition level. ⁽⁸¹⁾
Clonazepam is used in the treatment of absence seizures with automatisms. ⁽⁸²⁾
Clonazepam can be used as prophylactic treatment in busulfan related myoclonic epilepsy in autografted acute leukemia patients. ⁽⁸³⁾
Adjuvant use of lansoprazole, clonazepam and dimenhydrinate is effective to treat intractable hiccups in patients with gastritis and reflux esophagitis complicated with myocardial infarction. ⁽⁸⁵⁾
The combined paroxetine and clonazepam treatment resulted in more rapid response than with paroxetine monotherapy for panic disorder but there was no differential benefit beyond the initial few weeks of therapy. ⁽⁸⁶⁾
Clonazepam is efficacious as an intermittent therapy for febrile seizures if parents are informed of its side effects like lethargy and ataxia. ⁽⁸⁷⁾
Clonazepam is effective in the treatment of panic disorders. ⁽⁸⁸⁾
Pharmacokinetics
Oral absorption is good
It is 85% bound to plasma proteins, completely metabolized in liver and excreted in urine
T ½ averages 24 hours
It does not produce any active metabolite
There is a steady-state concentration of clonazepam in serum after chronic oral administration. ⁽⁸⁴⁾
Adverse effects
Sedation and dullness
Lack of concentration, irritability, temper and other behavioral abnormalities
Motor disturbances and ataxia is dose related
Salivation and increased respiratory secretions
Uses
Absence seizures
Used as an adjuvant in myoclonic and akinetic epilepsy
Infantile spasms
Also used to suppress acute mania

Clobazam

Used partial, secondarily generalized tonic clonic as well as absence and atonic seizures, including some refractory cases
Sedation and psychomotor retardation are less prominent, side effects is similar to other BZDs
It appears to act by facilitating GABA action
Oral bioavailability of clobazam is 90% and elimination t ½ is 18 hours, but an active metabolite is produced which has longer t ½ (> 35 hrs)
Generally used as an adjuvant to other antiepileptic drugs like phenytoin, carbamazepine or valproate in refractory epilepsy
Clobazam is effective as an intermittent therapy in febrile seizures. ⁽⁸⁹⁾
Clobazam is effective in catamenial epilepsy. ⁽⁹⁰⁾
Stable dosage of clobazam for Lennox-Gestaut syndrome is associated with sustained drop-seizure and total-seizure improvements over 3 years. ⁽⁹¹⁾
High and medium dosage clobazam is more efficacious than other epileptic therapies in Lennox Gestaut syndrome. ⁽⁹²⁾
Clobazam is a 1,5-benzodiazepine. It diplays a wide seperation of psychosedative or tranquillizing properties from impairment of motor coordination. It is effective anxiolytic agent when given in daily doses of 20-30 mg and produces minimal effects on psychomotor performance. It has a long elimination half life of 18 h; the main metabolite is N-desmethylclobazam. ⁽⁹³⁾
Clobazam can be used for the treatment of refractory epilepsy and chronic drug resistant complex partial seizures. ⁽⁹⁴⁾
Clobazam can be used in the treatment of partial status epilepticus. ⁽⁹⁵⁾
Clobazam is safe and effective in the treatment of focal epilepsy in childhood and should be considered in patients with refractory seizures. ⁽⁹⁶⁾

Diazepam

Anticonvulsant activity in variety of seizures
Prominent sedation action and rapid development of tolerance to the anti epileptic effect
1^st line drug for emergency control of convulsions, eg status epilepticus, tetanus, eclampsia, convulant drug poisoning etc.
Diazepam can be used in the treatment of seizures. ⁽⁹⁷⁾
Diazepam is relatively more discriminable than buspirone. ⁽⁹⁸⁾
The regular use of diazepam does not increase the risk of breast cancer. ⁽⁹⁹⁾
Pretreatment with diazepam exhibits anti-inflammtory property in cerulein induced acute pancreatitis possibly through peripheral benzodiazepine receptors. ⁽¹⁰⁰⁾
Diazepam with methadone in methadone maintenance appears to increase some physiologic and subjective opioids effects. ⁽¹⁰¹⁾
Diazepam can be used in suppressing gammahydroxybutyrate (GHB) dependence and realted withdrawal symptoms. ⁽¹⁰²⁾
Diazepam is a valuable drug in case of acute myocardial infarction. It causes a lower stress reaction, which is beneficial in diminishing the incidence of malignant arrhythmias and preventing the existing myocardial injury from spreading.⁽¹⁰³⁾
Low dose diazepam can be combined with kava to reduce harmful effects and is recommended for clinical use in patients chronically treated with this anticonvulsant drug. ⁽¹⁰⁴⁾
Adverse effects:
Thrombophlebitis in injected vein
Marked fall in BP
Respiratory depression
Rectal instillation of diazepam is preferred therapy for febrile convulsions in children

Lorazepam

0.1 mg/ kg injected iv at a rate not exceeding 2 mg/ min is better suited than diazepam in status epilepticus or for emergency control of convulsions of other etiology
Lesser thrombophlebitic complications and more sustained action than that of diazepam
Lorazepam impairs highway driving performance more than heavy alcohol consumption. ⁽¹⁰⁵⁾
Care should always be exercised when prescribing lorazepam in older patients. ⁽¹⁰⁶⁾
Lorazepam is safe and feasible to prevent complications associated with alcohol withdrawal in patients with acute myocardial infarction. ⁽¹⁰⁷⁾
High dose intravenous lorazepam may be an effective alternative to pentobarbital for the treatment of severe status epilepticus. ⁽¹⁰⁸⁾
Absorption kinetics for both oral and intramuscular lorazepam is dose dependent. Plasma t1/2 for intact lorazepam is independent of dose and administration route. ⁽¹⁰⁹⁾
Lorazepam is more effective than chlordiazepoxide in alcohol withdrawal in both a faster rate in the drop of withdrawal severity and lessening the total duration of withdrawal. ⁽¹¹⁰⁾
Propofol combined with lorazepam can be used for severe poly substance misuse and withdrawal states in intensive care unit. Lorazepam alone is ineffective in such cases. ⁽¹¹¹⁾

Lamotrigine

Carbamazepine like action profile: modifies electroshock and decreases electrically evoked as well as photic after discharge duration
Prolongation of Na⁺ channel inactivation and suppression of high frequency firing
It may directly block voltage sensitive Na⁺ channels, thus stabilizing the presynaptic membrane and preventing release of excitatory neurotransmitters, mainly glutamate and aspartate
It does not antagonize PTZ seizures or block NMDA type of glutamate receptors
Used as add on therapy in refractory cases of partial seizures and GTCS
Also effective in absence and myoclonic or akinetic seizures
Lamotrigine is well absorbed orally and metabolized completely in liver
Its t ½ is 24 hours, but is reduced to 16 hr in patient receiving phenytoin, carbamazepine or phenobarbitone
Valproate doubled the blood level of lamotrigine but lamotrigine reduce the valproate level
Women on lamotrigine are more likely to develop drug induced rashes. ⁽¹¹²⁾
Lamotrigine is used in the management of bipolar disorders. ⁽¹¹³⁾
Lamotrigine has a beneficial effect on the depressive symptoms in the depressed phase of bipolar disorder. ⁽¹¹⁴⁾
Aseptic meningitis is a rare complication of lamotrigine. ⁽¹¹⁵⁾
Lamotrigine is used in treating bipolar disorders particularly as maintenance therapy. It is used for treating bipolar depression and rapid cycling. It is generally well tolerated, but it can cause dose dependent CNS side effects and benign allergic rash. Drug interaction occurs with valproate (an inhibitor) and several enzyme inducers. ⁽¹¹⁶⁾
Lamotrigine and carbamazepine have similar efficacy against partial onset seizures and primary generalised tonic-clonic seizures in newly diagnosed epilepsy. Lamotrigine, however, is better tolerated. ⁽¹¹⁷⁾
Combined lamotrigine and valproate are effective in controlling seizures in refractory epilepsy in children and adolescents. ⁽¹¹⁸⁾
Leucopenia can be seen in patients treated with lamotrigine. Thus a close haematological monitoring of patients should be done during first few weeks of treatment. ⁽¹¹⁹⁾
Lamotrigine is safe and effective treatment option for adult attention deficit hyperactivity disorder comorbid with bipolar and recurrent depression. ⁽¹²⁰⁾
Side effects:
Sleepiness, dizziness
Diplopia
Ataxia and vomiting
Rashes are seen in children requiring withdrawal

Gabapentin

GABA derivative which cross to the brain and enhances GABA release
It modifies maximal electroshock as well as inhibits PTZ induced clonic seizures
Modulate voltage sensitive Ca²⁺ channels. Decrease entry of Ca²⁺ entry into these channels reduce glutamate release, lowers the neuronal excitability
Added to a first line drug, it reduced seizure frequency in refractory partial seizures with or without generalization
Effective in SPS and CPS
1^st line drug in neuralgic pain due to diabetic neuropathy and post herpetic neuralgia
The treatment of refractory chronic cough with gabapentin is both effective and wel tolerated. ⁽¹²¹⁾
Gabapentin improves the analgesic efficacy of opioids both at rest and with movement, reduces analgesic consumption and opioid-related adverse effects, but is associated with an increased incidence of sedation and dizziness. ⁽¹²²⁾
Gabapentin (Particularly 1800 mg dosage) is effective in treating alcohol dependence and relapse related symptoms of insomnia, dysphoria and craving with favourable safety profile. ⁽¹²³⁾
Gabapentin improves sensory and motor symptoms in restless leg syndrome and also improves sleep architecture and periodic leg movements during sleep (PLMS). ⁽¹²⁴⁾
Gabapentin induces cholestatic jaundice. ⁽¹²⁵⁾
Duloxetine was noninferior to pregabalin for the treatment of pain in patients with diabetic peripheral neuropathy who had inadequate pain response to gabapentin. ⁽¹²⁶⁾
The treatment of pain associated with diabetic peripheral neuropathy and post herpetic neuralgia with pregabalin is a cost effective intervention compared to gabapentin. ⁽¹²⁷⁾
Gabapentin is efefctive in treating refractory insomnia in children. ⁽¹²⁸⁾
Gabapentin is a safe alternative for the management of recurrent, refractory idiopathic priapism. ⁽¹²⁹⁾
3000 mg gabapentin extended release taken once daily is effective and well tolerated for the treatment of diabetic peripheral neuropathy pain. ⁽¹³⁰⁾
Monotherapy or adjuvant therapy with venlafaxine is comparable to gabapentin for neuropathic pain management. ⁽¹³¹⁾
Single preoperative or repeated doses of gabapentin continued up to few days after surgery decrease acute postoperative pain and/ or need of postoperative opioids. It also decrease chronic pain several weeks after surgery. ⁽¹³²⁾
A single low dose of 600 mg gabapentin administered 1 hour prior to surgery produce effective and significant postoperative analgesia after total mastectomy and axillary dissection without significant side effects. ⁽¹³³⁾
Perioperative administration of gabapentin significantly decreases the incidence of post operative nausea and vomiting and the requirement for postoperative antiemetic treatment following laparoscopic cholecystectomy. ⁽¹³⁴⁾
Gabapentin has an analgesic and opioid sparing effect in acute post operative pain management when used in conjunction with opioids. ⁽¹³⁵⁾
Prophylactic effect in migraine and is an alternate drug in phobic states
Gabapentin is well absorbed orally and excreted unchanged in urine with t ½ of 6 hours
Adverse effects:
Mild sedation
Tiredness
Dizziness
Unsteadiness

