CASE REPORT
Drug-Associated Spontaneous Orgasm: A Case Report
and Systematic Review of Literature
Wei-Hsi Chen, MDMSc LLM,* Yuan-Hsiang Chu, PhD,† and Kuo-Yen Chen, PhD†
Objectives: Spontaneous orgasm is characterized by a spontaneous onset
of orgasm without any preceding sexual or nonsexual trigger. It sheds in-
sight on the mechanisms underlying orgasms and the sexual response cycle
in humans.
Methods: We report a male patient of repetitive spontaneous orgasm un-
der trazodone treatment and systematically review the literature on drug-
associated spontaneous orgasm (DASO).
Results: A total of 25 patients (18 women and 7 men), including our re-
ported case, experienced 27 DASO events. Over half of them were under
50 years of age during the DASO event. Depression was the leading mor-
bidity for these patients, and a limited list of antidepressants and antipsy-
chotics were involved in 92.5% of all DASO events. Although offending
drugs possess variable pharmacological properties, their common effect
is an augmentation of serotonin-1A (5HT1A) neurotransmission. Offending
drugs seemingly increase personal susceptibility to DASO. Over half of the
patients, especially men, did not concurrently experience sexual arousal or
desire during the DASO event. In the remaining patients, the orgasm was
accompanied by or ensued with arousal or desire. A reduction of dose or
discontinuation of the offending drug usually abolished DASO.
Conclusions: It appears that 5HT1A has a key role in generating orgasm.
Orgasms may be activated through arousal-independent or arousal-
dependent pathways, and both orgasms and sexual arousal are bidirection-
ally activated. This double-bidirectional model of sexual response cycle
may promote the success of sexual procreation and recreation, and further
research on this pathway could offer an innovative method to manage
anorgasmia in the future.
Key Words: orgasm, sexual, arousal, libido, serotonin, antidepressant
(Clin Neuropharm 2017;00: 00–00)
T he orgasm is the climax of sexual pleasure and has a procre-
ative and recreational purpose in humans.1 Until now, the
neurobiological basis of orgasms was largely unknown, because
specific and unique biochemical and behavioral correlates were
confounded with various other biopsychosocial factors in previous
studies. Spontaneous orgasm (SPONO) is a condition in which or-
gasms occur spontaneously without any preceding sexual or non-
sexual trigger. Therefore, an understanding of SPONO may shed
insight on the fundamental mechanism underlying orgasms in
humans. Here, we report a case of episodic SPONO in a man un-
der trazodone treatment and systematically review the literature to
elucidate the mechanisms underlying orgasms in humans.
*Graduate Institute of Human Sexuality, Shu-Te University; and †Department
of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang
Gung University, Kaohsiung City, Taiwan.
Address correspondence and reprint requests to Kuo-Yen Chen, PhD, Graduate
School of Human Sexuality, Shu-Te University, 59 Hengshan Rd, Yanchao
District, Kaohsiung City 82445, Taiwan; E‐mail: c748686@stu.edu.tw
Conflicts of Interest and Source of Funding: All the authors hereby declare that
they have no conflicts of interest, including consulting fees, paid expert
testimony, employment, grants, honoraria, patents, royalties, stocks, or
other financial or material gain that may involve the subject matter of
this manuscript.
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
DOI: 10.1097/WNF.0000000000000259
Clinical Neuropharmacology • Volume 00, Number 00, Month 2017
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CASE
A 46-year-old man working a blue-collar job suffered a
closed head injury in a traffic accident on his way home 2 years
ago. Cranial computerized tomography did not reveal structural
abnormality; however, his wife found that the patient gradually
exhibited a decline in memory and social function, and dull re-
sponses, low mood, and suicidal ideation after the accident. Addi-
tionally, the patient also showed impotence and a decrease in
sexual interest and intercourse frequency. The patient had been
married for 12 years and had 2 children. According to his wife,
the patient was heterosexual, exhibited normal sexual performance,
committed intercourse once per week, and did not consume any
herbal, illicit, or sex-promoting drugs before the accident. Sexual
violence and paraphilic disorder was also denied. After psychiatric
intervention, fluoxetine was administered for the treatment of de-
pressive symptoms, but was later changed to trazodone because
