Efficacy
of riluzole in treatment-resistant depression
Regional
decreases in CNS volume, probably due to
impairment of structural plasticity, are
associated with mood
disorders. Neurodegenerative diseases are
characterised by glutamate-mediated impairments
of plasticity, and reducing excess glutamatergic
activity is the main strategic approach to these
disorders. It is not, therefore, surprising that
the glutamatergic system also appears to be
involved in the pathophysiology and treatment of
depression. N-methyl-D-aspartate receptor
antagonists show antidepressant effects in
animal models of depression and in humans.
Lamotrigine, which inhibits glutamate release,
has antidepressants effects in humans.
A recent study was conducted to examine the
efficacy of riluzole, a glutamate-modulating
agent currently indicated in the treatment of
amyotophic lateral sclerosis, to treat
treatment-resistant recurrent major
depression.
A group of 19 patients diagnosed with recurrent
major depression and a baseline MADRS
(Montgomery-Asberg Depression Rating Scale) of
20 or more and who had been previously
unresponsive to antidepressants were recruited.
After a one-week drug-free period they received,
on an open-label basis, for 6 weeks, riluzole
(100-200 mg/day) as monotherapy.
Thirteen patients completed the trial. A
significant improvement in MADRS score, compared
with baseline, was obtained at weeks 3 through 6
for all patients, and at weeks 2 through 6 for
trial completers. Overall 32% of patients and
46% of trial completers responded. Remission
rates (score < 10) were 21% and 31%,
respectively. Main adverse effects were
headache, decreased salivation, nausea,
vomiting, constipation, tension or inner
unrest.
These results show that response and remission
rates with riluzole are similar to those of
antidepressants used in studies of
treatment-resistant depression. Although larger
controlled studies are needed to confirm these
preliminary data, the glutamatergic system may
represent a potential fruitful target for future
drugs for the treatment-resistant
depression.
Zarate
et al., 2004 An open-label trial of riluzole in
patients with treatment-resistant major
depression.Am
J Psychiatry 161: 171-174.