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Pretreatment screening and counseling on prolonged erections for patients prescribed trazodone

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Purpose: We examined whether patients are appropriately screened for previous prolonged erections or priapism and counseled about trazodone complications, specifically prolonged erections and priapism, prior to trazodone treatment. Materials and methods: We identified patients under the age of 50 on trazodone as of February 27, 2019 at the VA New Jersey Health Care System. Patients were asked about information provided to them prior to medication initiation, occurrence of prolonged erections/priapism, and reporting rate of side effects. Results: Two hundred and twenty nine out of five hundred and twenty four male patients agreed to participate in the study. Forty three out of two hundred and twenty nine of patients were informed about the side effects of prolonged erections and 37/229 of patients were informed of risk of priapism prior to treatment. Only 17/229 of patients were asked if they had had any episodes of prolonged erection or priapism in the past. Eighteen patients developed prolonged erection while taking trazodone. Only 5/18 patients who had developed prolonged erections informed their physicians. Conclusions: Only a fraction of patients were properly screened for previous prolonged erections or priapism and properly informed about the side effects of trazodone. Urologist should better educate trazodone prescribers, such as family medicine and psychiatric colleagues, regarding the side effects of trazodone. It is imperative that prescribing physicians appropriately screen and educate patients prior to trazodone initiation and instruct patients to report any treatment side effects to avoid potential long-term adverse outcomes.
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85
Pretreatment screening and counseling on
prolonged erections for patients prescribed
trazodone
Tejash Shah , Juhi Deolanker , Thaiphi Luu , Hossein Sadeghi-Nejad
Department of Urology, Rutgers New Jersey Medical School, Newark, NJ, USA
Purpose: We examined whether patients are appropriately screened for previous prolonged erections or priapism and counseled
about trazodone complications, specifically prolonged erections and priapism, prior to trazodone treatment.
Materials and Methods: We identified patients under the age of 50 on trazodone as of February 27, 2019 at the VA New Jersey
Health Care System. Patients were asked about information provided to them prior to medication initiation, occurrence of pro-
longed erections/priapism, and reporting rate of side effects.
Results: Two hundred and twenty nine out of five hundred and twenty four male patients agreed to participate in the study. Forty
three out of two hundred and twenty nine of patients were informed about the side effects of prolonged erections and 37/229 of
patients were informed of risk of priapism prior to treatment. Only 17/229 of patients were asked if they had had any episodes of
prolonged erection or priapism in the past. Eighteen patients developed prolonged erection while taking trazodone. Only 5/18 pa-
tients who had developed prolonged erections informed their physicians.
Conclusions: Only a fraction of patients were properly screened for previous prolonged erections or priapism and properly in-
formed about the side effects of trazodone. Urologist should better educate trazodone prescribers, such as family medicine and
psychiatric colleagues, regarding the side effects of trazodone. It is imperative that prescribing physicians appropriately screen and
educate patients prior to trazodone initiation and instruct patients to report any treatment side effects to avoid potential long-
term adverse outcomes.
Keywords: Antipsychotic agents; Drug-related side effects and adverse reactions; Priapism
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Original Article - Sexual Dysfunction/Infertility
Received: 12 May, 2020 Revised: 22 June, 2020 Accepted: 2 September, 2020 Published online: 10 December, 2020
Corresponding Author: Tejash Shah https://orcid.org/0000-0002-5301-8103
Department of Urology, Rutgers New Jersey Medical School, 185 S Orange Ave, Newark, NJ 07103, USA
TEL: +1-917-804-6745, FAX: +1-973-972-3892, E-mail: shahtt@njms.rutgers.edu
The Korean Urological Association www.icurology.org
Investig Clin Urol 2021;62:85-89.
https://doi.org/10.4111/icu.20200195
pISSN 2466-0493 • eISSN 2466-054X
INTRODUCTION
Priapism is a urologic emergency defined as a prolonged,
painful erection lasting greater than 4 hours, not usually
initiated by sexual stimuli or desire. It has been established
that there are a variety of risk factors f or priapism, includ-
ing the use of antipsychotics such as trazodone, and having
a history of prolonged erections. There are several reports
in the literature of trazodone use leading to both prolonged
erections and priapism, but patients are often not counseled
on these well-known side ef f ects [1]. If patients are not aware
of such side effects, it is highly likely that they may delay
seeking care for priapism/prolonged erections, which ulti-
mately may lead to irreversible complications of ischemic
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Shah et al
https://doi.org/10.4111/icu.20200195
penile f ibrosis and subsequent erectile dysfunction.
