Anti epileptic Drugs : Applications Outside Epilepsy (Reverse Engineering) Dr. Ashok Kumar Batham,

Anti-epileptic Drugs : Applications OUTSIDE EPILEPSY
(Reverse Engineering)
Dr. Ashok Kumar Batham, MB,BS, MD, DCR,
Chief Consultant, Dr Batham Pharma Consultants,
Phone: +91 9328018777
Email: ashokpharmacol@gmail.com
Dr.Ashok Kumar Batham, 1

ANTI-EPILEPTIC DRUGS (AEDS) OUTSIDE EPILEPSY
There is a growing recognition of similarities in the pathophysiology of:
• Epilepsy,
• Cardiac arrhythmias,
• Trigeminal neuralgia,
• Other painful neuropathic conditions,
• Mood disorders,
• Anxiety, and
• Migraine.

ANTI-EPILEPTIC DRUGS ARE APPROVED AND
USED OUTSIDE EPILEPSY
• Phenytoin, Carbamazepine, and Oxcarbazepine have proven
efficacies in Trigeminal Neuralgia.
• Gabapentin and Pregabalin are established in the treatment of
postherpetic neuralgia (PHN) and painful diabetic neuropathy
(PDN).
• Divalproex sodium is approved for use in the treatment of bipolar
disorder and prevention of migraine.

DEVELOPMENT OF NEW DRUGS
• Epilepsy alone does not appear to be a lucrative therapeutic
application of anti-epileptic drugs (AEDs).
• A new AED with additional approved indications in bipolar
disorder and neuropathic pain etc. outside epilepsy might
have a potential market size 3-4 times larger than that of
epilepsy.

MOOD STABILIZING PROPERTIES
Bipolar disorder and epilepsy have some common features:
• episodic nature, and
• associated kindling phenomena.
Understanding of the basic mechanisms of mood-stabilizing action and
clinical trials have led to the regulatory approval and use of the AEDs,
carbamazepine (CBZ), valproic acid (VPA), and lamotrigine (LTG) in the
treatment of bipolar disorder.

NEUROPATHIC PAIN
• Alteration in sodium channels expression suggests that the mechanism underlying
epileptic hyperexcitability may be similar to those underlying neuropathic pain.
• AEDs with effects on voltage-gated sodium or calcium channels may be advantageous
in treating neuropathic pain, such as postherpetic neuralgia, and diabetic
polyneuropathy.
• Gabapentin and Pregabalin relieve neuropathic pain by selective binding to the
calcium-channel, subunit α2-δ in muscle tissue and brain.
• Gabapentin, Pregabalin, Carbamazepine, Oxcarbazepine, Lamotrigine and Valproate
have been found effective.

NEUROPATHIC PAIN (CONTD.)
• In neuropathic pain, chronic nerve injury is associated with the redistribution
and altered subunit compositions of sodium and calcium channels that
predispose neurons in sensory pathways to fire spontaneously or at
inappropriately high frequencies, often from ectopic sites.
• AEDs may counteract this abnormal activity by selectively affecting pain-specific
firing; for example, many AEDs suppress high-frequency action potentials by
blocking voltage-activated sodium channels in a use-dependent fashion.
• Alternatively, AEDs may specifically target pathological channels; for example,
gabapentin is a ligand of alpha2-delta voltage-activated calcium channel
subunits that are overexpressed in sensory neurons after nerve injury.

MIGRAINE
• Topiramate and divalproex sodium have utility in the
prophylaxis or acute treatment of migraine.
• Topiramate has efficacy in migraine possibly due to
enhancement of GABAergic and inhibition of glutamatergic
neurotransmission.

ANTIDEPRESSANT BENEFITS
• Variable levels of evidence suggest that lamotrigine and the
vagal nerve stimulator have antidepressant properties.
• Barbiturates, topiramate, levetiracetam, and possibly
phenytoin may precipitate or exacerbate depression.

