Annals of Clinical Psychiatry, Vol. 9, No.

1, 1997

Sertraline and Psychotic Symptoms: A Case Series

Anand P. Popli, M.D.,1'2 Matthew A. Fuller, Pharm. D.,1 and George E. Jaskiw, M.D.1

Sertraline and other SSRIs have a relatively favorable side-effect profile and are widely pre-
scribed. We report the emergence of psychotic symptoms during treatment with sertraline
in four patients. Three of these patients had a history of psychotic illness and were on an-
tipsychotic medication, when sertraline was added. The psychotic symptoms emerged within
3 days-7 weeks of starting sertraline and resolved on its discontinuation. We wish to alert
clinicians to the possibility that sertraline may provoke or exacerbate positive psychotic symp-
toms, particularly in patients on neuroleptics, with a previous history of psychosis.
KEY WORDS: Sertraline; psychotic symptoms; adverse drug reactions.

INTRODUCTION CASE REPORTS

Sertraline hydrochloride is a commonly pre- Patient 1

scribed serotonin reuptake inhibitor. Its more com-
mon side effects include nausea, diarrhea, dyspepsia,
tremors, dizziness, increased sweating, sexual dys-
function, insomnia, somnolence, and dry mouth (pre-
scribing information for sertraline hydrochloride,
Pfizer-Roerig Company), but to our knowledge ser-
traline has not been associated with the emergence
of psychotic symptoms. After noting the emergence
of psychotic symptoms in one of our patients during
sertraline treatment, we undertook an evaluation of
other such possible cases.
Our facility provides approximately 9800 veter-
ans with psychiatric care annually. All physicians are
required to notify the Adverse Drug Reactions
(ADRs) Committee of untoward side effects, includ-
ing medication-associated psychotic exacerbations.
Accordingly, we reviewed all reported ADRs associ-
ated with sertraline use (28) and determined the to-
tal number of patients treated with the drug (2302)
over a 5-year period.
Department of Psychiatry, Case Western Reserve University, and
Department of Veterans Affairs Medical Center, Cleveland,
Ohio.
^To whom correspondence should be addressed at Porter Starke
Counseling Centers, 601 Wall St., Valparaiso, Indiana 46383.
This 70-year-old white male (bipolar disorder
mixed, history of psychosis) was being treated with
lithium carbonate, 300 mg bid, perphenazine, 6 mg
hs, lorazepam, 0.5 mg bid, and propranolol, 10 mg
tid, when he developed a major depressive episode.
There was no evidence of psychosis. Treatment with
sertraline, 50 mg/day, was initiated, without any
change in the existing medication regimen. Six weeks
later he developed paranoid ideation and suspicious-
ness but remained depressed. Within 7 days of a ser-
traline dose increase to 50 mg bid, psychosis and
irritability increased. A reduction of sertraline to 50
mg/day for 7 days did not affect the psychosis. How-
ever, the psychosis did resolve within 16 days of dis-
continuing sertraline. There was no history of alcohol
or drug abuse.
Patient 2
This 35-year-old white male with schizophrenia
and alcohol abuse, both in remission, developed a
depressive syndrome without any psychotic concomi-
tants. His previously prescribed perphenazine, 24
mg/day, trihexiphenidyl, 5 mg/day, lorazepam, 1 mg
bid, and propranolol, 10 mg tid, were continued and
sertraline, 50 mg/day, was added. Within 3 days of