Pregabalin

Pharmacodynamic and pharmacokinetic properties similar to gabapentin
Used for neuropathic pain such as diabetic neuropathy, postherpetic neuralgia, complec regional pain syndrome (CRPS) and certain other types of chronic pain
Pregabalin is associated with a significant, dose related improvement in pain in patients with diabetic peripheral neuropathy. ⁽¹³⁶⁾
Pregabalin is safe and effective for the short treatment of generalised anxiety disorder. ⁽¹³⁷⁾
In patients with diabetic peripheral neuropathy, pregabalin demonstrated early and sustained improvement in pain and a beneficial effect on sleep. It is well tolerated at all doses. ⁽¹³⁸⁾
Combination of the standard doses of duloxetine and pregabalin is not superior to the maximum dose of either drug in patients with painful diabetic neuropathy. ⁽¹³⁹⁾
All antineuropathic drugs are effective in relieving cancer related neuropathic pain. There is a statistically and clinically significant morphine sparing effect of pregabalin in relieving neuropathic cancer pain and neuropathic symptoms as compared to other antineuropathic drugs. ⁽¹⁴⁰⁾
Pregabalin provides a significantly improved treatment outcomes in patients with restless leg syndrom. The augmentation rates are significantly lower with pregabalin than with 0.5 mg of pramipexole. ⁽¹⁴¹⁾
Pregabalin provides some pain relief in patients with fibromyalgia but does not cure the disease. ⁽¹⁴²⁾
Pregabalin treatment may be associated with rhabdomylysis.⁽¹⁴³⁾
Perioperative pregabalin administration reduces opioid consumption and opioid related adverse efefcts after surgery. ⁽¹⁴⁴⁾
Pregabalin is an effective adjuvant therapy for pain in patients with chronic pancreatitis. ⁽¹⁴⁵⁾
Preoperative pregabalin (300 mg) and gabapentin (900 mg) administered 1 hour before surgery leds to significant reduction in preoperative anxiety and improves sedation without producing significant side effects. ⁽¹⁴⁶⁾
Pre-emptive administration of 300 mg pregabalin reduces postoperative pain and morphine consumption. ⁽¹⁴⁷⁾
Pregabalin reduces pain and improves sleep and health related quality of life in fibromyalgia syndrome patients. While indicated dosing is 300-450 mg divided twice daily, initial dosing of 25-50 mg at night is recommended owing to side effects including somnolence, dizziness and cognitive dysfunction. It can be safely combined with other medications and can be used in patients with renal failure when the dose is appropriate. It can worsen sedation when combined with CNS depressants. It should be discontinued gradually. ⁽¹⁴⁸⁾
Insomnia is a common component of the clinical presentation of generalized anxiety disorder and pregabalin appears to be an efficacious treatment for this chronic an ddisbling symptom. ⁽¹⁴⁹⁾
Pregabalin has similar tolerability but seems to have inferior efficacy to lamotrigine for the treatment of newly diagnosed partial seizures in adults. ⁽¹⁵⁰⁾
Pregabalin, in doses of 150-600 mg/day is safe and effective treatment of generalised anxiety disorder in patients 65 years and older. It has an early onset and significantly improves both psychic and somatic symptoms of anxiety. ⁽¹⁵¹⁾
In post herpetic neuralgia patients, 600 mg/day dose of pregabalin demonstrates increased pain relief compared to 300 mg/day. BID and TID regimens demonstrates similar efficacy. ⁽¹⁵²⁾
In patients with diabetic peripheral neuropathic pain inadequately treated with gabapentin without concomitant use of antidepressants, switching to duloxetine insted of pregabalin provides better pain reduction. Conversely, in nonresponders to gabapentin who are concomitantly using an antidepressant, switching to duloxetine or pregabalin may provide similar pain reductions. ⁽¹⁵³⁾
Side effects:
Poor concentration
Rashes
Allergic reactions

Topiramate

Weak carbonic anhydrase inhibitor with broad spectrum anticonvulsant activity in maximal electroshock, PTZ induced clonic seizures and in kindling model
Mechanism of action
Prolongation of Na+ channel inactivation
GABA potentiation by post synaotic effect
Antagonism of certain glutamate receptor
Neuronal hyperpolarization through certain K⁺ channels
Topiramate is used as monotherapy as well as supplementing other antiepileptic drugs in refractory SPS, CPS and GTCS
Also used in myoclonic epilepsy
It is readily absorbed orally and mainly excreted unchanged in urine with an average t ½ of 24 hours
Topiramate is a valuable alterntive to existing mood stabilizers, either as an ajunct or monotherapy in patients with bipolar disorder or schizoaffective disorder. ⁽¹⁵⁴⁾
Topiramate lacks efficacy in the treatment of acute mania. It has potential implications in reversing increased body weight, normalisation of glycemic control and blood pressure. ⁽¹⁵⁵⁾
The rate of oral clefts observed is 11 times the background rate when topiramate is used in pregnancy. ⁽¹⁵⁶⁾
The combination of phentermine and topiramate might be a valuable treatment for obesity that can be provided by family doctors. ⁽¹⁵⁷⁾
Topiramate has a negative impact on cognition. It causes a decline in verbal intelelct. ⁽¹⁵⁸⁾
Topiramate is used in the treatment of alcohol use disorders. ⁽¹⁵⁹⁾
Topiramate might serve as a therapeutic option for inflammatory bowel disease in humans. ⁽¹⁶⁰⁾
Topiramate use is associated with secondary angle closure glaucoma. ⁽¹⁶¹⁾
Topiramate is used in the prophylaxis of pediatric migraine. Weight loss, decreased concentration in school, sedation and parasthesias are important side effects. ⁽¹⁶²⁾
Topiramate can induce acute transient myopia. ⁽¹⁶³⁾
Due to its anticraving effect, topiramate can be used as a useful adjuvant in the treatment of diabetes. ⁽¹⁶⁴⁾
Topiramate is a useful and well tolerated addition to the treatment of refractory epilepsy, but it should be titrated slowly in order to avoid adverse effects. ⁽¹⁶⁵⁾
Topirmate is effective in the prevention of migraine in pediatric patients. It is safe and well tolerated. ⁽¹⁶⁶⁾
Topiramate can be used for smoking cessation. ⁽¹⁶⁷⁾
Adverse effects:
Impairment of attention
Ataxia
Word finding difficulties
Poor memory
Weight loss
Paresthesia
Renal stones
Also used in prophylaxis of migraine

Zonisamide

Anticonvulsant with weak carbonic anhydrase inhibitor action that modifies maximal electroshock seizures and inhibit kindled seizures
It does not antagonize PTZ
Prolongation of Na+ channel inactivation resulting in suppression of repetitive neuronal firing
Also found to suppress T type of Ca²⁺ current in certain neurons
It is well absorbed orally and mainly excreted unchanged in urine with t ½ > 60 hours
A small fraction is oxidized and conjugated with glucuronic acid
It is used as add on drug in refractory partial seizures
Zonisamide is used in the treatment of partial seizures in pediatric and adult patients. It has a favorable linear pharmacokinetic profile, long half life and low incidence of protein binding interactions with other AEDs. It is metabolized in liver through cytochrome P450 pathway. ⁽¹⁶⁸⁾
Zinosamide has a good efficacy and tolerability profile and can be used as an adjunctive therapy for epileptic patients. ⁽¹⁶⁹⁾
Zonisamide is reasonably effective and generally well tolerated in children with poorly controlled epilepsy and provides another treatment option for children with refractory seizures. ⁽¹⁷⁰⁾
Zonisamide is non inferior to controlled relaease carbamazepine – according to International league against epilepsy guidelines- could be useful as an initial monotherapy for patients newly diagnosed with partial epilepsy. ⁽¹⁷¹⁾
Zonisamide is used in the treatment of refractory partial-onset seizures. ⁽¹⁷²⁾
Zonisamide attenuates α -synuclein-induced toxicity in a manner independent of the formation and maturation of α-synuclein aggregates in an in vivo model of familial Parkinson’ disease. Zonisamide may protect nigrostriatal dopamine neurons by modulating cellular damage or a cell death pathway commonly caused by neurotoxins and α-synuclein. ⁽¹⁷³⁾
Adjunctive zonisamide is well tolerated and efficacious over a period of at least 1 year in children with partial epilepsy, with no unexpected safety concerns and no consistent detrimental effects on growth and development. ⁽¹⁷⁴⁾
Zonisamide reduces obstructive sleep apnea independent of body weight potentially by mechanisms related to carbonic anhydrase inhibition. ⁽¹⁷⁵⁾
Zonisamide exerts beneficial effects on the motor symptoms of Parkinson’s Disease and can be used as an adjunctive treatment. ⁽¹⁷⁶⁾
Zonisamide induces crystalluria without alkalinization of the urine. Crystalluria should be carefully monitored in patients treated with zonisamide to prevent urolithiasis. ⁽¹⁷⁷⁾
Zonisamide is useful for treating overweight in binge eating disorder and bulimia nervosa patients and may be an option for controlling impulsive behaviours in patients with eating disorders. ⁽¹⁷⁸⁾
In short term, open label priliminary trial, combination treatment of zonisamide and bupropion resulted in more weight loss than treatment with zonisamide alone. ⁽¹⁷⁹⁾
Zonisamide is non inferior to carbamazepine for newly diagnosed epilepsy. ⁽¹⁸⁰⁾
Side effects:
Somnolence
Dizziness
Headache, irritability
Anorexia
Metabolic acidosis
Renal stones

