Sertraline and Akathisia: Spontaneous Resolution
Arturo A. Olivera
Key Words: Akathisia, sertraline, spontaneous resolution, serotonin-specific reuptake
inhibitors, bupropion
BIOL PSYCHIATRY 1997;41:241--242
Introduction
Akathisia is a distressing adverse reaction to antipsychotic drugs
(Van Putten 1975) that also occurs in the course of treatment
with serotonin (5-HT)-specific reuptake inhibitor (SSRI) antide-
pressants, including sertraline (Lipinski et al 1989; Adler and
Angrist 1995; Shihabuddin and Rapport 1994; Klee and Kronig
1992). It has been proposed that the dopamine (DA) deficiency
effected by 5-HT accumulation at the ventral tegmental area
(VTA) of the brain produced by SSRIs may lead to akathisia
(Lipinski et al 1989). The following is a report about sertraline-
induced akathisia that spontaneously resolved.
Case Reports
During the course of their psychiatric care at the outpatient clinic,
4 of 25 individuals (16%) receiving sertraline treatment for
mental disorders (diagnosed according DSM-III-R) complained
of inner tension, restlessness, and the inability to stay still; these
symptoms prompted retrospective, self-reported evaluation for
akathisia using the Barnes approach (Barnes 1989). Severity is
expressed as Global Clinical Assessment of Akathisia (GCAA).
Each patient consented to evaluation and follow-up for the
complication. They also received supportive psychotherapy and
psychoeducational interventions as part of their clinical manage-
ment. All 4 patients were physically healthy; blood cytology and
chemistries, as well as liver and thyroid functions, were normal.
From the Department of Psychiatry, MetroHealth Medical Center, Cleveland, Ohio
USA; and Department of Psychiatry, Case Western Reserve University,
Cleveland, Ohio.
Address reprint requests to Arturo A. Olivera, MD, 8015 Robin Lane, Brecksville.
OH 44141.
Received November 13, 1995; revised June 20, 1996.
© 1997 Society of Biological Psychiatry
Case #1
A 61-year-old white woman, with the diagnosis of major
depressive disorder and generalized anxiety, was a partial re-
sponder to fluoxetine and trazodone. Within 1 week, after
beginning 50 mg once a day (q.d.) sertraline, she complained of
feeling unusually restless and tense, despite continuation of
buspirone 20 mg three times a day (t.i.d.) that had successfully
controlled her anxiety for an extended length of time. Evaluation
for akathisia was positive with a GCAA of 2.8. Increasing
sertraline to 100 mg q.d. worsened her complaints about being
fidgety and uncomfortable; GCAA was 3.7. Reinstatement of the
initial dosage resulted in alleviation of her condition; GCAA
gradually declined to 2.2, and symptoms subsided totally in 12
weeks without pharmacologic interventions. According to the
patient's reports, the complication occurred within 2 hours of
sertraline intake, and was short-lasting. Fortunately, her depres-
sion responded favorably to the reduced dose of sertraline. She is
currently stable, and shows no signs of akathisia due to sertraline.
Case #2
A 29-year-old white woman, with the diagnosis of obsessive-
compulsive disorder (OCD), panic attacks, and major depressive
disorder, had responded well to tricyclic antidepressants (TCAs)
and trazodone; however, her low tolerance for these drugs (e.g.,
constipation and excessive perspiration, and drowsiness with
TCAs and trazodone, respectively) prompted their discontinua-
tion. She began the sertraline trial at 50 mg q.d. A week later, she
reported remarkable improvement of her panic attacks, while
remaining free of depression and of OCD; however, she com-
plained of feeling uncomfortable inner tension and was unable to
stay still within 2 hours after taking sertraline. Evaluation for
akathisia was positive, with a GCAA 3.0. Sertraline adjustment
to 25 mg two times a day (b.i.d.) did not eliminate the
discomfort. Substituting paroxetine up to 40 mg q.d. maintained
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242 BIOLPSYCHIATRY
1997;41:241-242
her overall improvement without adverse reactions. In a few
weeks she again felt anxious; at her request, sertraline was
reinstated at 50 mg in the AM. In 2 weeks she was feeling
comfortable, and akathisia was mild and better tolerated. She
currently takes 150 mg sertraline q.d. as a maintenance dose, and
is emotionally stable, free of akathisia.
