Escitalopram, an isomer of Celexatm
(citalopram HBr) and a more potent and selective serotonin reuptake inhibitor
(SSRI) produced significant improvement relative to placebo at 10 mg/day and
20 mg/day doses in a Phase III clinical trial of 366 patients with major
depressive disorder, reported researchers here today at the American College
of Neuropsychopharmacology 2000 Annual Meeting in San Juan, Puerto Rico.
Based on these Phase III clinical trial results, Forest Laboratories will
submit a New Drug Application in the first half of 2001 to the U.S. Food and
Drug Administration seeking an indication for the treatment of depression for
"We are extremely pleased with the robust results of escitalopram in this
Phase III clinical trial," said Howard Solomon, Chairman and Chief Executive
Officer, Forest Laboratories. "Escitalopram, the single isomer of Celexa, has
been demonstrated in numerous animal and laboratory studies to be at least
twice as potent as its parent compound in terms of antidepressant activity.
We are pleased that the results of this clinical trial confirm the unequivocal
antidepressant activity of escitalopram in patients."
Citalopram or Celexa is the fastest-growing anti-depressant in the United
States and is the top-selling antidepressant in 13 countries in which three or
more SSRIs are available. The U.S. market for antidepressants, which is one
of the fastest growing therapeutic categories, topped $7 billion in 1999.
An Isomer of Citalopram
Citalopram is a racemic mixture with two mirror image halves called the
S- and R-isomers. The S-isomer of citalopram is the active isomer in terms of
its contribution to citalopram's antidepressant effects, while the R-isomer
does not contribute to its antidepressant activity. With escitalopram, the
R-isomer has been removed, leaving only the active S-isomer or a single
Phase III Clinical Trial Details
A total of 366 patients with an ongoing major depressive episode were
randomized to placebo, escitalopram 10 mg/day, or escitalopram 20 mg/day and
entered an 8-week double-blind treatment period. Patients in the 20 mg/day
escitalopram group were titrated to their assigned dose after one week of
treatment at a dose of 10 mg/day.
Both escitalopram 10 mg/day and escitalopram 20 mg/day produced
significant improvement compared to placebo on all the clinical measures of
depression. Severity of depression symptoms was evaluated with the Montgomery
Asberg Depression Rating Scale (MADRS), the Hamilton Depression Rating Scale
(HAMD) and the Clinical Global Impressions (CGI) scale. Significant
improvement versus placebo was observed beginning at week 1 on the CGI
Improvement scale and the HAMD depressed mood item and from week 2 onwards on
the MADRS and HAMD. Once the significant improvement was established in week
one or two, it was maintained throughout the study period. "Escitalopram
exhibited strong efficacy versus placebo at doses of 10 and 20 mg/day, which
is noteworthy because no other anti-depressant is approved as effective in a
general population of depressed patients at 10 mg/day." noted William Burke,
MD, professor of psychiatry, University of Nebraska Medical Center and lead
investigator of the escitalopram clinical trial. "The magnitude of change for
escitalopram versus placebo from baseline to study endpoint on the Hamilton
Depression Rating Scale was especially impressive," noted Dr. Burke. "An
equally robust finding was observed on the MADRS scale."
Treatment with escitalopram in the Phase III clinical trial was well
tolerated: the incidence of discontinuations for adverse events was 2.5% in
the placebo group, 4.2% in the escitalopram 10 mg/day group, and 10.4% in the
escitalopram 20 mg/day group. "Escitalopram had remarkably low discontinuance
rates in our study due to its high tolerability," noted Dr. Burke.