Levetiracetam

It is effective in kindled seizures but is ineffective against maximal electroshock or PTZ
Clinically effective as adjuvant medication as well as monotherapy in refractory partial seizures with or without generalization
It is completely absorbed orally, party hydrolyzed but mainly excreted unchanged in urine with t ½ of 6-8 hours
Levetiracetam is effective as adjunctive therapy for refractory partial onset seizures, primary generalized tonic clonic seizures and myoclonic seizures of juvenile myoclonic epilepsy. It is equivalent to controlled release carbamazepine as a first line therapy for partial onset seizures. Its main adverse efefcts are somnolence, asthenia, infection and dizziness. ⁽¹⁸¹⁾
Levetiracetam is efefctive for treating idiopathic generalised epilepsy. ⁽¹⁸²⁾
Levetiracetam does not produce clinically significant increase in blleding time in healthy male volunteers. ⁽¹⁸³⁾
Levetiracetam and controlled release carbamazepine produces equivalent seizure freedom rates in newly diagnosed epilepsy at optimal dosing in a setting mimicking clinical practice. ⁽¹⁸⁴⁾
Levetiracetam suppresses acute seizures induced by perinatal hypoxia and diminishes later life seizure susceptibility and seizure induced neuronal injury. Thus, It may be effective in neonatal seizures. ⁽¹⁸⁵⁾
Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in Alzhemier’s disease model. ⁽¹⁸⁶⁾
Hallucination can be seen in seizure patients using levetiracetam. ⁽¹⁸⁷⁾
Cautious usage and concerns of levetiracetam associated potential alkaline phosphatase elevation should be considered when levetiracetam is prescribed to epilepsy patients, especially pediatric patients. ⁽¹⁸⁸⁾
There is insufficient evidence to recommend the use of levetiracetam instead of phenytoin for seizure prophylaxis in setting of severe traumatic brain injury. ⁽¹⁸⁹⁾
The spinal myoclonus is markedly ameliorated by levetiracetam. ⁽¹⁹⁰⁾
Levetiracetam is well tolerated and commonly used broad spectrum antiepileptic in both partial and generalised seizures. Levetiracetam induces psychosis may occur in children. ⁽¹⁹¹⁾
Levetiracetam is found to be safe in pregnancy. ⁽¹⁹²⁾
Levetiracetam appears to be a promising therapy for the treatment of hot flashes. ⁽¹⁹³⁾
Side effects:
Sleepiness
Dizziness
Weakness
Behavioral changes
Uses
In CPS, GTCS and myoclonic epilepsy

Tiagabine

Newer anticonvulsant potentiates GABA mediated neuronal inhibition by depressing GABA transporter GAT-1 which removes synaptically released GABA into neurons and glial cells
Maximal electroshock and kindled seizures are suppressed
Used as add on therapy in partial seizures with or without secondary generalization
In newly diagnosed patients with partial epilepsy, tiagabine monotherapy is as effective as carbamazepine. The side effects include dizziness/ lightheadedness, asthenia/ lack of energy and somnolence, Induction of nonconvulsive status epilepticus. ⁽¹⁹⁴⁾
There is increased risk of seizure activity with off label use of tiagabine. Off label use of tiagabine should be discouraged. ⁽¹⁹⁵⁾
Chronic tiagabine administration decrese the aggressive behaviour in individuals with a history of substance abuse and antisocial behaviour. ⁽¹⁹⁶⁾
Tiagabine in excess dosing scenarios has been rarely documented to cause status epilepticus. ⁽¹⁹⁷⁾
Tiagabine can induce typical absence status epilepticus in a pateint with primary generalized epilepsy. ⁽¹⁹⁸⁾
Tiagabine may be used as an add-on drug for drug resistant partial epilepsy. ⁽¹⁹⁹⁾
Tiagabine is efficacious and well tolerated as adjunctive therapy in complex partial seizures. There is a clear dose-response relationship. ⁽²⁰⁰⁾
Tiagabine has a slow wave sleep enhancement effect which reduces selective aspects of the behavioural, psychological and physiologic impact of sleep restriction. ⁽²⁰¹⁾
Side effects:
Mild sedation
Nervousness
Asthenia
Amnesia
Abdominal pain

Vigabatrin (gamma vinyl GABA)

It is an inhibitor of GABA transaminase
Anticonvulsant action may be due to increase in synaptic GABA concentration
Effective in patients with refractory epilepsy, especially CPS with or without generalization
Vigabatrin may be used for the treatment of refractory partial epilepsy. ⁽²⁰²⁾
Treatment with vigabatrin is associated with high prevalence of peripheral visual field defects. This is due to its toxic effect on the retina and persists even if the drug is withdrawn. ⁽²⁰³⁾
Vigabatrin is highly effective in eliminating infantile spasms caused by tuberous sclerosis complex but is less effective in patients with focal seizures. ⁽²⁰⁴⁾
Improvement in stiff man syndrome is seen with vigabatrin. ⁽²⁰⁵⁾
Light is a significant enhancer of vigabatrin toxicity and a portion of this is mediated, directly or indirectly, by phototransduction signalling in rod and cone photoreceptors. ⁽²⁰⁶⁾
Vigabatrin exert anxiolytic effects in CCK-4-induced panic in healthy volunteers. Vigabatrin might be useful in ameliorating panic symptoms in patients with panic disorders. ⁽²⁰⁷⁾
Vigabatrin can induce life threatening encephalopathy. ⁽²⁰⁸⁾
Vigabatrin therapy is efficacious at preventing CNS oxygen toxicity in swine and a single dose is not acutely associated with retinotoxicity. ⁽²⁰⁹⁾
The use of vigabatrin for complex partial seizures should be limited to those patients with seizures refractory to other treatments. Patients must have a baseline and follow up monitoring of visual fields, early assessment of its efficacy, and ongoing evaluation of the benefits and risks of vigabatrin therapy. ⁽²¹⁰⁾
Vigabatrin is an effective treatment in infantile spasms. The most serious side efefct is retinal toxicity characterized by irreversible bilateral concentric constriction of the visual fields (BCCVF). Every effort should be made to evaluate the retinal function. ⁽²¹¹⁾
Adverse effects:
Visual field contraction
Behavioural changes
Depression
Psychosis

Lacosamide

Recently approved anti seizure drug indicated in adults only for add on therapy of partial seizures with or without generalization
It acts by enhancing Na+ channel inactivation and suppressing repetitive firing of neurons
It is metabolized by CYP2C19 and excreted in urine.
Lacosamide as adjunctive therapy in patients with partial onset seizures increases the 50% responder rate but with significantly more adverse events. ⁽²¹²⁾
Lacosamide is an effective therapy for most seizure types and is particularly effective for partial onset seizures. It is effective in Lennox-Gastaut syndrome. ⁽²¹³⁾
Lacosamide is effective in seizure reduction as adjunctive theray in patients with uncontrolled partial onset seizures. It is generally well tolerated. The most frequent adverse events are dizziness, headache, nausea and diplopia. ⁽²¹⁴⁾
Intravenous loading dose of 200 and 300 mg lacosamide administered over 15 min followed by oral lacosamide is well tolerated in lacosamide-naive patients. The 400 mg loading dose is less well tolerated due to higher frequency of treatment emergent adverse events. ⁽²¹⁵⁾
Lacosamide may be effective in the treatment of juvenile myoclonic epilepsy. ⁽²¹⁶⁾
Lacosamide in combination with levetiracetam is effective in the treatment of Epilepsia Partialis Continua. ⁽²¹⁷⁾
Lacosamide reduces neuropathic pain and is well tolerated in patients with painful diabetic neuropathy. ⁽²¹⁸⁾
Acute liver failure is reported in patientswith levetiracetam and lacosamide combination treatment for unspecified epileptic disorder. ⁽²¹⁹⁾
Lacosamide can induce acute pancreatitis. ⁽²²⁰⁾
Adverse effects:
Ataxia
Vertigo
Diplopia
Tremor
Depression
Cardiac arrhythmia

Plasma half life and toxic plasma concentration range of antiepileptic drugs

Drug	Half life (hr)	Plasma concentration (mcg/ml)
Therapeutic	Toxic
Phenobarbitone	80-120	10-30	>30 mild >60 severe
Phenytoin	12-36	10-20	>20 mild > 35 severe
Carbamazepine	10-40	5-10	>12
Ethosuximide	30-50	50-100	>200
Valproate	10-15	40-100	—
Clonazepam	20-40	0.01-0.1	—

Choice of antiseizure drugs

Type of seizure	First choice drug	Second choice drug	Alternative/ add on drugs
Generalized tonic clonic/ simple partial with or without generalization	Carbamazepine, Phenytoin	Valproate, Phenobarbitone	Lamotrigine, Gabapentin, Topiramate, Primidone, Levetiracetam
Complex partial with or without generalization	Carbamazepine, Valproate, Phenytoin	Gabapentin, Lamotrigine, Levetiracetam	Clobazam, Zonisamide, Topiramate
Absence	Valproate	Ethosuximide, Lamotrigine	Clobazam, Clonazepam
Myoclonic	Valproate	Lamotrigine, Topiramate	Levetiracetam, Clonazepam
Atonic	Valproate	Clonazepam, Clobazam	Lamotrigine
Febrile seizures	Dizepam (rectal)	—	—
Status epilepticus	Lorazepam (iv), Diazepam (iv)	Fosphenytoin (iv) Phenobarbitone (iv, im)	General anesthetics

