ArticleLiterature Review

A Review of Antipsychotics and Priapism

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Introduction Pharmacologically induced priapism is now the most common cause of priapism, with approximately 50% of drug-related priapism being attributed to antipsychotic usage. The majority of pharmacologic priapism is believed to result in ischemic priapism (low flow), which may lead to irreversible complications, such as erectile dysfunction. It is imperative that prescribing physicians be aware of potentially inciting medications. Objectives To identify medications, specifically antipsychotics, associated with priapism and prolonged erections and understand the rates and treatment of these side effects. Methods A PubMed search of all articles available on the database relating to priapism, prolonged erections, and antipsychotics was performed. Results Various typical and atypical antipsychotic drugs (APDs) have been implicated in pharmacologically induced priapism. In addition to dopaminergic and serotoninergic receptors, APDs have affinities for a wide array of other receptors in the central nervous system, including histaminergic, noradrenergic, and cholinergic receptors. Although the exact mechanism is unknown, the most commonly proposed mechanism of priapism associated with APDs is α-adrenergic blockade in the corpora cavernosa of the penis. Priapism appears in only a small fraction of men using medications with α1-receptor–blocking properties, indicating differential sensitivities to the α-blocking effect among men, and/or additional risk factors that may contribute to the development of priapism. The best predictor for the subsequent development of priapism is a past history of having prolonged and painless erections. The acute management algorithm of APD-induced priapism is the same as for other causes of low-flow priapism. Conclusion Clinicians should educate patients treated with antipsychotics about the potential for priapism and its sequelae including permanent erectile dysfunction. Appropriate patient education will raise awareness, encourage early reporting, and help reduce the long-term consequences associated with priapism through early intervention. Hwang T, Shah T, Sadeghi-Nejad H. A Review of Antipsychotics and Priapism. Sex Med Rev 2020;XX:XXX–XXX.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... "stuttering priapism") shares its aetiology with ischaemic priapism and frequently progresses to a complete form [1]. Although idiopathic episodes of priapism are common, pharmacologically-induced priapism is now considered the predominant aetiology [6]. In fact, priapism has been related to a number of commonly prescribed medications, as well as illegal drugs [1]. ...
... 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]. ...
... Drug-induced priapism is associated with the low-flow mechanism, which is secondary to an inadequate corporal venous outflow [1]. Some antipsychotics and the antidepressant trazodone may cause priapism due to their high-affinity antagonism for the a1and a2-adrenergic receptors [6]. The overall result of this a-adrenergic blockage is a shift of the penile vascular equilibrium into the direction of prolonged erection/intracavernosal stasis. ...
Article
Full-text available
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.
... Its etiology includes hematologic disorders, history of medication use (α-Adrenergic receptor antagonists, anticoagulants, antidepressants, antipsychotics, antihypertensive drugs, hormones, vasoactive drugs), malignancies and neurological disorders. 3,4 Main objective of the treatment is rapid restoration of cavernous blood flow in order to prevent end organ damage and erectile dysfunction. Hypoxia and acidosis lead to cavernous fibrosis within four hours and focal necrosis within 24 hours and diffuse necrosis within 48 hours. ...
Article
Full-text available
A complete or partial involuntary erection that occurs in absence of a sexual stimulation and lasts longer than four hours is defined as priapism. Etiology usually includes sickle cell disease or hematologic malignancies. Less common causes include trauma, spinal cord injury, medications, congenital syphilis, parotitis, Fabry’s disease and retroperitoneal sarcoma. Priapism is a urologic emergency that varies by ischemic and non-ischemic episodes. Ischemic injury to cavernous tissues leads to erectile dysfunction. Early recognition of priapism, determination of the type and the treatment are crucial in preventing potential long-term complications caused by priapism. With this case of priapism caused by a treatment with valproic acid, it was aimed to point out priapism which is a urologic emergency.
Article
6R‐L‐erythro‐5,6,7,8‐tetrahydrobiopterin (BH4) is an essential cofactor for aromatic L‐amino acid hydroxylases, including tyrosine hydroxylase (TH), alkylglycerol monooxygenase and three types of nitric oxide synthases (NOS). Sepiapterin reductase (SPR) catalyzes the third step of BH4 biosynthesis. SPR gene‐disrupted (Spr‐/‐) mice exhibit a dystonic posture, low body weight, hyperphenylalaninemia, and unstable hypertension with endothelial dysfunction. In this study, we found that Spr‐/‐ mice suffered from a high incidence of severe priapism. Their erections persisted for months. The biopterin, BH4 and norepinephrine contents, and TH protein levels in the penile tissue of Spr‐/‐ mice without and with priapism were significantly reduced compared to those of Spr+/+ mice. In contrast, their neural NOS (nNOS) protein levels were increased and the cyclic guanosine monophosphate (cGMP) levels were remarkably elevated in the penises of Spr‐/‐ mice with priapism. The symptoms were relieved by repeated administration of BH4. The biopterin, BH4 and norepinephrine contents were increased in penile homogenates from BH4‐supplemented Spr‐/‐ mice, and the TH protein levels tended to increase, and their nitrite plus nitrate levels were significantly lower than those of vehicle‐treated Spr‐/‐ mice and were approximately the same as vehicle‐ and BH4‐supplemented Spr+/+ mice. Thus, we deduced that the priapism of Spr‐/‐ mice is primarily caused by hypofunction of the sympathetic neurons due to cofactor depletion and the loss of TH protein, and further, dysregulation of the NO/cGMP signaling pathway which would be caused by disinhibition of nNOS‐containing neurons and/or abnormal catabolism of cyclic nucleotides is suggested. This article is protected by copyright. All rights reserved.
