A few health risks
associated with SSRI Use: Research Abstracts
Association between selective serotonin reuptake
inhibitors & upper gastrointestinal bleeding
population based case-control study.
de Abajo, FJ, García Rodríguez LA, Montero D.
BMJ 1999;319:1106-1109 ( 23 October ).
The results of this study show that users of the
antidepressants selective serotonin reuptake
inhibitors (SSRI’s) have a significantly increased
risk of upper gastrointestinal (GI) bleeding,
compared to nonusers. The study was conducted on
1651 patients hospitalized with upper GI bleeding,
and 10,000 matched controls. Use of SSRI’s was
associated with a 3-fold increased risk of bleeding,
compared to nonuse. The incidence of this
complication was estimated at 1every 8,000
prescriptions. Combined use of SSRI’s and aspirin
was associated with a 7-fold increased risk of GI
hemorrhage, and combined use of SSRI’s and
non-steroidal anti-inflammatory drugs resulted in a
15.6-fold increased risk. The authors emphasize that
the large increase in risk of GI hemorrhage observed
in their study could have important public health
implications due to the frequent use of both classes
of drugs in industrialized countries.
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Hemorrhagic syndromes related to selective serotonin
reuptake inhibitor (SSRI) antidepressants.
Seven case reports and review of the literature.
French.
Nelva A, Guy C, Tardy-Poncet B, Beyens MN, Ratrema
M, Benedetti C, Ollagnier M.
Rev Med Interne 2000 Feb;21(2):152-60.
The results of this study suggest that intake of the
antidepressants selective serotonin reuptake
inhibitors is associated with an increased risk of
developing hemorrhagic syndromes. This adverse
effect is under-recognized and under-reported, and
may be due to a decrease in concentration of
platelet serotonin, leading to platelet dysfunction.
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Antidepressant Medication Use and Breast Cancer
Risk.
Cotterchio M, Kreiger N, Darlington G, and Steingart
A.
Am J Epidemiol 2000;151:951-57.
The results of this study indicate that women who
take antidepressants are at significantly higher
risk of developing breast cancer, compared to the
general population. The association between
antidepressant drugs and breast cancer first emerged
from animal and epidemiological data. This
case-control study, conducted to further test the
hypothesis, found that users of selective serotonin
reuptake inhibitors (SSRIs) and tryciclic
antidepressants have a 7- and 2-fold increased risk
of breast cancer, respectively, compared to
nonusers. The finding of a large increase in risk of
breast cancer in users of SSRIs may have public
health implications owing to the high prevalence of
use of this class of drugs.
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Comparative study of fluoxetine, sibutramine,
sertraline and dexfenfluramine on the morphology of
serotonergic nerve terminals using serotonin
immunohistochemistry.
Kalia M, et al.
Brain Res 2000 Mar 6;858(1):92-105.
The results of this study indicate that short-term
exposure to selective serotonin reuptake inhibitors
(SSRIs) results in changes of rat brain cells, which
resemble those induced by the recreational drug
Ecstasy. SSRIs work by increasing the concentration
of serotonin in the brain through inhibition of
their re-uptake by brain cells. Their mode of action
is similar to that of the recreational drug Ecstasy,
which also increases the concentration of serotonin
at the receptor site through a double action of
inhibited reuptake and stimulated secretion from
brain cells. While Ecstasy-induced brain damage has
been well demonstrated in both animal and human
studies, there are no data on the effects of SSRIs
on brain cells. This study documented that, after
only 4 days of intake of SSRIs, rat brain cells
underwent morphological changes characterized by
swelling and acquisition of a corkscrew shape,
indicative of occurred damage. These findings
indicate that SSRIs, the most commonly prescribed
class of antidepressant drugs, cause damage in
animal brain cells, after only 4 days of exposure.
More studies on humans are needed, before these
drugs can be considered safe.
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Discontinuation symptoms and psychotropic drugs
Young, A. and Haddad P.
Lancet 2000; 355: 1181 - 1190.