References:

RA Ouvrier, R Goldsmith. Phenobarbitone doses in neonatal convulsions. Arch Dis Child. Sept 1982;57(9):653-657.
S Velaphi, M Mokhachane, R Mphahlele. Effect of prophylactic phenobarbitol on seizures, encephalopathy adn mortality in neonates with perinatal asphyxia. The South African Journal of Child Health. 2013;7(1).
JM Wilmshurst, Ronald van Toorn, CRJC Newton. Withdrawal of parenteral phenobarbitone – implications for resource poor counteries. S Afr Med J. 2005;95:422-423.
CRB Joyce, PCE Edgecombe, DA Kennard, M Weatherall, DP Woods. Potentiation by phenobarbitone of effects of ethyl alcohol on human behaviour. The British Journal of Psychiatry. 1959;105:51-60.
DAR Boldy, JA Vale, LF Prescott. Treatment of phenobarbitone poisoning with repeated oral administration of activated charcoal. QJM 1986;61(2):997-1002.
Robert N Straw, CL Mitchell. A comparison of the effects of phenobarbital and pentobarbital on motor cortical threshold and righting reflex response in the cat. JPET June 1967;156(3):598-601.
Leslie J Findley, Lynn Cleeves. Phenobarbitone in essential tremor. Neurology. Dec 1985;35(12):1784.
Martin J Brodie, Patrik Kwan. Current position of phenobarbital in epilepsy and its future. Epilepsia. Dec 2012;53(s8):40-46.
WZ Wang, JZ Wu, GY Ma, XY Dai, B Yang, TP Wang, CL Yuan, Z Hong, GS Bell, L Prilipko, HM de Boer, JW Sander. Assessment of the efficacy of phenobarbital on a large community based intervention for epilepsy care in rural china. Neurologythelancet. Dec 2005.
MM Shah, R Balaraman. effect of phenobarbitone, carbamazepine and sodium valproate on the elimination kinetics of acetaminophen. Indian Journal of pharmacology. 1999;31(4):311-314.
P Satischandra, SL Rao, S Ravat, S Jayalakhshmi, A Senapathy, Urvashi Shah et al. The effect of phenobarbitone on cognition in adult patients with new onset epilepsy: A multi-centric prospective study from India. Epilepsy Research. April 2014.
Navreet K Natt, Tarsem Singh, Harmanjit Singh, Manu Sharma, gagandeep singh. Phenobarbitone induced drug reaction with eosinophilia and systemic symptoms (DRESS): a case report. Int J Basic Clin Pharmacol. 2013;2(3):333-335.
LJ Findley, L Cleeves, S Calzetti. Primidone in essential tremors of hands and head: a double blind controlled clinical study. J Neurol Neurosurg Psychiatry. Sept 1985;48(9):911-915.
William C Koller, Vicki L Royse. Efficacy of primidone in essential tremor. Neurology Jan 1986;36(1):121.
Phillip T White, Dwight Plott, James Norton. Relative anticonvulsant potency of primidone: a double blind comparison. Arch Neurol. 1966;14(1):31-35.
Irwin P Baumel, Brian B Gallagher, Joseph Dimicco and Hector Goico. Metabolism and anticonvulsant properties of primidone in the rat. JPET Aug 1973;186(2):305-314.
James C Cloyd, Kenneth W Miller, Ilo E leppik. Primidone kinetics: effect of concurrent drugs and duration of therapy. Clinical Pharmacology and therapeutics. 1981;29:402-407.
Dennis L DeSilvey, Arthur J Moss. Primidone in the treatment of the long QT syndrome: QT shortening and ventricular arrhythmia suppression. Ann Intern Med. 1980;93(1_Part_1):53-54.
Gallop K. Review article: phenytoin use and efficacy in the ED. Emerg Med Australas. April 2010;22(2):108-18.
DG Lambie, RH Johnson, RN Nanda, RA Shakir. Therapeutic and pharmacokinetic efefcts of increasing phenytoin in chronic epileptics on multiple drug therapy. The Lancet. Aug 1976;308(7982):386-389.
M Govindraj Muthukumarasamy, Gurumurthy Sivakumar, Govindam Manoharan. Topical phenytoin in diabetic foot ulcers. Diabetes Care. Oct 1991;41(10):909-911.
J Lindow, EF Wijdicks. Phenytoin toxicity associated with hypoalbuminemia in critically ill patients. Chest 1994;105(2):602-604.
Albert C lo, Carl Y Saab, Joel A Black, Stephe G Waxman. Phenytoin protects spinal cord axons and preserves axonal conduction and neurological function in a model of neuroinflammation in vivo. Journal of Neurophysiology, Nov. 2003;90:3566-3571.
EB Bromfield, J Dambrosia, O Devinsky, FJ Nice, WH Theodore. Phenytoin withdrawal and seizure frequency. Neurology. July 1989;39(7):905.
BJ Wilder, I Leppik, TJ Hietps, JC Cloyd, EJ Randinitis, J Cook. Effect of food on absorption of dilantin kapseals and mylan extended phenytoin sodium capsules. Neurology Aug 2001;57(4):582-589.
D Adam Algren, Michael R Christian. Phenytoin toxicity unlikely to result in arrhythmias. JAMA Intern Med. 2014;174(1):167.
E Perucca, S hebdige, GM Frigo, G Gatti, S Lecchini, A Crema. Interaction between phenytoin and valproic acid:plasma protein binding and metabolic effects. Clinical Pharmacology and therapeutics. 1980;28:779-789
Bernhards R Ogutu, Charles RJC Newton, Simon N Muchochi, Godfrey O Otieno, Geoffrey Edwards, William M Watkins, Gilbrt O Kokwaro. Pharmacological and clinical effects of phenytoin and fosphenytoin in children with severe malaria and status epilepticus. Br J Clin Pharmacol. Jul 2003;56(1):112-119.
John M Pellock. Fosphenytoin use in children. Neurology. June 1996;46(6):14S-16S.
Andrew Thomson. Fosphenytoin for the treatment of status epilepticus: an evidence based assessment of its clinical and economic outcomes. Core Evidence. March 2005;1(1&2).
Mark T Keegan, Lois R Bondy, Joseph L Blackshear, Willaim L Lanier. Hypocalcemia like electrocardiographic changes after administration of intravenous fosphenytoin. Mayo clinic proceedings. June 2002;77(6):584-586.
Lawrence Daniel Morton. Clinical experience with fosphenytoin in children. J Child Neurol. 1998;13(Suppl 1):S19-S22.
Samson A Gwer, Richard I Idro, Gregory Fegan, Eddie M Chengo, Ayub Mpoya et al. Fosphenytoin for seizure prevention in childhood coma in Africa: A randomized clinical trial. Journal of Critical care. Dec 2013;28(6):1086-1092.
Jeffrey Johnson, Keith Wrenn. Inappropriate fophenytoin use in the ED. American Journal of Emergency Medicine. July 2001;19(4):293-294.
Falvia M Pryor, Barry Gidal, R Eugene Ramsay, John deToledo, Robert O Morgan. Fosphenytoin: pharmacokinetics and tolerance of intramuscular loading dose. Epilepsia. feb 2001;42(Suppl S2):245-250.
Yushi Inoue, Naotaka Usui, Tadayuki Hiroki, Kenji Shimizu, Susumu Kobayashi, Shigki Shimasaki. Bioavailability of intravenous fosphenytoin sodium in healthy Japanese volunteers. European Journal of drug metabolism and pharmacokinetics. June 2013;38(2):139-148.
Chia-Hui Chen, Shih-Ku Lin. carbamazepine treatment of bipolar disorder: a retrospective evaluation of naturalistic long term outcomes. BMC Psychiatry 2012;12:47.
Felix Aigner, Wolfgang Aigner, Friedrich Hoppichler, Gerhard Luef, Hugo Bonatti. Diarrhea, negative t-waves, fever and skin rash, rare mainfestation of carbamazepine hypersensitivity: a case report. Case Journal 2008;1:312.
MJ Brodie, A Richens, AWC Yuen. Double blind comparison of lamotrigine an dcarbamazepine in newly diagnosed epilepsy. The Lancet Feb 1995;345(8948):476-479.
Youmei Lee, Takashi Hamamura, Kazuyo Ohashi, Masato Miki, Yukata Fujiwara, Shigetoshi Kuroda. Crabamazepine suppresses methamphetamine induced Fos expression in a regionally specific manner in the rat brain: possible neural substrates responsible for antimanic effects of mood stabilizers. Neuropsychopharmacology. May 2000;22(5):530-537.
Mahendran Chetty, Pralay Sarkar, Ashutosh Aggarwal, Vinay Sakhuja. Carbamazepine poisoning: treatment with haemodialysis. Nephrol. Dial. Transplant. 2003;18(1):220-221.
K Lertratanangkoon, MG Horning. Metabolism of carbamazepine. DMD Jan 1982;10(1):1-10.
Thaakur Santhrani, Eswaran Maheswari, Ganesan Rajalakshmi Saraswathy. Carbamazepine provoked hepatotoxicity: attenuation by vitamin C. Oxid Antioxid Med Sci. 2013;2(1):37-43.
Carl E Stafstrom, Virinder Nohria, Heidi Loganbill, Robert Nahouraii, Rose-Mary Boustany, Robert DeLong. Erythromycin-induced carbamazepine toxicity: a continuing problem. Arch Pediatr Adolesc Med. 1995;149(1):99-101.
Ozlem Guneysel, Ozge Onur, Arzu Denizbasi, Murat Saritemur. Carbamazepine overdose after exposure to simethicone: a case report. Journal of Medical Cae Reports. 2008;2:242.
Adina Kay Knight, Charlotte Cinningham Rundles. Oxcarbamazepine induced immunoglobulin deficiency. Clin Diagn Lab Immunol. Apr 2005;12(4):560-561.
JM Zakrzawska, PN Patsalos. Oxcarbamazepine: a new drug in the management of intractable trigeminal neuralgia. J Neurol Neurosurg Psychiatry 1989;52:472-476.
Sarah J Nolan, Martie Muller, Catrin Tudur Smith, Anthony G Marson. Oxcarbamazepine versus phenytoin monotherapy for epilepsy. The Cochrane Library. 31 May 2013.