of the lack of improvement. Two weeks after the initiation of trazo-
done treatment, the patient experienced spontaneous and episodic
orgasms. The frequency of orgasms was variable, ranging from 1
to 3 times per day, and they lasted for 1 minute. The intensity of in-
dex SPONO was more than half of his previous classical orgasm.
The orgasm was not concurrent with libido urge, penile erection,
ejaculation, or autonomic changes. When the patient discontinued
trazodone himself, the SPONO subsided within 2 days and did
not recur until the trazodone was resumed on the following day.
The patient tried to continue trazodone therapy 3 times, but suffered
from identical SPONO events on each occasion. An electroenceph-
alogram did not reveal any paroxysmal discharge, and his blood tes-
tosterone level was within reference range. Because of delusions,
the psychiatrist started the patient on quetiapine but this did not re-
duce the frequency or intensity of SPONO. After discussion, trazo-
done was replaced by venlafaxine which controlled the patient’s
mood well. No SPONO has occurred since then.
METHODOLOGY
A systematic literature search related to SPONO, sexual
function, and drugs was conducted while following the guidelines
of Preferred Reporting Items for Systematic Reviews and Meta-
analyses. All full-length articles, book chapters, proceedings,
and abstracts with English or Chinese characters2 published until
2016 were considered in this study.
A computer-based search of the literature was performed
using keywords including “spontaneous orgasm,” “spontaneous on-
set of orgasm,” “drug-induced orgasm,” “drug-related orgasm,” and
“drug-associated orgasm.” The following scientific databases were
used in the study: PROQUEST, PUBMED, SCOPUS, EMBASE,
Cochrane database of systematic reviews, and Chinese databases
including the Taiwan Periodical Literature System (http://
readopac.ncl.edu.tw/nclJournal) and the Airiti Library (http://
www.airitilibrary.com). Additionally, the references of each manu-
script, book chapter, and proceeding were further reviewed to en-
sure adequate coverage of literature.
Drug users frequently report a boost in the frequency and in-
tensity of orgasms after consumption of recreational drugs, such
www.clinicalneuropharm.com 1
Chen et al
as opiates and amphetamines. Scholars doubt whether the experience
reported by these users is truly an orgasm or simply an orgasm-
euphoric sensation. Some plants, such as tropical Dictyophora spe-
cies, have also been implicated in causing orgasms in humans3;
however, these reports are not greatly detailed and the pharmacol-
ogy of these plants is entirely uncertain. In 1 early report, intrace-
rebral injection of acetylcholine into the septal area produced
repetitive intense orgasms,4 but this could not be reproduced.
Therefore, cases of orgasms induced by recreational drugs, herbs,
plants, and intracerebral acetylcholine injection were not included
in the literature review.
Categorical variables were statistically analyzed using a χ2
test or Fisher exact test at a 0.05 significance level.
This study was approved by the Chang Gung Medical Foun-
dation Institutional Review Board (Code number: 201700188B0)
RESULTS
A total of 24 patients experiencing 26 drug-associated spon-
taneous orgasm (DASO) events were selected from the literature
using our criteria (Table 1).5–27 Including our patient, there were
25 patients, 18 women and 7 men, who collectively experienced
27 DASO events. The age of onset was younger than 50 years
in 60% of the patients (Table 1). The case involving our patient
was the first report of DASO in East Asia.
Underlying Morbidity
Index drugs were prescribed for depression in 16 (64%) pa-
tients, bipolar disorder in 2 (8%) patients, and paranoia, attention
deficit disorder, parkinsonism, dystonia, hypersomnia, insomnia,
and breast cancer in 1 (4.3%) patient each. Other associated co-
morbidities included conversion disorder, alcohol dependence,
T-cell lymphoma, breast cancer, human immunodeficiency virus,
diabetes mellitus, peripheral vascular disease, and amputation.
Responsible Drugs and Dosage
Drugs responsible for the DASO events included 10 antide-
pressants, including fluoxetine in 5, venlafaxine in 3, clomipramine
in 2, bupropion in 2, trazodone in 2, and citalopram, paroxetine,
duloxetine, mirtazapine, and moclobemide in 1 DASO event
each5–20; 2 antipsychotic drugs, ziprasidone and risperidone, in
1 DASO event21,22; 3 dopamine agonists, rasagiline, pramipexole,
and ropinirole, in 1 DASO event23,24; 1 benzodiazepine, lorazepam,
