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Tetrabenazine (TBZ), a synthetic benzoquinolizine, was first introduced as a neuroleptic agent in 1960, and is now widely used in the treatment of hyperkinetic movement disorders such as chorea, tics, or tardive dyskinesia. The side effect profile is mainly characterised by the triad of drowsiness/fatigue, parkinsonism, and depression; depression is found in about 15% of patients treated with TBZ.1 We here report on the rapid reversal of depressive symptoms in a patient treated with TBZ for orofacial dystonia by administering the new and highly selective noradrenaline (norepinephrine) reuptake inhibitor (SNRI) reboxetine.2
On admission, the 64 year old woman presented with perioral and lingual hyperkinesias as well as intermittent and involuntary movements of her lower jaw, which had lasted for about 2 years, causing her a considerable impairment of articulation. No history of neuroleptic treatment or Parkinson’s disease was evident. Her cranial CT and blood chemistry were normal. We diagnosed a segmental dystonia, which improved dramatically after initiation of a tetrabenazine medication (60 mg a day). This successful treatment response, however, was accompanied by a severe depressive syndrome, which was characterised by a mixed anxious-depressive mood, low self esteem, a complete loss of drive, and intermittent suicidal ideations. After switching from TBZ to tiapride, the patient recovered from depression, but her neurological status worsened significantly. The re-exposure to TBZ again ameliorated hyperkinesia, but provoked a depressive relapse. A comedication with reboxetine (6 mg/day), a new and selective noradrenaline reuptake inhibitor, finally led to a stable remission of the depressive symptoms within a week, without any worsening of the dystonic syndrome.
Tetrabenanzine (TBZ) is known to act as a monoamine depleting and dopamine receptor blocking drug.1 In more detail, TBZ binds to and inhibits specifically the human vesicular monoamine transporter isoform 2 (hVMAT2). Whereas the indolamine serotonin (5-HT) performs a similar affinity for both hVMAT1 and hVMAT2, catecholamines such as noradrenaline exhibit a threefold higher affinity for hVMAT2.3 As these specific transporters are responsible for packaging monoamine neurotransmitters into presynaptic secretory vesicles for release by exocytosis, the inhibition of hVMAT2 by compounds such as tetrabenazine thus results in consecutive noradrenaline depletion.4
Alterations of noradrenergic neurotransmission—that is, a neuronal noradrenaline depletion—can therefore be postulated to form one major origin of TBZ induced depression. In line with this assumption, brain-specific catecholaminergic activity enhancers (CAEs) such as phenylethylamine have been shown to antagonise TBZ induced depression-like behaviour in rats.5 Modulating this altered noradrenergic neurotransmission pattern by the administration of selective noradrenaline reuptake inhibitors such as reboxetine may thus provide a new, specific, and fast acting tool in the management of depression caused by TBZ and related (neuroleptic) compounds.