Trazodone & Priapism: Earning the Nickname TrazoBONE

Trazodone is a serotonin receptor antagonist and reuptake inhibitor (SARI) that is used primarily for the treatment of major depression.

It is also utilized as an off-label treatment for anxiety disorders (e.g. generalized anxiety disorder; panic disorder; PTSD; OCD) and sleep disorders (e.g. insomnia).

Although trazodone is an extremely effective drug for various medical conditions – one concern prospective trazodone users have is the well-documented adverse reaction of priapism.

Table of Contents

What is priapism?

Priapism is a urologic emergency characterized by abnormal, prolonged, painful erection of the penis that is unrelated to sexual stimulation.

Though definition specifics vary, any erection lasting 4+ hours is generally regarded as priapism.

Early intervention is essential for the recovery of erectile function in priapism patients.

If priapism is left untreated, penile corporal tissue necrosis and eventually fibrosis occur along with permanent erectile dysfunction.

The etiology of priapism can be categorized as “low flow” (ischemic) or high-flow (non-ischemic) – with the former being more common than the latter. (Flow = arterial flow).

The incidence rate of priapism in the general population has been reported at 1.5 in 10,000. (R)

How often does trazodone cause priapism? (Prevalence)

The exact occurrence of trazodone-induced priapism remains somewhat unclear, however, it is generally considered a rare, infrequent side effect.

Shah et al. (2021): “Priapism is considered as an adverse effect occurring in less than 1% of patients on trazodone.” (R)

Haria et al. (1994): Reported an incidence rate of 1/1,000 (0.1%) to 1/10,000 (0.01%) for trazodone-induced priapism in males. (R)

Some medical doctors believe the incidence rate may be higher than what’s reported in the literature and have appropriately nicknamed this drug “TrazoBONE.”

How does trazodone cause priapism? (Mechanisms)

Trazodone-induced priapism is almost always associated with low flow (ischemic) pathology and is currently hypothesized to be caused by alpha-1 adrenergic receptor antagonism.

Alpha-1 adrenergic antagonism within the corpora cavernosa inhibits detumescence. (R1, R2)

During REM (rapid eye movement) sleep spontaneous erectile activity typically occurs – and trazodone administration seems to prolong this by 2.4-fold the duration. (R)

In vitro research found that trazodone concentrations akin to those achieved in plasma with treatment considerably alter corporeal smooth muscle contractions resulting from stimulation of adrenergic nerves (antagonizing norepinephrine-induced contractions).

Research suggests that trazodone reduces local sympathetic tone substantially relative to local parasympathetic tone – thus increasing susceptibility to priapism. (R)

The local action of trazodone (specifically within the penis) is likely responsible for priapism occurring. (R)

What are the signs & symptoms of trazodone priapism?

Trazodone induces low flow (ischemic) priapism – and may have various signs/symptoms.

Evaluation of priapism starts with a thorough and complete history and physical examination performed by a medical doctor (MD).

If the underlying cause(s) of priapism cannot be determined based on history and physical exam – then penile hemodynamics and intracorporeal blood gasses require evaluation. (R)

Prolonged erection in males (or clitoral engorgement in females)
Pain in the penile area (or clitoral area in females)
Rigid & fully erect corpora cavernosa
Tenderness of the penile region
Glans soft or partially engorged but not rigid
Aspirated corporal blood gas: pH = 7 (or <7.2), pO2 < 30 mmHg, pCO2 > 60 mmHg
Gangrene (rare and extreme cases resulting from necrosis)

Note: High-flow (non-ischemic) priapism will present with different signs/symptoms than low-flow priapism. Evidence seems to suggest that trazodone exclusively causes low-flow priapism.

Trazodone & Priapism (Research)

Included below are studies, papers, and case reports in which priapism associated with trazodone was mentioned or discussed.

2021: Pretreatment screening & counseling on prolonged erections in trazodone users (R)

Shah et al.