in 1 DASO event25; 1 antineoplastic drug combination consisting of
docetaxel, doxorubicin, and fluorouracil in 1 DASO event26; and 1
dopamine transporter inhibitor, modafinil, in 1 DASO event.27 The
doses of all index drugs were within the recommended range when
the SPONO occurred.
Sexual Response Cycle
Sexual desire was assessed in 21 events, of which desire oc-
curred in 7 (33.3%) events, but was absent in the other 14 (66.7%)
events. Arousal was assessed in 19 events, of which arousal oc-
curred in 10 (52.6%) events, but was absent in the other 9
(47.4%) events (χ2 = 7.50, P < 0.01). Desire and arousal concur-
rently occurred in 6 events, were absent in 8 events, and in 5
events, either desire or arousal occurred. The data for the remain-
ing 8 cases was incomplete. When both desire and arousal were
present, they occurred almost simultaneously with or shortly after
SPONO, except in 1 female patient who experienced a rapid and
subsequent onset of desire, arousal, and then SPONO.25
A difference in desire and arousal activation was seen be-
tween sexes. Men usually did not show activation (activation vs
no activation = 16.7% vs 83.3%), whereas women frequently
2 www.clinicalneuropharm.com
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Clinical Neuropharmacology • Volume 00, Number 00, Month 2017
exhibited activation of desire or arousal (activation vs no activa-
tion = 80.0% vs 20.0%) (Fisher exact test, P = 0.03).
Sexual desire or arousal tended to occur more frequently in
sexually active patients. Orgasmic ejaculation occurred in 50%
of all reported male patients (Table 1).
Orgasmic Quality
There were 4 types of orgasms in the DASO events. The first
type was single orgasm, seen in 15 patients; the second type was
multiple orgasms, seen in 1 patient11; the third type was premature
onset of orgasm during intercourse, seen in 1 patient16; and the
fourth type was task-specific orgasm, seen in 5 patients.12,14,15,20
The intensity of the SPONO relative to the intensity of clas-
sical orgasms experienced previously during intercourse was
clearly reported in 6 patients. The intensity of the SPONO was
higher in 3, lower in 2, and not different in 1 patient. The fre-
quency of the SPONO was reported in 10 patients. The SPONO
was reported less than 6 times per day in 7, between 7 and 15 times
per day in 2, and between 5 and 45 times per day in 1 patient. The
duration of the SPONO was reported in 8 patients. The SPONO
duration was less than 1 minute in 6, between 15 and 30 minutes
in 1, and 3 hours in 1 patient. There was no significant correlation
between drug types and intensity, frequency, or duration of orgasm.
The task-specific orgasm was induced by walking,12 exercis-
ing,14 sleeping,15 or yawning.20 Drugs responsible for this type of
orgasm were fluoxetine, venlafaxine, trazodone, and clomipra-
mine. They did not elicit SPONO and task-specific orgasms in
the same patient.
Pleasurableness
The orgasm was described as pleasurable in 6, without plea-
sure in 3, and unpleasant in 1 patient, respectively. Of 6 patients
with pleasurable orgasms, the induced pleasure from the SPONO
was stronger than that from previously experienced classical or-
gasms in 3, no change in 1, but weaker in 2 patients, respectively.
The magnitude of intensity of pleasurableness was generally par-
allel to the intensity of SPONO.
Time Interval for Orgasmic Occurrence
The time interval between index drug use and orgasmic occur-
rence varied from 1 day to 1 year. There were 7 SPONO events that
occurred within 7 days, 9 SPONO events that occurred between
8 days and 1 month, 2 SPONO events that occurred between 1
and 3 months, and 1 SPONO event that occurred 1 year after drug
use. The time interval between drug use and orgasmic event was not
clear in 1 patient and was not mentioned for another patient.
Outcome
The occurrence of SPONO ceased after complete withdrawal
of the drug in 20 patients and dose reduction of the index drug in
another 5 patients.5,6,18,19,22 The time interval between discontin-
uation or dose reduction of the index drug and disappearance of
SPONO was reported in 7 patients. This occurred within 3 days
in 4, within 1 week in 1, and within 2 weeks in 2 patients.
Summary of Literature Findings
The literature findings are summarized into the following
8 points.
(1) DASO is an uncommon condition. It occurs in a few spe-
cific neuropsychiatric disorders, especially depression and bi-
polar disorder, because of the treatment with a limited list of
© 2017 Wolters Kluwer Health, Inc. All rights reserved.
 TABLE 1. The Summary of DASO in Literature