ANTI-ANXIETY BENEFITS
Some AEDs acting through enhancement of GABAergic
neurotransmission, produce significant anti-anxiety effects:
• Gabapentin,
• Pregabalin, and
• Tiagabine
These drugs may also be effective in essential tremor.

PHENYTOIN SODIUM (DILANTIN)
• Hydantoin derivative used as a major first-line AED since 1938.
• Avoided by epileptologists because of ADRs, Drug Interactions and Availability of
better drugs.
• Still prescribed by primary care physicians because of good efficacy, once-a-day
dosing, availability of blood level monitoring facility, availability in injectable form,
and extensive cumulative experience, despite the difficult pharmacokinetics and
ADRs.
• Available as capsules (25 mg, 50 mg, 100 mg, 200 mg), chewable tablets (50 mg),
suspension (30 mg/5 mL, 125 mg/5 mL), and injection (250 mg/5 mL).
• Dosing frequency is 1-2 times a day.
26-01-2020Antiepileptic Drugs. Dr.Ashok Kumar Batham, M.D., 11

PHENYTOIN SODIUM: MECHANISM OF ACTION
• Blocks voltage-dependent membrane sodium channels and delays recovery of
inactivated sodium-channels resulting in reduction of: (i) sustained high-
frequency neuronal discharges or repetitive firing and (ii) post-tetanic
potentiation.
• Enhances GABA-mediated synaptic inhibition.
• Reduces excitatory synaptic transmission.
• Reduces pre-synaptic calcium entry and blocks release of neurotransmitters.
• Consequently, stabilises seizure threshold and prevents spread of seizure activity
(does not abolish the primary focus of seizure discharge).

PHENYTOIN SODIUM: IN EPILEPSY
Indicated for the treatment of:
• Generalized tonic-clonic seizures (grand mal epilepsy),
• Complex partial seizures (psychomotor, temporal lobe epilepsy),
• Combination of the above seizures,
• Prevention and treatment of seizures occurring during or following neurosurgery
and/or severe head injury,
• Lennox-Gastaut syndrome, status epilepticus, and childhood epilepsies.
• Phenytoin sodium is not effective in absence status epilepticus or in the
prophylaxis and treatment of febrile convulsions.
• Not indicated for myoclonus and absence seizures.

PHENYTOIN SODIUM: IN TRIGEMINAL NEURALGIA
• Approved for treating trigeminal neuralgia.
• Used as a second-line drug therapy, if
carbamazepine is ineffective or not tolerated.

PHENYTOIN SODIUM: AS AN ANTI-ARRHYTHMIC
• It is a class 1b antiarrhythmic.
• Used in the treatment of ventricular tachycardia and sudden
episodes of atrial tachycardia not responding to other
antiarrhythmics and/or cardioversion.
• Drug of choice for treating arrhythmias caused by Digoxin
(cardiac glycoside) toxicity. Used intravenously for this
purpose.

PHENYTOIN SODIUM CREAM (5 % AND 10 %)
• Clinical trials and their meta-analysis support the use of
phenytoin in managing various non-healing ulcers and
wounds.
• Useful in treating neuropathic pain as shown by number of
clinical trials.

CARBAMAZEPINE (TEGRETOL)
• Iminostilbene derivative.
• Used in Switzerland since 1963 for trigeminal neuralgia and epilepsy,
approved in the UK in 1965 and in the US in 1974 for epilepsy.
• First-line AED for partial seizures and generalized tonic-clonic seizures.
• Available as tablets (100 mg, 200 mg, 400 mg), chewable tablets (100 mg,
200 mg), extended-release capsules (100 mg, 200 mg, 400 mg), suspension,
syrup, and rectal suppositories.

CARBAMAZEPINE (TEGRETOL): MECHANISMS OF
ACTION
• Acts by blocking neuronal sodium channels:
• delays the recovery of sodium channels to active state,
• prevent the repetitive firing of the axons,
• blocks and prevents post-tetanic potentiation,
• causes stabilization of the neuronal membranes,
• limits the development of maximal seizure activity, and
• reduces the spread of seizures.