Article
Full-text available
It is well established that 1 in 50 individuals receives a diagnosis of body dysmorphic disorder (BDD). Within body image disorders, there is genital retraction syndrome also known as Koro. A unique syndrome in which there is a heightened belief that one’s genitals will diminish in size, retract into the abdomen and ultimately lead to death. However, we have recently discovered a separate form of BDD that is directly opposite of Koro, in which the patient presents a strong belief that his penis will enlarge and extend out of their body. We present a unique case report of a counter-Koro syndrome. This syndrome is characterized by the delusion that one’s penis is growing larger and that it will result in its extreme protrusion from the abdomen and a consequent fear of recurring and visible erections. Given its mirror-like presentation and uniqueness to occurring only in males, we refer to it as Roko Syndrome. To our knowledge, this syndrome has not yet been reported in the literature and requires further study to understand whether it fits as a separate syndrome or falls along the spectrum of body dysmorphia. Thus, assessments used to identify body image disorders can be broadened to include items representing the behavior and presentation of Roko that we delineate in comparison of Koro. The new syndrome is also easily distinguishable from a priapism which is a urological emergency.
Article
Full-text available
Background: Priapism has been linked to many commonly prescribed medications, as well as recreational drugs and toxins. Although the incidence of priapism as a result of medication is small, the increasing use of antidepressants, antipsychotics, and recreational drugs may lead to more cases of pharmacologically-induced priapism in the future. Aim: To provide a comprehensive, up-to-date review of the most common causes of pharmacologically induced priapism and discuss incidence, pathophysiology, and basic management strategies. Methods: A review of the available literature from 1960 to 2018 was performed using PubMed with regards to pharmacologically induced priapism. Main Outcome Measure: We reviewed publications that outlined incidence, pathophysiology, and management strategies for various pharmacologic causes of priapism: antidepressants, antipsychotics, antihypertensives, methylphenidate, cocaine, heparin, gonadotropin-releasing hormone, propofol, spider bites, and other miscellaneous causes. Results: An understanding of the pathophysiology behind common pharmacologic causes of priapism can assist in the development of better treatment strategies and prevent future episodes of priapism. By understanding the potential risks associated with the use of medications with α-blocking or sympathomimetic properties, physicians can reduce the likelihood of priapism in their patients, especially those with other medical conditions that put them at increased baseline risk. Early corporal aspiration and injection of phenylephrine reduces additional complications related to priapism. In select patients, early placement of a penile prosthesis may prevent further morbidity. Conclusion: By developing a greater understanding of common pharmacologic causes of priapism, physicians can promptly identify and manage symptoms, leading to decreased patient morbidity. Scherzer ND, Reddy AG, Le TV, Chernobylsky D, Hellstrom WJG. Unintended Consequences: A Review of Pharmacologically Induced Priapism. Sex Med Rev 2018;XX:XXX‒XXX.
Article
Full-text available
Background Priapism is a potentially painful and prolonged erection that occurs in the absence of any stimulation. Olanzapine has been reported to induce priapism in several adult cases with schizophrenia and/or mood disorders but very rarely reported in children. Case Report 9-year-old male with Asperger’s Syndrome (AS) referred to our clinic with the complaints of inattention, hyperactivity and impulsivity. He was diagnosed with attention deficit hyperactivity disorder (ADHD) and given methylphenidate treatment which ameliorated his ADHD symptoms. He started to have severe loss of appetite after methylphenidate treatment so olanzapine 2.5 mg/day was added to cope with severe inappetence. However he experienced priapism after olanzapine and priapism resolved after ceasing the drug. His mother restarted olanzapine because he benefited from olanzapine. But the same episodes occurred soon after olanzapine again and his mother had to stop the medication. Conclusion Because atypical antipsychotics are now widely used in children, unusual side effects such as priapism should be taken into consideration for the differential diagnosis.
Article
Full-text available
Priapism is a urologic emergency defined as a prolonged, possibly painful, penile erection. There are several known causes of priapism including psychotropic medications. One of the mechanisms by which antipsychotics are believed to induce priapism is through alpha-1 antagonism. This is case of a 50-year-old male with a history of schizophrenia with previous priapism related to trazodone, who presents with new onset priapism associated with risperidone. In this case, the treatment of priapism includes discontinuation of the offending agent and drainage of the corpus cavernosum twice along with intracavernosal phenylephrine injections. It is important to educate patients on priapism as a possible side effect of medications. It is also important to consider previous episodes of medication-induced priapism when prescribing psychotropic medications as this may increase the patient's future risk of priapism.
Article
Full-text available
Priapism is a urological emergency defined as persistent penile erection that is unrelated to sexual stimulation and typically involving only the corporal cavernosa. It can occur as a rare side effect of antipsychotic medications and is mediated via their α-adrenergic antagonist effect. In this paper we describe a case of priapism in a patient started on risperidone and sodium valproate. We also review the South London and Maudsley Case Register Interactive Search database to assess how many other cases of priapism were reported in patients taking risperidone. We add this information to a literature review of cases of priapism associated with risperidone.
Article
Full-text available
Priapism is a rare but important side effect of antipsychotic drugs which may evolve into a urological emergency. Most antipsychotic drugs are alpha-1 adrenergic antagonists, which is thought to be the principal mechanism involved in antipsychotic-induced priapism. Other aetiologies exist, however. A case is presented with multiple episodes of priapism during the use of several different antipsychotic drugs. The case is representative of many patients treated with antipsychotic drugs, as there were hyperprolactinemia, and illicit drug use, which are known causes of priapism. Moreover, the patient used combinations of antipsychotic drugs. The case thus illustrates the etiological complexity which could delay a diagnosis of antipsychotic-induced priapism, and the problem of establishing a link between priapism and one particular ingredient of a drug combination. The case presents how a treatment regimen was finally established balancing antipsychotic efficacy to acceptable side effects and offers guidance to physicians regarding how antipsychotic-induced priapism may be resolved.