Medications, including antidepressants, antihyperten-
sives, anticoagulants, alpha-blockers and some psychoactive
substances such as alcohol and cocaine, are responsible f or
the onset of 25% to 40% of cases of priapism. However, about
50% of all drugs related priapism is due to antipsychotics
usage [2]. It is the prescri bing physicians’ duty to inf orm
patients about all risks prior to initiating therapy, especially
in this population who may be on an extensive pharmaco-
logic regimen. It has been noted that all patients should be
questioned about previous episodes of prolonged erections as
a past significant history of delayed detumescence is present
in approximately 50% of any subsequent cases of priapism [1].
Previous data also suggests that priapism is most likely to
occur within the first 28 days of treatment initiation with
a majority of the patients taking a dosage of 150 mg/day or
less [3]. While medication side ef f ects are never desired, if
patients are aware of them, it is only intuitive that they can
seek side ef f ect management sooner and avoid long term
conseq ue nces.
The veterans af fairs (VA ) system is the one of the larg-
est health care systems in the United States, with almost
over 8 million veterans enrolled and about 5 million receiv-
ing care. It is critical to investigate all adverse events re-
lated to antipsychotic medication use, particularly in view
of studies indicating usage as high as 47.5% in the nursing
home population and veteran af fairs health care system [4].
Furthermore, off-label use of antipsychotic medications is
extremely prevalent in the VA population, as almost 60% of
patients had no record of a diagnosis for which these drugs
were off icially approved. The most common mental illnesses
receiving antipsychotic prescriptions were post-traumatic
stress disorder (41.8%), minor depression (39.5%), major de-
pression (23.4%), and anxiety disorder (20.0%) [5]. Male veter-
ans, especially those with suicidal ideation and psychiatric
comorbidities, are more likely to receive antipsychotics than
any other types of psychiatric medications [6]. With this
high percentage of use, providers should be cautious when
prescribing these medications.
In our clinical practice at the East Orange Veterans Af-
fairs Hospital, we recently came across two patients with
priapism in the emergency room that were on trazodone,
but were never informed about the medication side ef fects.
We therefore set out to evaluate whether the larger cohort
of patients on trazodone were appropriately counseled about
prolonged erections and priapism prior to starting the medi-
cation. We also sought to identify the incidence of prolonged
erections in those taking trazodone, as well as the rate of pa-
tient reported events of prolonged erection to the prescribing
physicians.
MATERIALS AND METHODS
Institutional Board Review of VA New Jersey Health
Care System approval was obtained (approval number:
00001450) and su bsequently a pharmacy search was per-
formed at the V A New Jersey Health Care System (VAN-
JHS), to identify all male patients under the age of 50 cur-
rently taking trazodone as of February 27, 2019. Patients
previously on trazodone or those who discontinued it prior
to this date for any reason, including priapism, were not in-
cluded. Patients were contacted via telephone, informed con-
sent about study participation was obtained, and were asked
about information provided prior to medication initiation,
whether history of prolonged erection or priapism was elic-
ited prior to medication initiation, occurrence of prolonged
erections/priapism while on trazodone therapy, and commu-
nication with prescribing physicians in case these adverse
events had been encountered. We defined prolonged erec-
tions as erections lasting anywhere from one to f our hours.
RESULTS
Two hundred and twenty nine out of a total of 524 male
patients on trazodone at the V ANJHS participated in the
study, with an average age of 38.57±6.88 years. Indications
for prescribing trazodone were insomnia, depression or post-
traumatic stress disorder in all cases. Dosages of trazodone
administered ranged from 50–100 mg, two to three times
a day (Table 1). Prior to prescribing trazodone, only 43/229
(18.78%) of patients were informed about the side ef fects of
prolonged erections. Even fewer numbers of patients were
inf orm ed abo ut t he r isk of p r iapism, 37 /229 (16.16%).
