Side effects of tiagabine are dose related.[6] The most common side effect of tiagabine is dizziness.[8] Other side effects that have been observed with a rate of statistical significance relative to placebo include asthenia, somnolence, nervousness, memory impairment, tremor, headache, diarrhea, and depression.[8][9] Adverse effects such as confusion, aphasia (difficulty speaking clearly)/stuttering, and paresthesia (a tingling sensation in the body's extremities, particularly the hands and fingers) may occur at higher dosages of the drug (e.g., over 8 mg/day).[8] Tiagabine may induce seizures in those without epilepsy, particularly if they are taking another drug which lowers the seizure threshold.[5] There may be an increased risk of psychosis with tiagabine treatment, although data is mixed and inconclusive.[2][10] Tiagabine can also reportedly interfere with visual color perception.[2]
Tiagabine is primarily used as an anticonvulsant in the treatment of epilepsy as a supplement. Although the exact mechanism by which Tiagabine exerts its antiseizure effect is unknown, it is thought to be related to its ability to increase the activity of gamma aminobutyric acid (GABA), the central nervous system's major inhibitory neurotransmitter. Tiagabine attaches to the GABA uptake carrier's recognition sites. Tiagabine is thought to block GABA uptake into presynaptic neurons as a result of this action, allowing more GABA to be available for receptor binding on the surfaces of post-synaptic cells.[14]
Effects on cortical delta oscillations
Tiagabine enhances the power of cortical delta (< 4 Hz) oscillations up to 1000% relative to placebo, which may result in an EEG or MEG signature resembling non-rapid eye movement sleep even while the person who has taken tiagabine is awake and conscious.[15] This demonstrates that cortical delta activity and wakeful consciousness are not mutually exclusive, i.e., high amplitude delta oscillations are not always a reliable indicator of unconsciousness.
Tiagabine (15 mg) enhances MEGdelta power in healthy volunteers.
Monitoring Parameters
Seizure frequency, liver function tests, suicidality[16]
History
Tiagabine was discovered at Novo Nordisk in Denmark in 1988 by a team of medicinal chemists and pharmacologists under the general direction of Claus Bræstrup.[17] The drug was co-developed with Abbott Laboratories, in a 40/60 cost sharing deal, with Abbott paying a premium for licensing the IP from the Danish company.[citation needed]
U.S. patents on tiagabine listed in the Orange Book expired in April 2016.[18]
^ abcdeLeduc B (24 January 2012). "Antiseizure Drugs". In Lemke TL, Williams DA (eds.). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 562–. ISBN978-1-60913-345-0.
^ abStahl SM (2009). Stahl's essential psychopharmacology: the prescriber's guide; antipsychotics and mood stabilizers (3rd ed.). New York, NY: Cambridge University Press. pp. 523–526. ISBN978-0-521-75900-7.
^ ab"Tiagabine", LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases, 2012, PMID31643697, retrieved 2021-12-24
^ abSpiller HA, Winter ML, Ryan M, Krenzelok EP, Anderson DL, Thompson M, Kumar S (2009). "Retrospective evaluation of tiagabine overdose". Clinical Toxicology. 43 (7): 855–859. doi:10.1080/15563650500357529. PMID16440513. S2CID25469390.
^Pollack MH, Roy-Byrne PP, Van Ameringen M, Snyder H, Brown C, Ondrasik J, Rickels K (November 2005). "The selective GABA reuptake inhibitor tiagabine for the treatment of generalized anxiety disorder: results of a placebo-controlled study". The Journal of Clinical Psychiatry. 66 (11): 1401–1408. doi:10.4088/JCP.v66n1109. PMID16420077.
^Adkins JC, Noble S (March 1998). "Tiagabine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the management of epilepsy". Drugs. 55 (3): 437–460. doi:10.2165/00003495-199855030-00013. PMID9530548. S2CID70426629.
^Andersen KE, Braestrup C, Grønwald FC, Jørgensen AS, Nielsen EB, Sonnewald U, et al. (June 1993). "The synthesis of novel GABA uptake inhibitors. 1. Elucidation of the structure-activity studies leading to the choice of (R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid (tiagabine) as an anticonvulsant drug candidate". Journal of Medicinal Chemistry. 36 (12): 1716–1725. doi:10.1021/jm00064a005. PMID8510100.
^"Search Results for Tiagabine". Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. U.S. Food and Drug Administration. Archived from the original on 22 April 2016. Retrieved 22 March 2016.
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