Article
Full-text available
A cohort of 20 patients with delayed priapism who underwent treatment at the Emergency Department of our academic referral centers between January 2002 and April 2010 was studied. Of these, 16 cases suffered from a low-flow priapism. A total of 6 cases were managed non-surgically, 10 required shunt surgery, and of these 5 were treated by early penile prosthesis surgery. Prostheses were easily implanted in all patients with a mean operative time of 94 min. No intraoperative complications and no infection were registered. All patients with an inflatable prosthesis complained a reduction in penile sensibility that lasted 3 months. All patients were satisfied with the results of surgery (International Index of Erectile Function Questionnaire-5, Q5 mean value 4), and all were successfully engaging in satisfactory sexual intercourses. No significant loss of penile length, neither apical erosion nor extrusion was recorded. Early insertion of a penile prosthesis is a simple and safe procedure in patients with ischemic priapism, which failed to respond to conservative management. Early insertion of a prosthesis helps to maintain adequate penile length, resolve priapism and, in the long term, it results in high satisfaction rates.
Article
Full-text available
With upwards of 48% of human immunodeficiency virus (HIV)-infected persons having a probable psychiatric disorder, the possibility of cross-class drug interactions causing adverse effects or fatalities exists. This report discusses an emergent case of low-flow priapism caused by an interaction between a previously prescribed combination protease inhibitor (PI) and newly added antipsychotic medications. A 50-year-old HIV-positive man on highly active antiretroviral therapy (HAART), including the combination PI, lopinavir/ritonavir (Kaletra((R))), experienced an episode of priapism hours after beginning two new antipsychotic medications. Quetiapine (Seroquel((R))) and perphenazine (Trilafon((R))) were added to treat a diagnosed schizoaffective disorder. The patient presented to the emergency department complaining of a constant, painful erection lasting approximately 42 h. Treatment with intracavernous ephedrine, irrigation, and aspiration helped achieve detumescence. This case displays the immediate and detrimental effects due to the addition of antipsychotic medications to previously altered cytochrome P450 (CYP450) enzyme levels. The inhibition of CYP450 enzymes 3A4 and 2D6 by the combination PI, lopinavir/ritonavir, was likely the major culprit in causing greater than expected free levels of perphenazine and quetiapine resulting in priapism.
Article
Full-text available
Priapism is characterised by a persistent erection that cannot be relieved by sexual intercourse or masturbation. Although priapism subsides spontaneously in a few days, impotence frequently follows. Both vascular and neural mechanisms are implicated in the pathophysiology of priapism, but it is not clear which initiates the process. Idiopathic cases of priapism are the most frequent (near 50%); other medical conditions that can result in priapism are haematological diseases (mainly sickle cell anaemia and leukaemia), traumatism, and neoplastic processes. Drug-induced priapism comprises about 30% of cases. The drugs most frequently implicated are psychotropic drugs (phenothiazines and trazodone), antihypertensives (mainly prazosin) and heparin. Recently, the intracav-ernosal injection of vasoactive drugs (papaverine and phentolamine) has been described in patients treated for impotence. With the exception of heparin, an α-adrenergic blocking mechanism has been suggested in the priapism-inducing action of these drugs. A significant number of anecdotal case reports link priapism and drugs, and it is possible that certain cases of idiopathic priapism could be reclassified if accurate pharmacological anamnesis were to be performed. Priapism must be considered a urological emergency. Surgical procedures are the most preferred treatment for this condition but, in selected cases, drug treatment seems to be an alternative approach.
Article
Full-text available
Patients with priapism often develop permanent erectile dysfunction and personal sexual distress. This report is intended to help educate the public by reviewing the varied definitions and classifications of priapism and limited literature reports of pathophysiology, diagnosis and treatment outcomes of priapism. The AUA priapism guidelines committee is responsible for creating consensus as to appropriate individual patient management of priapism by physicians. A multidisciplinary panel, consisting of 19 thought leaders in priapism, was convened by the Sexual Function Health Council of the American Foundation for Urologic Disease to address pertinent issues concerning the role of the urologist, primary care providers and other health care professionals in the education of the public regarding management of men with priapism. The panel utilized a modified Delphi method and built upon the peer review literature on priapism. The Thought Leader Panel recommended adoption of the definition of priapism as a pathological condition of a penile erection that persists beyond or is unrelated to sexual stimulation. Priapism is stressed to be an important medical condition that requires evaluation and may require emergency management. The classification system is categorized into ischemic and non-ischemic priapism. Essential elements of the ischemic classification are the inclusion of: (i) clinical characteristics of pain and rigidity; (ii) diagnostic characteristics of absence of cavernosal arterial blood flow; (iii) pathophysiological characteristics of a closed compartment syndrome; (iv) a time limit of 4 h prior to emergent medical care; and (v) a description of the potential consequences of delayed treatment. Essential elements of the non-ischemic classification are the inclusion of: (i) clinical characteristics of absence of pain and presence of partial rigidity; (ii) diagnostic and pathophysiological characteristics of unregulated cavernosal arterial inflow; and (iii) the need for evaluation but emphasizing the lack of a medical emergency. The panel recommended adoption of a rational management algorithm for the assessment and treatment of priapism where the cornerstone of initial assessment includes a careful clinical history, a focused physical examination and selected laboratory and/or radiologic tests. The panel recommended that specific criteria and clinical profiles requiring specialist referral should be identified. The panel further recommended that patient (and partner) needs and education concerning priapism should be addressed prior to therapeutic intervention, however only in the case of chronic management or post acute presentation evaluation should this delay intervention. Treatment goals to be discussed include management of the priapism with concomitant prevention of permanent and irreversible erectile dysfunction and associated psychosocial consequences. The panel recommended that when specific therapies for priapism are required, a step-care treatment approach based upon reversibility and invasiveness should be followed. The Thought Leader Panel calls for research to expand our understanding of the prevalence and diagnosis of priapism and education to create awareness among the public of the potential urgency of this condition. Critical areas to be addressed include the multiple pathophysiologies of priapism as well as multi-institutional trials to objectively assess safety and efficacy in the various treatment modalities.