Table 1. Patient demographics
Patient characteristic Result (n=229)
Age (y) 38.57 (25–50)
Sex
Male 229 (100.0)
Female 0 (0.0)
Trazodone dosage (mg)
50 138 (60.3)
100 91 (39.7)
Indications Insomnia; depression; PTSD
Values are presented as mean (range) or number (%).
PTSD, post-traumatic stress disorder.
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Investig Clin Urol 2021;62:85-89. www.icurology.org
Trazodone screening and side effect counseling
Only 17/229 (7.42%) of patients were asked if they previ-
ously had any episodes of prolonged erection. Similarly, only
17/229 (7.42%) of patients were asked if they ever had pria-
pism in the past. Af ter the initiation of trazodone therapy,
18/229 (7.86%) of patients developed prolonged erection and
only 2/18 were informed about the risk of prolonged erec-
tions prior to initiation of therapy. Only 5/18 of those who
developed prolonged erections told their physicians. Patients
did not report these events to physicians due to embarrass-
ment and/or lack of awareness that this side ef f ect was pos-
sibly associated with trazodone. None of the patients who
were actively taking trazodone had an episode of priapism
requiring an emergency room visit while on the medication
(Table 2 ).
DISCUSSION
Priapism is a true urologic emergency as a delay in care
can lead to deleterious long-term consequences. There are
a variety of risk factors for priapism, including the use of
antipsychotics such as trazodone as there are several reports
in the literature of trazodone use leading to both prolonged
erections and priapism. Initially, priapism was only noted to
be associated with the use of the more typical first genera-
tion antipsychotic medications and trazodone, but now there
have been some reports of the newer atypical antipsychot-
ics causing priapism as well [7]. Trazodone is U.S. Food and
Drug Administration-approved f or treating major depres-
sive disorder, but it can also be used for of f-label purposes
such as insomnia, post-traumatic stress disorder, anxiety,
Alzheimer’s, personality disorders, and cocaine/alcohol with-
drawal. The medication can be orally dosed in 50, 100, 150,
and 300 mg tablets with 300 mg/day being the maximum
dosage for outpatient and 600 mg/day f or inpatient usage.
Priapism is considered as an adverse effect occurring in
less than 1% of patients on trazodone. This is more likely to
occur in male who have multiple myeloma, sickle cell ane-
mia, leukemia, autonomic dysfunction, or those who have
a penile anatomic variation such as cavernosal fibrosis,
angulation, or Peyronie’s disease [8]. One study by Haria et
al. [9] reported a priapism incidence ra te of 1:1,000 to 1:10,000
for male on trazodone, while the incidence of priapism in
the general population has been reported to significantly
lower at 1.5:10,000 [10]. Psychotropic-induced priapism is
thought to be caused by the alpha1-adrenergic antagonism
of these medications within the corpora cavernosa which
inhibits detumescence [11,12]. It has been shown that during
the rapid eye movement sleep period, during which spon-
taneous erectile activity usually occurs, the detumescence
phase of erection which is under sympathetic control, was
signif icantly prolonged 2.4 times by trazodone compared to
placebo.
In vitro
, trazodone at similar concentrations to those
that are achieved in plasma considerably af fected corporeal
smooth muscle contractions that were induced by electrical
stimulation of adrenergic nerves and antagonized contrac-
tions caused by exogenous norepinephrine [13]. With all the
studies perf ormed to understand the mechanism of action
of trazodone and other antipsychotics, the most widely ac-
cepted mechanism involves a decrease in local sympathetic
tone with respect to the local parasympathetic tone [14]. In
addition to the alpha1-adrenergic antagonism with which
priapism is caused by, trazodone also inhibits the neuronal
uptake of serotonin and is a histamine antagonist [15].
