Response
of selective serotonin reuptake inhibitor
(SSRI)-resistant depressed patients with
ziprasidone added to SSRI
Around
30 to 50% of depressed people exhibit only
partial or no response to selective serotonin
(5-HT) reuptake inhibitors (SSRIs). In addition
many patients who respond still have residual
symptoms and the risk of relapse is high. Thus
refractory depression remains a major problem.
The atypical antipsychotic, ziprasidone is a
strong 5-HT1A receptor agonist and possesses a
potent affinity for the 5-HT1D, 5-HT2, and
dopamine D2 receptors. A study examined the
effect of adding ziprasidone in patients with
major depressive disorder not showing clinical
improvement following treatment with SSRIs.
Twenty men and women, aged 18 to 65 years, with
major depressive disorder according to DSM-IV,
who had failed to respond to SSRI treatment,
were treated on an open-label basis with
ziprasidone in addition to their SSRI for 6
weeks. The Hamilton Depression rating scale
(HAM-D-17) was used to measure the total score
and evaluate the clinical response (50% or
greater decrease in depressive symptoms during
the course of the study).
Thirteen of 20 patients (65%) completed the
6-week trial, intolerance, cessation of the
SSRI, and lost to follow-up being the reasons
for premature discontinuation although no severe
adverse events were observed. Of those who
completed treatment, 8 patients (61.5%) were
classified as responders and 5 (38.5%) were in
remission. An intent-to-treat analysis of all
patients showed 50.0% reponders and 25.0% in
remission. Improvement with ziprasidone was
rapid, occuring within one week of its addition
to the SSRI treatment and its efficacy
persisted.
The addition of ziprasidone to a SSRI treatment
should therefore be considered as an interesting
option in SSRI-resistant major depression. This
important finding now requires replication in a
larger placebo-controlled study. Papakostas
GI, Petersen TJ, Nierenberg AA, Murakami JL,
Alpert JE, Rosenbaum JF, Fava M. Ziprasidone
augmentation of selective serotonin reuptake
inhibitors (SSRIs) for SSRI-resistant major
depressive disorder. J Clin Psychiatry 65:
217-221, 2004