No
correlation between paroxetine plasma levels and
clinical outcome
During
the course of antidepressant treatment, drug
serum levels are often monitored to improve
treatment outcome. In contrast to tricyclic
antidepressants (TCA), there is very limited
clinical evidence for an optimal range of drug
plasma concentrations in the case of selective
serotonin reuptake inhibitors (SSRI). A recent
study investigated the potential correlation
between drug plasma levels and symptom
improvement in depressed patients treated with
paroxetine.
Forty patients with major depression, according
to DSM-IV criteria, were treated with paroxetine
for 9 weeks, at 20 mg/day as a single dose in
the morning from day 1 to 14 and 40 mg/day from
day 15 to 63. The Hamilton depression (HAMD)
rating scale was used weekly to measure
treatment response and blood samples for
determination of paroxetine plasma levels were
drawn at screening, baseline, day 7, 14, 28, 35
and 63. Receiver operated characteristic (ROC)
analysis was performed for the correlation.
Eighteen out of 40 patients responded to
treatment. Paroxetine plasma levels on day 14 at
20 mg/day (median 24 (range 4-358) µg/l)
were significantly different from those on day
63 at 40 mg/day (median 92 (range 30-398)
µg/l). Responders had significantly higher
plasma concentrations at day 7 (responder 33
(4-107) µg/l; non-responder 13 (3-77)
µg/l), but this difference disappeared at
day 63 (responder 93 (30-361) µg/l;
non-responder 94 (59-398) µg/l). No
correlation was found between paroxetine plasma
levels and clinical response or adverse
events.
These findings show no evidence for a
therapeutic window or optimal range of drug
plasma levels for paroxetine and thus
differentiates it from TCA. The authors conclude
that routine screening of plasma concentrations
of paroxetine in clinical practice serves no
useful purpose. Normann
C, Hörn M, Hummel B, Grunze H, Walden J.
Paroxetine in major depression: correlating
plasma concentrations and clinical response.
Pharmacopsychiatry 37: 123-126, 2004.