Tetrabenazine is a drug for the symptomatic treatment of
hyperkineticmovement disorders. It is sold under the brand names Nitoman and Xenazine among others. On August 15, 2008, the U.S.
Food and Drug Administration approved the use of tetrabenazine to treat
chorea associated with
Huntington's disease. Although other drugs had been used "
off label," tetrabenazine was the first approved treatment for Huntington's disease in the U.S.[5] The compound has been known since the 1950s.
Medical uses
Tetrabenazine is used as a treatment, but not as a
cure, for hyperkinetic disorders such as:[6][7]
The most common adverse reactions, which have occurred in at least 10% of subjects in studies and at least 5% greater than in subjects who received placebo, have been: sedation or somnolence, fatigue, insomnia, depression, suicidal thoughts,
akathisia, anxiety and nausea.[4]
Warnings
There is a
boxed warning associated with the use of tetrabenazine:[4]
Increases the risk of depression and suicidal thoughts and behavior in patients with Huntington's disease
Balance risks of depression and suicidality with the clinical need for control of chorea when considering the use of tetrabenazine
Monitor patients for emergence or worsening of depression, suicidality or unusual changes in behavior
Inform patients, caregivers and families of the risk of depression and suicidality and instruct to report behaviours of concern promptly to the treating physician
Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation
Tetrabenazine is contraindicated in patients who are actively suicidal and in patients with untreated or inadequately treated depression
The precise mechanism of action of tetrabenazine is unknown. Its anti-chorea effect is believed to be due to a reversible depletion of monoamines such as
dopamine,
serotonin,
norepinephrine, and
histamine from nerve terminals. Tetrabenazine reversibly inhibits
vesicular monoamine transporter 2, resulting in decreased uptake of monoamines into synaptic vesicles, as well as depletion of monoamine storage.[4]
^Kenney C, Hunter C, Jankovic J (January 2007). "Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders". Movement Disorders. 22 (2): 193–7.
doi:
10.1002/mds.21222.
PMID17133512.
S2CID22001960.
^Smith ME (March 1960). "Clinical comparison of tetrabenazine (Ro 1-9569), reserpine and placebo in chronic schizophrenics". Diseases of the Nervous System. 21(3)Suppl (3 Suppl): 120–123.
PMID13832091.
^Sacerdoti G (1960). "[First clinical experiences with tetrabenazine]" [First clinical experiences with tetrabenazine]. Rassegna di Studi Psichiatrici (in Italian). 49: 450–460.
PMID13745210.
^Schmitt W (July 1960). "[On the pharmacotherapy of psychoses: clinical research on tetrabenazine]" [On the pharmacotherapy of psychoses: clinical research on tetrabenazine]. Psychiatria et Neurologia (in German). 140: 23–29.
doi:
10.1159/000131224.
PMID13748124.
^Ashcroft GW, Macdougall EJ, Barker PA (March 1961). "A comparison of tetrabenazine and chlorpromazine in chronic schizophrenia". The Journal of Mental Science. 107 (447): 287–293.
doi:
10.1192/bjp.107.447.287.
PMID13684728.
^Burckard E, Medhaoui M, Montigneaux P, Pfitzenmeyer J, Pfitzenmeyer H, Schaetzel JC, et al. (January 1962). "[Clinical, biological and electroencephalographic study of the action of tetrabenazine (Ro 956) in various chronic psychoses]" [Clinical, biological and electroencephalographic study of the action of tetrabenazine (Ro 956) in various chronic psychoses]. Annales Médico-Psychologiques (in French). 120 (1): 115–119.
PMID13874731.
^Kammerer T, Singer L, Geissmann P, Wetta JM (January 1962). "[Use of a new neuroleptic: tetrabenazine. Clinical, biological and electroencephalographic results]" [Use of a new neuroleptic: tetrabenazine. Clinical, biological and electroencephalographic results]. Annales Médico-Psychologiques (in French). 120 (1): 106–115.
PMID14453492.
^Lingjaerde O (1963). "Tetrabenazine (Nitoman) in the treatment of psychoses. With a discussion on the central mode of action of tetrabenazine and reserpine". Acta Psychiatrica Scandinavica. 39: SUPPL170:1–SUPPL17109.
PMID14081399.
^Matsumoto Y, Totsuka S, Kato M, Inoue M, Okagami K (July 1966). "[Therapy of schizophrenia with tetrabenazine]". Nihon Rinsho. Japanese Journal of Clinical Medicine (in Japanese). 24 (7): 1360–1364.
PMID6007641.
^Malik A, Balkoski V (November 2007). "Neurotransmitter depleter tetrabenazine; potential candidate for schizophrenia treatment?". Schizophrenia Research. 96 (1–3): 267–268.
doi:
10.1016/j.schres.2007.07.010.
PMID17683910.
S2CID39312847.
^Remington G, Kapur S, Foussias G, Agid O, Mann S, Borlido C, et al. (February 2012). "Tetrabenazine augmentation in treatment-resistant schizophrenia: a 12-week, double-blind, placebo-controlled trial". Journal of Clinical Psychopharmacology. 32 (1): 95–99.
doi:
10.1097/JCP.0b013e31823f913e.
PMID22198452.
S2CID2649261.
