Tuberous Sclerosis Medication

Updated: Aug 06, 2020
  • Author: David Neal Franz, MD; Chief Editor: George I Jallo, MD  more...
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Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.


mTOr Kinase Inhibitors

Class Summary

Immunosuppressant, which forms an inhibitory complex with the immunophilin FKBP12, which binds to and inhibits the ability of mTOr to phosphorylate downstream substrates such as the S6Ks and 4EBPs.

Everolimus (Afinitor, Afinitor Disperz)

Rapamycin-derivative kinase inhibitor. Reduces cell proliferation and angiogenesis by inhibition of mTOr pathway. Afinitor is indicated for treatment of adults with TSC-associated renal angiomyolipoma, not requiring immediate surgery. Afinitor and Afinitor Disperz are indicated for TSC-associated subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention, but cannot be curatively resected in adults and children aged 1 y or older. Afinitor Disperz is also indicated for adjunctive treatment of adults and children aged 2 y or older with TSC-associated partial-onset seizures. Available as tablets (Afinitor) or tablets for oral suspension (Afinitor Disperz).



Class Summary

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.

Vigabatrin (Sabril)

Irreversible inhibitor of GABA transaminase, approved in the summer of 2009 by the US FDA as an orphan drug for the treatment of infantile spasms. Vigabatrin is considered to be standard of care for infants with infantile spasms (West syndrome) due to tuberous sclerosis complex. Due to the potential for irreversible peripheral visual field loss with vigabatrin, careful ophthalmologic follow-up is a condition to obtaining the drug through approved US pharmacies. Vigabatrin may also cause reversible areas of T2 hyperintensity on MRI, which, like the fluctuating signal changes seen on MRI scans of neurofibromatosis 1 patients, are of uncertain clinical significance.

Valproic acid (Depakote, Depakene, Depacon)

Considered effective first-line AED therapy against infantile spasms (West syndrome) and other seizure types seen in patients with TSC.

Lamotrigine (Lamictal)

Inhibits release of glutamate and inhibits voltage-sensitive sodium channels, leading to stabilization of neuronal membrane. Effectiveness in patients with TSC has been investigated in open-label study with promising results.

Initial dose, maintenance dose, titration intervals, and titration increments depend on concomitant medications.

Topiramate (Topamax, Qudexy XR, Trokendi XR)

Sulfamate-substituted monosaccharide with broad spectrum of antiepileptic activity that may have state-dependent sodium channel blocking action, potentiates inhibitory activity of neurotransmitter GABA. May block glutamate activity. Effectiveness in TSC has been investigated in one open-label study with promising results.

Carbamazepine (Tegretol, Carbatrol, Epitol)

Drug of choice for partial onset seizures in children and adults. Some investigators believe carbamazepine can aggravate certain seizure types in young children with TSC.

Cannabidiol (Epidiolex)

Purified formulation of cannabidiol indicated for treatment of seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex in patients aged 1 years or older. Cannabidiol is a structurally novel anticonvulsant and the exact mechanism by which it produces anticonvulsant effects is unknown. It does not appear to exert its anticonvulsant effects through CB1 receptors, nor through voltage-gated sodium channels.


Adrenocorticotropic Agents

Class Summary

These agents cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Corticotropin (HP Acthar, ACTH)

Used in infants with infantile spasms (West syndrome) due to TSC. Estimated overall efficacy (percentage of infants with infantile spasms due to any cause reaching seizure freedom) is 50-67%. Associated with serious, potentially life-threatening adverse effects.

Must be administered IM, which is painful to infant and unpleasant for parent to perform. Daily dosages expressed as U/d (most common), U/m2/d, or U/kg/d.

Prospective single-blind study demonstrated no difference in effectiveness of high-dose, long-duration corticotropin (150 U/m2/d for 3 wk, tapering over 9 wk) versus low-dose, short-duration corticotropin (20-30 U/d for 2-6 wk, tapering over 1 wk) with respect to spasm cessation and improvement in patient's EEG. Hypertension was more common with larger doses.

Prednisone (Rayos)

Like ACTH, has been used for infants with infantile spasms (West syndrome) due to TSC. Few studies comparing ACTH and prednisone have been performed; one double-blind, placebo-controlled, crossover study demonstrated no difference between low-dose ACTH (20-30 U/d) and prednisone (2 mg/kg/d), while a second prospective, randomized, single-blinded study demonstrated high-dose ACTH at 150 U/m2/d was superior to prednisone (2 mg/kg/d) in suppressing clinical spasms and hypsarrhythmic EEG in infants with infantile spasms.



Class Summary

By binding to specific receptor sites, these agents appear to potentiate the effects of GABA and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters. Nitrazepam is not approved by US FDA but is available in many countries worldwide and may be more effective and better tolerated in specific individuals.

Clonazepam (Klonopin)

Considered first- or second-line AED therapy depending on seizure type. Adverse effects and development of tolerance limit usefulness over time. 

Clobazam (ONFI)

Clobazam was approved by the FDA in 2011 for adjunctive therapy for seizures in patients age 2 and older with Lennox-Gastaut syndrome. It is a 1,5-benzodiazepine, and seems to differ from traditional 1,4-benzodiazepines. Some studies suggest lower neurotoxicity and greater efficacy.