Researchers examined whether patients are properly screened for previous prolonged erections of priapism and/or informed of trazodone complications (e.g. priapism) prior to trazodone treatment.
Patients under the age of 50 who use trazodone were identified via a specific healthcare system – yielding a total of 524 patients. 229/524 agreed to participate in the study.
43/229 (18.77%) patients were informed of priapism risk prior to treatment.
Only 17/229 (7.4%) patients were asked if they had episodes of priapism before starting trazodone.
18/229 (7.86%) patients developed prolonged erection while taking trazodone.
5/18 (27.77%) with trazodone-induced priapism informed their physicians.

Conclusion: Only a fraction of patients were properly screened for prior priapism and properly informed about this trazodone side effect. Urologists need to better educate trazodone prescribers regarding this side effect. Prescribing physicians need to do a better job of screening and educating patients of trazodone-induced priapism before starting treatment.

2012: Priapism lasting 19 hours from combined use of trazodone & mirtazapine (R)

Sharma (MD)

41-year-old single African-American man with hypertension, allergic rhinitis, primary insomnia – but no history of other medical conditions.
Tolerated trazodone 200 mg per night for at least 8 months – but discontinued due to personal preference.
Reinstated trazodone 100 mg per night ~13 months after initially stopping to help with sleep – in addition to ongoing mirtazapine therapy (mirtazapine dosage not reported).
Presented to ER with persistent and painful erection that lasted ~15 hours following his first dose of trazodone (100 mg).
Urology treated this individual with terbutaline 7.5 mg in 2 doses separated by 15 minutes.
- This caused less penile throbbing but he continued to report 10/10-level pain.
- Pharmacy recommended not giving a third dose of terbutaline.
Intracorporeal aspiration and irrigations with saline and 1000 ug/mL phenylephrine solution were performed – possibly followed by creation of corporeal-spongiosal shunt through glans under anesthesia.
- These procedures helped remove the clot, which completely resolved this individuals priapism and priapism-related pain.
Morphine and saline (intravenous) were continued for 24 hours post-procedure, followed by eventual discharge from the hospital in stable condition.
Patient was advised to avoid trazodone in the future.

2010: Penile amputation after trazodone-induced priapism (R)

35-year-old white male admitted to ER with priapism lasting 15 hours.
Clinical interview didn’t reveal prior episodes of priapism, substance abuse, or genital trauma.
Clinical history: Deep vein thrombosis (episode) & pulmonary embolism (at age 21) – causes of these remained unknown.
Patient was being treated with antivitamin K anticoagulant medication (acenocoumarol) which resulted in a higher international normalized ratio of 3.8 (reference range: 0.8-1.2).
Aspirated blood from the corpus cavernosum was submitted for blood/gas testing and was consistent with ischemic priapism.
Winter shunting procedure was performed and complete remission of priapism was obtained and the patient was discharged within 3 days.
Unfortunately, the patient did NOT inform the medical doctors about his use of trazodone – which had been prescribed by a psychiatrist for a sleep disorder.
The patient was readmitted 10 days thereafter for priapism lasting 4 hours – and mentioned in this clinical interview that he had been taking trazodone (150-300 mg/night) for 3 weeks.
Treatment consisted of: new shunting, an incision at the corpus cavernous and spongious, and anticoagulant therapy with an INR at 12.
The patient exhibited persistent thrombosis and 48-hours later exhibited dry necrosis of the glans.
After 3 weeks of conservative treatment – amputation of the penis with perineostomy was performed.
Though there were risk factors for priapism in this patient: deep venous thrombosis, genotype heterozygote mutation (R506Q for Leiden V factor) – priapism did NOT occur prior to the use of trazodone.

2002: Priapism associated with trazodone in an adolescent (R)

Kem et al.

13-year-old white male with autism and moderate retardation presented to doctors.
Due to having depression and insomnia, the patient received both sertraline (50 mg/morning) and trazodone (50 mg/night) for symptom management.
After 8 months, the patient exhibited more sleep problems and trazodone dosage was increased to 100 mg/night.
About 5 months after the trazodone dosage increase, the patient woke up to a painful and sustained erection – and he reported intense pain to his parents such that they called a medical doctor.
Trazodone was discontinued and the patient’s priapism spontaneously subsided ~12 hours after the report.

