Psychiatria Danubina, 2013; Vol. 25, No. 3, pp 266-267 Medicinska naklada - Zagreb, Croatia DULOXETINE-RELATED GALACTORRHEA AND RESTLESS LEGS SYNDROME: A CASE REPORT Hasan Belli, Mahir Akbudak & Cenk Ural Department of Psychiatry, Bagcilar Education and Research Hospital, Istanbul, Turkey INTRODUCTION
weeks. Six weeks later, she applied to our clinic with the complaints of milky discharge, fullness, breast pain,
High prolactin hormone level in the blood is known
distressing sensations deep inside the limbs occurring at
as hyperprolactinemia. The most common symptom of
bedtime and paresthesias consisting in an irresistible
hyperprolactinemia is galactorrhea, in which sponta-
urge to move the limb. The patient reported that there
neous milky discharge is seen from all ducts of the two
was not this kind of complaints before duloxetin
mammary glands. Dopamine has an inhibitor effect on
prolactin, in the tuberoinfundibular tract and inhibition
Results of neurological, general physical examina-
of dopamine increases the serum prolactin level
tion, and laboratory investigation, including blood
(Feuchtl et al. 2004). Monoaminoxidase inhibitors, tri-
chemistry, thyroid function test, FSH, LH levels, liver
cyclic antidepressants, and selective serotonin reuptake
and renal functions were normal. Magnetic resonance
inhibitors (SSRIs) were identified as a cause of hyper-
imaging (MRI) focused on the brain and particularly the
prolactinemia (Wieck et al. 2004). However, data
pituitary gland, and result of this test was within normal
regarding hyperprolactinemia due to duloxetine, a novel
limit. Her serum prolactin level was measured as 37.9
serotonin-noradrenaline reuptake inhibitor, are limited
ng mL. As repeated serum prolactin levels gave the
same results. We sought to eliminate the most likely
Restless legs syndrome (RLS) is a sensorimotor
causes of galactorrhoea. She was married but was not
disorder characterized by distressing sensations deep
having menstrual periods. No evidence of any
inside the limbs, typically occurring at bedtime or rest.
These paresthesias involve an irresistible urge to move
Duloxetine treatment was stopped and bupropion
the limb, which provides temporary relief but at the
was started at the dose of 150 mg per day and the dose
expense of sleep and quality of life. RLS may be a
was increased to 300 mg per day within 4 weeks. At the
primary or a secondary condition. Secondary causes of
end of the 2nd week under bupropion treatment, her
RLS include iron deficiency, chronic kidney disease,
galactorrhea and RLS symptoms improved consider-
pregnancy, and various medications (Allen et al. 2003).
ably. Six week after initiated bupropion, her serum
In a study, RLS was noted as a possible side effect of
prolactin level was measured as 20.2 ng mL. At the end
the use of fluoxetine, paroxetine, citalopram, sertraline,
of 12th week under bupropion treatment, she was also
escitalopram, venlafaxine, duloxetine, and mirtazapine
In the present paper, we report a case of duloxetine-
DISCUSSION
related galactorrhea and restless legs syndrome.
It was reported that women are more vulnerable to
CASE REPORT
prolactin elevation when using antidepressants (Hal-breich et al. 2003). Our case had been suffering from
Ms. P, female, 46 years old. She applied to our clinic
depression without any galactorrhea and RLS symp-
with the complaints of depression. A screen for symp-
toms. Furthermore, patients treated with duloxetine may
toms of depression revealed that she had hopelessness,
present with galactorrhea and RLS as unwanted side
low energy, anhedonia, appetite, poor concentration, a
effects of therapy. The mechanism by which antide-
strong sense of guilt and insomnia. Beck Depression
pressants may cause hyperprolactinaemia is not fully
Inventory (BDI) (Beck 1961) was used to screen for
understood, though several theories have been postu-
depression. BDI scores for depression was determined
lated, such as serotonin stimulation of GABAergic
as 42. She had become increasingly upset over 2 months
neurons and indirect modulation of prolactin release by
and noticed depressive symptoms. Her psychiatric
serotonin (Coker & Taylor 2010). However, hyper-
history did not include previous episodes of depression.
prolactinemia may be caused by two distinct mecha-
Duloxetine was started with the dose of 30 mg per day
nisms, the presynaptic inhibition of dopamine discharge
and the dose was increased to 60 mg per day within 4
by serotonergic receptors (Egberts et al. 1997), or the
Hasan Belli, Mahir Akbudak & Cenk Ural: DULOXETINE-RELATED GALACTORRHEA AND RESTLESS LEGS SYNDROME: A CASE REPORT Psychiatria Danubina, 2013; Vol. 25, No. 3, pp 266–267
direct stimulation of hypothalamic postsynaptic seroto-
and epidemiology workshop at the National Institutes of
nergic receptors (Bronzo & Stahl 1993). In one study,
Health. Sleep Med 2003; 4:101–19.
RLS was noted as a possible side effect of the use of
2. Ashton AK & Longdon MC: Hyperprolactinemia and
fluoxetine, paroxetine, citalopram, sertraline, escitalo-
galactorrhea induced by serotonin and norepinephrine
pram, venlafaxine, duloxetine, and mirtazapine (Rottach
reuptake inhibiting antidepressants. Am J Psychiatry 2007; 164:1121-2.
et al. 2008). Mechanisms mentioned in here, dopami-
3. Beck AT: An inventory for measuring depression. Arch
nergic transmission may also play an important role in
4. Bronzo MR & Stahl SM: Galactorrhea induced by
We have prefered switching to bupropion as another
sertraline. Am J Psychiatry 1993; 150:1269–70.
antidepressant. At the end of the 2nd week under
5. Coker F & Taylor D: Antidepressant-induced hyperpro-
bupropion treatment, galactorrhea and RLS symptoms
lactinaemia: incidence, mechanisms and management.
improved considerably in our case. Bupropion should be
considered for depressed patients with galactorrhea and
6. Egberts AC, Meyboom RH, De Koning FH, Bakker A & Leufkens HG: Non puerperal lactation associated with
Clinicians need to be aware of these unusual side-
antidepressant drug use. Br J Clin Pharmacol 1997;
effects of duloxetine, because galactorrhea and RLS
may play an important role in compliance with
7. Halbreich U, Kinon BJ, Gilmore JA & Kahn LS: Elevated prolactin levels in patients with schizophrenia: mecha-
treatment and can act as an additional stress factor for
nisms and related adverse effects. Psychoneuroendo-crinology 2003; 28(suppl 1):53-67. 8. Feuchtl A, Bagli M, Stephan R, Frahnert C, Kölsch H, Kühn KU, et al: Pharmacokinetics of m-chloro-Acknowledgements: None. phenylpiperazine after intravenous and oral admini-stration in healthy male volunteers: implication for the Conflict of interest: None to declare. pharmacodynamic profile. Pharmacopsychiatry 2004; 9. Rottach KG, Schaner BM, Kirch MH, Zivotofsky AF, References Teufel LM, Galwitz T et al: Restless legs syndrome as side effect of second generation antidepressants. J Psychiatr 1. Allen RP, Picchietti D, Hening WA, Trankwalder C, Walters AS & Montplaisi J: Restless legs syndrome: 10. Wieck A & Haddad PM: Antipsychotic-induced hyper-diagnostic criteria, special considerations, and epidemio-prolactinaemia in women: pathophysiology, severity and logy. A report from the restless legs syndrome diagnosisconsequences. Br J Psychiatry 2003; 182:199-204. Department of Psychiatry, Bagcilar Education and Research Hospital
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