Article
Full-text available
The treatment of schizophrenia has evolved over the past half century primarily in the context of antipsychotic drug development. Although there has been significant progress resulting in the availability and use of numerous medications, these reflect three basic classes of medications (conventional (typical), atypical and dopamine partial agonist antipsychotics) all of which, despite working by varying mechanisms of actions, act principally on dopamine systems. Many of the second-generation (atypical and dopamine partial agonist) antipsychotics are believed to offer advantages over first-generation agents in the treatment for schizophrenia. However, the pharmacological properties that confer the different therapeutic effects of the new generation of antipsychotic drugs have remained elusive, and certain side effects can still impact patient health and quality of life. Moreover, the efficacy of antipsychotic drugs is limited prompting the clinical use of adjunctive pharmacy to augment the effects of treatment. In addition, the search for novel and nondopaminergic antipsychotic drugs has not been successful to date, though numerous development strategies continue to be pursued, guided by various pathophysiologic hypotheses. This article provides a brief review and critique of the current therapeutic armamentarium for treating schizophrenia and drug development strategies and theories of mechanisms of action of antipsychotics, and focuses on novel targets for therapeutic agents for future drug development.
Article
Full-text available
The objective of this study was to evaluate the relationship between compliance with an antipsychotic medication regimen and risk of hospitalization in a cohort of California Medicaid patients with schizophrenia. Compliance behavior was estimated by using a retrospective review of California Medicaid pharmacy refill and medical claims for 4,325 outpatients for whom antipsychotics were prescribed for treatment of schizophrenia from 1999 to 2001. Compliance behavior was estimated by using four different definitions: gaps in medication therapy, medication consistency and persistence, and a medication possession ratio. Patients were followed for one year and had an average of 19.1 dispensing events. Logistic regression models using each compliance estimate were used to determine the odds of hospitalization. Risk of hospitalization was significantly correlated with compliance. With all definitions, lower compliance was associated with a greater risk of hospitalization over and above any other risk factors for hospitalization. For example, the presence of any gap in medication coverage was associated with increased risk of hospitalization, including gaps as small as one to ten days (odds ratio [OR]=1.98). A gap of 11 to 30 days was associated with an OR of 2.81, and a gap of more than 30 days was associated with an OR of 3.96. This study showed a direct correlation between estimated partial compliance and hospitalization risk among patients with schizophrenia across a continuum of compliance behavior.
Article
Stuttering Priapism is a recurrent, persistent penile erection in the absence of sexual desire due to altered genital hemodynamics, affecting the arterial component (high flow, non-ischemic) or the veno-occlusive mechanism (low flow, ischemic). Both typical and atypical antipsychotics increase the risk for priapism with greater implications in typicals than atypicals. Prompt recognition and treatment are important as 40% to 50% of patients with stuttering priapism may develop an erectile dysfunction if left untreated. There are several case reports in the literature about the association between psychotropic agents and priapism. However, there are no reports of successfully treating stuttering priapism using pseudoephedrine (sudafed) in the adult population. Here we present successful management of psychotropics induced stuttering priapism with pseudoephedrine in a male patient with schizophrenia.
Article
Background: Antipsychotic-induced metabolic side effects are major concerns in psychopharmacology and clinical psychiatry. Their pathogenetic mechanisms are still not elucidated. Methods: Herein, we review the impact of neurotransmitters on metabolic regulation, providing insights into antipsychotic-induced metabolic side effects. Results: Antipsychotic drugs seem to interfere with feeding behaviors and energy balance, processes that control metabolic regulation. Reward and energy balance centers in central nervous system constitute the central level of metabolic regulation. The peripheral level consists of skeletal muscles, the liver, the pancreas, the adipose tissue and neuroendocrine connections. Neurotransmitter receptors have crucial roles in metabolic regulation and they are also targets of antipsychotic drugs. Interaction of antipsychotics with neurotransmitters could have both protective and harmful effects on metabolism. Conclusion: Emerging evidence suggests that antipsychotics have different liabilities to induce obesity, diabetes and dyslipidemia. However this diversity cannot be explained merely by drugs'pharmacodynamic profiles, highlighting the need for further research.
Article
Therapeutic drug monitoring of risperidone (Risperdal®) was used by our pharmacist clinical department (E.P.S.M. Lille Métropole - Armentières) to compute a pharmacokinetic population by a modelling program USCPACK (10.7 version), in order to do an adaptive control of this antipsychotic. 19 patients had been included in this study. To assess a bicompartimental model, with distribution volume to body weight and total clearance, estimated by a non-parametric method, 2 low samplings are carried out. Variability of estimated parameters is the same as observed results in clinical therapeutic drug monitoring. More informative samplings and more patients should be included to use this population for planning monitoring and adjusting dosage regimen of risperidone.