2005: Safety of Trazodone as a Sleep Agent for Inpatients (R)

Jayaram & Rao present a case of trazodone-induced priapism.

42-year-old African American male presented to ER with suicidal ideation and auditory hallucinations – and his family history included alcohol and cocaine use.
His personal history included prolonged depressive episodes accompanied by psychotic symptoms when using cocaine.
At presentation, the patient reported nightmares from trazodone and admitted to using cocaine within a week of presentation (~0.5 grams per week) – as well as alcohol and marijuana.
The patient was treated with fluoxetine (20 mg/day) and olanzapine (2.5 mg/night) but still struggled to get adequate sleep and thus he received a trazodone prescription.
4 hours after his first dose of trazodone (100 mg) – the patient noticed a persistent and painful erection but didn’t tell the nurse due to embarrassment.
Once the pain became unbearable he informed the nurse and a urological team was assembled for treatment.
The priapism was successfully treated with saline irrigation and phenylephrine under local analgesia and normal tumescence was achieved by the following day.

2000: Trazodone-induced priapism (R)

Gomez et al.

41-year-old patient with a history of appendectomy was diagnosed with depression and treated with trazodone (100 mg/night).
In January 1997 the patient presented to the ER with priapism lasting 72 hours which didn’t subside with anti-inflammatory and muscle relaxant treatment.
During the 6 months of trazodone treatment (prior to priapism onset) the patient claimed to have had one episode of prolonged erection that went away on its own.
Patient was diagnosed with low flow priapism and received local injection of methoxamine in 3 doses followed by adrenaline with neither achieving detumescence.
A cavernous-spongiosum fistula was performed at the glans level and a saphenous-cavernous fistula was made using the Grayhack technique to achieve detumescence.
The patient reported erectile dysfunction and fibrosis in the penile root – and surgical closure of the saphenous-cavernous fistula was decided and the patient required a prosthesis.

1993: Priapism of the clitoris following trazodone use (R)

Pescatori et al.

34-year-old white female presented to a psychiatrist in November 1990.
Medical history: Alcohol and drug abuse & family history of depression.
Patient was prescribed: fluoxetine (40 mg/day) – and had taken this for 10 months but complained of fluoxetine-induced insomnia.
Trazodone was prescribed to counteract the fluoxetine-induced insomnia – initially at a dose of 25 mg/night for 2 days then 50 mg/night thereafter. Fluoxetine dose was simultaneously reduced to 20 mg/day.
5 days after starting trazodone, the patient complained of new-onset irritation and itch-like discomfort in the clitoral region.
The patient reported: pain, discomfort, erection, reddening, distention – in the clitoris.
A gynecologist examined this patient and diagnosed clitoral priapism characterized by tenderness, firmness, and engorgement.
Treatment included: (1) Discontinuation of trazodone and fluoxetine & (2) alpha-agonist (phenylpropanolamine/guaifenesin, b.i.d.) administration.
24 hours after these treatments the clitoral discomfort and erection resolved – and treatment was continued for an additional 24 hours.
Patient continues to do well at 13-month follow-up appointment with normalization of clitoral function.

Authors noted that as of this publication, a total of 10 cases of clitoral erection associated with trazodone use have been reported to the manufacturers over an 8-year period.

1990: Pharmacological priapism: Trazodone vs. Papaverine (R)

Bardin & Krieger

Reported priapism in 3 men undergoing treatment with trazodone for depression.
Each patient experienced priapism within the first month of trazodone treatment initiation.
The daily dosage of trazodone in these priapism cases ranged from 200-300 mg/day.
Erections had been present for 13 hours, 24 hours, and 36 hours – respectively – prior to treatment.
Each patient underwent aspiration and irrigation treatment with saline until detumescence was achieved – but priapism recurred rapidly.
Shunting procedures were required in all 3 patients using the “Winter technique” and detumescence was achieved in 2/3 cases with the third patient requiring the El Ghorab technique.