Tetrabenazine is a drug for the symptomatic treatment of
hyperkineticmovement disorders. It is sold under the brand names Nitoman and Xenazine among others. On August 15, 2008, the U.S.
Food and Drug Administration approved the use of tetrabenazine to treat
chorea associated with
Huntington's disease. Although other drugs had been used "
off label," tetrabenazine was the first approved treatment for Huntington's disease in the U.S.[5] The compound has been known since the 1950s.
Medical uses
Tetrabenazine is used as a treatment, but not as a
cure, for hyperkinetic disorders such as:[6][7]
The most common adverse reactions, which have occurred in at least 10% of subjects in studies and at least 5% greater than in subjects who received placebo, have been: sedation or somnolence, fatigue, insomnia, depression, suicidal thoughts,
akathisia, anxiety and nausea.[4]
Warnings
There is a
boxed warning associated with the use of tetrabenazine:[4]
Increases the risk of depression and suicidal thoughts and behavior in patients with Huntington's disease
Balance risks of depression and suicidality with the clinical need for control of chorea when considering the use of tetrabenazine
Monitor patients for emergence or worsening of depression, suicidality or unusual changes in behavior
Inform patients, caregivers and families of the risk of depression and suicidality and instruct to report behaviours of concern promptly to the treating physician
Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation
Tetrabenazine is contraindicated in patients who are actively suicidal and in patients with untreated or inadequately treated depression
The precise mechanism of action of tetrabenazine is unknown. Its anti-chorea effect is believed to be due to a reversible depletion of monoamines such as
dopamine,
serotonin,
norepinephrine, and
histamine from nerve terminals. Tetrabenazine reversibly inhibits
vesicular monoamine transporter 2, resulting in decreased uptake of monoamines into synaptic vesicles, as well as depletion of monoamine storage.[4]
^Kenney C, Hunter C, Jankovic J (January 2007). "Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders". Movement Disorders. 22 (2): 193–7.
doi:
10.1002/mds.21222.
PMID17133512.
S2CID22001960.
^Smith ME (March 1960). "Clinical comparison of tetrabenazine (Ro 1-9569), reserpine and placebo in chronic schizophrenics". Diseases of the Nervous System. 21(3)Suppl (3 Suppl): 120–123.
PMID13832091.
^Sacerdoti G (1960). "[First clinical experiences with tetrabenazine]" [First clinical experiences with tetrabenazine]. Rassegna di Studi Psichiatrici (in Italian). 49: 450–460.
PMID13745210.
^Schmitt W (July 1960). "[On the pharmacotherapy of psychoses: clinical research on tetrabenazine]" [On the pharmacotherapy of psychoses: clinical research on tetrabenazine]. Psychiatria et Neurologia (in German). 140: 23–29.
doi:
10.1159/000131224.
PMID13748124.
^Ashcroft GW, Macdougall EJ, Barker PA (March 1961). "A comparison of tetrabenazine and chlorpromazine in chronic schizophrenia". The Journal of Mental Science. 107 (447): 287–293.
doi:
10.1192/bjp.107.447.287.
PMID13684728.
^Burckard E, Medhaoui M, Montigneaux P, Pfitzenmeyer J, Pfitzenmeyer H, Schaetzel JC, et al. (January 1962). "[Clinical, biological and electroencephalographic study of the action of tetrabenazine (Ro 956) in various chronic psychoses]" [Clinical, biological and electroencephalographic study of the action of tetrabenazine (Ro 956) in various chronic psychoses]. Annales Médico-Psychologiques (in French). 120 (1): 115–119.
PMID13874731.
^Kammerer T, Singer L, Geissmann P, Wetta JM (January 1962). "[Use of a new neuroleptic: tetrabenazine. Clinical, biological and electroencephalographic results]" [Use of a new neuroleptic: tetrabenazine. Clinical, biological and electroencephalographic results]. Annales Médico-Psychologiques (in French). 120 (1): 106–115.
PMID14453492.
^Lingjaerde O (1963). "Tetrabenazine (Nitoman) in the treatment of psychoses. With a discussion on the central mode of action of tetrabenazine and reserpine". Acta Psychiatrica Scandinavica. 39: SUPPL170:1–SUPPL17109.
PMID14081399.
^Matsumoto Y, Totsuka S, Kato M, Inoue M, Okagami K (July 1966). "[Therapy of schizophrenia with tetrabenazine]". Nihon Rinsho. Japanese Journal of Clinical Medicine (in Japanese). 24 (7): 1360–1364.
PMID6007641.
^Malik A, Balkoski V (November 2007). "Neurotransmitter depleter tetrabenazine; potential candidate for schizophrenia treatment?". Schizophrenia Research. 96 (1–3): 267–268.
doi:
10.1016/j.schres.2007.07.010.
PMID17683910.
S2CID39312847.
^Remington G, Kapur S, Foussias G, Agid O, Mann S, Borlido C, et al. (February 2012). "Tetrabenazine augmentation in treatment-resistant schizophrenia: a 12-week, double-blind, placebo-controlled trial". Journal of Clinical Psychopharmacology. 32 (1): 95–99.
doi:
10.1097/JCP.0b013e31823f913e.
PMID22198452.
S2CID2649261.