CARBAMAZEPINE (TEGRETOL): MECHANISMS OF
ACTION (CONTD.)
• Evidence suggests that carbamazepine is a serotonin releasing agent
and possibly also a serotonin reuptake inhibitor.
• Reduces or abolishes pain induced by stimulation of the infraorbital
nerve in cats and rats.
• Depresses thalamic potential and bulbar and polysynaptic reflexes,
including the linguomandibular reflex in cats.
• In addition to blockade of sodium-channels, the above mechanisms also
contribute to the pain relieving effects of the drug.

CARBAMAZEPINE (TEGRETOL) : IN EPILEPSY
• Approved in the United States by the FDA for:
• Partial seizures,
• Generalized tonic-clonic seizures and
• Mixed seizures).

CARBAMAZEPINE (TEGRETOL): OTHER APPROVED
INDICATIONS
Trigeminal neuralgia.

CARBAMAZEPINE (TEGRETOL): OTHER APPROVED
INDICATIONS
Prophylaxis of manic and mixed episodes of Bipolar I
Disorder.
Canadian Network for Mood and Anxiety Treatments
(CANMAT) and International Society for Bipolar Disorders
(ISBD) : Recommended as an alternative to preferred agents
for patients with bipolar major depression.

CARBAMAZEPINE (TEGRETOL): EMERGING
INDICATIONS
• Attention Deficiency Hyperactivity Disorder (ADHD).

VALPROIC ACID
• Valproic acid is a simple molecule, similar to endogenous fatty acids.
• Most commonly used AED world over.
• Licensed in Europe in the early 1960s, where it is used extensively.
• Used in different forms (divalproex sodium, magnesium or calcium salt, and
valpromide), which do not differ significantly.
• Valproate is available 125 mg, 250 mg, and 500 mg delayed-release tablets; 125
mg and 250 mg sprinkle capsules; 500 mg extended-release tablets; 250 mg/5 mL
syrup; and parenteral preparation for IV injection.

VALPROIC ACID : MECHANISMS OF ACTION
• Causes selective modulation of voltage-gated sodium currents during
sustained, rapid, repetitive neuronal firing (delays the recovery of
inactivated sodium channels-like phenytoin and carbamazepine).
• Facilitates synthesis of GABA by stimulating Glutamic Acid Decarboxylase
(GAD).
• Blocks GABA degradation by inhibiting GABA Transaminase as well as
Succinic Semialdehyde Dehydrogenase (SSD).

VALPROIC ACID : MECHANISMS OF ACTION (CONTD.)
• Inhibits histone deacetylase, by promoting more transcriptionally active
chromatin structures – epigenetic mechanism for many of the neuroprotective
effects.
• Anti-androgen - antagonist of the androgen receptors, at concentrations much
lower than therapeutic serum levels
• Anti-progesterone - antagonist of progesterone receptors, at concentrations
much lower than therapeutic serum levels.
• Potent aromatase inhibitor - suppresses estrogen concentrations.
• The ant-hormonal actions are likely to be involved in the reproductive
endocrine disturbances.Dr.Ashok Kumar Batham, 26

VALPROIC ACID : IN EPILEPSY
Effective against a wide range of seizure types.
• Idiopathic generalized tonic-clonic epilepsy - drug of choice.
• Complex partial seizures secondarily generalized.
• Typical absence seizure - drug of choice.
• Juvenile myoclonic epilepsy - drug of choice (can also be use in other types of
myoclonus).
• Photosensitive epilepsy - first-line drug
• Lennox-Gastaut syndrome - first-line drug.
• Infantile spasms - second choice.
• Focal epilepsy - as effective as other first-line agents.

VALPROIC ACID: IN MANIA IN BIPOLAR DISORDER
• Indicated for the treatment of the manic episodes in bipolar disorder,
that are characterized by distinct period of abnormally and persistently
elevated, expansive, or irritable mood.
• Typical symptoms of mania include pressure of speech, motor
hyperactivity, reduced need for sleep, flight of ideas, grandiosity, poor
judgment, aggressiveness, and possible hostility.
• The efficacy of Depakote was established in 3-week trials in patients
meeting DSM-III-R criteria for bipolar disorder, hospitalized for acute
mania.

