Case 1 : A married woman in her late
twenties presented with a three month history of
depression. Psychiatrie assessment led to a
diagnosis of a unipolar depressive illness,
arising in an anancastic personality. She was
treated as an out-patient, with clomipramine 100
mg per 24 hours. Complete symptom remission
occurred within ten days. At that point,
however, the patient questioned how long she
would be "allowed" to take the medication. She
sheepishly admitted that she hoped to take the
medication on a long terrn basis, not so much
because of the symptom relief that she had
experienced, but rather because she had noted
that since taking the medication, every time she
yawned she had an orgasm. She found she was able
to experience orgasm hy deliberate yawning. With
discontinuation of the medication several weeks
later, this phenomena disappeared.
Case 2 : A married male in his
mid-twenties presented with symptoms of
depression of three or four months duration.
Psychiatric assessment established a diagnosis
of unipolar depressive illness, occurring in a
passive-aggressive personality. Treatment with
clomipramine, 75 mg per 24 hours, on an
out-patient basis produced complete symptorn
relief within fourteen days. However, the
patient was particularly ambivalent about
continuing the medication, because he had noted
a frequent intense urge to yawn without
tiredness and that on many occasions when he
yawned, he experienced orgasm, with ejaculation.
He denied increased libidinal drive or related
fantasy. Although he found this both awkward and
embarrassing, he elected to continue the
medication because of the therapeutic benefit he
obtained. The awkwardness and embarrassment was
overcorne by continuously wearing a condom. With
discontinuation of the medication several weeks
later, the phenomenon disappeared.
Case 3 : A single woman in her carly
forties was seen in consultation at the
Department of Urology of a Regional General
Hospital, where she was admitted originally with
presenting complaints of renal calculus.
Following proper treatment she was observed
displaving depressive symptornatology for
approximately four months. A psychiatric
consultation established the diagnosis of a
unipolar depressive illness, occurring in an
obsessive-compulsive personality. Following
transfer to the psychiatric unit, treatment with
clomipramine 100 mg per 24 hours began and
produced complete symptom relief within twelve
days. At the beginning of her third week of her
hospitalization, the patient began to complain
of, what she termed "yawningspells" during which
she experienced "unresistable sexual urges." In
view of the environmental limitations and
despite her occasional masturbatory relief, she
found these peculiar symptoms niost difficult to
tolerate and requested the psychiatrist to
discontinue this medication, since she had
observed that her sensations began shortly after
the prescription of the medication.
Discontinuation led to remission of these
symptoms
Case 4 : A rnarried man in his early
thirties presented with symptoms of depression
that lasted eighteen months. Psychiatric
assessment led to a diagnosis of a pathological
grief reaction, occurring in a
passive-aggressive personality. An outpatient
treatment regime of psychotherapy and
clomipramine 50 mg per 24 hours, was initiated.
The patient subsequently reported that he had
stopped taking clomipramine after seven days
because he had noted that every time he yawned
he experienced such as intense sense of
exhaustion and weakness, that he had to lie down
for 10 to 15 minutes after each yawn, until the
sensation subsided. This phenomenon disappeared
within 48 hours after discontinuing the
medication.
Discussion : These reported side
effects have been discovered coincidentally
during routine side-effect queries. However, no
placebo-replacement or challenge by clomipramine
following discontinuation has been attempted.
The authors are unable to explain the origins of
these peculiar phenomena, coinciding with the
administration of clomipramine. These cases are
being reported not only for the benefit of
readers who might wish to explore the origins of
these occurrences, but also because of the
clinical implications for patient compliance.
The authors suspect that these side effects may
not have been reported previously (particularly
the phenomenon of orgasm) because of
patientunwillingless to reveal the experience.
It is suggested that all patients receiving this
medication should routinely be queried about
their experiences with orgasm in order to more
clearly establish the frequency of this
phenomenon.
References
Cooper-Smartt J D. A technique for surveying
side-effects of tricyclic drugs with reference
to reported sexual effects. J Int Med 1973; 1:
473-6.
NiningerJE. Inhibition of ejaculation by
amitriptyline. Am J Psychiatrv 1978; 135:
750-1.
Yassa R. Sexual disorders in the course of
clomipramine treatment: a report of three cases.
Can J Psychiatry 1982, 27(2): 148-9.
Résumé : Bien que l'on
connaisse dans la littérature
médicale certains cas de diminution de la
puissance sexuelle comme effet secondaire des
antidépresseurs (1-3), les auteurs ne
connaissent aucun cas où l'on rapporte
une augmentation de la capacité sexuelle
du type décrit dans le présent
article, ni d'instances où des effets
secondaires de ce genre ont été
associés au bâillement. Les auteurs
font état d'effets secondaires
inhabituels associés au bâillement,
dans le but d'éveiller l'attention des
cliniciens en ce qui touche les effets
secondaires possibles des
antidépresseurs; ces effets peuvent
rendre les patients moins disposés
à prendre ce genre de médicaments
lorsque ceux-ci leur sont
prescrits.
Unusual Side
Effects of Clomipramine Associated with
Yawning
W Harrison, J Stewart, P McGrath, F Quitkin
Canadian J of Psychiatry 1984; vol 29, n°6;
p546
McLean, Forsythe, and Kapkin (November 1983
issue) described an interesting and unusual
sexual side effect observed in several patients
treated with clomipramine, namely, repetitive
yawning associated with spontaneous orgasm. The
authors stated that they were unable to explain
the mechanism for this peculiar phenomenon. We
would like to suggest the following explanation
for the reported side effect.
Injection of ACTH-like peptides into the
cerebrospinal fluid of mammals, including
primates, has been shown to induce a syndrome of
frequent repetition of stretching and yawing
movements called the "stretching yawning
syndrome" (SYS) (1). When these peptides are
injected into hypothalamic areas the frequency
of the reaction isincreased (2). Injection of
ACTH-like peptides into the CSF of animals has
also been shown to result in recurrent episodes
of spontaneous penile erection and ejaculation
(3).The SYS and sexual response have a similar
time onset. Studies of the structure of the
peptide responsible for these effects suggest
that it is the esopeptide
Gll-Hist-Phel-Arginyl-tryl-Glycine and that it
is synthesized in the hypothalamus (3). This
peptide sequence is contained in the
corticotropin releasing factor (CRF) molecule.
Hypothalamic release of CRF is regulated by
serotonin (4). We propose that the increase in
brain serotonin levels resulting from
clomipramine's effect on serotonin re-uptake may
stimulate released of hypothalamic CRF. The CRF
relaesed has the potential to activate neural
circuits responsible for the previously
described behavior patterns, i.c., yawning and
spontaneous sexual response.
Drs Mc Lean, Forsythe and Kaplin
reply
We wish to express our thanks to Drs
Harrison, Stewart, McGrath and Quitkin for their
most interesting comments on our observation of
unusual side effects of Clomipramine.
Initially during the composition stage of our
paper, in our literature review, we had noted
the existence of a simillar stretching-yawning
behaviour (SYB) and spontaneous orgasm in opium
withdrawal (1). This parallel observation
between Clomipramine side effects and opium
withdrawal momentarily tempted us to speculate
on a possibility of endorphine connection.
However, we decided to leave the explanation to
future careful explorations.
Reference
Mark S. Gold, A. Carter Pottash, Donald R.
Sweeney, Herbert D. Kleber. Opiate withdrawal
using clonidine (A safe effective and rapid
monopiate treatment.) J AMA 1980; 243(4):
343-6.