These findings indicate that trazodone-induced trazodone may be difficult to treat – particularly in patients taking high doses (200-300 mg/day).

1988: Trazodone-induced priapism (R)

Hanno et al.

The Division of Urology at University of Pennsylvania Hospital reported a case of trazodone-induced priapism.

38-year-old male admitted to ER with painful, prolonged erection lasting ~48 hours.
Patient had recently fractured arm and began taking trazodone (50 mg/night) for insomnia – but had no history of priapism or risk factors for priapism.
On the third day of trazodone treatment the patient developed a sustained erection lasting ~3 hours and he stopped the drug for 3 days.
He reinstated treatment with trazodone (50 mg/night) after the 3-day hiatus and awoke with an erection that led to his ER admission.
A cavernosal-spongiosum shunt was performed – and it was presumably effective as a treatment because the authors didn’t elaborate and patient didn’t return for follow-up.

Hanno et al. stated that 22 cases of trazodone-induced priapism were documented from 1982-1988 in the medical literature.

1988: Priapism associated with trazodone therapy (R)

Carson & Mino

The Division of Urologic Surgery at Duke University Medical Center reported 2 cases of priapism and prolonged erection associated with trazodone.

Case #1

39-year-old white male in the ER with symptoms of painful erection for 31 hours.
No history of prolonged erections, priapism, or genitourinary surgery, or other major medical problems.
Patient had been using trazodone for the treatment of mild depression for ~3 weeks.
Initial dose was 200 mg/night but was increased to 600 mg/night – and he had used the higher dose for ~72 hours prior to priapism onset.
Treatment included: analgesics (morphine); sedatives (diazepam); corpora cavernosa irrigation (1 to 100,000 norepinephrine); Al-Ghorab corpus cavernosum-to-corpus songiosum shunt; post-operative compression.
Dark viscous clotted blood was seen within the corporeal bodies after opening the corpus cavernosum.
Priapism resolved within 4 days of the treatment but patient remained impotent at an 8-week follow-up appointment.

Case #2

34-year-old white male engineer presented with a 48-hour history of swelling and pain at the base of the penis and prolonged erection.
Patient had been seen by his local physician 14 days prior for symptoms of depression, sleeplessness, and anxiety.
Trazodone was prescribed (initial dose: 50 mg, b.i.d. – followed by 100 mg, b.i.d. ~48 hours before the pain onset).
Distention of the corpora cavernosa bilaterally was observed – indicative of priapism.
Treatment included: expectant treatment; bed rest; cold compresses; analgesics (meperidine); sedatives (diazepam); aspiration of the corpora cavernosa and irrigation with 25 mL of a 1 to 100,0000 norepinephrine solution).
During the next 3 hours the erection began to soften and discomfort significantly improved.
Conservative treatment with expectant therapy was continued and priapism completely resolved within ~24 hours.

It was stated that priapism should be considered a serious side effect of trazodone and that prolonged erections should be rapidly treated with injection of norepinephrine or dopamine within the corpus cavernosum to resolve the prolonged erection before priapism develops.

1985: Trazodone & Priapism (R)

Raskin

40-year-old white male diagnosed with dysthymic disorder and had sleep problems – was prescribed trazodone.
Patient had no history of urological conditions, drug abuse, or physical disease.
Patient started trazodone at 50 mg/day and increased the dosage by 50 mg every 3 days until a dose of 300 mg/day was reached.
After his very first dose of trazodone (50 mg/night) the patient awoke in the morning with a painful erection which subsided after ~15 minutes.
The patient informed his doctor and he was told to discontinue trazodone.

Raskin concluded that even low doses of trazodone can cause changes in erectile function.

Raskin suggested that doctors prescribe a low dose of trazodone (50 mg/night) for a few nights and have the patient report whether they experience any changes in erectile function, morning erections, etc.