Article
Priapism is defined as a penile erection that persists beyond or is unrelated to sexual interest or stimulation. It can be classified into ischaemic (low flow), arterial (high flow), or stuttering (recurrent or intermittent). To provide guidelines on the diagnosis and treatment of priapism. Systematic literature search on the epidemiology, diagnosis, and treatment of priapism. Articles with highest evidence available were selected to form the basis of these recommendations. Ischaemic priapism is usually idiopathic and the most common form. Arterial priapism usually occurs after blunt perineal trauma. History is the mainstay of diagnosis and helps determine the pathogenesis. Laboratory testing is used to support clinical findings. Ischaemic priapism is an emergency condition. Intervention should start within 4-6h, including decompression of the corpora cavernosa by aspiration and intracavernous injection of sympathomimetic drugs (e.g. phenylephrine). Surgical treatment is recommended for failed conservative management, although the best procedure is unclear. Immediate implantation of a prosthesis should be considered for long-lasting priapism. Arterial priapism is not an emergency. Selective embolization is the suggested treatment modality and has high success rates. Stuttering priapism is poorly understood and the main therapeutic goal is the prevention of future episodes. This may be achieved pharmacologically, but data on efficacy are limited. These guidelines summarise current information on priapism. The extended version are available on the European Association of Urology Website (www.uroweb.org/guidelines/). Priapism is a persistent, often painful, penile erection lasting more than 4h unrelated to sexual stimulation. It is more common in patients with sickle cell disease. This article represents the shortened EAU priapism guidelines, based on a systematic literature review. Cases of priapism are classified into ischaemic (low flow), arterial (high flow), or stuttering (recurrent). Treatment for ischaemic priapism must be prompt in order to avoid the risk of permanent erectile dysfunction. This is not the case for arterial priapism.
Article
Antipsychotic drugs (APDs) are best classified as typical or atypical. The distinction is based solely on their ability to cause extrapyramidal side effects (EPS), including tardive dyskinesia (TD). The two classes differ in mechanism of action, with atypical APDs providing important modulation of serotonergic neurotransmission.TDincreases the death rate and can be minimized by limiting use of typical APDs. Clozapine is unique among the atypical APDs in its efficacy for ameliorating psychosis in patients with treatment-resistant schizophrenia (TRS), for reduction of suicide, and for improving longevity. The typical and atypical APDs do not differ in improving psychopathology in non-TRS. The atypicals vary in metabolic side effects: some have little burden. Cognitive benefits of the atypical APDs may be superior for some domains of cognition and require less use of anticholinergic drugs, which impair memory, for treatment of EPS. Overall, choosing among the atypical APDs as firstline treatment represents the best course for schizophrenia and most likely other settings where APDs are used. Expected final online publication date for the Annual Review of Medicine Volume 64 is January 07, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
Article
Introduction. Ischemic priapism is associated with cavernosal acidosis, which decreases the efficacy of adrenergic agonists. We determined the effect of acidosis on ligand dissociation from adrenergic receptors and assessed the efficacy of high-dose phenylephrine in treating patients with acute ischemic priapism. Methods. Dissociation rates of [3H]prazosin were determined at pH 7.2 and 6.9 in membrane preparations of rabbit penile cavernosal tissue. Vital signs were recorded from patients before injection, and at 1 minute and 5 minutes after injection of high-dose phenylephrine (1,000 mg q 5 minutes) for 17 consecutive cases of iatrogenic ischemic priapism that occurred after vascular assessment. We also provide two case reports of prolonged ischemic priapism successfully managed with high-dose phenylephrine. Results. Dissociation rates of [3H]prazosin were greater at pH 6.9 (K −1 = 0.23/minute) than at pH 7.2 (K −1 = 0.10/minute), suggesting decreased receptor affinity at acidic pH. Intracavernosal therapy with high-dose phenylephrine (mean dose 2,059 ± 807 µg) was 100% effective with no adverse events or significant changes in vital signs. In addition, two patients with ischemic priapism for ≥36 hours were successfully treated with high-dose intracavernosal phenylephrine (mean dose 45,000 µg) without any adverse event. Both patients are currently potent. Conclusions. Acidic pH may decrease the binding affinity of adrenergic ligands to their receptors. Phenylephrine at doses higher than previously reported may be necessary to overcome this decreased affinity in acidosis associated with ischemic priapism. High-dose intracavernosal phenylephrine administration is safe and effective in the management of ischemic priapism. Continuous cardiovascular monitoring is advised. Wen CC, Munarriz R, McAuley I, Goldstein I, Traish A, and Kim N. Management of ischemic priapism with high-dose intracavernosal phenylephrine: from bench to bedside. J Sex Med 2006;3:918–922.
Article
Aim: To provide standard operating procedures for the diagnosis and management of priapism. Methods: Review of the literature. Main outcome measures: Reduction of priapism and preservation of erectile function. Results: Priapism is a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation. Priapism requires prompt evaluation and usually requires emergency management. There are two types of priapism: (i) ischemic (veno-occlusive or low flow), which is found in 95% of cases, and (ii) nonischemic (arterial or high flow). Stuttering (intermittent) priapism is a recurrent form of ischemic priapism. To initiate appropriate management, the physician must determine whether the priapism is ischemic or nonischemic. Necessary diagnostic steps are an accurate history, physical examination, and cavernous blood gas analysis and/or color duplex ultrasonography of the corpora cavernosa. Management of ischemic priapism should achieve resolution as promptly as possible. Initial treatment is therapeutic aspiration with or without irrigation of the corpora. If this fails, intracavernous injection of sympathomimetic drugs is the next step. Surgical shunts should be performed if nonsurgical treatment has failed. The initial management of nonischemic priapism should be observation. Selective arterial embolization is recommended for the management of nonischemic priapism in patients who request treatment. The goal of management for a patient with recurrent (stuttering) priapism is prevention of future episodes. Conclusion: Management of priapism has become increasingly successful as scientific understanding of the pathophysiology and molecular biology of priapism improves. The key to further success in the treatment of priapism is basic research of this uncommon but potentially devastating condition.