VALPROIC ACID : IN THE PROPHYLAXIS OF MIGRAINE
Divalproex is approved and used for the prevention of
attacks of acute migraine (but not for the termination of
migraine attacks).

VALPROIC ACID: IN FAMILIAL ADENOMATOUS
POLYPOSIS & FRAGILE X-SYNDROME
Enjoys status of Orphan Drug for the treatment of:
• Familial Adenomatous Polyposis &
• Fragile X Syndrome
despite of weak evidence of clinical efficacy.

VALPROIC ACID : NEW EMERGING INDICATIONS
• Dopamine dysregulation syndrome that develops due to treatment of
Parkinson’s disease with levodopa.
• Alcohol induced hallucinosis - One randomized double-blind clinical trial.
• Cluster headaches - 2 case reports support this application. Limited
evidence.
• Chronic pain and fibromyalgia - Limited evidence.
• Intractable hiccup - 2 case reports support this application. Limited
evidence.
• Impulse Control Disorder - Limited support to the use by clinical trials.

VALPROIC ACID : NEW EMERGING INDICATIONS
(CONTD.)
• West syndrome - A prospective clinical trial supported its efficacy in treating infantile
spasms.
• Non-epileptic myoclonus - 3 case reports support this application. Limited evidence.
• Myelodysplastic Syndrome - several clinical trials have confirmed efficacy as a
monotherapy,as an adjunct to tretinoin, and as an adjunct to hydralazine.
• Acute Myeloid Leukemia - Limited evidence supports application.
• Cervical Cancer - Use is supported by one clinical trial.
• Breast Cancer - Use is supported by one Phase II clinical trial.

LAMOTRIGINE (LAMICTAL)
• A triazine compound, chemically unrelated other AEDs.
• Approved in the US in 1994.
• Lamictal is available as:
Tablets : 25 mg, 100 mg, 150 mg, and 200 mg scored. Orally
Disintegrating Tablets of similar strengths are also available.
Chewable Dispersible Tablets: 2 mg, 5 mg, and 25 mg.

LAMOTRIGINE (LAMICTAL) - MECHANISMS OF ACTION
• Lamotrigine blocks sodium channel.
• Consequently, suppresses the release of glutamate and aspartate
(dominant excitatory neurotransmitters).
• Also blocks high voltage-activated calcium channels, L-, N-, and P/Q/R-
types, which possibly accounts for it's broader clinical spectrum of activity.
• Weakly inhibits the serotonin, 5-HT3 receptor.
• GABAergic mechanism may also be involved (suggested by animal studies).

LAMOTRIGINE (LAMICTAL): USE IN EPILEPSY
I. Epilepsy - adjunctive therapy in patients ≥2 years of age for partial seizures,
primary generalized tonic-clonic seizures, generalized seizures of Lennox-Gastaut
syndrome.
II. Bipolar Disorder in patients ≥18 years of age: maintenance treatment of Bipolar I
Disorder to delay the time to occurrence of mood episodes in patients treated for
acute mood episodes with standard therapy.
The goal of maintenance treatment with LAMICTAL is to delay the time to occurrence
of mood episodes (depression, mania, hypomania, mixed episodes) in patients
treated for acute mood episodes with standard therapy.
The target dose of LAMICTAL is 200 mg/day.