He believes by starting with a low dose and communicating with patients, it may be possible to identify and prevent patients at risk for trazodone-induced priapism before it occurs.

1984: Priapism associated with trazodone therapy (R)

Lansky & Selzer documented a case of priapism associated with trazodone in which the priapism spontaneously resolved after ~4 hours with subsequent potency unaffected.

1983: Trazodone & Priapism (R)

Scher et al.

It was noted that between March 1982 and this publication in 1983 – a total of 11 cases of priapism (5 which required surgical procedures) occurred in trazodone users.

Authors discuss a patient with trazodone-induced priapism in this case report.

45-year-old male presented to the ER with “pain and a bearing down sensation” in his rectum.
Further questioning revealed a persistent erection lasting 24-28 hours and that he initiated trazodone ~7 days prior at a dose of 100 mg/night.
He discontinued trazodone when the erections began thinking that it could be a side effect.
The patient was diagnosed with priapism and underwent initial treatment with: diazepam, saline enema, morphine, nitroprusside drip, and anesthesia with no relief.
Phenylephrine infusion, physostigmine/ketamine infusion, blood-pressure reduction procedures, and anesthesia all yielded no significant improvement.
Corpora cavernosa with heparinized saline induced detumescence and a shunt was performed to maintain drainage.
A few days after these procedures, the priapism returned but then gradually resolved.
This patient had zero risk factors for priapism other than trazodone use.

What can we learn from research of trazodone & priapism?

Many patients are not properly informed of priapism as a side effect of trazodone – or told what to do if it occurs (e.g. seek urgent medical care).

Many patients with preexisting risk factors for priapism are not properly screened by medical doctors prior to the prescribing of trazodone.

Many patients who experience priapism from trazodone may not recognize priapism as a serious side effect of trazodone and/or may not attribute this reaction to trazodone – and thus delay medical treatment.

Certain medical conditions (e.g. clotting & coagulation disorders) may increase risk and/or severity of trazodone-induced priapism.

Combining trazodone with other medications may increase risk of priapism relative to trazodone monotherapy.

Trazodone-induced priapism seems to occur within the initial 1-4 weeks of use for most individuals but can also occur after many months of consistent, fixed-dose use.

Trazodone-induced priapism can occur at any dosage – regardless of whether low or high.

Trazodone-induced priapism can occur in individuals with no risk factors for priapism (e.g. history of priapism) and in patients of all ages.

How is trazodone-induced priapism treated?

Trazodone-induced priapism is classified as “low flow” (i.e. ischemic) priapism and treated in accordance with this presentation.

Ischemic priapism is considered a true emergency and requires medical treatment as soon as possible to decrease odds of irreversible corporal damage and permanent erectile dysfunction.

The goal is to achieving detumescence (i.e. reduced penile tension).

Trazodone discontinuation

This should be obvious but if trazodone is being used it should be discontinued.

Any other substances (drugs and/or supplements) that have potential to cause and/or exacerbate preexisting priapism should also be stopped.

Basically all substances (drugs and/or supplements) should be discontinued on the basis that they may cause or exacerbate priapism and/or interfere with priapism treatment.

Oral therapies

Oral therapies are often administered while a patient awaits appropriate medical equipment and supplies that are necessary to effectively treat priapism.

The success rate of oral therapies is generally low (~25%) for the treatment of priapism, resulting in the need to perform emergency corporal aspiration of blood, saline irrigation, and intracavernous injections.

Pseudoephedrine: Some medical doctors may administer pseudoephedrine (60-120 mg) – an adrenoreceptor agonist & decongestant. It is considered potentially useful on the basis that it acts as an alpha receptor agonist (which may counteract the alpha antagonism of trazodone).
Terbutaline: Some medical doctors may opt to administer terbutaline (a beta-adrenoreceptor agonist) at a dose of 5-10 mg followed by another 5-10 mg ~15 minutes later. In patients with prostaglandin-induced priapism it works in about 36% of cases – but is considered to have suboptimal efficacy according to the American Urological Association. (R)

Overall, oral therapies are not very effective for priapism in part because priapism occurs locally and oral therapies probably won’t deliver sufficient quantities of these drugs to the penile (or clitoral) region to reverse the low flow (ischemic) effect.