Multiple case reports have established a connection
between the use of a combination of trazodone and other
antipsychotics with priapism occurrence [16]. A particular
case report of a military veteran receiving treatment f or
PTSD (post-traumatic stress disorder) with trazodone and
three other antipsychotic medications notes the patient hav-
ing recurrent priapism with the f irst episode being three
months after initiation of treatment. At that time, he was
instructed to stop trazodone. The second episode presented
one month af ter discontinuation, at which he then discon-
tinued prazosin, and after 6 weeks he did not experience
recurrence [17]. Several cases with the use of other antipsy-
chotics such as quetiapine, carbamazepine, olanzapine, and
clozapine have also been reported, signifying the prevalence
of priapism when on these medications. Olanzapine and que-
tiapine, specif ically, have been implicated numerous times.
A case report of an individual with schizoaf fective disorder
discusses recurrent priapism over a three year period, each
time related to the ingestion of quetiapine [18]. More recent-
ly, a case series f rom the AMSP ( Arzneimittelsicherheit in
der Psychiatrie) database reviews 19 case reports of priapism
Table 2. Rates of screening, side effect counseling and side effect reporting
Asked about previous
prolonged
erection/priapism
Informed about risk of
prolonged erection
Informed about
risk of priapism
Incidence of
prolonged
erections
Incidence of
priapism
Reporting rate to
physician about
side effect
17/229 (7.42) 43/229 (18.78) 37/229 (16.16) 18/229 (7.86) 0 5/18 (27.78)
Values are presented as number (%).
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Shah et al
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that are likely caused by typical and atypical antipsychotics,
as well as trazodone. Common amongst the reports was the
introduction of a psychotropic drug causing the immediate
development of priapism and a shif t in drug plasma concen-
tration due to a change in drug dosage or due to co-adminis-
tration of specific selective serotonin reuptake inhibitors [19].
Physicians should also be aware that there are reports of
priapism occurring even in children under the age of 6 who
are on trazodone [20].
Patients on trazodone or other antipsychotics should be
made aware of such side effects prior to initiating treatment
as the lack of awareness of the side effects may lead to a
delay in patients seeking medical attention and thus lead-
ing to irreversible damage and poor erectile f unction. The
prescribing physicians must inf orm patients about all risks
prior to initiating therapy. When patients taking trazodone
or other antipsychotics present with priapism, the treatment
algorithm is the same as for ischemic, low f low priapism
[21]. The main goals of medical therapy are decompression
of the corporal bodies and restoration of arterial blood f low
to reduce ischemia and the potential risk of tissue necrosis.
Prompt treatment within 4 to 6 hours of onset has been
shown to reduce long term ef f ects and decrease the need for
surgical intervention.
In the present study, patients were not appropriately
counseled as only 43/229 (18.78%) of patients were inf ormed
about the side effects of prolonged erections and even f ewer
numbers of patients were informed about the risk of pria-
pism, 37/229 (16.16%). It is also concerning that prior to tra-
zodone initiation, only 17/229 (7.42%) of patients were asked
if they previously had any episodes of prolonged erection
and priapism. A change in the prescribing algorithm must
be made to include clear disclosure of trazodone side effects.
While medication side ef fects are never desired, if patients
are aware of potential adverse ef f ects, then they can get
seek medical care and side effect management sooner to
hopefully avoid long term consequences. Interestingly, in
the past 2 years at various private and academic hospitals
covered by Rutgers New Jersey Medical School urology
residents, in addition to the two patients on trazodone who
developed priapism at the VANJHS there have been three
cases of patients with priapism on trazodone, all who were
never counseled on this side effect. While anecdotal, this
suggests that there is not proper discussion of trazodone side
ef f ects regarding prolonged erection and priapism in the
community as well.
This study f ocuses on veteran patients, a population
that has a high percentage of usage of trazodone and other
antipsychotic medication. Given the patient population and
the complex psychotropic regimen, the study population may
be at higher risk for priapism and prolonged erections. It is
noteworthy that despite multiple episodes of prolonged erec-
tions, none of the patients in the study required an emer-
gency room visit f or priapism during the study. This is likely
because patients who did have priapism while taking trazo-
done, the medication was discontinued and not captured in
our study. Based on our f indings, it is clear that patient edu-
cation and counseling needs to be drastically improved prior
to starting trazodone. Providing the proper inf ormation to
patients can f oster a more communicati ve and well-inf ormed
patient-doctor relationship that allows patients with compli-
cations to f eel comfortable discussing adverse ef f ects with
their physician.