LAMOTRIGINE (LAMICTAL): OTHER USES
1. Bipolar Disorder in patients ≥18 years of age: maintenance treatment
of Bipolar I Disorder to delay the time to occurrence of mood episodes in
patients treated for acute mood episodes with standard therapy (Use is
approved by the USFDA).
The goal of maintenance treatment with LAMICTAL is to delay the time
to occurrence of mood episodes (depression, mania, hypomania, mixed
episodes) in patients treated for acute mood episodes with standard
therapy.
The target dose of LAMICTAL is 200 mg/day.Dr.Ashok Kumar Batham, 36

LAMOTRIGINE (LAMICTAL) : OTHER USES (CONTD.)
2. Peripheral neuropathy
3. Trigeminal neuralgia
4. Cluster headaches
5. Migraines
6. Visual snow.
7. Treatment-resistant
obsessive-compulsive disorder
8. Depersonalization disorder
9. Hallucinogen persisting
perception disorder
10. Schizoaffective disorder
11. Borderline personality
disorder

PREGABALIN (LYRICA)
• GABA analogue with an attached isobutane chain.
• Possesses analgesic, anticonvulsant, and anxiolytic properties.
• Available as: Capsules: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg,
200 mg, 225 mg, and 300 mg; and Oral Solution: 20 mg/mL.
• To be administered in 2 or 3 divided doses per day, with an initial
dosing at 150 mg/day, increased to 300 mg/day in most of the
cases. Maximum dose of 600 mg/day.

PREGABALIN (LYRICA): MECHANISM OF ACTION
• Inactive at GABA receptors, including GABA-A, benzodiazepine, t-
butylbicyclophosphorothionate (TBPS), and GABA-B radioligand binding
sites.
• Does not bind directly to GABA-A, GABA-B, or benzodiazepine receptors
(despite being chemical analogue of GABA).
• Does not alter rat brain GABA concentration or have acute effects on
GABA uptake or degradation.
• In cultured neurons prolonged application of pregabalin, increases the
density of GABA transporter protein and increases the rate of functional
GABA transport in cultured neurons. 26-01-2020Antiepileptic Drugs. Dr.Ashok Kumar Batham, M.D., 39

PREGABALIN : MECHANISMS OF ACTION (CONTD.)
• Does not block sodium channels.
• Not active at opiate receptors.
• Does not alter cyclooxygenase (COX) enzyme.
• Inactive at serotonin and dopamine receptors.
• Does not inhibit dopamine, serotonin, or noradrenaline reuptake.

PREGABALIN : MECHANISMS OF ACTION (CONTD.)
• Binds with high affinity to the alpha2-delta site (an auxiliary subunit of
voltage-gated calcium channels) in CNS involved in anti-nociceptive and
antiseizure effects.
• Shown to reduce calcium-dependent release of pro-nociceptive
neurotransmitters in the spinal cord, possibly by disrupting alpha2-delta
containing-calcium channel trafficking and/or reducing calcium currents.
• Anti-nociceptive activities may be mediated through interactions with
descending noradrenergic and serotonergic pathways originating from the
brainstem that modulate pain transmission in the spinal cord.

PREGABALIN (LYRICA): USE IN EPILEPSY
Approved in the US by FDA in 2005 for treatment of
Partial onset epilepsy

PREGABALIN (LYRICA): OTHER USES
Approved in the US by FDA in 2005 for:
• Diabetic neuropathic pain,
• Post-herpetic neuralgia,
• Neuropathic pain associated with spinal cord injury, and
• Fibromyalgia.

PREGABALIN (LYRICA) IN NEUROPATHIC PAIN
The European Federation of Neurological Societies
recommends Pregabalin as a first line agent for the treatment
of:
• Pain associated with diabetic neuropathy,
• Post-herpetic neuralgia, and
• Central neuropathic pain.

PREGABALIN (LYRICA) IN ANXIETY
• Moderately effective and safe for treatment of generalized anxiety disorder.
• Appears to have anxiolytic effects similar to benzodiazepines with less risk of
tolerance, dependence and abuse.
• Beneficial effects appear after 1 week of use and are similar to lorazepam,
alprazolam, and venlafaxine.
• Superior in terms of producing more consistent benefits on psychosomatic anxiety
symptoms.
• Produces beneficial effect on sleep and sleep architecture, characterized by
enhancement of slow-wave sleep.
• Produces less severe cognitive and psychomotor impairment compared to
benzodiazepines.Dr.Ashok Kumar Batham, 45

PREGABALIN (LYRICA) IN ANXIETY
The World Federation of Biological Psychiatry
recommends:
Pregabalin as one of several First-Line agents for the
treatment of Generalized Anxiety Disorder.