Nonetheless, oral therapies are probably worth trying as a quick first-line therapy while preparing for more invasive treatment methods. There’s a chance they might help and/or work as an adjunct along with invasive interventions.

Aspiration & saline irrigation

These are recommended as the first-line treatment for priapism – and are typically performed by a urologist.

A dorsal penile block prior to these interventions is recommended to reduce patient discomfort.
A large diameter needle, butterfly, or angiocath (19 gauge or larger) are inserted at either the 2 o’clock or 10 o’clock position on the penis near the base while controlling the shaft.
Around 20-30 mL are aspirated and the color of blood is generally noted.
Irrigation with saline or diluted sympathomimetic agents should also be performed.

Aspiration as a standalone intervention is effective in about 1/3 patients (~33%) – therefore it should be combined with other treatments.

Aspiration plus saline irrigation achieves detumescence in ~66% of patients. (R)

After several rounds of aspiration plus saline irrigation – blood turns bright red which indicates increased oxygenation.

Reoxygenation of the corpora improves responsiveness to injections with sympathomimetic agents.

Intracavernosal drug therapy

This is the second-line intervention for most cases of priapism.

Various sympathomimetic agents can be used for intracorporeal injection, however, phenylephrine is most commonly used and recommended for its efficacy and safety. (R)

The phenylephrine is diluted with normal saline prior to injection and then injected every 3-5 minutes for up to 60 minutes or until complete detumescence is achieved. (R)

Sympathomimetic agents can cause some side effects such as heart palpitations, dizziness, headache, etc.

When combined with aspiration and irrigation, the success rate of diluted phenylephrine injections is estimated to be ~81%. (R)

Surgery

If both first-line (aspiration & saline irrigation) and second-line (intracavernosal drug therapy) interventions fail to treat the priapism for ~16 hours, emergency surgery is performed.

Surgery for priapism typically involves shunt procedures to reduce corporal pressures, drainage, and penile pain.

Shunts: Create a fistula between the corpora cavernosa and corpora spongiosum which retains venous drainage. Occasionally several shunts are required. All shunt procedures have roughly equal rates of efficacy in resolving priapism.

Corporal snake maneuver: A specific maneuver involving a probe getting inserted into a shunt opening into the glans and corpora cavernosa to reach the crura to create a pathway for drainage.

Penoscrotal decompression: Suggested to be an alternative to shunting procedure and bypasses trauma to the glans and distal corpora. The corpora are opened enough to allow a suction to enter then it is advanced to remove debris and thrombus. Has shown high efficacy in cases of prolonged priapism. (R)

Amputation

In the event that no first-line (aspiration & irrigation), second-line (intracavernosal drug therapy), or third-line (surgical) interventions prove effective for the treatment of trazodone-induced priapism – penile necrosis may ensue.

Necrosis of penile tissue may require amputation wherein you permanently lose your penis. (This has been documented in the medical literature in a trazodone user who experienced recurrent bouts of priapism without stopping trazodone).

Risk factors for priapism on trazodone

Included below are some hypothesized risk factors associated with trazodone-induced priapism.

Male sex

Although trazodone can cause priapism in both males and females – the severity of priapism in males is generally significantly more problematic due to sex-specific anatomical differences.

Duration of trazodone use

The duration of trazodone use may influence the likelihood of trazodone-induced priapism.

Short-term use: Early research from 1987 stated that trazodone-induced priapism is most common within the first 28 days of treatment. (R)

Long-term use: Various case reports document trazodone-induced priapism after 6+ months of treatment without a change in dosage or concomitant medications and medical status.

Based on everything I’ve read, it seems as though many people affected by trazodone-induced priapism will notice it within the first 4 weeks (1 month) of treatment.

