Tiagabine, sold under the brand name Gabitril, is an

anticonvulsant Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatme ...

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

produced by

Cephalon Cephalon, Inc. was an American biopharmaceutical company co-founded in 1987 by pharmacologist Frank Baldino Jr., Frank Baldino, Jr., neuroscientist Michael Lewis, and organic chemist James C. Kauer—all three former scientists with the DuPont ...

that is used in the treatment of

epilepsy Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...

. The drug is also used

off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication (medicine), indication or in an unapproved age group, dose (biochemistry), dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) ca ...

in the treatment of

anxiety disorder Anxiety disorders are a group of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal functions are significantly impaired. Anxiety may cause phys ...

s including

panic disorder Panic disorder is a mental disorder, specifically an anxiety disorder, characterized by reoccurring unexpected panic attacks. Panic attacks are sudden periods of intense fear that may include palpitations, sweating, shaking, shortness of breath ...

Medical uses

Tiagabine is approved by US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) as an adjunctive treatment for partial

seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

s in individuals of age 12 and up. It may also be prescribed off-label by physicians to treat anxiety disorders, such as panic disorder, as well as

neuropathic pain Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuo ...

(e.g.,

fibromyalgia Fibromyalgia (FM) is a functional somatic syndrome with symptoms of widespread chronic pain, accompanied by fatigue, sleep disturbance including awakening unrefreshed, and Cognitive deficit, cognitive symptoms. Other symptoms can include he ...

). For

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

and neuropathic pain, tiagabine is used primarily to augment other treatments. Tiagabine may be used alongside

selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by blo ...

s (SSRIs),

serotonin–norepinephrine reuptake inhibitor Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant medications used to treat major depressive disorder (MDD), anxiety disorders, social phobia, chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopaus ...

s (SNRIs), or

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

s for anxiety, and

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

gabapentin Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat neuropathic pain and also for partial seizures of epilepsy. It is a commonly used medication for the treatment of neuropath ...

, other anticonvulsants, or

opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...

s for neuropathic pain. It is effective as monotherapy and combination therapy with other anticonvulsant drugs in the treatment of

partial seizure Focal seizures are Seizure, seizures that originate within brain networks limited to one Cerebral hemisphere, hemisphere of the brain. In most cases, each seizure type has a consistent site of onset and characteristic patterns of spread, although ...

. The

American Academy of Sleep Medicine The American Academy of Sleep Medicine (AASM) is a United States professional society for the medical subspecialty of sleep medicine which includes disorders of circadian rhythms. It was established in 1975. The organization's functions includ ...

's 2017

clinical practice guideline A medical guideline (also called a clinical guideline, standard treatment guideline, or clinical practice guideline) is a document with the aim of guiding decisions and criteria regarding diagnosis, management, and treatment in specific areas of ...

s recommended against the use of tiagabine in the treatment of insomnia due to poor effectiveness and very low

quality of evidence Evidence-based medicine (EBM) is "the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients. It means integrating individual clinical expertise with the best available exte ...

Side effects

Side effects of tiagabine are dose related. The most common side effect of tiagabine is

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a ...

. Other side effects that have been observed with a rate of statistical significance relative to

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

include

asthenia Weakness is a symptom of many different medical conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, ...

somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling aslee ...

, nervousness,

memory impairment Amnesia is a deficit in memory caused by brain damage or brain diseases,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be temporarily caused by t ...

tremor A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

, and depression. Adverse effects such as

confusion In psychology, confusion is the quality or emotional state of being bewildered or unclear. The term "acute mental confusion"

aphasia Aphasia, also known as dysphasia, is an impairment in a person's ability to comprehend or formulate language because of dysfunction in specific brain regions. The major causes are stroke and head trauma; prevalence is hard to determine, but aph ...

stuttering Stuttering, also known as stammering, is a speech disorder characterized externally by involuntary repetitions and prolongations of sounds, syllables, words, or phrases as well as involuntary silent pauses called blocks in which the person who ...

, and

paresthesia Paresthesia is a sensation of the skin that may feel like numbness (''hypoesthesia''), tingling, pricking, chilling, or burning. It can be temporary or Chronic condition, chronic and has many possible underlying causes. Paresthesia is usually p ...

(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). Tiagabine may induce

s in those without

, particularly if they are taking another drug which lowers the

seizure threshold The term seizure threshold is used to describe the balance between excitatory (glutaminergic) and inhibitory (GABA-ergic) forces in the brain which affect how susceptible a person is to seizures. Those diagnosed with epilepsy or certain other neuro ...

