LETIERS
TO ThE
depression,
EDITOR
recurrent.
psychotherapy,
and
I treated she
her with
responded
well.
desipramine After
and
(personal
communication
the response
termination
of her treatment, she was euthymic for 7 years, until she had a recurrence during the sixth week of a commercial weightreduction diet. This program involved a low-calorie diet and a food supplement but no appetite suppressants. Her weight had decreased by 20 ib, from 174 to 154 lb. She responded well to a therapeutic level of the antidepressant. Ms. B was a 31-year-old woman who had had five previous episodes of depression, treated elsewhere, dating back to age 22. Her diagnosis was major depression, recurrent. When she was 29 she experienced a depression that I treated with psychotherapy and perphenazine, which had previously been successful for her. Upon termination of this treatment, she remained euthymic for 20 months. Then she had a recurrence after 8 weeks of a self-structured, reducedcalorie diet in which she used no appetite suppressants. She had sustained a 27-lb weight loss, from 167 to 140 lb. Her depression responded well to perphenazine and psychotherapy.
),
20
1 . Smoller
a critical 2.
Wing RR, behavioral
Wadden TA, Stunkard AJ: Dieting and depression: review. J Psychosom Res 1987; 31:429-449 Epstein weight
LH, loss
Marcus programs.
MD,
J
et al: Mood Psychosom
changes in Res 1984;
20:189-196 ALAN
Cognitive
Dysfunction
Associated
With
M. KRAFT,
M.D.
Albany,
N.Y.
Fluoxetine
Sut: Cognitive impairment associated with tricyclic antidepressants has been attributed to sedative and/or anticholinergic effects (1). Accordingly, fluoxetine, with its low propensities for both, may be relatively free of adverse cognitive effects. Even so, cognitive dysfunction has been linked with fluoxetine
948
Lilly
and
treated
Company),
and
illustrates
this.
whose recurto fluoxetine,
mg/day,
prescribed along with conjugated estrogens, and L-thyroxine, 0.15 mg/day (for chronic hypothyroidism). She presented with a 9-month history of difficuities with memory and learning unaccompanied by depression, sedation, anticholinergic signs, sleep disturbance,
progesterone,
or current nesic
or prior
effects.
use of licit or illicit substances
Examples
of her difficulties
with
included
am-
forgetting
that she had made bank deposits, leaving out key ingredients in recipes, failing to learn piano pieces (which caused her to retire as a piano teacher), and inability to learn a foreign language in preparation for a trip. Although euthymic, alert, and oriented to person, place, and time on mental status examination, Ms. A, a college graduate, was able to recall only one of eight associative word pairs (four of eight is normal), only two of three items after S minutes, and only one president. Her fund of general was
poor,
and
she
made
several
errors
during
serial subtraction of sevens. Her interpretation of proverbs was concrete and personalized. Her thyroid functions were normal, as were the results of both medical and neurological evaluations. Fluoxetine was discontinued at Ms. A’s first visit, while her other medications remained constant. Over the ensuing week, she reported that her mind seemed clearer and her memory better. Then, since she reported recurrent depressive symptoms, she was started on a regimen of nortniptyline, 40 mg h.s. (which produced a 12-hour steady-state plasma level of 137 ng/mt) and responded well. Eighteen days after discontinuing fluoxetine, she returned for a fol-
low-up
functioning
was
significantly improved: she was now able to remember associative learning pairs, remember three of three after S minutes, perform serial subtraction of sevens
five items with-
visit,
during
which
her cognitive
out error, and recall five past presidents. When her nortniptyline dose was reduced to 30 mg h.s. because of weight gain, she became more depressed but experienced no cognitive
dysfunction.