However, because trazodone-induced priapism can occur at any time, patients should be informed to remain vigilant of this adverse reaction – regardless of how long they’ve used trazodone.

Trazodone dosage

Trazodone can cause priapism at any dosage – but likelihood of priapism probably increases with higher dosages.

Early research reported that trazodone-induced priapism commonly occurs in patients taking doses of 150 mg/day or less. (R)

This finding probably indicates that most patients using trazodone are taking 150 mg/day or less – such that a higher percentage of priapism cases involve lower doses.

This finding should not be assumed to suggest that incidence rates of priapism are lower at higher trazodone dosages.

Numerous case reports I’ve read reported priapism onset only after increasing the trazodone dosage – indicating that priapism risk is probably greater with higher trazodone dosages.

This makes logical sense given that: (1) plasma concentrations of trazodone will be greater at higher dosages and (2) the magnitude of alpha-1 receptor antagonism would be greater at higher trazodone dosages (vs. lower dosages).

Priapism risk factors (Individual)

Using other substances: Use of other substances (OTC or illicit drugs, supplements, medications) with trazodone may increase risk of priapism – particularly if those substances themselves are capable of inducing priapism. Substances that exacerbate alpha adrenergic receptor antagonism associated with trazodone may be particularly problematic.
History of priapism: Individuals with a history of priapism (regardless of underlying etiology) may be at increased risk of developing priapism on trazodone.
Certain medical conditions: Certain medical conditions may increase risk of trazodone-induced priapism via physiological synergism. Clotting disorders or coagulopathy; multiple myeloma; sickle cell anemia; leukemia; autonomic dysfunction; penile anatomic variations (e.g. cavernosal fibrosis, angulation, Peyronie’s disease).
Genetics: There may be certain genetic variants that increase/decrease risk of priapism. Individuals with specific gene combinations may be at increased risk of trazodone-induced priapism.

How to reduce risk of priapism with trazodone… (Ideas)

Included below are hypothetical strategies for reducing risk of priapism from trazodone – and/or severity of priapism in the event that it occurs.

Note: Patients with a history of priapism or risk factors for priapism should probably avoid trazodone altogether. It is important that medical providers screen patients for these risk factors prior to considering trazodone.

Start with a low dose

Since trazodone-induced priapism may occur more often in the first 30 days of treatment, patients and medical doctors should be particularly vigilant in this initiation period.

Raskin believes that patients should start with a dose of ~50 mg/night for at least several nights – and patients should monitor for any changes in penile appearance and/or function (e.g. morning erections, prolonged erections, changes in erectile function). (R)

I agree with Raskin and think that it’s best to play it safe with a low dose.

If erections are noticed, stopping trazodone should be advised – and patients should seek urgent urological examination to rule out and/or treat priapism.

A low dose essentially means lower levels of trazodone acting as an alpha-adrenergic receptor antagonist within the penile region – such that the significance of blood flow change should be less relative to higher doses… this increases odds of recovery with prompt recognition and treatment.

Use the lowest effective dose

In addition to careful monitoring of erectile function while taking a low initial dose, patients should utilize the lowest effective dose of trazodone to effectively treat their specific medical condition(s).

Case reports indicate that while priapism can occur at any trazodone dose, those who tolerated a low dose without this reaction may end up developing priapism with dosage increases.

It makes logical sense that dosage increases and higher doses would be more likely to induce priapism based on the fact that there’s more of the drug in systemic circulation and a stronger alpha receptor antagonistic effect (relative to lower doses).

Avoid other substances (especially if linked to priapism)

It is probably a good idea to avoid any substances associated with induction of priapism – or that might increase risk of developing priapism.

For example, combining trazodone with additional psychotropic medications (e.g. antipsychotics) may exacerbate priapism risk due to potentiation of alpha adrenergic receptor antagonism.

Remain vigilant (regardless of dose & duration of use)

Patients should be encouraged to remain vigilant of prolonged erections (priapism) while using trazodone regardless of their dosing and duration of use.