Medications Sexual response

Author Age, y (Combined Drug) Previous Usage of Underlying Previous Orgasmic Final
(s) Year Gender and Daily Dose ANTIDEPRESSANT(s) Morbidity Sexual Quality SD SA EE Yawn Quality Onset Outcome
(1) Antidepressants
Chen et al., 46, M Trazodone, Fluxetine THI Normal x x x x 1–3 times/d, < 2 min, 2 wk Subsided after withdrawal
present case 50 mg less intense and mild
pleasureness
Shalev et al., 51, F Mirtazapine, Escitalopram, Depression NR v v NR 5–6 times/d; no 3d Frequency decreased when
2009 3.75–11.25 mg Duloxetine report of intensity, dose was increased to
60 mg duration or 15 mg/day, subsided
pleasureness a few days after
withdrawal
Altindag and 41, F Venlafaxine, No Depression NR v v NR No report of 6 wk Subsided when dose
Gunes, 2008 600 mg Conversion disorder frequency, intensity was shifted to

© 2017 Wolters Kluwer Health, Inc. All rights reserved.

Alprazolam, or duration; not 450 mg/d; continued
1 mg pleasurable with paroxetine 20 mg/d
Campbell and 74, F Duloxetine Venlafaxine Depression NR NR NR NR NR 5–45 times/d, a few NR Subsided after withdrawal;
Schubert, Duloxetine Hypertension minutes, interval continued with
2007 Sleep apnea 15–30 min; no citalopram 10 mg/d and
report of intensity trazodone 50 mg/d
or pleasureness
Clinical Neuropharmacology • Volume 00, Number 00, Month 2017

Pae et al., 64, F Paroxetine, 10 mg NR Minor depression Normal x v NR 10–15 times/d, 0.5–1 2 wk Subsided 10 d after
2005 (Lorazepam, min; intense and withdrawal; continued
0.5 mg) pleasurable orgasm; with tianeptine
also easily exaggerated 12.5 mg/d
by bumpyride
Yanik, 2004 48, F Venlafaxine, Moclobomide Major depression NR NR NR NR 4–5 times/d in both 3 wk after Subsided within 2 wk
150 mg; 900 mg/day drugs; no report of Venlafaxine; after withdrawal
citalopram, Olanzapine intensity, duration 10 d after
20 mg 10 mg or pleasureness citalopram
Ramasubbu, 27, F Fluoxetine, 20 mg NR Bipolar disorder NR x NR NR Only record of orgasm 24 months Subsided after shifting
1999 increased; no report to moclobemide
of frequency, intensity, 300 mg/d
duration or pleasureness
Labbate, 37, M Bupropion-SR, No attention-deficit Normal v v v NR Second orgasm, intense, Within 6 wk* Subsided within weeks
1998 450 mg disorder pleasurable orgasm after withdrawal and
recurred after reuse
Ravsten et al., 51, M Venlafaxine, No Depression, HIV, Normal x x v NR Walking-induced orgasm; 6d Subsided after withdrawal
1997 50–100 mg Alcohol dependence no report of intensity

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
(Perphenazine, or pleasureness; no
6 mg/d) erection
Grimes and 35, F Bupropion, 75 mg; Nortriptyline, Depression NR x v x A 3-h orgasm without 6 wk* Subside after withdrawal
Labbate, Sertraline, Sertraline Sertraline-related change of intensity;
1996 100 mg/d anorgasmia pleasurable

www.clinicalneuropharm.com
Continued next page

3
Drugs and Spontaneous Orgasm
 4
TABLE 1. (Continued)

Medications Sexual response

Chen et al

Author Age, y (Combined Drug) Previous Usage of Underlying Previous Orgasmic Final
(s) Year Gender and Daily Dose ANTIDEPRESSANT(s) Morbidity Sexual Quality SD SA EE Yawn Quality Onset Outcome
Ellison, 1996 50, F Fluoxetine, 20 mg No Depression Normal x x x Anorgasmia during Several months (1) No adverse effect
intercourse; orgasm under 10 mg/d
occurred 10 min after (2) Cyproheptadine
exercise; less intense; partially resolved
pleasureness is less anorgasmia but not
intense for spontaneous one
Purcell and 67, F Trazodone, 100 mg NR Major depression Sexually x NR NR Episodic orgasm at First day Subsided after withdrawal;