Limitations of the study include the study population
as we only included patients who were on trazodone at the
time of our study, and did not account for patients who
may have discontinued trazodone for priapism or any other
adverse ef f ect. We defined prolonged erections as lasting
between one to f our hours but did not obtain more detailed
inf ormation as to the specif ic length of each patients pro-
longed erections. Additionally, our study only looked at the
practice patterns at one veterans af f air system. Further in-
vestigation needs to be done regarding the true incidence of
prolonged erections and priapism in patients in the general
population taking trazodone, other antipsychotics, or a com-
bination of antipsychotic medications.
CONCLUSIONS
Patients taking trazodone are known to have an in-
creased risk of prolonged erections and priapism. Only a
fraction of patients were properly screened for previous pro-
longed erections or priapism and properly informed about
the side effects of trazodone treatment prior to receiving the
medication. Urologist should better educate trazodone pre-
scribers, such as family medicine and psychiatric colleagues,
regarding the side ef f ects of trazodone. It is imperative that
physicians appropriately screen patients prior to trazodone
initiation, educate patients about the risks of prolonged erec-
tions and priapism and instruct patients to report any treat-
ment side e f fec ts.
CONFLICTS OF INTEREST
The authors have nothing to disclose.
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Investig Clin Urol 2021;62:85-89. www.icurology.org
Trazodone screening and side effect counseling
AUTHORS’ CONTRIBUTIONS
Research conception and design: Thaiphi Luu and Hos-
sein Sadeghi-Nejad. Data acquisition: Thaiphi Luu and Juhi
Deolanker. Statistical analysis: Tejash Shah and Juhi Deo-
lanker. Data analysis and interpretation: Tejash Shah. Draf t-
ing of the manuscript: Tejash Shah and Juhi Deolanker.
Critical revision of the manuscript: Tejash Shah and Hossein
Sadeghi-Nejad. Supervision: Hossein Sadeghi-Nejad. Approval
of the f inal manuscript: Tejash Shah, Hossein Sadeghi-Nejad,
and Juhi Deolanker.
REFERENCES
1. Thompson JW Jr, Ware MR, Blashfield RK. Psychotropic medi-
cation and priapism: a comprehensive review. J Clin Psychiatry
1990;51:430-3.
2. Doufik J, Otheman Y, Khalili L, Ghanmi J, Ouanass A. Anti-
psychotic-induced priapism and management challenges: a
case report. Encephale 2014;40:518-21.
3. Warner MD, Peabody CA, Whiteford HA, Hollister LE. Trazo-
done and priapism. J Clin Psychiatry 1987;48:244-5.
4. Hanlon JT, Wang X, Castle NG, Stone RA, Handler SM, Semla
TP, et al. Potential underuse, overuse, and inappropriate use of
antidepressants in older veteran nursing home residents. J Am
Geriatr Soc 2011;59:1412-20.
5. Leslie DL, Mohamed S, Rosenheck RA. Off-label use of anti-
psychotic medications in the department of Veterans Affairs
health care system. Psychiatr Serv 2009;60:1175-81.
6. Cohen BE, Shi Y, Neylan TC, Maguen S, Seal KH. Antipsy-
chotic prescriptions in Iraq and Afghanistan veterans with
posttraumatic stress disorder in Department of Veterans Af-
fairs Healthcare, 2007-2012. J Clin Psychiatry 2015;76:406-12.
7. Sood S, James W, Bailon MJ. Priapism associated with atypical
antipsychotic medications: a review. Int Clin Psychopharmacol
2008;23:9-17.
8. Schwasinger-Schmidt TE, Macaluso M. Other antidepressants.
Handb Exp Pharmacol 2019;250:325-55.
9. Haria M, Fitton A, McTavish D. Trazodone. A review of its
pharmacology, therapeutic use in depression and therapeutic
potential in other disorders. Drugs Aging 1994;4:331-55.
