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InterPsych/PsyComNet Psychopharmacology Conference Reading
The Potentiation of the Antidepressant Effects of
Selective Serotonin Reuptake Blockers by Pindolol.
11 June 1995
Presented by Ivan Goldberg, MD
Reference: Blier P and Bergerom R Effectiveness
of pindolol with selected antidepressant drugs in
the treatment of major depression. Journal of
Clinical Psychopharmacology, 1995, 15, 217-222.
I. INTRODUCTION
In a letter published in the March, 1994 in the
Archives of General Psychiatry, Artigas,
Perez, and Alvarez reported that they had
coadministered pindolol, 2.5 mg t.i.d., along
with SSRIs or MAOIs to 12 patients. They
reported that the treatment had brought about
a rapid and full antidepressant effect, even
in patients who had initially faile to respond to
antidepressants. The authors reported that all of
the patients that they had treated with pindolol
+ (SSRI or MAOI) did well with the combined
therapy.
At this year's New Clinical Drug Evaluation Unit
meetings it was also reported that pindolol poten-
tiated the antidepressants. Most interestingly,
pindolol was not found to potentiate the anti-OCD
effects of SSRIs. This again points out the
differences between the effects of
antidepressants when used to treat depression and
when used to treat OCD.
Pindolol is known as a beta-adrenergic blocker,
and beta-blockers are associated with the
induction or worsening of depression. Pindolol
has actions beyond blocking the beta-adrenergic
system. One of pindolol's other actions is that
it is a 5-HT1A antagonist. There is reason to
believe that the blockade of 5-HT1A autoreceptors
should accelerate the antidepressant effects of
SSRIs.
In the June, 1995 issue of the Journal of Clinical
Psychopharmacology Blier and Bergeron report on
open studies to assess the safety and
effectiveness of the combination of pindolol and
an SSRI (P+SSRI).
II. METHODS
28 out-patients, all meeting the DSM-IV criteria
for major unipolar depression were entered into
two studies. With the exception of three female
patients taking oral contraceptives, none of the
patients were taking any other medication.
In the first study, nine patients were treated
with P+paroxetine upon entering the study. Four
of these patients had a prior history of
depression. The duration of the current
depressive episode was from 4-weeks to 7-months.
None of the patients had received an SSRI in the
past.
The duration of the first study was 28-days.
The second study involved the treatment of 19
"drug-resistant" patients. Five of these patients
had failed to respond to treatment with one
antidepressant, 11 patients had two unsuccessful
antidepressant trials, and 3 had undergone
three trials. All but one of the patients had
failed to respond to standard potentiating
techniques such as the addition of lithium,
buspirone, or desipramine.
The severity of depression was measured by use of
the 21-item Hamilton Scale for Depression
(HAM-D-21).
The regimens of antidepressants were not altered
once pindolol 2.5 mg t.i.d. was initiated
The duration of the second study was also 28-days.
III. RESULTS
Three patients stopped taking pindolol within the
first 3-days because of increased irritability
(IKG's note: Possible mixed state?) Three
non-menopausal women reported increased sweating.
Otherwise P+SSRI was well tolerated. One patient
had to be hospitalized following a switch to
mania. There were no significant effects on pulse
or blood pressure
In the first study in which 9 patients whose
depression were initially treated with P+SSRI, 7
of the nine had more than 50% decrease in their
HAM-D-21 scores after 7-days of treatment. More
improvement was seen after the first week than
during it. For the entire 28-days og the study
the changes in HAM-D-21 scores were:
Mean initial score = 28 (SE = 1)
Mean final score = 8 (SE = 2)
(p < 0.001).
In the second study in which 19 drug resistant
patients were entered, 10 patients had reductions
in their HAM-D-21 scores after 7-days.
The authors differentiate between the patients who
were taking sertraline (50 - 100 mg/day) (IKG's
note: an inadequate dose) and those who were
taking other antidepressants.
In the patients taking antidepressants other than
sertraline:
Mean initial score = 31 (SE = 2)
Mean day-14 score = 6 (SE = 1)
(p < 0.01)
HAM-D-21 scores continued to drop to day-28.
IV. DISCUSSION
The results of this study replicate and extend the
findings of Artigas et al.
It is unfortunate that placebo wash-out periods
were not utilized in both studies.
The beta-blockade induced by pindolol is not
thought to be responsible for the observed
potentiation of antidepressants, because previous
work attempting to induce a similar effect with
propranolol failed, to be successful.
While the authors would like to blame the failure
of pindolol to potentiate sertraline on
pharmacodynamic differences between sertraline and
other SSRIs, the probably correct explanation is
that inadequate amounts of sertraline were
administered.
It is interesting that both in the Artigas et al.
study and the replication, there was one patient
taking an MAOI. Both of these patients showed a
dramatic effect of pindolol addition.
The authors are currently conducting
double-blind, placebo-controlled studies to
establish the validity of this most remarkable
advance in the psychochemotherapeutic treatment of
depression
\\\\
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||-----------------------------------------------------ooOo-( )-oOoo----||
|| Ivan Goldberg, MD ~ ||
|| ikg1@columbia.edu psydoc@netcom.com ||
|| V: 212 876 7800 / 1346 Lexington Ave NYC 10128 / F: 212 737 0473 ||
|| http://avocado.pc.helsinki.fi/~janne/ikg/ ||
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Dr. Bob is Robert Hsiung, MD,
dr-bob@uchicago.edu
Revised: February 7, 1999 (formatting)
URL: http://www.dr-bob.org/tips/pindolol .html