Article
Surgery is a mainstay in the management of ischemic priapism. The surgical armamentarium for this condition has recently been expanded with the introduction of several innovative procedures. To review surgical procedures offered in the treatment of ischemic priapism and present a rational framework for their use. Medline searches through July 2010 were conducted using the terms priapism, surgery, shunt, and prosthesis. Expert opinion was based on review of the medical literature related to this subject matter. A host of surgical procedures exist to address the genital complications of both acute presentations of ischemic priapism and its non-acute pathologic sequelae, which include penile deformities and erectile dysfunction. For the former, the intervention is used principally in an emergent context with the intention to relieve the acute pathologic effects of the condition and preserve erectile function. For the latter, the intervention is aimed generally toward restoring anatomic normalcy and the functional ability to perform sexual intercourse. A rational framework for surgical management, based on the circumstances of the clinical presentation, is described. The surgical management for ischemic priapism has evolved with the application of a host of surgical procedures. These procedures address acute and non-acute genital complications of the condition and are intended to retain or restore sexual ability effectively and safely. They can be applied using a rational clinical management framework.
Article
Priapism is defined as a prolonged and persistent erection of the penis without sexual stimulation. This is a poorly understood disease process with little information on the pathophysiology of this erectile disorder. Complications from this disorder are devastating due to the irreversible erectile damage and resultant erectile dysfunction (ED). Stuttering priapism, though relatively rare, affects a high prevalence of men with sickle-cell disease (SCD) and presents a challenging problem with guidelines for treatment lacking or resulting in permanent ED. The mechanisms involved in the development of priapism in this cohort are poorly characterized; therefore, medical management of priapism represents a therapeutic challenge to urologists. Additional research is warranted, so we can effectively target treatments for these patients with prevention as the goal. This review gives an introduction to stuttering priapism and its clinical significance, specifically with regards to the patient with SCD. Additionally, the proposed mechanisms behind its pathophysiology and a summary of the current and future targets for medical management are discussed.
Article
Advances have recently been made in both medical and surgical management of priapism, and these offer improvements in the level of care afforded such patients. Further developments can be expected based on ongoing progress, particularly in the area of molecular science, which is the primary source for driving novel therapeutic approaches. Continued action to address the health care administrative concerns of those most commonly affected by priapism, specifically individuals with sickle cell disease, is also appropriate. All successes in these arenas ensure that afflicted individuals avoid the health burdens of priapism and preserve sexual function.
Article
Refractory ischemic priapism results in cavernous smooth muscle necrosis, fibrosis and eventual penile shortening. Immediate penile implant insertion for acute ischemic priapism is done to avoid consequent fibrosis and shortening but ineffective shunt surgery trials may lead to potential weakness and erosion at the corporeal tip. We evaluate nonabsorbable sling sutures to fix the implant cylinder in place and prevent protrusion through the weak corporeal tip. We prospectively evaluated 12 men who presented with prolonged refractory ischemic priapism a median of 120 hours (range 60 to 168) in duration. All patients were unresponsive to conventional treatment and 11 had undergone unsuccessful shunt surgery. Early malleable penile prosthesis implantation had been done in all cases. To avoid possible distal protrusion a nonabsorbable sling suture was taken through the cylinder and the edges of the opened tunicae albuginea to fix the cylinder to the corporotomy edges. Penile implants were successfully inserted in all patients. No intraoperative or early postoperative complications were noted except in 1 with sickle cell priapism, in whom dilation led to unilateral corporeal perforation, which was managed intraoperatively. All patients were satisfied with the surgical results. No distal erosion was noted through the weak corporeal tip. No postoperative infection was reported at a median followup of 15 months (range 6 to 36). All patients successfully achieved sexual intercourse. Early penile prosthesis insertion for acute ischemic priapism is simple and successful. Distal cylinder protrusion through the defective corpora due to previous shunt surgery remains to confound surgical success. Nonabsorbable sling suture of the cylinder to the tunica albuginea is effective, simple and safe treatment for this formidable complication.
Article
Priapism describes a persistent erection arising from dysfunction of mechanisms regulating penile tumescence, rigidity, and flaccidity. A correct diagnosis of priapism is a matter of urgency requiring identification of underlying hemodynamics. To define the types of priapism, address its pathogenesis and epidemiology, and develop an evidence-based guideline for effective management. Six experts from four countries developed a consensus document on priapism; this document was presented for peer review and debate in a public forum and revisions were made based on recommendations of chairpersons to the International Consultation on Sexual Medicine. This report focuses on guidelines written over the past decade and reviews the priapism literature from 2003 to 2009. Although the literature is predominantly case series, recent reports have more detailed methodology including duration of priapism, etiology of priapism, and erectile function outcomes. Consensus recommendations were based on evidence-based literature, best medical practices, and bench research. Basic science supporting current concepts in the pathophysiology of priapism, and clinical research supporting the most effective treatment strategies are summarized in this review. Prompt diagnosis and appropriate management of priapism are necessary to spare patients ineffective interventions and maximize erectile function outcomes. Future research is needed to understand corporal smooth muscle pathology associated with genetic and acquired conditions resulting in ischemic priapism. Better understanding of molecular mechanisms involved in the pathogenesis of stuttering ischemic priapism will offer new avenues for medical intervention. Documenting erectile function outcomes based on duration of ischemic priapism, time to interventions, and types of interventions is needed to establish evidence-based guidance. In contrast, pathogenesis of nonischemic priapism is understood, and largely attributable to trauma. Better documentation of onset of high-flow priapism in relation to time of injury, and response to conservative management vs. angiogroaphic or surgical interventions is needed to establish evidence-based guidance.