10. Eland IA, van der Lei J, Stricker BH, Sturkenboom MJ. In-
cidence of priapism in the general population. Urology
2001;57:970-2.
11. Compton MT, Miller AH. Priapism associated with conven-
tional and atypical antipsychotic medications: a review. J Clin
Psychiatry 2001;62:362-6.
12. Krege S, Goepel M, Sperling H, Michel MC. Affinity of trazo-
done for human penile alpha1- andalpha2-adrenoceptors. BJU
Int 2000;85:959-61.
13. Saenz de Tejada I, Ware JC, Blanco R, Pittard JT, Nadig PW,
Azadzoi KM, et al. Pathophysiology of prolonged penile erec-
tion associated with trazodone use. J Urol 1991;145:60-4.
14. Weiner DM, Lowe FC. Psychotropic drug-induced priapism.
CNS Drugs 1998;9:371-9.
15. Settimo L, Taylor D. Evaluating the dose-dependent mecha-
nism of action of trazodone by estimation of occupancies for
different brain neurotransmitter targets. J Psychopharmacol
2018;32:96-104.
16. Burk BG, Nelson LA. Psychotropic-induced priapism in a
treatment-refractory patient: a case report. J Pharm Pract 2019
Nov 6 [Epub]. https://doi.org/10.1177/0897190019885233.
17. Mann RA, George AK. Recurrent priapism in a military vet-
eran receiving treatment for PTSD. Mil Med 2017;182:e2104-7.
18. Saghafi O, Kao A, Druck J. Recurrent priapism from therapeu-
tic quetiapine. West J Emerg Med 2014;15:114-6.
19. Greiner T, Schneider M, Regente J, Toto S, Bleich S, Grohmann
R, et al. Priapism induced by various psychotropics: a case se-
ries. World J Biol Psychiatry 2019;20:505-12.
20. El Zahran T, Morgan BW, Hon S, Herrington L, Geller RJ. Un-
intentional trazodone overdoses in children ≤6 years of age:
data from poison center over a period of 16 years. Clin Toxicol
(Phila) 2019;57:56-9.
21. Rosenberg I, Aniskin D, Bernay L. Psychiatric treatment of
patients predisposed to priapism induced by quetapine, traza-
done and risperidone: a case report. Gen Hosp Psychiatry
2009;31:98.
... Based on these premises, it appears that, among the high-risk list of drugs here analysed, trazodone generated indeed the strongest SDR, whilst olanzapine and tadalafil seemed somewhat more prone to cause priapism vs. the other drugs of the database (except for trazodone). The propensity of trazodone to elicit priapism is already well documented in the literature [19][20][21]. Although a number of medications identified in this list may be prescribed by sexual medicine specialists, most of these drugs are typically prescribed by psychiatrists and primary care doctors. ...
... Although a number of medications identified in this list may be prescribed by sexual medicine specialists, most of these drugs are typically prescribed by psychiatrists and primary care doctors. It is of outmost importance that physicians prescribing trazodone are aware and prepared to face this possible detrimental side effect [20], as this medication is still prescribed to more than 27 million Americans [17]. To this respect, some 229 male patients younger than 50 years taking trazodone were surveyed regarding their pretreatment counselling: only less than 20% of the patients were informed about the possible risk of prolonged erections and priapism [20]. ...
... It is of outmost importance that physicians prescribing trazodone are aware and prepared to face this possible detrimental side effect [20], as this medication is still prescribed to more than 27 million Americans [17]. To this respect, some 229 male patients younger than 50 years taking trazodone were surveyed regarding their pretreatment counselling: only less than 20% of the patients were informed about the possible risk of prolonged erections and priapism [20]. The concomitant use/abuse of other legal and/or illegal drugs known to cause priapism may increase the risk of trazodone-induced priapism, due to a synergistic effect [6]. ...