Her
dose
of nortniptyline
was
then
in-
creased to 40 mg h.s. (producing a 12-hour steady-state plasma level of 97 ng/ml), and her depressive symptoms resolved. Over the ensuing 3 months, she reported no memory difficulties, and after successfully resuming hen household duties and her career as a piano teacher and learning the foreign language she had been unable to master while taking
REFERENCES
I recently
Ms. A was a 60-year-old Caucasian woman rent major depressive disorder had responded
information
studies of mood disorders following weightreduction dieting have yielded conflicting and inconclusive mesuits; some patients improve affectively and others become depressed. Smoller et al. (1 in an extensive review of the literature, found that the apparent conflict among studies mesulted from the ways in which mood changes were measured. Wing et al. (2) proposed that the more recent studies failed to find serious mood disorders because persons with preexisting psychopathology were excluded from these studies. I could find no references in the literature published since 1 986 that addressed the impact of such diets on previously depressed patients. While persons without previous depression may not be at risk as a result of a weight-reduction regimen, these cases indicate that persons with such a history are at risk of recurrence, particularly with a weight loss of 20 lb or more (1). It is possible that some psychological process, such as a concern for low self-esteem, may have been a precursor of the depression. Or the connection between the depression and the diet may have been coincidental, so that to conclude that dieting was the cause of the depression is unwarranted. Nonetheless, these cases suggest that previously depressed patients may be at risk and should be monitored carefully if they embark on a weight-reduction diet. Cumulatively,
Eli
from
of a patient
fluoxetine,
she departed
on her
trip.
Ms. A’s reversible cognitive dysfunction appeared to be related to fluoxetine treatment. Although depression has been associated with cognitive dysfunction, Ms. A was euthymic at the time of her first mental status examination and did not develop cognitive difficulties when she became more depressed
upon
discontinuing
fluoxetine
or upon
reducing
her
dose of nortniptyline. Moreover, she was not sedated, sleep deprived, or hypothyroid, nor did she have a fluoxetine-induced syndrome of inappropriate secretion of antidiuretic hormone or anticholinergic symptoms or signs. Although diminished performance on a coding task has been associated with fluoxetine in one study (2), two others (3, 4) have reported unchanged or improved cognitive function during fluoxetine treatment. The mechanism by may impair short-term memory or learning awaits further investigation.
Am
J
Psychiatry
which fluoxetine in some patients
1 48:7,
July
1991
LE1TERS
REFERENCES 1 . Deptula 2.
formance:
D, Pomara a review.
Nicholson
AN,
J
Clin
Pascoe
sleep-wakefulness take inhibitor. 3.
N: Effects
particularly
of antidepressants
tidepressants,
alone
27:597-602
and
in combination
with
Biol Psychiatry
diazepam.
1988;
SUSAN
MIROW,
Bleeding
2.
AC: The
in Medical
Physiology.
J.A. YARYURA-TOBIAS, H. KIRSCHEN, P. NINAN, H.J. MOSBERG,
M.D. M.D. M.D. D.O.
Mineola,
N.Y.
Disorder
Reactivation
and
of the Herpes
Simplex
Virus
Fluoxetine
We would suffering
like to report
from
patients
eight
cases
obsessive-compulsive
had
ever
noticed
of bleeding disorder.
any
bleeding
in patients
None
episodes
of these
before
they
fluoxetine.
The patients’ ages ranged from 1 6 to 75 years, of 35. 1 years. One patient was taking fluoxetine 20 mg/day,
one
patient
was
taking
40 mg/day,
with a mean at a dose of
and
six patients
were taking 80 mg/day. The duration of treatment ranged from 21 days to 1 year, with a mean of 150 days. There was one report of metena, the cause of which was undetermined because the patient refused to be tested. There were four reports of rectal bleeding, three caused by internal hemorrhoids and one due to unknown factors, all confirmed by rectosigmoidoscopy. One patient reported scattered bruises on arms enzymes. Another taxis; rhinoscopy
lowing
case
and
legs
and
had
an
elevated
level
of liver
patient suffered from mild bilateral episshowed mucosal vascular dilation. The folhelp to illustrate this report.
may
SIR: We
ms infection
colitis.
She
was
mg/day,
for
mg/day,
and
a
placed
on
month.
she took
a regimen
Then this
had a history heart disease, the
dose
dose
of concomiangina, and
of
fluoxetine,
was
raised
for 2 months,
until
20
to 40 she had
to be hospitalized because of constant generalized abdominal pain of sudden onset. The pathology report indicated a segment of the small bowel with moderate acute ulcerating inflammation and vascular dilation, recent hemorrhages, and submucosal edema consistent with vascular compro-
cases of reactivated herpes with fluoxetine treatment.
tions.