This letter emphasizes that 35% to 78% of
individuals who take the antidepressants selective
reuptake inhibitors (SSRIs) for several months,
experience, upon abrupt treatment interruption,
physical and psychological symptoms such as: changes
in mood, affect, appetite and sleep, dizziness,
fatigue, anxiety, agitation, nausea, headache, and
sensory disturbance. The symptoms are so typical
that the clinical entity "SSRI discontinuation
syndrome" is now widely accepted, after its
existence had been negated for several years
following the introduction of SSRIs on the market.
Symptoms are usually mild and short-term, but
occasionally can be severe and long lasting. They
have often been interpreted as a sign of relapse
into depression, leading to re-institution of
treatment. The authors propose that all new
psychotropic drugs be tested in double-blind
placebo-controlled studies lasting several weeks
beyond the actual drug trial, in order to properly
monitor adverse reactions that may occur only upon
discontinuation of treatment.
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Hormonal markers of stress response following
interruption of selective serotonin reuptake
inhibitor treatment.
Michelson D, et al.
Psychoneuroendocrinology 2000 Feb;25(2):169-77.
The results of this study show that following abrupt
interruption of treatment with selective serotonin
reuptake inhibitors patients develop signs of
activation of a stress response, as shown by
significantly increased plasma levels of IGF-1 and
heart rate.
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Antidepressant discontinuation reactions.
Haddad P, Lejoyeux M, and Young A.
BMJ 1998;316:1105-1106 ( 11 April ).
This article reports on the frequency and nature of
adverse reactions occurring upon discontinuation of
antidepressant treatment. It explains that the
existence of discontinuation reactions is often
unrecognized by clinicians and that the extent of
their occurrence is largely unknown because very few
studies have ever addressed this issue.
Discontinuation reactions usually start after few
days of interruption of antidepressant treatment,
and may consist of nausea, diarrhea, abdominal pain,
insomnia, nightmares, headaches, lethargy, anxiety,
and irritability. With selective serotonin-reuptake
inhibitors, withdrawal is more commonly associated
with symptoms such as dizziness, paraesthesia,
numbness, and electric shock-like sensations.
Results of a double blind placebo controlled study
have shown that adverse reactions occur in 35% of
patients after discontinuation of a 12-week
treatment with the serotonin reuptake inhibitor
paroxetine. Such reactions usually resolve within
one day to three weeks, but occasionally they can be
more severe and persist chronically, causing
substantial morbidity.
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Discontinuation symptoms after treatment with
serotonin reuptake inhibitors
a literature review.
Zajecka J, et al.
J Clin Psychiatry 1997 Jul;58(7):291-7.
The results of this study indicate that
discontinuation of selective serotonin-reuptake
inhibitor therapy is associated with the development
of a cluster of symptoms including dizziness,
light-headedness, insomnia, fatigue, anxiety,
nausea, headache, and sensory disturbance. These
symptoms may last up to three weeks after
interruption of treatment, and may be relieved by
restarting antidepressant therapy (!).
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Antidepressant-induced sexual dysfunction during
treatment with moclobemide, paroxetine, sertraline,
and venlafaxine.
Kennedy SH, Eisfeld BS, Dickens SE, Bacchiochi JR,
Bagby RM.
J Clin Psychiatry 2000 Apr;61(4):276-81.
The results of this study indicate that 30%-70% of
patients who take the selective serotonin reuptake
inhibitors (SSRIs) paroxetine and sertraline
experience sexual dysfunction as a side effect of
treatment. Impairment in drive and/or desire occurs
more frequently in men than women, while impairment
in level of arousal and orgasm is experienced at
similar rates by both sexes. These data indicate
that the majority of patients treated with SSRIs
experience sexual dysfunction. The low rates of this
complication reported in previous studies were due
to underreporting and was not confirmed in
subsequent trials.
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Sexual dysfunction induced by serotonin reuptake
antidepressants.
Labbate LA, Grimes J, Hines A, Oleshansky MA, Arana
GW.
J Sex Marital Ther 1998 Jan-Mar;24(1):3-12.
The results of this study show that the
antidepressants selective serotonin reuptake
inhibitors negatively affect sexual functios. The
study was conducted on 61 individuals who took these
drugs for at least two months. Both men and women
experienced a significant worsening of quality of
orgasm after 1 and 2 months of treatment, compared
to baseline. Women reported failure to achieve an
orgasm significantly more often than men, while both
sexes experienced prolongation of time to orgasm
induction after 1, 2, and 3 months of treatment,
compared to baseline.