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A range of drugs have a direct role in triggering ischaemic priapism. We aimed at identifying: a) which medications are associated with most priapism-reports; and, b) within these medications, comparing their potential to elicit priapism through a disproportionality analysis. The FDA Adverse Event Reporting System (FAERS) database was queried to identify those drugs associated the most with priapism reports over the last 5 years. Only those drugs being associated with a minimum of 30 priapism reports were considered. The Proportional Reporting Ratios (PRRs), and their 95% confidence intervals were computed. Out of the whole 2015–2020 database, 1233 priapism reports were identified, 933 of which (75.7%) were associated with 11 medications with a minimum of 30 priapism-reports each. Trazodone, olanzapine and tadalafil showed levels of disproportionate reporting, with a PRR of 9.04 (CI95%: 7.73–10.58), 1.55 (CI95%: 1.27–1.89), and 1.42 (CI95%: 1.10–1.43), respectively. Most (57.5%) of the reports associated with the phosphodiesterase type 5 inhibitors (PDE5Is) were related with concomitant priapism-eliciting drugs taken at the same time and/or inappropriate intake/excessive dosage. Patients taking trazodone and/or antipsychotics need to be aware of the priapism-risk; awareness among prescribers would help in reducing priapism-related detrimental sequelae; PDE5I-intake is not responsible for priapism by itself, when appropriate medical supervision is provided.
... Based on 210 these premises, it appears that, among the high-risk list of drugs here analysed, trazodone generated 211 indeed the strongest SDR, whilst olanzapine and tadalafil seemed somewhat more prone to cause 212 priapism vs. the other drugs of the database (except for trazodone). The propensity of trazodone to 213 elicit priapism is already well documented in the literature [19][20][21]. Although a number of medications 214 identified in this list may be prescribed by sexual medicine specialists, most of these drugs are typically medication is still prescribed to more than 27 million Americans [17]. ...
... Although a number of medications 214 identified in this list may be prescribed by sexual medicine specialists, most of these drugs are typically medication is still prescribed to more than 27 million Americans [17]. To this respect, some 229 male 218 patients younger than 50 years taking trazodone were surveyed regarding their pre-treatment 219 counselling: only less than 20% of the patients were informed about the possible risk of prolonged 220 erections and priapism [20]. The concomitant use/abuse of other legal and/or illegal drugs known to 221 cause priapism may increase the risk of trazodone-induced priapism, due to a synergistic effect [6]. ...
... prescribing trazodone are aware and prepared to face this possible detrimental side effect[20], as this ...
... The most common side effects are drowsiness, dry mouth, blurred vision, headaches, and falls [22]. Less common side-effects include priapism, a persistent painful penile or clitoral erection; the penile erection can lead to impotence in men [23][24][25][26][27][28] It is important to note that the view that the clinical evidence does not support trazodone as a treatment for first-line treatment for insomnia was the majority view of our sleep expert appraisal panel, but it was not the universal view. One expert appraisal panel member disagreed with the statement. ...
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Priapism is a persistent, and often painful, penile erection, lasting more than 3hours, not usually associated with sexual stimuli. It is a urological emergency that can cause serious complications. Drugs are responsible of the onset of 25 to 40% of cases of priapism. Several classes of medication are involved: antidepressants, antihypertensives, anticoagulants, alpha-blockers and some psychoactive substances (alcohol, cocaine, cannabis…). However, about 50% of drug related priapism is due to antipsychotics (AP). Clinicians should be aware of this rare side effect because of the severity of its complications and the difficulty of its management, especially in non-stabilized psychotic patients. We report a case of a 22-year-old male Moroccan patient, diagnosed with schizophrenia, who had been admitted for the first time to a psychiatric hospital for management of a psychotic episode. First, he received 15mg per day of haloperidol, and seven days later he developed priapism. The patient was immediately referred for urological care. Aspiration and irrigation of the corpora cavernosa was proposed, but could not be performed because of patient refusal, and the erection resolved spontaneously after 10hours. Haloperidol was stopped, and four days later the patient was switched to 10mg per day of olanzapine. After 10days of treatment, he developed a second episode of priapism, and olanzapine was also stopped. A cavernosal aspiration-irrigation was performed in emergency; which resulted in the partial detumescence of the penis. Two days later, and despite therapeutic abstention, the patient presented another episode