| Vol 7 n°3 - Pharmacology
in mood disorders |
 Alert |
|
To
print this page in good conditions, please select the "Landscape" mode
of your printer.
|
|
hatever the antidepressant drug prescribed,
30%1 to 50%2 of adult patients with major depression fail
to respond to adequate first-line treatment, defined as a
dose in the therapeutic range given for an adequate dura-
tion, ie, 4 to 6 weeks.3 In clinical practice, when a patient
responds insufficiently to an initial antidepressant dose,
several options are available, such as temporizing,
increasing the dose, switching to another antidepressant,
or combining several drugs.4 A survey by Fredman et al5
of attendees at a psychopharmacology course showed
that 80% or more indicated that their first choice would
be to raise the selective serotonin reuptake inhibitor
(SSRI) dose for a hypothetical patient with minimal
response after 4 weeks, or partial response after 8 weeks,
of adequate treatment, ie, fluoxetine 20 mg/day, sertra-
line 100 mg/day, or paroxetine 20 mg/day. For a patient
with no response after 8 weeks of adequate SSRI treat-
ment, a switch to a non-SSRI drug was the first and pre-
ferred strategy. Hirschfeld et al4 advocated switching,
combination therapy, or augmentation therapy after
4 weeks for patients who fail to respond at an adequate
dosage of SSRI (ie, <25% decrease in the Hamilton
Rating Scale for Depression [HAMD] or Montgomery
and Åsberg Depression Rating Scale [MADRS] score).
For those patients who achieve a partial response on first-
line therapy (ie, 25% to 50% decrease in HAMD or
MADRS score), they proposed that treatment should be
continued for 6 to 8 weeks at an adequate dose before
considering a change in therapeutic management.4
An important question is whether the frequently applied
strategy of increasing the dose of antidepressant is justi-
fied. The issue is of fundamental and clinical relevance.
C l i n i c a l r e s e a r c h
Copyright © 2005 LLS SAS. All rights reserved
Dose–response relationship of recent
antidepressants in the short-term
Keywords: antidepressant; fixed-dose; dose–response; dose–effect; dose esca-
lation; dose range; major depression; efficacy
Author affiliations: Unité
de Psychopharmacologie Clinique, Hô
pitaux
Universitaires de Genève, Chêne-Bourg, Switzerland
Address for correspondence: Unité
de Psychopharmacologie Clinique, 2 chemin
du Petit Bel-Air 1225 Chêne-Bourg, Switzerland
Antidepressant drugs are widely recommended for the
treatment of depressive disorders, and finding the “right
dose for the right patient” is an important issue.
Whatever antidepressant is prescribed, a proportion of
adult patients with major depression fail to respond sat-
isfactorily to adequate first-line treatment. A frequent
strategy for patients with insufficient response to an ini-
tial antidepressant dose is to increase the dose. This
review is about this strategy, ie, the possible benefits of
prescribing higher doses of recent antidepressants. The
results show that a flat dose–response curve is a class
phenomenon for selective serotonin reuptake inhibitors
(SSRIs), according to randomized, controlled, fixed-dose
clinical trials. For the serotonin and noradrenaline reup-
take inhibitors (SNRIs), the strategy of dose increase may
be relevant for venlafaxine, in order to increase the
number of responders. Thus, the subgroup of patients
for whom high doses of SSRIs could be useful remains to
Dialogues Clin Neurosci
. 2005;7:249-262.