www.clinicalneuropharm.com
Ghurye, inactive sleep time; no report no orgasmic change
1995 of pleasureness under paroxetine
20 mg/d or fluoxetine
20 mg/d
Lauerma, 1995 42, F Moclobemide, No Depression Normal v v NR Premature intense Fifth to seventh Subsided within 6 d after
300 mg (Doxepin, orgasm, no day withdrawal
100 mg/d) pleasureness
Garcia-Campayo 69, M Fluoxetine, Clomipramine Depression T cell Normal x x x NR 1–2 times/d; 30–60 s; 1 month Subside 2 d after withdrawal
et al., 1995 20 mg lymphoma no penile erection; no
(Radiotherapy) report of pleasureness
Morris, 1991 69, M Fluoxetine, 20 mg Buspirone 5 mg Poststroke depression Sexually inactive NR NR NR 2–4 times/d; 10–30 s; no 1 month Subside on fluoxetine
Trazodone 100 mg diabetes mellitus (impotence) erection, nocturnal 20 mg qod twice
Nortriptyline 50 mg PVD, Amputation emission; no report
of pleasureness
Modell, 1989 30, F Fluoxetine, 40 mg Nortriptyline Major depression Normal x v — v Yawning, non-painful Second day* No attack with 20 mg/d
75–100 mg/d clitoral engorgement and mild yawning with
occurred, following with 60 mg/d. Subsided after
paroxysmal orgasm withdrawal
shortly after intake; no
mention of intensity or
duration; no pleasureness
McLean et al., 20+, F Clomipramine, NR Depression NR NR NR — v Yawning provoked orgasm. 10 d Subsided after withdrawal
1983 100 mg No report of pleasureness
McLean et al., 20+, M Clomipramine, NR Depression NR x x Yes v Yawning provoked 14 d Subsided after withdrawal
1983 75 mg pleasurable orgasm
(2) Antipsychotic drugs
Boora et al., 50, F Ziprasidone, Venlafaxine Bipolar disorder Sexually inactive x v NR 10–15 times/day, 0.5–1 min/ 7 d Subsided 3 d after withdrawal
2010 40 mg time; no report of
intensity
Alcántara and 40, M Risperidone, Trifluoperazine Paranoid Libido decreased x x x x 3 times; no report of 7d Subsided after shifting to

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Nieto, 1998 6 mg/d schizophrenia by trifluoperazine duration, intensity or 3 mg/d
pleasureness
(3) Antiparkinsonian drug
Uca and Kozak, 42, F Rasagiline, No Early-onset Parkinson NR v v — NR 3–5 times/d, 5–20 s Seventh day Subsided after withdrawal;
2014 1 mg/d disease orgasm recurred after
reused 15 later

© 2017 Wolters Kluwer Health, Inc. All rights reserved.

Clinical Neuropharmacology • Volume 00, Number 00, Month 2017
Clinical Neuropharmacology • Volume 00, Number 00, Month 2017 Drugs and Spontaneous Orgasm

Subsided 2 d after withdrawal

EE indicates ejaculatory emission; HIV, human immunodeficiency virus; NR, Not reported; qod, every other day; PVD, peripheral vascular disease; THI, traumatic head injury; SA, sexual arousal; SD, sexual
Subsided after withdrawal

drugs, mainly antidepressants and antipsychotics. Sex and age

Subsided a few days after

Subsided progressively
seem to have no influence on occurrence of DASO events.
(2) Index drugs induced SPONO but did not change the quality

after withdrawal
of the classical orgasm. Preexisting sexual function does not

withdrawal
predict DASO. The intensity and duration of DASO are usually
similar to that of a classical orgasm. Personal susceptibility has
an effect of SPONO occurrence, as a specific drug may elicit
SPONO repetitively in one person but not in another person.
(3) Use of antidepressants or dopaminergic modulators (ago-
modafinil,

modafinil nists and antagonists), including modafinil, contributed to 25

Second day

A few days
Ninth day
3 months

First day

(92.5%) of all 27 DASO events.

then

(4) There is an equal likelihood that SPONO will occur within

7 days or between 8 days and 1 month after drug use regardless
of drug type. An immediate reaction following drug administra-
4 times/d; 1 h after intake

identical to intercourse
report of intensity and

tion is rare.
increased desire, then

ascending from thigh

no report of intensity
5–6 times/d, 0.5–1 min;

to genitalia for a few

3–5 times/d, 5–15 s; no
or during sleep; no

(5) Most of the index antidepressants and dopaminergic modu-

1 h after intake with

orgasm sensation
or pleasureness

lators can change the serotonin (5HT) neurotransmission as

pleasureness

pleasureness

hours twice

they are pharmacologically the postsynaptic 5HT2A and/or

5HT2c receptor antagonists or inverse agonists, postsynaptic
5HT1A receptor agonists or partial agonists, or serotonin trans-
porter (SERT) inhibitors (Table 2).28 Any action results from an
increased synaptic 5HT, activation of 5HT1A activity or
suppression of 5HT2A or 5HT2C activity. In a previous
NR