Suad Kapetanovic. Oxcarbamazepine in youths with autistic disorder and significant disruptive behaviors. Am J Psychiatry. 2007;164:832-833.
Amita Bhargavam, Bharat Bhushan, Subhakaran Khichar, Gaurav Kasundra. Acute dyskinesia: A rare adverse effect of oxcarbamazepine in epilepsy with neurobehavioral symptoms. International Journal of nutrition, pharmacology, Neurological diseases. 2014;4(1):74-76.
Ulrike Hoffmann, Ergin Dilekoz, Chiho Kudo, Cenk Ayata. Oxcarbamazepine does not suppress cortical spreading depression. Cephalalgia April 2011;31:5537-542.
Kirk Lalwani, Allen Shoham, Jeffrey L Koh, Terrence McGraw. Use of oxcarbamazepine to treat a pediatric patient with resistant complec regional pain syndrome. The Journal of Pain. Oct 2005;6(10):704-706.
Li-Li Wu, Tzu-Hsun Tsai, Fung-Rong Hu. Treatment of superior oblique myokymia with oxcarbamazepine. Taiwan Journal of Ophthalmology. march 2014;4(1):49-51.
SR Sharma, Nalini Sharma, ME Yeolekar. Oxcarbamazepine-induced Stevens Johnson syndrome: A rare case report. Indian Dermatology Online Journal. 2011;2(1):13-15.
Thomas R Browne, Fritz E Dreifuss, Paul R Dyken, David J Goode, J Kiffin Penry, Roger J Porter, Billy G White, Phillip T White. Ethosuximde in the treatment of absence (petit mal) seizures. Neurology June 1975;25(6):515.
Chinekwu Anyanwu, Forough Ghavami, Marianne Schuelein, Gholam K Motamedi. Ethosuximide induced conversion of typical childhood absence to rolandic spikes. J Child Neurol. Jan 2013;28(1):111-114.
Kiana Sandossi, Maryam Majdzadeh, Padideh Ghaeli, Mohammed Hossein Ghahremani, Hamed Shafaroodi, Babak Pakneiad, Seved Nasser Ostad. Analysis of the antiepileptic, ethosuximide impacts on neurogenesis of rat forebrain stem cells. Fundamental and Clinical Pharmacology. 21 Jan 2014.
E Koutsoulieris. Granulopenia and thrombocytopenia after ethosuximide. The Lancet Aug 1967;290(7510):310-311.
MG Horning, C Stratton, J Nowlin, DJ Harvey, RM Hill. Metabolism of 2-ethyl-2methylsuccinimide (ethosuximide) in the rat and human. DMD May 1973;1: 3569-576.
Melissa A Riegle, Melissa M Masicampo, Erin H Caulder, Dwayne W Godwin. Ethosuximide reduces electrographical and behavioral correlates of alcohol withdrawal seizure in DBA/2J mice. Alcohol. An international biomedical journal. 5 May 2014.
GA Smith, L McKauge, D Dubetz, JH Tyrer, MJ eadie. Factors influencing plasma concentrations of ethosuximide. Feb 1979;4(1):38-52.
Anthony J Williams, Charisma C Bautista, Ren-Wu, Jitendra R Dave, Xi-Chun M Lu, Frank C Tortella, Jed A Hartings. Evaluattion of gabapentin and ethosuximide for the treatment of acute nonconvulsive seizures folloing ischemic brain injury in rats. JPET Sept 2006;318(3):947-955.
Judit Gervain, Bradley W Vines, Allan H Young. Valproate reopens critical period learning of absolute pitch. Front Syst Neurosci. 2013;7:102.
JE redenbaugh, S Sato, JK Penry, FE Dreifuss, HJ Kupferberg. Sodium valproate. Pharmacokinetics and effectiveness in treating intractable seizures. Neurology. Jan 1980;30(1).
Jakob Christensen, Therese Koops Gronborg, Merete Juul Sorensen, Diana Schendel, Erik Thorlund Parner, Lars Henning Pedersen, Mogens Vestergaard. Prenatal valproate exposure and risk of autism spectrum dosorders and childhood autism. JAMA 2013;309(16):1696-1703.
Somsak Tiamkao, Kittisak Sawanyawisuth, Alongkorn Chancharoen. The efficacy of intravenous sodium valproate and phenytoin as the first line treatment in status epilepticus: a comparison study. BMC Neurology 2013;13:98.
James G Longhurst. Mania. The Lancet July 1997;350(9073):292.
Mortyn T Jones, Brian Gillham, Ursula Beckford, Anne Dornhorst, Mary Seed, Rlph R Abraham, Victor Wynn. Effect of treatment with sodium valproate and diazepma on plasma corticotropin in Neson’s syndrome. The Lancet. May 1981;317(8231):1179-1181.
Jim Wadzinski, Ronald Franks, David Roane, Max Bayard. Valproate-associated hyperammonemic encephalopathy. J Am Board Fam Med. Sept-Oct 2007;20(5):499-502.
Vishal Mehta, Pratibha Singhi, Sunit Singhi. Intravenous sodium valproate versus diazepam infusion for the control of refractory status epilepticus in children: A randomized controlled trial. J Child Neurol. Oct 2007;22(10):1191-1197.
Viktoria Remenyi, Anna Kekesi, Klara Pentelenyi, Aniko Gal, Vivien Harsfalvi, Maria Judit Molnar. Prectiting valproate toxicity in patients with mitochondrial disorders. EPMA Journal 2014;5(Suppl 1): A140.
Steven C Stout, Michael J Owens, Kimberly P Lindsey, David L Knight, Charles B Nemeroff. Effects of sodium valproate on corticotropin-releasing factor systems in rat brain. Neuropsychopharmacology. June 2001;24(6):624-631.
Shan Huang, Minghui Zhu, Wei Wu, Abid Rashid, Yan Liang, Ling Hou, Qin Ning, Xiaoping Luo. Valproate pretreatment protects pancreatic beta-cells from palmitate-induced ER stress and apoptosis by inhibiting glycogen synthase kinase-3beta. Journal of Biomedical Science. 2014;21:38.
Steven C Stoner, Megan M Dahmen. Extended release divalproex in bipolar and other psychiatric disorders: A comprehensive review. Neuropsychiatr Dis Treat. Dec 2007;3(6):839-846.
AS Fleisher, D Truran, JT Mai, JBS Langbaum, PS Aisen, JL Cummings, CR Jack Jr, MW Weiner, RG Thomas, LS Schneider, PN Tariot. Chronic divalproex sodium use and brain atrophy in Alzheimer disease. Neurology Sept 2011;77(13):1263-1271.
Ninan T Mathew Joel R Saper, Stephen D Silberstein, Lynn Rankin, Hebert G Markley, Seymour Solomon, Alan M Rapoport, Christopher J Silber, Roger L Deaton. Migraine prophylaxis with divalproex. Arch Neurol. 1995;52(3):281-286.
RM Gallagher, LL Mueller, FG Freitag. Divalproex sodium in the treatment of migraine and cluster headaches. J Am Osteopath assoc. Feb 2002;102(2):92-94.
RN Nanda, RH Johnson, HJ Keogh, DG Lambie, ID Melville. Treatment of epilepsy with clonazepam and its effect on other anticonvulsant. J neurol Neurosurg Psychiatry. Jun 1977;40(6):538-543.
Marnelli A Bautista-Quach, Yu-Min Liao, Chung-Tsen Hsueh. Pancytopenia associated with clonazepam. Journal of Hematology & Oncology 2010;3:24.
Nitesh D Kuhadiya, Akshata Desai, Michelle Reisner. SLeep related painful erections in an elderly man successfully treated using clonazepam. Journal of the American Geriatrics Society. Feb 2014;62(2):407-408.
Angelo Giovanni Icro Maremmani, Luca Rovai, Fabio Rugani, Silvia Bacciardi, Matteo Pacini, Liliana Dell’Osso, Icro Maremmani. Clonazepam as aginist substitution treatment for benzodiazepine dependence: A case report. Case Reports in Psychiatry. 2013; Article ID 367594, 4 pages.
David S Bachman. Clonazepam in treatment of absence seizures with automatisms. Arch Neurol. 1978;35(11):773-774.
G Meloni, L Nasta, RM Pinto, A Spalice, U Raucci, P Lannetti. Clonazepam prophylaxis and busulfan related myoclonic epilepsy in autografted acute leukemia patients. Haematol Nov-Dec 1995;80(6):532-534.
PM Edelbroek, FA De Wolff. Improved micromethod for determination of underivatized clonazepam in serum by gas chromatography. Clinical Chemistry. Oct 1978;24(10):1774-1777.
Georgi Konstantinov Maximov, Deepak Kamnasaran. The adjuvant use of lansoprazole, clonazepam and dimenhydrinate for treating intractable hiccups in a patient with gastritis and reflux esophagitis complicated with myocardial infarction: a case report. BMC Research Notes 2013;6:327.
Mark H Pollack, Naomi M Simon, John J worthington, Alicia L Doyle, Patricia Peters, Fany Toshkov, Michael W Otto. Combined paroxetine and clonazepam treatment strategies compared to paroxetine monotherapy for panic disorder. J Psychopharmacol. Sept 2003;17(3):276-282.
Touran Mahmoudian, Omid Yaghini, Shirin Bajoghli. Intermittent clonazepam in the prevention of recurrent febrile seizures. Iranian Journal of Child Neurology. 2010;4(2):
Alexandre Martins Valenca, Antonio Egidio Nardi, Isabella Nascimento, Marco A Mezzasalma, Fabiana L Lopes, Walter Zin. Double blind clonazepam vs placebo in panic disorder treatment. Arq Neuropsiquiatr. 2000;58(4):1025-1029.
Winsley Rose, Chellam Kirubakaran, Julius Xavier Scott. Intermittent clobazam therpy in febrile seizures. Indian Journal of Pediatrics. 2005;72(1):31-3.
Morgan Feely, Robert Calvert, John Gibson. Clobazam in catamenial epilepsy. The Lancet. July 1982;320(8289):71-73.