of priapism. The indication of a revascularization of the corpora cavernosa was proposed, but again the patient refused the surgery. Finally, the patient was administered 400mg/day of amisulpride, with a favorable outcome. Priapism disappeared after a month with the installation of fibrosis and partial loss of erectile function. The precise mechanisms of the role of AP in the occurrence of priapism are not all known and a multifactor etiology seems the most likely. Neuromuscular hypothesis is the most mentioned, involving the blocking action of alpha1-adrenergic receptors of the corpora cavernosa for which most of AP have an affinity. The occurrence of priapism in a psychotic patient, especially during periods of decompensation, raises a number of challenges for the medical staff. First, the non-recognition by the patient of this side effect, and its potentially severe consequences. Second, the absence of link between dose and duration of AP treatment on one side, and the onset of priapism on the other, which makes it hard to predict. The third challenge is the choice and initiation of another AP. The literature reveals many cases of priapism in both conventional and atypical AP, the presence of a predisposition to this type of incident has been reported. However, few authors have focused on alternatives to provide for these patients. Amisulpride is currently the only molecule that does not have alpha-adrenergic affinity and is therefore preferred in these cases. Priapism is a rare but serious adverse event of AP medication. Informing patient about the risk of priapism would help to report it early and prevent erectile dysfunction. Switching to another AP with less alpha1-blocking properties is generally recommended.
Article
Introduction Priapism is a persistent, and often painful, penile erection, lasting more than 3 hours, not usually associated with sexual stimuli. It is a urological emergency that can cause serious complications. Drugs are responsible of the onset of 25 to 40% of cases of priapism. Several classes of medication are involved: antidepressants, antihypertensives, anticoagulants, alpha-blockers and some psychoactive substances (alcohol, cocaine, cannabis…). However, about 50% of drug related priapism is due to antipsychotics (AP). Clinicians should be aware of this rare side effect because of the severity of its complications and the difficulty of its management, especially in non-stabilized psychotic patients. Case report We report a case of a 22-year-old male Moroccan patient, diagnosed with schizophrenia, who had been admitted for the first time to a psychiatric hospital for management of a psychotic episode. First, he received 15 mg per day of haloperidol, and seven days later he developed priapism. The patient was immediately referred for urological care. Aspiration and irrigation of the corpora cavernosa was proposed, but could not be performed because of patient refusal, and the erection resolved spontaneously after 10 hours. Haloperidol was stopped, and four days later the patient was switched to 10 mg per day of olanzapine. After 10 days of treatment, he developed a second episode of priapism, and olanzapine was also stopped. A cavernosal aspiration-irrigation was performed in emergency; which resulted in the partial detumescence of the penis. Two days later, and despite therapeutic abstention, the patient presented another episode of priapism. The indication of a revascularization of the corpora cavernosa was proposed, but again the patient refused the surgery. Finally, the patient was administered 400 mg/day of amisulpride, with a favorable outcome. Priapism disappeared after a month with the installation of fibrosis and partial loss of erectile function. Discussion The precise mechanisms of the role of AP in the occurrence of priapism are not all known and a multifactor etiology seems the most likely. Neuromuscular hypothesis is the most mentioned, involving the blocking action of alpha1-adrenergic receptors of the corpora cavernosa for which most of AP have an affinity. The occurrence of priapism in a psychotic patient, especially during periods of decompensation, raises a number of challenges for the medical staff. First, the non-recognition by the patient of this side effect, and its potentially severe consequences. Second, the absence of link between dose and duration of AP treatment on one side, and the onset of priapism on the other, which makes it hard to predict. The third challenge is the choice and initiation of another AP. The literature reveals many cases of priapism in both conventional and atypical AP, the presence of a predisposition to this type of incident has been reported. However, few authors have focused on alternatives to provide for these patients. Amisulpride is currently the only molecule that does not have alpha-adrenergic affinity and is therefore preferred in these cases. Conclusion Priapism is a rare but serious adverse event of AP medication. Informing patient about the risk of priapism would help to report it early and prevent erectile dysfunction. Switching to another AP with less alpha1-blocking properties is generally recommended.