NR

NR

study, cyproheptadine use did not change the SPONO in a

female patient.14 Quetiapine did not have any effect on SPONO
NR NR NR

occurrence in our patient. Nevertheless, DASO rapidly and

x

completely subsides after discontinuation or reduction of dosage

of the index drug.
x

(6) Extrafrontal features, such as yawning, were occasionally

associated with SPONO occurring because of antidepressant
Sexually inactive

use, but were not caused by dopaminergic modulators or other

index drugs.
(7) Task-specific orgasms were observed in 5 patients. The
tasks included sleeping, exercising, walking, and yawning.
NR

NR

The offending drugs were trazodone, fluoxetine, venlafaxine, and

cancer, hypertension

clomipramine. These drugs induce either only task-specific or only

non-task-specific orgasm, but not both, in the same patient.
Insomnia, breast

(8) Sexual arousal was absent in over half of DASO patients, but
Breast cancer

Hypersomnia

accompanied or induced SPONO in the remaining patients.

Dystonia

Male patients mainly presented with isolated orgasm, while fe-

male patients frequently experienced sexual arousal concur-
rently with SPONO.

DISCUSSION
The current findings show that the quality of orgasms in
drive; Symbol for sexual response: X, absence; v, presence.
Levodopa

DASO events is similar to that of classical orgasms in affected pa-

tients, suggesting that the offending drugs involve the pathways
Modafinil, 300 mg/d No
No

No

regulating classical orgasms and index orgasmic response in both

sexes. Most of the index drugs exhibit 5HT1A agonism and/or
Ropinirole, 0.5 mg/d

doxorubicin, and

5HT2A or 5HT2C antagonism or inverse agonism (Table 2).28

Pramipexole,
0.17 mg/d;

These findings are in line with the current understanding that

fluorouracil

Lorazepam,

activation of central 5HT1A receptors benefit, whereas that of

Docetaxel,

1 mg/d

central 5HT2A or peripheral 5HT2C receptor reduces orgasmic

response.29 Therefore, DASO is an ideal model to study
human orgasm.
This study reveals three potentially interesting findings that
30, F

62, F
52, F

Kilickap et al., 53, F

will help in expanding the understanding of orgasms. First, DASO

is an unusual condition, as antidepressants and antipsychotics
(4) Chemotherapy

generally have negative effects on sexual function. Most index

Uca and Atlas,

Simoes et al.,

drugs pharmacologically facilitate 5HT1A neurotransmission,

Kaut et al.,

(5) Others

such as inhibition of SERT to increase synaptic 5HT which pre-

2012

2012

2014

2010

dominately binds to the 5HT1A receptor, agonism of the 5HT1A

receptor, and/or antagonism of the 5HT2A or 5HT2C receptors.28

© 2017 Wolters Kluwer Health, Inc. All rights reserved. www.clinicalneuropharm.com 5

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Chen et al Clinical Neuropharmacology • Volume 00, Number 00, Month 2017

TABLE 2. The Inhibitory Constant (Ki) of the 20 Index Drugs Reported in DASO

Compound SERT NET DAT 5HT1AR 5HT2AR 5HT2CR

agn anta
Fluoxetine 1 660 >1000 >1000 197 255anta
Trazodone 367 >1000 >1000 113pagn 35.9anta 224anta
Venlafaxine 7.7 >1000 >1000 >1000 >1000 >1000
Clomipramine 0.21 45.9 >1000 >1000 35.5anta/iagn 64.6iagn
Bupropion >1000 >1000 526 >1000 >1000 >1000
Mirtazapine >1000 >1000 >1000 18agn 69anta 39iagn
Duloxetine 0.8 5.9 278 >1000 504anta 916anta
Paroxetine 0.08 56.7 574 >1000 >1000 >1000
Citalopram 1.38 >1000 >1000 >1000 >1000 617anta
Meclobemide NR NR NR NR NR NR
Ziprasidone 39 >1000 >1000 28.7pagn 0.52anta 4.9iagn
Risperidone NR >1000 >1000 210anta 0.6anta 26iagn
Rasagiline NR NR NR NR NR NR
Pramipexole NR >1000 >1000 >1000 >1000 >1000
Ropinirole NR NR NR 288agn >1000 >1000
Lorazepam NR NR NR NR NR NR
Docetaxel NR NR NR NR NR NR
Doxorubicin NR NR NR NR NR NR
Fluorouracil NR NR NR NR NR NR
Modafinil >1000 >1000 >1000 NR NR NR
5HTR, serotonin receptor; agn, agonist; anta, antagonist; DAT, dopamine transporter; iagn, inverse agonist; NET, norepinephrine transporter.
The Ki was retrieved from the Psychoactive Drug Screening Program Ki database28 and the species was human only. The unit of Ki was nM/L. A lower
Ki represents a higher affinity of drug on receptor or transporter, and vice versa. The pharmacological action of drug on receptor was mentioned only when
Ki was < 1000 nM/L.