Joan A Conry, Yu-Tze Ng, Lydia Kernitsky, Wendy G Mitchell, Rima Veidemanis, Rebecca Drummond, Jouko Isojarvi, Deborah Lee, Juliann M Paolicchi. Stable dosages of clobazam for Lennox-Gestaut syndrome are associated with sustained dro-seizure and total-seizure improvements over 3 years. Epilepsia April 2014;55(4):558-567.
JA Cramer, C Sapin, C Francois. Indirect comparison of clobazam and other therapies for Lenoox-Gestaut syndrome. Acta Neurologica Scandinavica. Aug 2013;128(2):91-99.
GW Hanks. Clobazam: Pharmacological and therpeutic profile. Br J Clin Pharmacol. 1979;7(Suppl 1):151S-155S.
AJ Heller, HA Ring, EH Reynolds. Clobazam for refractory epilepsy. Arch Neurol. 1987;44(6):578.
C Corman, A Guberman, O Benavente. Clobazam in partial status epilepticus. Seizure- European Journal of Epilepsy. June 1998;7(3):243-247.
Mariana Ribeiro Marcondes da Silveria, Maria Augusta Montenegro, Renata Cristina Franzon, Carlos AM Guerreiro, Marilisa M Guerreiro. Effectiveness of clobazam as add-on therapy in children with refractory focal epilepsy. Arq. Neuro-Psiquiatr. Sept 2006;64(3).
Tom W Robinson. Valium in the treatment of epilepsy. Calif Med. Mar 1970;112(3):63-64.
CR Rush, TS Critchfield, JR Troisi, RR Griffiths. Discriminative stimulus effects of diazepam and buspirone in normal volunteers. J Exp Anal Behav. May 1995;63(3):277-294.
David W Kaufman, Dennis Slone, Samuel Shapiro, Lynn Rosenberg, Susan P Helmrich, Ollis MiettinenPaul D Stolley, Micha Levy, David Schottenfeld. Diazepam and risk of breast cancer. The Lancet Mar 1982;319(8271):537-539.
Alireza Abed, Mohsen Minaiyan, Azadeh Safaei, Diana Taheri. Effect of diazepam on severity of acute pancreatitis: possible involvement of peripheral benzodiazepine receptors. ISRN Gastroenterology. Volume 2013 (2013), article ID 484128, 6 pages.
Kenzie L Preston, Roland Griffiths, Maxine L Stitzer, George E Bigelow, Ira A Liebson. Diazepam and methadone interactions in methadone maintenance. Clinical Pharmacology and Therapeutics. 1984;36:534-541.
C Addolorato, F Caputo, E Capristo, G Gasbarrini. Diazepam in the treatment of GHB dependence. The British Journal of Psychiatry. 2001;178:183.
M Melson, P Andreassen, H Melsom, T Hansen, H Grenahl, LK Hillestad. Diazepam in acute myocardial infarction. CLinical effects and effects on catecholamines, free fatty acids and cortisol. Br Heart J 1976;38:804-810.
Rasha A Tawfiq, Noha N Nassar, Wafaa I El-Eraky, Ezzeldein S El-denshary. Enhanced efficacy and reduced side effects of diazepam by kava combination. The Journal of Advanced Research. 22 August 2013.
Agnes Daurat, Patricia Sagaspe, Ladislav Motak, Jacques Taillard, Laetitia Bayssac, Nathalie Huet, Colas Authie, Daniel Mestre, Pierre Philip. Lorazepam impairs highway driving performance more than heavy alcohol consumption. Accident analysis and prevention. Nov 2013;60:31-34.
RJ Ancill, GD Embury, GW MacEwan, JS Kennedy. Lorazepam in elderly- a retrospective study of the side efefcts in 20 patients. J Psychopharmacol. Mar 1987;1(1):126-127.
Joyce E Fullwood, Zhila Mostaghimi, Christopher B Granger, Jeffrey B Washam, Wanda Bride, Yanfang Zhao, Bradi B Granger. Alcohol withdrawal prevention: A randomized evaluation of lorazepam and ethanol- a pilot study. Am J Crit Care. Sept 2013;22(5);398-406.
Douglas R Labar, Auslim Ali, Jonathan Root. High dose intravenous lorazepam for the treatment of refractory status epilepticus. Neurology Aug 1994;44(8):1400.
David J Greenblatt, Richard I Shader, Kate Franke, Dean S Maclaughlin, Jerold S Harmatz, Marcia Divoll Allen, Ann Werner, Elaine Woo. Pharmacokinetics and bioavailability of intravenous, intramuscular and oral lorazepam in humans. Journal of Pharmaceutical Sciences. Jan 1979;68(1):57-63.
V Rajmohan, K Sushil, E Mohandas. A double blind randomised comparison of chlordiazepoxide and lorazepam in alcohol withdrawal. Asian Journal of Psychiatry. Oct 2013;6(5):401-403.
K Subramaniam, RM Gowda, K Jani, W Zewedie, R Ute. Propofol combined with lorazepam for severe poly substance misuse and withdrawal states in intensive care unit: a case series and review. Emerg Med J. 2004;21:632-634.
Andreas M Kanner. Lamotrigine induced rash: can we stop worrying? Epilepsy Curr. Sept 2005;5(5):190-191.
Felicity Ng, Karen Hallam, Michael Berk. The role of lamotrigine in the management of bipolar disorder. Neuropsychiatr Dis Treat. Aug 2007;3(4):463-474.
John R Geddes, Joseph R Calabrese, Guy M Goodwin. Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomized trials. The British Journal of Psychiatry. 2009;194:4-9.
William Tatum, Nitin K Sethi, Kelley M Simms et al. Lamotrigine and aseptic meningitis. Neurology 2012;79:833-834.
James W Jefferson. Lamotrigine in psychiatry: Pharmacology and Therapeutics. CNS Spectr. 2005;10(3):224-232.
MJ Brodie, A Richens, AWC Yuen. Double blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy. The Lancet. Feb 1995;345(8948):476-479.
Karen P Grisotto, Isac Bruck, Sergio A Antoniuk, Lucia HC Santos. Association of lamotrigine and valproate in refractory epilepsies of children and adolescents. Arq. Neuro-Psiquiatr. Sept 2008;66(3).
RJ Nicholson, KP Kelly, IS Grant. Drug points: Leucopenia associated with lamotrigine. BMJ 1995;310.
Bedriye Oncu, Okan Er, Burcin Colak, David J Nutt. Lamotrigine for attention deficit-hyperactivity disorder comorbid with mood disorders: a case series. J Psychopharmacol. Mar 2014;28(3):282-283.
Nicole M Ryan, Surinder S Birring, Peter G Gibson. Gabapentin for refractory chronic cough: a randomised, double blind, placebo controlled trial. The Lancet. Nov 2012;380(9853):1583-1589.
Philip WH Peng, Duminda N Wijeysundera, Carina CF Li. Use of gabapentin for perioperative pain control- A meta-analysis. Pain Res Manag. 2007;12(2):85-92.
Barbara J Mason, Susan Quello, Vivian Goodell, Farhad Shadan, Mark Kyle, Adan Begovic. Gabapentin treatment for alcohol dependence. A randomized clinical trial. JAMA Intern Med. 2014;174(1):70-77.
D Garcia-Borreguero, O Larrosa, Y de La Llave, K Verger, X Masramon, G Hernandez. Treatment of restless leg syndrome with gabapentin. Neurology 2002;59(10):1573-1579.
Charles E Richardson, Dylan W Williams, Jeremy GC Kingham. Gabapentin induced cholestasis. BMJ 2002;325:635.
Robert J Tanenberg, Gordon A Irving, Richard C Risser, Jonna Ahl, Michael J Robinson, Vladimir Skljarevski, Sandra K Malcolm. Duloxetine, pregabalin, and duloxetine plus gabapentin for diabetic peripheral neuropathic pain management in patients with inadequate pain response to gabapentin: An open label, rndomized, noninferiority comparison. Mayo Clinic Proceedings. July 2011;86(7):615-626.
Kostas Athanasakis Ioannis Petrakis, Eleftheria Karampli, Elli Vitsou, Leonidas Lyras, John Kyriopoulos. Pregabalin Versus gabapentin in the management of peripheral neuropathic pain associated with post herpetic neuralgia and diabetic neuropathy: a cost effective analysis for the Greek health care setting. BMC Neurology. 2013;13:56.
Althea A Robinson, Beth A Malow. Gabapentin shows promise in treating refractory insomnia in children. J Child Neurol. Dec 2013;28(12):1618-1621.
P Perimenis, A Athanasopoulos, P Papathanasopoulos, G Barbalias. Gabapentin in the management of the recurrent, refractory, idiopathic priapism. International Journal of Impotence Research. 2004;16:84-85.
David Sandercock, Marilou Cramer, Jacqueline Wu, Yu-Kun Chiang, Victor Biton, Michelle Heritier. Gabapentin extended release for the treatment of painful diabetic peripheral neuropathy. Efficacy and tolerability in a double-bling, randomized, controlled clinical trial. Diabetes Care. Feb 2009;32(2):e2o.
William Eardley, Cory Toth. An open label, non randomized comparison of venlafaxine and gabapentin as monotherapy or adjuvant therapy in the management of neuropathic pain in patients with peripheral neurpathy. Journal of Pain Research. April 2010;3:33-49.
Aikaterini Melemeni, Chryssoula Staikou, Argyro Fassoulaki. Gabapentin for acute and chronic post-surgical pain. Signa Vitae 2007;2(Suppl 1): S42-S51.
VK Grover, PJ Mathew, S Yaddanapudi, S Sehgal. A single dose of preoperative gabapentin for pain reduction and requirement of morphine after total mastectomy and axillary dissection: Randomized placebo-controlled double-blind trial. Journal of post graduate medicine. 2009;55(4):257-260.
Ahmadreza Soroush, Hosein Masoomi, Zhamak Khorgami, Seyed Marashi, Roza Mofid. Effect of prophylactic gabapentin on post operative nausea and vomiting after laparoscopic cholecystectomy: a randomized controlled trial. Journal of minimally invasive surgical sciences. Dec 2012;1(1):17-20.