. There may be an increased risk of

psychosis In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...

with tiagabine treatment, although data is mixed and inconclusive. Tiagabine can also reportedly interfere with visual

color perception Color vision, a feature of visual perception, is an ability to perceive differences between light composed of different frequencies independently of light intensity. Color perception is a part of the larger visual system and is mediated by a co ...

Overdose

Tiagabine

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Retrieved on September 20, 2014.

can produce neurological symptoms such as

lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness, or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overw ...

, single or multiple

status epilepticus Status epilepticus (SE), or status seizure, is a medical condition with abnormally prolonged seizures. It can have long-term consequences, manifesting as a single seizure lasting more than a defined time (time point 1), or 2 or more seizures over ...

coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to Nociception, respond normally to Pain, painful stimuli, light, or sound, lacks a normal Circadian rhythm, sleep-wake cycle and does not initiate ...

confusion In psychology, confusion is the quality or emotional state of being bewildered or unclear. The term "acute mental confusion"

, agitation,

dystonia Dystonia is a neurology, neurological Hyperkinesia, hyperkinetic Movement disorders, movement disorder in which sustained or repetitive muscle contractions occur involuntarily, resulting in twisting and repetitive movements or abnormal fixed po ...

abnormal posturing Abnormal posturing is an involuntary flexion or extension of the arms and legs, indicating severe brain injury. It occurs when one set of muscles becomes incapacitated while the opposing set is not, and an external stimulus such as pain caus ...

, and

hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...

s, as well as

respiratory depression Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapni ...

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...

, and

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

. Overdose may be fatal especially if the victim presents with severe respiratory depression or unresponsiveness.

Pharmacology

Tiagabine increases the level of

γ-aminobutyric acid GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. GA ...

(GABA), the major inhibitory

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

, by blocking the GABA transporter 1 (GAT-1), and hence is classified as a

GABA reuptake inhibitor A GABA reuptake inhibitor (GRI) is a type of drug which acts as a reuptake inhibitor for the neurotransmitter gamma-Aminobutyric acid (GABA) by blocking the action of the gamma-Aminobutyric acid transporters (GATs). This in turn leads to incr ...

(GRI).

Pharmacodynamics

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 γ-aminobutyric acid (GABA), the central nervous system's major inhibitory neurotransmitter. Tiagabine attaches to the GABA reuptake carrier's recognition sites. Tiagabine is thought to block GABA reuptake 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.

History

Tiagabine was discovered at

Novo Nordisk Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, with production facilities in nine countries and affiliates or offices in five. Novo Nordisk is controlled by majority shareholder Novo Holdings A/S ...

in Denmark in 1988 by a team of medicinal chemists and

pharmacologists Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur between ...

under the general direction of Claus Bræstrup. The drug was co-developed with

Abbott Laboratories Abbott Laboratories is an American multinational medical devices and health care company with headquarters in Abbott Park, Illinois, in the United States. The company was founded by Chicago physician Wallace Calvin Abbott in 1888 to formulate k ...

, in a 40/60 cost sharing deal, with Abbott paying a premium for licensing the IP from the Danish company. US patents on tiagabine listed in the Orange Book expired in April 2016.

Research

Effects on cortical delta oscillations

Tiagabine enhances the power of cortical

delta Delta commonly refers to: * Delta (letter) (Δ or δ), the fourth letter of the Greek alphabet * D (NATO phonetic alphabet: "Delta"), the fourth letter in the Latin alphabet * River delta, at a river mouth * Delta Air Lines, a major US carrier ...

(< 4 Hz) oscillations up to 1000% relative to placebo, which may result in an

EEG Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The bio signals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neoc ...

MEG Meg is a feminine given name, often a short form of Margaret, Megan, Megumi (Japanese), etc. It may refer to: People *Meg (singer) (born 1980), Japanese singer *Meg Baird, American musician *Meg Bateman, Scottish writer * Meg Bellamy, British ac ...

signature resembling non-rapid eye movement sleep even while the person who has taken tiagabine is awake and conscious. 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.

References

External links

Gabitril
manufacturer's website) {{GABA metabolism and transport modulators Drugs developed by AbbVie Anticonvulsants Anxiolytics Carboxylic acids GABA reuptake inhibitors Piperidines Thiophenes

Medical uses

Side effects

Overdose

Pharmacology

Pharmacodynamics

History

Research

Effects on cortical delta oscillations

See also

References

External links