However, flibanserin, a selective agonist for the 5HT1A receptor
and antagonist for the 5HT2A receptor,30 does not elicit SPONO
or increase the intensity of classical orgasms under therapeutic
or higher doses. Moreover, cyproheptadine, which blocks the
5HT2A and 5HT2C receptors to correct drug-induced anorgasmia,
does not trigger or enhance SPONO in DASO patients.14 There-
fore, as found in this study, other factors, such as specific brain
conditions,31 peculiar drug-brain interactions,31 and personal
susceptibility are believed to collectively determine the occur-
rence of DASO. Nevertheless, 5HT1A activation is important
for generating orgasm.
Second, index drugs provoke orgasms spontaneously but do
not change the intensity or duration of classical orgasms, suggest-
ing a diversity of orgasmic pathways in humans. This is consistent
with multiple triggers of orgasm in the real world, especially in
women.32 Accordingly, classical and nonclassical orgasmic path-
ways share some commonalities. The drugs fluoxetine, venlafaxine,
and trazodone are capable of inducing either task-specific or non–
task-specific orgasms in patients, though one patient never experi-
ences both. This specific drug-individual-orgasm interaction
supports the individualized plasticity of orgasms in some people
and suggests that orgasms can be explored through other appro-
priate ways in anorgasmic patients.
Third, sexual arousal is absent during SPONO in nearly half
of the DASO patients, especially in men, as seen in our patient,
but it co-occurs or ensues with SPONO in the remaining patients.
Therefore, orgasms have both arousal-independent and arousal-
dependent pathways, and orgasms and sexual arousal are bidirec-
tionally activated. Indeed, orgasms can be provoked alone without
arousal or desire initially, such as in rape or incest.33 This double-
bidirectional model of orgasms further signifies the heterogeneity
and flexibility of human orgasms, differing from the traditional
linear and circular models of the sexual response cycle.34–36 It
may perhaps promise the success of procreation during sexual in-
tercourse.1 More importantly, this model can alternatively initiate
orgasms for sexual enjoyment even when arousal is difficult
to provoke.
In conclusion, DASO is usually provoked by antidepressants
or dopaminergic modulators and is involved with a co-operative
interaction of intrinsic and extrinsic factors. Orgasms can be pro-
voked through classic and non-classical pathways which share
some common mechanisms. In contrast to traditional linear and
circular models, orgasms can be activated through arousal-
dependent as well as arousal-independent pathways and orgasms
and arousal are bidirectionally activated, leading to a double-
bidirectional model of sexual response cycle. These findings pro-
vide novel insight into orgasm mechanisms and sexual function.
REFERENCES
1. Levin RJ. Recreation and procreation: a critical view of sex in the human
female. Clin Anat 2015;28:339–354.
2. Chen LW, Chen MY, Chen KY, et al. Topiramate-associated sexual
dysfunction: a systematic review. Epilepsy Behav 2017;73:10–17.
3. Holliday JC, Soule N. Spontaneous female orgasms triggered by smell of a
newly found tropical Dictyphora species. Int J Med Mushrooms 2001;3:
162–167.
4. Heath RG. Pleasure and brain activity in man. Deep and surface
electroencephalograms during orgasm. J Nerv Ment Dis 1972;154:3–18.
5. Shalev H, Ben-Zion I, Shiber A. A case of mirtazapine-induced
spontaneous orgasms in a female patient. J Psychopharmacol 2009;23:
109–110.
6. Altindag A, Gunes M. A case series of increased libido and spontaneous
orgasm associated with venlafaxine treatment. Prog
Neuropsychopharmacol Biol Psychiatry 2008;32:895–896.

6 www.clinicalneuropharm.com © 2017 Wolters Kluwer Health, Inc. All rights reserved.

