Objectives: The mechanisms of tardive dyskinesia (TD) remain unclear, although
pathophysiologic theories have proposed mechanisms such as dopamine receptor
supersensitivity, the degeneration of cholinergic striatal interneurons, γ-aminobutyric acid
(GABA) depletion, and an excess of free radicals.
Prior development of second generation antipsychotic agents, tardive movement disorders were
widespread among neuroleptics treated patients. There were great expectations of the new
novel drugs. Unfortunately, reports about tardive movement disturbances induced by these
medications became more and more frequent, although it has been in use for less than two
decades.
A recent study demonstrated that schizophrenic and schizoaffective patients suffering from TD
had the mean level of pyridoxal 5'-phosphate (PLP) below lower limit of normal range, while
those patients without TD had normal values. At the same time, some open and double-blind
placebo-controlled, randomized clinical studies showed that vitamin B6 was very effective in
treatment of TD.
Pyridoxal kinase is a key enzyme for the biosynthesis of PLP, the biologically active form of
vitamin B6. Some publications reported that the finding of high vitamin B6 levels is
consistent with recent reports of low levels of PLP and low activity of pyridoxal kinase. It
may explain the functional need for high-dose vitamin B6 supplementation in subjects with TD.
Methods: A multicenter study including 300 schizophrenia and schizoaffective subjects will be
performed. The trial will be consisted of 2 parts: the first part a single comparison
pyridoxal kinase plasma activity in patients with and without TD; in the second part only TD
schizophrenia and schizoaffective patients will continue. It will be a 12-week, randomized,
double-blind placebo-controlled trial. Vitamin B6 (1200 mg/day) or placebo capsules will be
added to the stable ongoing antipsychotic treatment of 150 schizophrenia patients.
Participants will be assessed at baseline and after every 2 weeks of treatment till week 12.
Pyridoxal kinase activity will be compared between patients who positively respond to vitamin
B6 versus non responders. In addition, PLP levels will be monitored at baseline and at the
end of the study.
A battery of research tools will be used for assessment of movement disorders,
psychopathology, and side effects. The study will be performed along a period of 2 years.
Phase:
Phase 3
Details
Lead Sponsor:
Beersheva Mental Health Center
Collaborators:
Sha'ar Menashe Mental Health Center Sha’ar Menashe Mental Health Center Tirat Carmel Mental Health Center
Treatments:
Pyridoxal Pyridoxine Vitamin B 6 Vitamin B Complex Vitamins