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1040-1237/97/0300-0015$ 12.50/1 © 1997 American Academy of Clinical Psychiatrists
16
starting sertraline, he developed auditory hallucina-
tions, restlessness, and difficulty concentrating. The
psychotic symptoms resolved within 3 days of stop-
ping sertraline treatment, and his previous regimen
was continued.
Patient 3
This 29-year-old white male with schizoaffective
disorder and a history of substance abuse was stable
and had no psychotic symptoms on a regimen of
haloperidol, 25 mg/day, and nortriptyline, 75 mg/day.
Due to complaints about oversedation, nortriptyline
was replaced with sertraline, 50 mg/day; after 7 days
the latter was increased to 100 mg/day. Haloperidol
was kept at a constant dose. After 3 days on ser-
traline, 100 mg/day, the patient presented at the hos-
pital with marked psychotic incoherence and
unintelligible speech. Sertraline was discontinued
and the psychotic symptoms resolved within 1 week.
The patient did not report any substance abuse as-
sociated with this episode.
Patient 4
This 69-year-old white male with a history of
major depression, alcohol abuse, possible organic af-
fective disorder, diabetes mellitus, and a cerebrovas-
cular accident with residual hemiparesis was
medically stable on a regimen of captopril, 12.5 mg
bid, furosemide, 40 mg/day, and nifedipine SR, 90
mg/day. Eight months after his cerebrovascular acci-
dent, in the context of the deaths of his wife and
daughter, he developed a depressive episode. The
depression was only partially responsive to fluoxetine
and then bupropion. Accordingly, he was started on
sertraline, 25 mg/day for 21 days and then 50 mg/day.
Within 7 weeks he developed frank paranoid delu-
sions. The addition of loxapine up to 20 mg/day for
1 week had no effect. He was switched to haloperi-
dol, 1 mg/day, and sertraline discontinued. Within 2
weeks, the psychosis resolved. Depressive symptoms
responded to nortriptyline while low-dose haloperi-
dol was continued. There was no emergence of psy-
chotic symptoms after haloperidol was tapered.
Incidentally a urinary tract infection was noted after
the development of psychosis and treated with
ciprofloxacin. There was no report of substance
abuse.
Popli, Fuller, and Jaskiw
DISCUSSION
Three patients whose psychotic symptoms were
suppressed during neuroleptic treatment and one
poststroke patient developed positive psychotic
symptoms (paranoia, auditory hallucinations, inco-
herence, and paranoid delusions) within 3 days-7
weeks of initiation of sertraline treatment. These
symptoms disappeared when sertraline was discontin-
ued. None of our patients expressed suicidal or homi-
cidal ideation. The strength of the association
between the psychotic symptoms and sertraline treat-
ment is mitigated by several considerations. First, pa-
tients were not rechallenged with sertraline. Second,
three of the patients had a history of substance
abuse; on the other hand, the psychotic symptoms
were clinically judged as not substance abuse related.
Third, the diagnoses were clinically determined. In
the case of patient 4, a contribution by several medi-
cal factors cannot be precluded. Finally, patients in
remission from psychosis may experience spontane-
ous exacerbations despite compliance with neurolep-
tics. Thus while a definitive causal link between the
emergence of psychotic symptoms and the sertraline
treatment cannot be drawn (Naranjo's criteria) (1),
such an association cannot be ruled out. The devel-
opment of psychotic symptoms following sertraline
administration and their eventual disappearance af-
ter its discontinuation suggest that sertraline brought
out the psychotic symptoms.
Antidepressants of several classes, including the
SSRIs, tricyclics, and MAO inhibitors have been im-
plicated in inducing mania in patients both with and
without a history of bipolar illness (2, 3), as well as
in inducing or exacerbating psychosis in other psy-
chotic illnesses (4-6). The prescribing literature for
the SSRIs mentions that psychosis was infrequently
observed during premarketing studies. Our Medline
search identified four published reports of fluoxet-
ine-associated psychosis, involving a total of seven
patients (7-10), as well as one case report of an
SSRI-associated LSD flashback syndrome (11). Two
possible cases of sertraline-associated psychosis have
been reported to the manufacturer (Pfizer, personal
communication). Overall, the incidence of delusions
and hallucinations associated with SSRIs such as
fluoxetine and sertraline is estimated to be between
1/100 and 1/1000 patients (Prescribing Information,
Pfizer-Roerig Company, Eli Lilly Company). In our
survey, notwithstanding the possibility that all ADRs
may not have been reported, 28 patients treated with
Sertraline and Psychotic Symptoms
sertraline had a reported ADR and 4 of these de-
veloped psychotic symptoms. We found that approxi-
mately 2302 patients had been treated with sertraline
over a 5-year period. Five hundred ninety-four of
these patients were on neuroleptics at the time of
initiation of sertraline treatment. Of these, four re-
ported ADRs; three of the patients had been main-
tained on neuroleptics and carried diagnosis of
bipolar illness, schizoaffective illness, or schizophre-
nia. There were no reports of fluoxetine-associated
psychosis during the same time period (fluoxetine is
the only other SSRI available at our institution).
Sertraline shows a higher potency than other
SSRIs at blocking uptake of dopamine into rat sy-
naptosomes (12). Pharmacologically induced in-
creases in central dopamine transmission have been
linked to the induction or exacerbation of psychosis
(13, 14). Fluoxetine has been reported to reduce
negative symptoms in otherwise treatment refractory
patients with schizophrenia (15). Our experience sug-
gests that clinicians should be alerted to the possi-
bility that SSRIs may provoke positive psychotic
symptoms, particularly in patients on neuroleptics,
with a history of psychosis.
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