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Incidence of sexual dysfunction in healthy
volunteers on fluvoxamine therapy.
Nafziger AN, et al.
J Clin Psychiatry 1999 Mar;60(3):187-90.
The results of this study show that 35% of healthy
volunteer who took the antidepressant fluvoxamine
developed, after 4 weeks of treatment, sexual
dysfunction.
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Adverse reactions of selective serotonin reuptake
inhibitors
reports from a spontaneous reporting system.
Spigset O.
Drug Saf 1999 Mar;20(3):277-87.
This study evaluated 1202 spontaneous reports on
1861 adverse reactions to selective serotonin
reuptake inhibitors (SSRIs), and found that 22.4% of
such reports consisted of neurological disturbances,
20% of psychiatric disorders, and 18% of
gastrointestinal symptoms. The elderly were
particularly susceptible to Parkinsonism, confusion,
hallucinations, and hypotension, while younger
patients experienced more frequently hematological,
endocrine, and sexual dysfunction. Akathisia and
aggression occurred more frequently in men than
women.
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A survey of antidepressant drug use in Parkinson's
disease. Parkinson Study Group.
Richard IH, et al.
Neurology 1997 Oct;49(4):1168-70.
The results of this study indicate that
approximately 26% of patients with Parkinson's
disease (PD) are given antidepressant medications,
which consist, in over half of the cases, of
serotonin reuptake inhibitors (SSRIs). Forty-three
percent of physicians of the Parkinson Study Group
showed concern that use of SSRIs might induce
worsening of motor function in PD patients, and 37%
of physicians had at least one patient in which they
believed such aggravation occurred.
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Prenatal exposure to fluoxetine (Prozac) produces
site-specific & age-dependent alterations in brain
serotonin transporters in rat progeny
Evidence from autoradiographic studies.
Cabrera-Vera TM, Battaglia G.
J Pharmacol Exp Ther 1998 Sep;286(3):1474-81.
The results of this study show that prenatal
exposure to the selective serotonin reuptake
inhibitor fluoxetine (Prozac) induces changes in the
density of brain serotonin transporters in rats,
which are particularly evident in regions of the
limbic system, such as the hypothalamus, hippocampus
and amygdala. These data indicate that fluoxetine
alters brain function in rats exposed to the drug
while in uterus.
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Pregnancy outcome following first-trimester exposure
to fluoxetine.
Pastuszak A, Schick-Boschetto B, Zuber C, Feldkamp
M, Pinelli M, Sihn S, et al.
JAMA 1993 May 5;269(17):2246-8.
The results of this study show that women who use
the antidepressant fluoxetine (Prozac) in the first
trimester of pregnancy have approximately a 2-fold
increased risk of miscarriage, compared to nonusers.
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Birth outcomes in pregnant women taking fluoxetine.
Chambers CD, et al.
N Engl J Med, 335(14):1010-5 1996 Oct 3.
This study evaluated pregnancy outcome of women who
took the antidepressant fluoxetine (a serotonin
uptake inhibitor) while expecting, and compared it
to that of women who did not take the drug. In
infants exposed to the drug, the incidence of three
or more minor anomalies was 15.5% vs. 6.5% in
controls. Infants exposed to fluoxetine during the
third trimester had, compared to those exposed only
during the first and second trimester, reduced birth
weight and length, an almost 5-fold increased risk
of premature delivery, a 2.6-fold increased risk of
being admitted to special-care nurseries, and an
almost 9-fold increased risk of experiencing
respiratory difficulties, cyanosis on feeding, and
jitteriness.
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Antidepressants and suicidal risk.
Muller-Oerlinghausen B, Berghofer A.
J Clin Psychiatry 1999;60 Suppl 2:94-9; discussion
111-6.
This article emphasizes that selective serotonin
reuptake inhibitors and other non-lithium
antidepressants may increase the risk of suicide in
certain patients by inducing akathisia (a condition
characterized by restlessness and psychomotor
agitation and associated with self-destructive
impulses) and by liberating suppressed energies that
may be used to act upon suicidal thoughts.