GABAPENTIN (NEURONTIN) : MECHANISMS OF ACTION
• Gabapentin is structurally related to the neurotransmitter gamma-aminobutyric acid (GABA)
but has no effect on GABA binding, uptake, or degradation.
• In vitro studies have shown that gabapentin binds with high-affinity to the α2δ subunit of
voltage-activated calcium channels in the cerebral neocortex, hippocampus, and spinal cord.
This action is probably responsible for the analgesic property.

GABAPENTIN (NEURONTIN) : MECHANISMS OF ACTION
(CONTD.)
• Reduces brain glutamate (excitatory neurotransmitter) levels by
stimulation of Glutamic Acid Decarboxylase (GAD) which converts
Glutamic acid into GABA.
• Competitively inhibits branched chain amino acid transferase, which
metabolizes leucine, isoleucine, and valine to glutamate.
• Increases brain levels of GABA and its metabolites homocarnosine and
pyrrolidinone.
• May reduce monoamines and affect serotonin release.

GABAPENTIN (NEURONTIN)
• Structural analogue of GABA; however, it does not act on
GABA-receptor.
• Approved in the UK in 1993 and in the US in 1994.
• Available as capsules of 100 mg, 300 mg, 400 mg, and 600 mg
and tablets of 800 mg.

GABAPENTIN (NEURONTIN) : IN EPILEPSY
USFDA Approved Indication: Epilepsy with Partial Onset Seizures:
Starting dose 300 mg three times daily; may be titrated up to 600
mg three times daily.

GABAPENTIN (NEURONTIN) : IN POST-HERPETIC
NEURALGIA
USFDA Approved Indication: Postherpetic Neuralgia.
Dosage - Day 1: Single 300 mg dose, Day 2: 600 mg/day (300 mg
two times a day), Day 3: 900 mg/day (300 mg three times a day).
Maximum upto 1800 mg per day.

GABAPENTIN (NEURONTIN) : IN NEUROPATHIES
• A 2010 European Federation of Neurological Societies task force clinical
guideline recommended gabapentin as a first-line treatment for:
• diabetic neuropathy,
• postherpetic neuralgia, and
• central neuropathic pain.
• Good evidence of better efficacy of the combination of gabapentin and
morphine or oxycodone or nortriptyline or venlafaxine than either drug
alone.

GABAPENTIN (NEURONTIN) : EMERGING USES
• Uremic pruritus and itching of other causes- reported effective.
• Restless legs syndrome - established treatment (augments sleep
efficiency).
• Essential or orthostatic tremor - treatment option.
• Acquired pendular nystagmus and infantile nystagmus - possibly
effective (but not periodic alternating nystagmus).
• Pain and spasticity in multiple sclerosis - possibly effective.
• Alcohol withdrawal, alcohol dependence and craving - possibly effective.

GABAPENTIN (NEURONTIN) : IN MIGRAINE &
ANXIETY
Migraine prophylaxis
The American Headache Society (AHS) and American Academy of Neurology (AAN)
guidelines classify gabapentin as a drug with "insufficient data to support or refute
use for migraine prophylaxis".
A 2013 Cochrane review concluded that gabapentin was not useful for the prevention
of episodic migraine in adults.
Anxiety disorders
• Gabapentin has been used off-label for the treatment of anxiety disorders.
However, there is dispute over whether evidence is sufficient to support it being
routinely prescribed for this purpose.

TOPIRAMATE (TOPAMAX)
• Very potent D-fructose derivative, used in epilepsy since 1996.
• Available as Tablets of 25 mg, 50 mg, 100 mg, and 200 mg,
and as Sprinkle Formulations of 15 mg and 25 mg.

TOPIRAMATE (TOPAMAX) : MECHANISMS OF
ACTION
Electrophysiological and biochemical evidence suggests that topiramate:
• blocks voltage-dependent sodium channels
• augments the activity of GABA at some subtypes of the GABA-A
receptor
• antagonizes the AMPA/kainate subtype of the glutamate receptor
• and inhibits the carbonic anhydrase enzyme, particularly isozymes II and
IV.