Kok-Yuen Ho, Tong J Gan, Ashraf S Habib. Gabapentin and postoperative pain- a systematic review of randomized controlled trials. Pain Dec 2006;126(1):91-101.
Roy Freeman, Edith Durso-DeCruz, Birol Emir. Efficacy, safety and tolerability of pregabalin treatment for painful diabetic peripheral neuropathy. Diabetes Care. Jul 2008;31(7):1448-1454.
Feltner DE, Crockatt JG, Dubovsky SJ. High dose pregbalin is effective for the treatment of generalised anxiety disorder. Evid Based Mental Health. 2004;7:17.
H lesser, U Sharma, L LaMoreaux, RM Poole. Pregabalin relieves symptoms of painful diabetic neuropathy. Neurology Dec 2004;63(11):2104-2110.
Solomon Tesfaye, Stefan Wilhelm, Alberto Lledo, Alexander Schacht, Thomas Tolle, Didier Bouhassira, Giorgio Cruccu, Vladimir Skljarevski, Rainer Freynhagen. Duloxetine and pregabalin: High dose monotherapy or their combination? The “COMBO-DN study”- a multinational, randomized, double blind, parallel-group study in patients with diabetic peripheral neuropathic pain. Pain. Dec 2013;154(12):2616-2625.
Seema Mishra, Sushma Bhatnagar, Gaurav Nirvani Goyal, Shiv Pratap Singh Rana, Surjya Prasad Upadhya. A comparative efficacy of amitriptylline, gabapentin and pregabalin in neuropathic cancer pain. A prospective randomized double blind placebo controlled study. Am J Hosp Palliat Care. May 2012;29(3):177-182.
Richard P Allen, Crystal Chen, Diego Garcia-Borreguero, Olll Polo, Saran DuBrava, Jeffrey Micell, Lloyd Knapp, John W Winkelman. Comparison of pregabalin with pramipexole for restless legs syndrome. N Engl J Med. 2014;370:621-631.
Lauren Kim, Sarah Lipton, Atul Deodhar. Pregabalin for fibromyalgia: Some relief but no cure. Cleveland Clinic Journal of Medicine. April 2009;76(4):255-261.
Roshan Gunathilake, Laura E Boyce, Anne T Knight. Pregabalin associated rhabdomyolysis. Med J Aust 2013;199(9):624-625.
J Zhang, K-Y Ho, Y Wang. Efficacy of pregabalin in acute postoperative pain: a meta-analysis. Br J Anaesth. 2011;106(4):454-462.
Soren Schou Olesen, Stefan AW Bouwense, Oliver HG Wilder-Smith, Harry van Goor, Asbjorn Mohr Drewes. Pregabalin reduces pain in patients with chronic pancreatitis in a randomized, controlled trial. Gastroenterology. Aug 2011;141(2):536-543.
Anju Ghai, Monika Gupta, Neha Rana, Raman Wadhera. The effect of pregabalin and gabapentin on preoperative anxiety and sedation: a double blind study. Anaesth Pain & Intensive Care. 2012;16(3):257-261.
Krzysztof Przesmycki, Ewa Waiter Koziol, Jan Kotarski, Miroslaw Czuczwar, Robert Jaskowiak, Marta Zabek et al. Effect of pre-emptive pregabalin on pain intensity and morphine requirement after hysterectomy. Anaesthesiology Intensive Therapy. 2011;XLIII(1):12-15.
Chad S Boomershine. Pregabalin for the management of fibromyalgia syndrome. Journal of pain research. June 2010;3:81-88.
Edith Holsboer-Trachsler, Rita Prieto. Effects of pregabalin on sleep in generalized anxiety disorder. The International Journal of Neuropsychopharmacology. May 2013;16(4):925-936.
Patrick Kwan, Martin J Brodie, Reetta Kalviainen, Lorraine Yurkewicz, Jerry Weaver, Lloyd E Knapp. Efficacy and safety of pregabalin versus lamotrigine in patients with newly diagnosed partial seizures: a phase 3, double blind, randomized, parallel group trial. The Lancet Neurology. Oct 2011;10(10):881-890.
Stuart Montgomery, Krai Chatamra, Lynne Pauer, Ed Whalen, Francesca Baldinetti. Efficacy and safety of pregabalin in elderly people with generalized anxiety disorder. The British Journal of Psychiatry. 2008;193:389-394.
S Chapel, K Kowalski, M Hutmacher, H Bockbrader. Pregabalin exposure-response analysis in patients with post herpetic neuralgia. Clinical Pharmacology & Therapeutics. 2005;77:P88
Robert J Tanenberg, David B Clemow, Joseph M Giaconia, Richard C Risser. Duloxetine compared with pregabalin for diabetic peripheral neuropathic pain management in patients with suboptimal response to gabapentin and treated with or without antidepressants: A Post Hoc Analysis. Pain Practice. 24 Oct 2013. doi:10.1111/papr.12121.
Sanjay Gupta, Prakash S Masand, Peggy L Keller. Topiramate in Bipolar and Schizoaffective disorders: weight loss and efficacy. Prim Care Companion J Clin Psychiatry. Jun 2000;2(3):96-100.
Danilo Arnone. Review of the use of topiramate for the treatment of psychiatric disorders. Annals of General Psychiatry 2005;4:5.
S Hunt, A Russell, WH Smithson, L Parsons, I Robertson, R Waddell, B Irwin, PJ Morrison, J Morrow, J Craig. Topiramate in pregnancy. Neurology. July 2008;71(4):272-276.
Kishore M Gadde, David B Allison, Donna H Ryan, Craig A Peterson, Barbara Troupin, Michael L Schwiers, Wesley W Day. effects of low dose, controlled release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo controlled phase 3 trial. The Lancet. April 2011;377(9774):1341-1352.
PJ Thompson, SA Baxendale, JS Duncan, JWAS Sander. Effects of topiramate on cognitive function. J Neurol Neurosurg Psychiatry. 2000;69:636-641.
AC Del Re, Adam J Gordon, Anna Lembke, ALex HS Harris. Prescription of topiramate to treat alcohol use in the veterans health administration. Addiction Science & Clinical Practice 2013;8:12.
Joel T Dudley, Marina Sirota, Mohan Shenoy, Reetesh K Pai, Silke Roedder, Annie O Chiang, ALex A Morgan, Minnie M Sarwal, Pankaj Jay Pasricha, Atul J Butte. Computational Repositioning of the anticonvulsant topiramate for inflammatory bowel disease. Sci Transl Med. Aug 2011;3(96):96ra76.
Lopa Thambi, Leonard P Kapcala, Wiley Chambers, Parivash Nourjah, Julie Beitz, Min Chen, Susan Lu. Topiramate-associated angle-closure glaucoma: a case series. Arch Ophthalmol 2002;120(8):1108.
CVS Lakshmi, Pratibha Singhi, Prahbhjot Malhi, Munni Ray. Topiramate in the prophylaxis of pediatric migraine: A double blind placebo controlled trial. J Child Neurol. July 2007;22(7):829-835.
Sandra D Gawley. Topiramate induced acute transient myopia: a case report. Cases Journal 2009;2:7430.
Syed Nizamuddin Ahmed, Yasmin Rashid. Anticraving effects of topiramate in a diabetic patient. Diabetes Care. July 2005;28(7):1837-1838.
MC Walker, JWAS Sander. Topiramate: a new antiepileptic drug for refreactory epilepsy. Seizure-European Journal of Epilepsy. Sept 1996;5(3):199-203.
Donald Lewis, Paul Winner, Joel Saper, Seth Ness, Elena Polverejan, Steven Wang, Caryn L Kurland, Jeff Nye et al. Randomized, double blind, Placeno controlled study to evaluate the efficacy and safety of topiramate for migraine prevention in pediatric subjects 12-17 years of age. Pediatrics March 2009;123(3):924-934.
Cheryl Oncken, Albert J Arias, Richard Feinn, Mark Litt, Jonathan Covault, Mehmet Sofuoglu, Henry R Kranzler. Topiramate for smoking cessation: A randomized, placebo-controlled, pilot study. Nicotine Tob Res. Sept 2013. doi:10.1093/ntr/ntt141.
Angus A Wilfong, L James Willmore. Zonisamide- a review of experience and use in partial seizures. Neuropsychiatr Dis Treat. Sept 2006;2(3):269-280.
Gaetano Zaccara, Luigi M Specchio. Long term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of literature. Neuropsychiatric Disease and Treatment. April 2009;5:249-259.
Hui Jeen Tan, Timothy R Martland, Richard E Appleton, Rachel Kneen. Effectiveness and tolerabilityof zinosamide in children with epilepsy: A retrospective review. Seizure- European Journal of Epilepsy. Jan 2010;19(1):31-35.
Michel Baulac, Martin J Brodie, Anna Patten, Joanna Segieth, Luigi Giorgi. Efficacy and tolerability of zonisamide versus controlled release carbamazepine for newly diagnosed partial epilepsy: a phase 3, randomised, double-blind, non inferiority trial. The Lancet Neurology. July 2012;11(7):579-588.
E Faught, R Ayala, GG Montouris, IE Leppik. Randomised controlled trial for zonisamide for the treatment of refractory partial-onset seizures. Neurology. Nov 27,2001;57:1774-1779.
Shigeki Arawaka, Shingo Fukushima, Hiroyasu Sato, Asuka Sasaki, Kaori Koga, Shingo Koyama, Takeo Kato. Zonisamide attenuates -synuclein neurotoxicity by an aggregation-independent mechanism in a rat modelof familial parkinson’s disease. Journal pone Feb 20, 2014. doi: 10.1371/journal.pone.0089076.
Renzo Guerrini, Anna Rosati, Kate Bradshaw, Luigi Giorgi. Adjunctive zonisamide therapy in long term management of children with partial epilepsy: results of an open-label extension study of a phase III, randomized, double blind, placebo controlled trial. Epilepsia. APril 2014;55(4):568-578.