Article
Ischemic (veno-occlusive, low flow) priapism is a painful and persistent penile erection unrelated to sexual desire or stimulation. In some cases, it is an adverse event of antipsychotic medications. Between 1st January 2000 and 30th September 2007, four men (range 25/55 years), treated with antipsychotic agents (amisulpride, clozapine, levomepromazine, olanzapine, pipotiazine, risperidone or zuclopenthixol), presented one or several episodes of ischemic priapism. No other etiological factor was diagnosed. The patients were treated with aspiration and irrigation of the corpa cavernosa with intracavernous injection of sympathomimetic drugs followed in one case by a surgical distal cavernoglanular shunt. Many conventional or atypical antipsychotic agents have been reported to cause priapism. Drug-induced priapism comprised of about 30% of the cases and an estimated 50% of them occurred with antipsychotic agents. The mechanism of priapism associated with antipsychotics agents thought to be related to alpha-adrenergic blocking properties. The decision of whether to restart a patient on a specific antipsychotic agent after an episode of priapism is a difficult clinical decision. An agent with low peripheral alpha-adrenergic blocking affinity would be preferred. Ischemic priapism is an urologic emergency. Clinicians should be familiar with this rare but serious adverse event of antipsychotic agents to avoid long-term sequelae including erectile dysfunction.
Article
Numerous reports have emphasized the association between priapism and the ingestion of psychotropic medication. Clinicians are becoming increasingly aware of this association and its subsequent severe morbidity. Review of the literature reveals that medications possessing alpha-adrenergic blocking properties are most frequently associated with priapism. These medications include trazodone, several antipsychotics, and the antihypertensive agent, prazosin. Awareness of these associations and an appreciation of potentially serious consequences of this disorder may assist clinicians in choosing psychotropic agents that minimize the risk of developing priapism. It is essential that patients who are to receive psychotropic medications be forewarned about priapism. In addition, patients should be questioned concerning prior occurrence of prolonged erections, since a past history of delayed detumescence is present in approximately 50% of subsequent cases of priapism.
Article
The treatment options for the management of the patient with priapism have changed markedly within the past several years. When possible, the underlying cause of the priapism should be identified. Therapy should be guided by the results of aspiration of the blood-filled corpora cavernosa of the erect penis. Early intervention through pharmacologic manipulation or surgical shunting should not be delayed while trying conservative measures.
Article
Evidence concerning pharmacological effects on human sexuality suggests that dopaminergic receptor activation may be associated with penile erection. Erection also appears to involve inhibition of alpha-adrenergic influences and beta-adrenergic stimulation plus the release of a noncholinergic vasodilator substance, possibly vasoactive intestinal peptide. Ejaculation appears to be mediated primarily by alpha-adrenergic fibers. Serotonergic neurotransmission may inhibit the ejaculatory reflex. An understanding of the neurobiological substrate of human sexuality may assist clinicians in choosing psychotropic agents with minimal adverse effects on sexual behavior and may also contribute to the development of pharmacological interventions for sexual difficulties.
Article
The selective serotonin reuptake inhibitors (SSRIs) and venlafaxine display the following rank order of in vitro potency against the cytochrome P450 (CYP) isoenzyme CYP2D6 as measured by their inhibition of sparteine and/or dextromethorphan metabolism: paroxetine > fluoxetine ≡ norfluoxetine ≥ sertraline ≥ fluvoxamine > venlafaxine. On this basis, paroxetine would appear to have the greatest and fluvoxamine and venlafaxine the least potential for drug interactions with CYP2D6-dependent drugs. In vivo, inhibitory potency is affected by the plasma concentration of the free (unbound) drug, a potentially important consideration since many CYP2D6-metabolised drugs exhibit nonlinear (saturable) kinetics, and by the presence of metabolites, which might accumulate and interact with the CYP system. Under steady-state conditions, paroxetine and fluoxetine are approximately clinically equipotent inhibitors of CYP2D6 in vivo (as determined through their effects on desipramine metabolism); sertraline, in contrast, shows lower steady-state plasma concentrations than fluoxetine and, hence, a less pronounced inhibition of CYP2D6. Of the drugs that are metabolised by CYP2D6, secondary amine tricyclic antidepressants, antipsychotics (e.g. phenothiazines and risperidone), codeine, some antiarrhythmics (e.g. flecainide) and β-blockers form the focus of clinical attention with regard to their potential interactions with the SSRIs. Coadministration of desipramine and fluoxetine (20 mg/day) at steady-state produced an ≈ 4-fold elevation in peak plasma desipramine concentrations, while the long half-life of the active metabolite norfluoxetine was responsible for a significant and long lasting (≈ 3 weeks) elevation of plasma desipramine concentrations after discontinuation of fluoxetine. Similarly, coadministration of desipramine with paroxetine produced an ≈ 3-fold increase in plasma desipramine concentrations. In contrast, coadministration of desipramine and sertraline (50 mg/day) for 4 weeks resulted in a considerably more modest (≈ 30%) elevation in plasma desipramine concentrations. Coadministration of fluoxetine (60 mg/day, as a loading dose) [equivalent to serum concentrations obtained with 20 mg/day at steady-state] with imipramine or desipramime resulted in ≈ 3- to 4-fold increases in plasma area under the curve (AUC) values for both imipramine and desipramine (illustrating a significant drug interaction potential at multiple isoenzymes). Consistent with its minimal in vitro effect on CYP2D6, fluvoxamine shows minimal in vivo pharmacokinetic interaction with desipramine, but does interact with imipramine (≈ 3- to 4-fold increase in AUC) through inhibition of CYP3A3/4, CYP1A2, and CYP2C19. Thus, the extent of the in vivo interaction between the SSRIs and tricyclic antidepressants mirrors to a large extent their in vitro inhibitory potencies against CYP2D6 and other isoenzyme systems, especially if one takes into account pharmacokinetic factors.