TOPIRAMATE (TOPAMAX) : IN EPILEPSY
US FDA Approved Indications:
I. Monotherapy in epilepsy: Initial monotherapy in patients ≥ 2 years of
age with partial onset or primary generalized tonic-clonic seizures.
II. Adjunctive therapy in epilepsy:
For adults and pediatric patients (2 to 16 years of age) with:
• partial onset seizures or
• primary generalized tonic-clonic seizures, and
For patients ≥2 years of age with seizures associated with Lennox-
Gastaut syndrome (LGS).

TOPIRAMATE (TOPAMAX) : IN MIGRAINE
US FDA Approved Indication:
• Migraine: Treatment for adults for prophylaxis of
migraine headache.

TOPIRAMATE (TOPAMAX) : OTHER USES
• Bipolar Disorder. One randomized controlled trial suggested a benefit of
topiramate in the treatment of symptoms of borderline personality disorder.
• Treatment for alcoholism. The VA/DoD 2015 guideline on substance use
disorders lists topiramate as a "strong for" in its recommendations for
alcohol use disorder.
• Obesity and antipsychotic-induced weight gain.
• A combination phentermine/topiramate was approved in the United States
for weight loss in 2012.
Dr.Ashok Kr Batham, 59

TOPIRAMATE (TOPAMAX) : OTHER USES (CONTD.)
• Post traumatic stress disorder – being evaluated.
• Chronic low back pain - Review of literature revealed topiramate of no
use.
• Diabetic neuropathy - Not been found effective in clinical trials.
Dr.Ashok Kr Batham, 60

TOPIRAMATE-PHENTERMINE IN OBESITY
• Topiramate, an anticonvulsant was found to cause weight loss as a
side effects.
• Phentermine is a sympathomimetic CNS stimulant which has anorexic
effects.
• The exact mechanism of action for both drugs is unknown.
• Sold under the brand name – Qsymia.
• Qsymia capsules areavailable in the following four strength
combinations (phentermine mg/topiramate mg extended-release):
3.75 mg/23 mg | 7.5 mg/46 mg | 11.25 mg/69 mg | 15 mg/92 mg

TOPIRAMATE-PHENTERMINE IN OBESITY (CONTD.)
• Approved for medical use in the United States in 2012.
• Use and distribution of Qsymia is under strict control under
Risk Evaluation and Mitigation Strategy (REMS) program by
the federal government because it contains phentermine,
that has a high potential for abuse and drug dependence.
Qsymia is classified as a schedule IV controlled substance.
• Approval denied in Europe because safety concerns.

TOPIRAMATE-PHENTERMINE IN OBESITY (CONTD.)
• Causes modest weight loss.
• The effectiveness of Qsymia was proven by two placebo-controlled clinical studies.
• At the end of 1 year of treatment patients had an average weight loss of 7.8% compared to 1.2 to 1.6%
for placebo treated patients.
• 62 to 70% of patients lost 5% of their body weight compared to about 17 to 21% of patients who
received placebo.
• If less than 3% weight loss is seen after 3 months it is recommended the medication be stopped.
• Effects on heart related health problems or death is unclear.
• Common side effects include tingling, dizziness, trouble sleeping, and constipation.
• Serious side effects may include suicide, abuse.
• Use is not recommended during pregnancy.Dr.Ashok Kumar Batham, 63

CONCLUSION
• Overlapping pathophysiology of some disorders and
mechanisms of action of many antiepileptic drugs are
evidently responsible for the applications of anti-epileptic
drugs (AEDs) in clinical conditions outside epilepsy.
• New drug candidates will, therefore, be developed for both the
sets of therapeutic applications (epilepsy and outside epilepsy).

Thank You

Anti epileptic Drugs : Applications Outside Epilepsy (Reverse Engineering) Dr. Ashok Kumar Batham,

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