Davoud Eskandari, Ding Zou, Mahssa Karimi, Kaj Stenlof, Ludger Grote, Jan Hadner. Zonisamide reduces obstructive sleep apnoea: a randomised placebo-controlled study. European respiratory journal. March 13,2014. doi: 10.1183/09031936.00158413.
Sabine Skodda. Zonisamide in Parkinson’s disease: an evidence based review of its impact on clinical outcomes. Clinical Medicine reviews in therapeutics. 2012;4:89-96.
Tohshin Go. Zonisamide induces crystalluria without urinary pH changes in children and young adults. ISRN Neurology. Volume 2013. Article ID 841902, 3 pages.
Ester Is=dini, Imma Buj-Alvarez, Josep Pifarre-Paradero, Stella Rodriguez-Picasso, Ester Castan-Campanera. Patients with eating disorders (ED) treated with zinosamide. Rev. Bras. Psiquiatr. Dec 2011;33(4).
Kishore M Gadde, Gretchen M Yonish, Mariko S Foust, H Ryan Wagner. Combination therapy with zonisamide and bupropion for weight reduction in obese women: A preliminary, randomized open label study. J Clin Psychiatry. Aug 2007;68:8.:1226-1229.
Valeo Tom. Zonisamide found non inferior to carbamazepine for nely diagnosed epilepsy. Sept 2012;12(17):10.
Bassel Abou-Khalil. Levetiracetam in the treatment of epilepsy. Neuropsychiatr Dis Treat. Jun 2008;4(3):507-523.
Gregory L Krauss, Tim Betts, Bassel Abou-Khalil, Gregory Bergey, Helen Yarrow, Akemi Miller. Levetiracetam treatment of idiopathic generalised epilepsy. Seizure- European Journal of Epilepsy. Dec 2003;12(8):617-620.
Paul Boon, Reginald Hulhoven, Fritz Offenr. Levetiracetam and bleeding disorders. Acta Neurol. Belg. 2007;107:97-102.
MJ Brodie, E Perucca, P Ryvlin, E Ben Menachem, HJ Meencke. Comparison of levetiracetam and controlled release carbamazepine in newly diagnosed epilepsy. Neurology. Feb 2007;68(6):402-408.
Delia M Talos, Meayoung Chang, Bela Kosaras, Erin Fitzgerald, Andrew Murphy, Rebecca Dunn Folkerth, Frances E Jensen. Antiepileptic effects of levetiracetam in a rodent neonatal seizure model. Pediatric Research. 2013;73:24-30.
Pascal E Sanchez, Lei Zhu, Laure Verret, Keith A Vossel, Anna G orr, John R Cirrito, Nino Devidze, Kaitlyn Ho, Gui-Qui Yu, Jorge J Palop, Lennart Mucke. Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer’s disease model. PNAS August 6,2012. doi:10.1073/pnas.1121081109.
DR Shakya, A Dutta, R Gautam. Hallucination in a seizure patient using levetiracetam: a case report. Case Reports in Medicine. 2012. Article ID 706243, 3 pages.
Nian Xiong, Lingling Hou, Na Lu, Asrah A Mohamed, Tao Wang, Yaling Huang. Probable levetiracetam related serum alkaline phosphatase elevation. BMC Neurology 2012;12:97.
Kosloff Gregg V. The use of levetiracetam and phenytoin for seizure prophylaxis in the setting of severe traumatic bain injury. 2012. School of Physician Assistant Studies. Paper 300. http://commons.pacificu.edu/pa/300.
SC Keswani, EH Kossoff, GL Krauss, C Hagerty. Amelioration of spinal myoclonus with levetiracetam. J Neurol Psychiatry. 2002;73:457-458.
Syed Ahmed Zaki, Saurabh Gupta. Levetiracetam induced acute psychosis in a child. Indian Journal of Pharmacology. 2014;46(3):341-342.
Mohammed Koubeissi. Levetiracetam: More evidence of safety in pregnancy. Epilepsy Currents. Nov/Dec 2013;13(6):279-281.
SL Thompson, A Bardia, A Tan, D Barton, L Kottschade, J Sloan, B Christensen, D Smith, C Loprinzi. Levetiracetam for the treatment of hot flashes: A pilot study. Journal of Clinical Oncology. 2007;25(18S):9116.
Jurgen Bauer, Deirdre Cooper-Mahkorn. Tiagabine: efficacy and safety in partial seizures- current status. Neuropsychiatr Dis Treat. Aug 2008;4(4):731-736.
Charlene M Flowers, Judith A Racoosin, Cindy Kortepeter. Seizure activity and off-label use of tiagabine. N Engl J Med. 2006;354:773-774.
Joshua L Gowin, Charles E Green, Joseph L Alcorn, ALan C Swann, F Gerard Moeller, Scott D Lane. Chronic tiagabine administration and aggressive responding in individuals with a history of substance abuse and antisocial behavior. J Psychopharmacol. July 2012;26(7):982-993.
Leikin Jerrold, Beningo Jennifer, Dubow Jordan, Fisher Merk. Status epilepticus due to tiagabine ingestion. American Journal of Therpeutics. May/June 2008;15(3):290-291.
S Knake, HM Hamer, U Schomburg, WH Oertel, F Rosenow. Tiagabine induced absence status in idiopathic generalised epilepsy. Seizure- European Journal of epilepsy. Aug 1999;8(5):314-317.
Pulman J, Hutton JL, Marson AG. Tiagabine add-on for drug-resistant partial epilepsy. Cochrane Database of Systematic Reviews 2014, Issue 2. Art No.:CD001908. DOI: 10.1002/14651858.CD001908.pub3.
Basim M Uthman, James Rowan, Peter A Ahmann, IIO E Leppik, Steven C Schachter, Kenneth W Sommerville, Vincent Shu. Tiagabine for complex partial seizures. A randomised, add-on, dose-response trial. Arch Neurol. 1998;55(1):56-62.
James K Walsh, Angela C Randazzo,Kara Stone. Tiagabine is associated with sustained attention during sleep restriction. Evidence for the value of Slow-Wave Sleep Enhancement? Sleep 2006;29(4).
Hemming K, Maguire MJ, Hutton JL, Marson AG. Vigabatrin for refractory partial epilepsy. Cochrane summaries. 31 Jan 2013.
M Lawden, T Eke, C Degg, G Harding, J Wild. Visual field defects associated with vigabatrin therapy. J Neurol Neurosurg Psychiatry. Dec 1999;67(6):716-722.
Mi-Sun Yum, Eun Hye Lee, Tae-Sung Ko. Vigabatrin and mental retardation in tuberous sclerosis. Infantile spasms versus focal seizures. J Child Neurol. March 2013;28(3):308-313.
Frederique H Vermeji, Pieter A van Doorn, Herman FM Busch. Improvement of stiff man syndrome with vigabatrin. The Lancet. Aug 1996;348(9027):612.
Yang J, Naumann MC, Tsai Y-T, Tosi J, Erol D et al. Vigabatrin induced retinal toxicity is partially by signalling in rod and cone photoceptors. PLoS ONE. 2012;7(8):e43889. doi:10.1371/journal.pone.0043889.
Peter Zwanger, Thomas C Bhagai, Cornelius Schuele, ANdreas Strohle, Frank Padberg, Norbert Kathmann et al. Vigarbatrin decreases cholecystokinin-Tetrapeptide (CCK-4) induced panic in healthy volunteers. Neuropsychopharmacology. 2001;25:699-703.
Yaiza Hernandez Vega, Marios Kaliakatsos, Jean-Marie-U-King-Im, Karine Lascelles, Ming Lim. Reversible vigabatrin induced life threatening encephalopathy. JAMA Neurol. 2014;71(1):108-109.
Aaron A Hall, Colin Young, Michael Bodo, Richard T Mahon. Vigabatrin prevents seizure in swine subjected to hyperbaric hyperoxia. Journal of applied physiology. Sept 2013;115:861-867.
Elizabeth J Waterhouse, Kimberly N Mims, Soundarya N Gowda. Treatment of refractory complex partial seizures: role of vigabatrin. Neuropsychiatric Diagnosis and Treatment. Oct 2009;5:505-515.
Susane E Camposano, Elizabeth A Thiele. Vigabatrin in the treatment of infantile spasms. US Neurology. 2010;5(2):82-84.
Sawh SC, Newman JJ, Deshpande S, Jones PM. Lacosamide adjunctive therapy for partial onset seizures: a meta-analysis. Peer J. 2013;1:e114.
Reena Gogia Rastogi, Yu-Tze Ng. Lacosamide in refractory mixed pediatric epilepsy: A prospective add-on study. J Child Neurol. April 2012;27(4):492-495.
Anna Kelemen, Peter Halasz. Lacosamide for the prevention of partial onset seizures in epileptic adults. Neuropsychiatric Disease and Treatment. July 2010;6(1):465-471.
Nathan B Fountain, Gregory Krauss, Jouko Isojarvi, Deanne Dilley, Pamela Doty, G David Rudd. Safety and tolerability of adjunctive intravenous loading dose in lacosamide naive patients with partial onset seizures. Epilepsia. Jan 2013;54(1):58-65.
Pegah Afra, Bola Adamolekun. Lacosamide treatment of juvenile myoclonic epilepsy. Seizure. April 2012;21(3):202-204.
Devanshi Jadhav, Daniel Birnbaum, Kathleen Burger, Mohamad KouBeissi. Efficacy of lacosamide in epilepsia partialis continua. Neurology April 8,2014;82(10):P4.254
Dan Ziegler, Tibor Hidvegi, Irina Gurieva, Sabine Bongardt, Rainer Freynhagen, David Sen, Kenneth Sommerville. Efficacy and safety of lacosamide in painful diabetic neuropathy. Diabetes Care. April 2010;33(4):839-841.
Ylse Gutierrez-Grobe, Jose Antonio Bahena-Gonzalez, Magali Herrera-Gomar, Pedro Mendoza-Diaz, Sandra Garcia-Lopez, Octavio Gonzalez-Chon. Acute liver failure associated with levetiracetam and lacosamide combination treatment for unspecified epileptic disorder. Case Reports in Emergency Medicine. 2013, Article ID 634174, 3 pages.
A del Van Antonana, M Ble Caso, Higon Ballester, JA Ortuno Cortes. Lacosamide-induced acute pancreatitis with positive rechallenge test. Pancreatology. July-Aug 2013;13(4):Suppl 1 page e11.

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