Article
Intractable, therapy-resistant priapism in a patient with sickle cell disease is presented. The patient was managed with insertion of an inflatable penile prosthesis. He consequently maintained potency and remains free of priapitic episodes. To our knowledge, immediate penile prosthesis insertion for management of priapism has not been reported. We discuss the indications and advantages of this approach and review the current literature.
Article
The limited available information on plasma risperidone levels shows a stable relationship between daily doses of risperidone and total plasma concentration (risperidone plus its active metabolite 9-hydroxyrisperidone). The ratio between risperidone and 9-hydroxyrisperidone characterizes cytochrome P450 2D6 (CYP2D6) status. According to the manufacturer, the CYP2D6 genotype or drugs that influence CYP2D6 or other cytochrome P450 isoenzyme activity are not expected to be clinically significant. One case report suggests that CYP3A participates in the metabolism of risperidone. A case series of 13 risperidone patients (the initial case and 12 new cases) who were genotyped for CYP2D6 were followed, and another 20 risperidone patients from a case-control study for the CYP2D6 genotype were reviewed. The CYP2D6 poor metabolizers, who are enzyme deficient (2/13 in the case series and 3/20 in the case-control study), did not appear to tolerate risperidone well. Drugs affecting CYP3A, in particular powerful inducers and inhibitors, resulted in at least a 2-fold decrease or increase in plasma risperidone levels. The anecdotal nature of this study is clearly a limitation. Drugs influencing CYP3A and CYP2D6 metabolic activity may significantly affect risperidone levels. Thus, plasma level monitoring of risperidone in a clinical setting may be useful, especially if patients are taking multiple medications or a CYP2D6 deficiency is suspected. New prospective studies under more controlled conditions are needed to verify these hypotheses.
Article
Citalopram is a relatively new selective serotonin reuptake inhibitor (SSRI) that is becoming widely administered for the treatment of depression. Selective serotonin reuptake inhibitors generally are associated with mild adverse sexual side effects; however, more serious reactions may occur. A 58-year-old man experienced priapism several hours after inadvertently taking three tablets of citalopram 20 mg, which he had mistaken for aspirin, in addition to his usual dosage of 20 mg twice/day. Three days later, he was hospitalized and treated with intracavernous phenylephrine. He ultimately required surgical intervention. Although the citalopram overdose appears to be largely responsible for the patient developing priapism, he also was taking tamsulosin 0.4 mg/day at bedtime for benign prostatic hyperplasia. As alpha1-blockers have been associated with priapism on rare occasions, tamsulosin may have been a contributing factor. The patient also had a history of priapism associated with trazodone. Health care professionals should vigilantly monitor patients who take citalopram in high dosages or in combination with other drugs associated with priapism. Patients who have a history of priapism with other drugs may be more susceptible to citalopram-associated priapism.
Article
Priapism has been associated with many antipsychotic agents, including clozapine, risperidone, and olanzapine. This prolonged, usually painful, penile erection rarely results from the alpha-adrenergic blocking action of antipsychotics. A 22-year-old African-American man developed priapism during treatment with risperidone and, on a later occasion, during treatment with ziprasidone. The problem resolved only with substitution of other drugs for these antipsychotics. Certain patients may be more vulnerable than others to this adverse effect. Clinicians must be aware of such complications and use caution when prescribing these drugs.
Article
Awareness of the metabolism of second-generation antipsychotics by the cytochrome P450 (CYP) system can inform the clinician about how to avoid and manage drug-drug interactions involving these enzymes. Clozapine is metabolized primarily by CYP1A2, with additional contributions by CYP2C19, CYP2D6 and CYP3A4. Risperidone is metabolized primarily by CYP2D6 and to a lesser extent by CYP3A4. Olanzapine is metabolized primarily by CYP1A2 and to a lesser extent by CYP2D6. Quetiapine and ziprasidone are metabolized by CYP3A4. At the usual clinical doses, these drugs appear not to significantly affect the metabolism of other medications. There is, however, a lack of in vivo metabolic data, especially for the 3 newest second-generation antipsychotics: olanzapine, quetiapine and ziprasidone.
Article
Priapism is a relatively uncommon condition that may present as a medical emergency associated with significant pain and anxiety in the veno-occlusive or low-flow variant. Pharmacologic advances and, specifically, the availability of intracavemosal alpha-agonist therapy have dramatically improved the prospects of resolution for patients with low-flow priapism presenting within the first few hours of the acute episode. High-flow priapism is not considered an emergency and treatment measures are typically conservative aimed at preservation of potency. Urologists, radiologists, and other health care personnel caring for the patient with priapism must be familiar with various etiologic factors implicated in low-flow and high-flow priapism to formulate a logical step-care approach. Differentiation of the low-flow from the high-flow state is perhaps the most critical initial diagnostic challenge that determines the sequence of further interventions including surgical shunts in low-flow priapism refractory to medical therapy.