Case//3
A 54-year-old white woman, with the diagnosis of major
depressive disorder and generalized anxiety, was highly sensitive
to the adverse reactions of TCAs (restlessness, excitement) and
trazodone (dizziness), despite effective resolution of her depres-
sion. Her tolerance for buspirone was excellent, maintaining a
stable anxiety-free state. Without interrupting buspirone, the
sertraline trial began at 50 mg q.d. Within 72 hours, she
interrupted the treatment because she became "extremely" rest-
less, felt "encaged," and "things were too bad." Evaluation was
positive for akathisia, with a GCAA of 3.4; symptoms subsided
rapidly upon sertraline discontinuation. A bupropion trial, up to
200 mg q.d., succeeded in reducing her depression within 3
weeks without adverse reactions.
Case//4
A 28-year-old white woman, with the diagnosis of major
depressive disorder before admission, was treated with 50 mg
q.d. sertraline for 4 months without noticeable improvement and
no adverse reactions. Sertraline was increased to 100 mg at
bedtime. On her next visit, she complained that within 2 hours
after medication intake she became unusually restless, pacing,
felt tense inside, and was unable to lay still in bed. After 2 days,
she resumed 50 mg sertraline q.d. without further complaints.
Retrospective assessment was positive for akathisia, with a
GCAA of 3.2. She agreed to a new sertraline trial of 50 mg b.i.d.
References
Adler LA, Angrist BM (1995): Paroxetine and akathisia. Biol
Psychiatry 37:336-337.
Adler LA, Angrist B, Rotrosen J (1992): Acute neuroleptic-
induced akathisia. In Lang AE and Weiner WJ (eds), Drug-
Induced Movement Disorders, Mount Kisco, NY, Futura
Press, pp 85-119.
Bames TRE (1989): A rating scale for drug-induced akathisia.
Br J Psychiatry 154:672-676.
Klee B, Kronig MH (1992): Case report of probable sertraline-
induced akathisia. Am J Psychiatry 150:986-987.
Lipinski JF Jr, Mallya G, Zimmerman P, Pope HG Jr (1989):
Case Reports
Two weeks later, she reported feeling less depressed and free of
akathisia. In 7 weeks, she was free of depression, and functioning
without problems.
Discussion
The findings of sertraline-induced akathisia reported here indi-
cate that the complication invariably occurred close to the
sertraline-intake time, with approximately a 2-hour lag period.
Each episode was time-limited, rapidly subsiding, but recurred
after the following dose. The complication resolved permanently
in each case without the need for pharmacologic interventions.
Comorbid anxiety and excitatory response to TCAs, as predis-
posing factors to akathisia (Lipinski et al 1989), were identified
in 3 of these cases. None of these individuals had shown other
associated extrapyramidal symptoms (Shihabuddin and Rapport
1994). These findings need further validation through formal
research with a larger group of patients. If akathisia occurs, the
ultimate management decisions should be based on the assess-
ment of: severity and distress levels; dose dependence and need
for a divided dose schedule; duration of each episode; and total
life span and natural resolution profile. Management should
include: frequent visits; supportive and psychoeducational,
and/or pharmacologic interventions, e.g., administration of ser-
traline in divided doses; dose reduction; and antidepressant
substitution or prescription of antiakathisia medications (Lipinski
et al 1989; Klee and Kronig 1992; Adler et al 1992; Adler and
Angrist 1995). These observations support the suggestion that the
severity of ser~aline-inducedadverse reactions may be dose- and
time-related, i.e., adverse reactions decreasing at lower doses or
with longer administration periods (Reimherr et al 1990).
The author acknowledges Dr. Daniel S.P. Schubert for his review and
comments on this article.
Akathisia: Clinical and theoretical implications. J Clin Psy-
chiatry 50:339-342.
Reimherr FW, Chouinard G, Cohn CK, et al (1990): Antidepres-
sant efficacy of sertraline: A double-blind, placebo- and
amitriptyline-controlled, multicenter comparison study in
outpatients with major depression. J Clin Psychiatry 51 (suppl
B): 18-27.
Shihabuddin L, Rapport D (1994): Sertraline and extrapyramidal
side effects [letter]. Am J Psychiatry 151:228.
Van Putten T (1975): The many faces of akathisia. Compr
Psychiatry 16:43-47.