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Clinical Neuropharmacology • Volume 00, Number 00, Month 2017
7. Campbell N, Schubert C. Spontaneous orgasm with duloxetine and
citalopram in an elderly woman. J Am Geriatr Soc 2007;55:S21–S22.
8. Pae CU, Kim TS, Lee KU, et al. Paroxetine-associated spontaneous sexual
stimulation. Int Clin Psychopharmacol 2005;20:339–341.
9. Yanik M. Spontaneous orgasm started with venlafaxine and continued with
citalopram. Can J Psychiatry 2004;49:786.
10. Ramasubbu R. Switching to moclobemide to reverse fluoxetine-induced
sexual dysfunction in patients with depression. J Psychiatry Neurosci 1999;
24:45–50.
11. Labbate LA. Bupropion-SR-induced increased libido and spontaneous
orgasm. Can J Psychiatry 1998;43:644–645.
12. Ravsten DV, Smith NB, Thatcher GW. Spontaneous male orgasm in
association with venlafaxine. Am Fam Physician 1997;55:1561. 1564,
1574.
13. Grimes JB, Labbate LA. Spontaneous orgasm with the combined use of
bupropion and sertraline. Biol Psychiatry 1996;40:1184–1185.
14. Ellison JM. Exercise-induced orgasms associated with fluoxetine treatment
of depression. J Clin Psychiatry 1996;57:596–597.
15. Purcell P, Ghurye R. Trazodone and spontaneous orgasms in an elderly
postmenopausal woman: a case report. J Clin Psychopharmacol 1995;15:
293–295.
16. Lauerma H. A case of moclobemide-induced hyperorgasmia. Int Clin
Psychopharmacol 1995;10:123–124.
17. Garcia-Campayo J, Sanz-Carrillo C, Lobo A. Orgasmic sexual experiences
as a side effect of fluoxetine: a case report. Acta Psychiatr Scand 1995;91:
69–70.
18. Morris PL. Fluoxetine and orgasmic sexual experiences. Int J Psychiatry
Med 1991;21:379–382.
19. Modell JG. Repeated observations of yawning, clitoral engorgement, and
orgasm associated with fluoxetine administration. J Clin Psychopharmacol
1989;9:63–65.
20. McLean JD, Forsythe RG, Kapkin IA. Unusual side effects of
clomipramine associated with yawning. Can J Psychiatry 1983;28:
569–570.
21. Boora K, Chiappone K, Dubovsky S, et al. Ziprasidone-induced
spontaneous orgasm. J Psychopharmacol 2010;24:947–948.
© 2017 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Drugs and Spontaneous Orgasm
22. Alcántara AG, Nieto J. Spontaneous orgasms during risperidone treatment
in a schizophrenic patient: a case report. Hum Psychopharmacol 1998;13:
135–136.
23. Kaut O, Asmus F, Paus S. Spontaneous unwelcome orgasms due to
pramipexole and ropinirole. Mov Disord 2012;27:1327–1328.
24. Uca AU, Kozak HH. A case of rasagiline-induced spontaneous orgasms in
a female patient. Parkinsonism Relat Disord 2014;20:929–930.
25. Simoes S, Amorim J, Machado A. Intense lorazepam-induced sexual
arousal. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:236–237.
26. Kilickap S, Kesikli SA, Erdis E, et al. Chemotherapy-induced spontaneous
orgasms in a patient with breast cancer. Ann Pharmacother 2012;46:
144–145.
27. Uca AU, Atlas M. Modafinil-induced spontaneous unwelcome orgasms.
Sleep Biol Rhythms 2014;12:227–228.
28. National Institute of Mental Health's Psychoactive Drug Screening
Program. PDSP Ki Database. Available at: http://kidbdev.med.unc.edu/
databases/pdsp.php. Accessed September 10, 2017.
29. Komisaruk BR, Beyer-Flores C. WhippleB. The Science of Orgasm.
Baltimore: Johns Hopkins University Press; 2008.
30. Stahl SM, Sommer B, Allers KA. Multifunctional pharmacology of
flibanserin: possible mechanism of therapeutic action in hypoactive sexual
desire disorder. J Sex Med 2011;8:15–27.
31. Metzger CD, Walter M, Graf H, et al. SSRI-related modulation of sexual
functioning is predicted by pre-treatment resting state functional
connectivity in healthy men. Arch Sex Behav 2013;42:935–947.
32. Levin RJ. The mechanisms of human female sexual arousal. Ann Rev Sex
Res 1992;2:1–48.
33. Allen JG. Copying with trauma. Hope through understanding, 2nd edition.
Washington DC: American Psychiatric Publishing, Inc.; 2005.
34. Ferenidou F, Kirana PS, Fokas K, et al. Sexual response models: toward a
more flexible pattern of women's sexuality. J Sex Med 2016;13:1369–1376.
35. Basson R. The female sexual response: a different model. J Sex Marital
Ther 2000;26:51–65.
36. Masters W, Johnson V. Human sexual response. Boston: Little & Brown
Co.; 1966.
www.clinicalneuropharm.com 7