Although priapism may be less likely to occur in long-term, fixed-dose users – it can emerge at any time and the specific reasons certain people develop it while on trazodone remain relatively unclear.

What should you do if priapism occurs on trazodone?

Stop trazodone treatment immediately. The last thing you want to do if priapism occurs is continue taking trazodone – as this may exacerbate the preexisting priapism and make the priapism less likely to respond to treatment.

Seek emergency medical care. Do NOT take a “wait and see” approach with priapism. Seek emergency medical care as soon as the priapism is noticed – do not think twice or hesitate (or this could result in amputation). Do NOT be embarrassed to report this – as doctors will be familiar with it. Tell the doctors every single medication, drug, and supplement you take.

Follow urological instruction. Follow whatever advice the urologist gives for managing the priapism upon discharge. This will increase likelihood that functional ability (e.g. erectile function) recovers and/or priapism doesn’t recur. If necessary, make follow-up appointments.

Can women experience priapism with trazodone?

Yes. Priapism of the clitoris has been documented with trazodone use.

In the clitoral corpora cavernosa, priapism usually only occurs from malignancy, but I found 1 case report in which a female developed clitoral priapism from trazodone.

The pathophysiology of trazodone-induced clitoral priapism is thought to involve extravascular veno-occlusive mechanisms.

Should you be concerned about priapism from trazodone?

Yes. Everyone who uses trazodone should be informed of this potential side effect.

Failure to recognize and treat priapism in a timely manner may result in chronic penile or clitoral dysfunction and/or penile amputation.

All medical doctors should inform trazodone users of this potential side effect – and all patients should due their due diligence and understand this potential side effect so that it can be promptly recognized and treated in the event it occurs.

Should you avoid trazodone because of the priapism risk?

This is a personal decision. The prevalence of priapism among trazodone users is generally considered low, however, it is up to you to decide whether you’re willing to take on this risk.

Some people have a low risk tolerance such that they avoid trazodone altogether in fear of potential priapism – even when priapism likelihood is low and efficacy of trazodone for a particular medical condition would be high.

Keep in mind that even if you were to develop priapism – as long as you seek urgent medical care, odds are good that you’ll make a full recovery back to normal (although it might take a bit of time).

Interestingly some may actually like trazodone on the basis that it may help with impotence (a physician self-treated his impotence with trazodone). (R)

Can priapism suddenly occur after long-term trazodone use?

Yes. Priapism is a risk regardless of how long you’ve been using trazodone without issues.

I would hypothesize that dosage increases over time (for whatever reason) could cause priapism in those who’d previously used trazodone for a long-term without priapism.

Additionally, it’s possible that priapism may emerge after a long-term with fixed-dosing (and no dosing adjustments) as a result of: aging, long-term physiologic changes, altering drug/supplement regimen, environmental changes, epigenetic shifts, etc.

My thoughts on trazodone & priapism

As of 2022, I personally think that trazodone is likely among the best interventions for insomnia and sleep enhancement for a variety of reasons.

Although it is technically “off-label” for sleep – trazodone effectively induces and maintains sleep without causing daytime drowsiness or tolerance, making it a superior intervention [in many cases] to nonbenzodiazepine sleep aids. (R)

Trazodone may simultaneously treat depression, anxiety disorders, and sleep disturbances – such that combining medications (e.g. antidepressant + anxiolytic + hypnotic) becomes less necessary or unnecessary.

However, because I’m extremely risk-averse, I do not personally elect to use trazodone – as I fear any risk of priapism and hypothesize that priapism rates associated trazodone may be underestimated in the scientific literature.

What are your thoughts re: trazodone & priapism?

Have you considered this side effect before using trazodone?
Does this side effect scare you away from considering trazodone?
Have you experienced priapism from trazodone? (If so, what were the signs/symptoms and what was the outcome? Did penile function eventually normalize?)
Do you know someone who experienced priapism from trazodone? (What was the aftermath?)