After
depression
with
Serotonin striction and
of fluoxetine, no further episodes by any of these eight patients.
is associated with the regulation dilation, notably that of mucosal
cause
large
(2)
a defective
doses
of fluoxetine vascular bed,
of
of vessel convessels (1 ). Be-
may cause hypersemotonemia as seen in our patients, an in-
crease in S-HT may serve as a mediator to precipitate the bleeding episode. When large doses of fluoxetine are prescnibed for the treatment of obsessive-compulsive disorder, potentially significant bleeding problems in some patients,
AmJPsychiatry
148:7,July
1991
vi-
8
months
of
fluoxetine
treatment,
major
has remitted. B was
major
a 64-year-old
depression
simplex.
She was
mg/day.
Approximately
and
white
woman
a remote
history
who
presented
of labial
herpes
started
on a regimen of fluoxetine, 20 2 weeks later, she developed yeslip that were typical of those she had had
ides on her lower in the past. Her regular
physician
diagnosed
herpes
simplex.
The patient discontinued fluoxetine and the lesions healed. Two weeks later she restarted fluoxetine, which she now has been taking for 2 months. There have been no further herpes outbreaks and her depression is well controlled.
etine,
discontinuation were reported
simplex
a 43-year-old white woman with recurrent and a history of genital herpes, quiescent a year. Within 1 month of her beginning to 20 mg/day, the herpes became reactivated. depression responded well, the patient beexacerbation of herpes was related to fluoxetine. Fluoxetine was replaced with desipramine, and there was partial relapse of the patient into depression but remission of the herpes. After 1 8 months on the desipramine regimen, Ms. A requested retreatment with fluoxetine. At 20 mg/day there was no improvement in her depression, so the dose was increased to 40 mg/day, and outbreaks of herpes began within 1 month. Because her depressive symptoms improved markedly with the dose of4O mg/day, she elected to continue fluoxetine and to control the herpes with oral acyclovir. She continues to experience the tingling of an imminent outbreak of herpes monthly. When the tingling begins, one to two doses of acyclovir prevent vesicular erup-
Mr. C was a 42-year-old
misc.
Upon bleeding
report three associated
Ms. A was major depression for more than take fluoxetine, Although her lieved that the
Ms. Ms. A, a 7S-year-old woman, tant emphysema, arteriosclerotic
in
circulation,
Utah
Fluoxetine
took
systemic
M.D.
City,
is a bicyclic antidepressant and a selective blocker of serotonin (S-HT) reuptake. Adverse vascular effects such as bruises, metrorrhagia, cerebrovascular accidents, hemoptysis, melena, hematemesis, hematuria, and vaginal bleeding after drug withdrawal have been sporadically reported (Dista Products Company, Fluoxetine Hydrochloride, Adverse Reactions, 1989). SIR:
should
Prog
PH.D.,
in Obsessive-Compulsive
conditions,
Philadelphia, WB Saunders, 1981 Steiner W, Fontaine R: Toxic reaction following combined administration of fluoxetine and L-tryptophan: five case reports. Biol Psychiatry 1986; 21:1067-1 071
12:783-792
Salt Lake
and
predisposing
REFERENCES 1. Guyton
MJ, et al: A comparison of the effect on the cognitive functioning of de-
Affective Disord 1990; 18:275-280 M: The effects on performance of two an-
Neuropsychopharmacol
Fluoxetine
have
1 990; 10:105-111 the modulation of the by fluoxetine, a S-HT up-
Fudge JS, Perry PJ, Garvey of fluoxetine and trazodone
J
per-
who
EDITOR
be considered.
Psychopharmacol PA: Studies on
continuum in man Neuropharmacology 1988;
pressed outpatients. 4. Moskowitz H, Burns
on human
those
TO THE
20
mg/day,
for
had recurrent
genital
herpes
of his genitals.
After
beginning
herpes changed resolved
white
recurrent
man who was given major
involving fluoxetine,
depression.
fluoxHe
also
the skin on one side the
frequency
of
outbreaks to involve with
the increase
remained the same, but the pattern both sides of his genitals. His depression fluoxetine, and he continues to take it despite in herpetic lesions.
Recurrences of herpes simplex are thought to be related to lapses in cell-mediated immunity. After primary infection the virus lies dormant in sensory ganglia, and under various cm-
949