Across the globe, recreational ketamine use has been increasing, along with a spike in young adult patients presenting with lower urinary tract symptoms.

Ketamine-induced urinary symptoms occur in more than 25% of recreational users and worsen with higher doses and more frequent use. With chronic use, roughly a third eventually develop ketamine cystitis (ketamine bladder), which, left untreated, leads to progressive bladder injury, permanent scarring, and kidney failure.

One of the largest challenges facing practitioners, especially nurse practitioners (NPs) who are likely to be the initial point of contact for many patients, is the broad range of presenting symptoms disproportionate to age (a majority of patients are between the ages of 16 and 35). They include urinary frequency, dysuria, suprapelvic or pelvic pain, disrupted sleep, depression, and rapidly progressing functional impairment.

“Patients with urinary tract symptoms often first end up in urgent care,” said Elisabeth Okroi, APRN-CNP, CUNP, an Oklahoma City, Oklahoma-based urology NP at SSM Health Oklahoma City, and secretary on the Board of Directors at the Society of Urologic Nurses and Associates.

Despite her urology training and certification, Okroi said she had never heard of or encountered ketamine cystitis before being contacted by Medscape Medical News. However, she believed NPs were uniquely positioned to detect early symptoms.

“After looking into this the last few days, it’s something I will add to my questions during history taking — not just because illicit drug use of many kinds can affect the bladder — but because this seems to be underreported and not very well known in some urology circles,” said Okroi.

NPs Key to Diagnosis

Because ketamine cystitis presentation is similar to conditions like urinary tract infections, interstitial cystitis, and somatic symptom disorder, accurate diagnosis might take weeks, subjecting patients to multiple clinical encounters with specialists and progressing, debilitating symptoms.

An important key to diagnosis is a substance use history that includes lifetime and current exposure to ketamine, administration route (recreational ketamine is often used intranasally or orally), dose and frequency, and any patterns of dose escalation. Ketamine cystitis tends to develop after roughly 1 or 2 years of chronic, heavy administration (1 g or more daily). Though its pathogenesis is not entirely clear, researchers have argued that significant bladder dysfunction results from the presence of ketamine in urine rather than systemic exposure.

Ultimately, symptoms become so severe that they exceed care offered by outpatient treatment but do not meet the criteria for hospitalization, underscoring the need to catch these patients in primary care settings before they land in psychiatric-mental health facilities.

Currently, a psychiatric NP is often the first to recognize the tell-tale pattern: anxiety, depression, dysphoria, panic, and sleep issues coupled with urinary symptoms that fail to respond to antibiotics.

“Quite often, someone with ketamine-induced cystitis falls right into the bucket where I sit; we see people who have urgency and frequency of urination and some pain, with ketamine use,” said Lem Scott, DNP, PMHNP, psychiatric NP, assistant professor, and director of the Psychiatric-Mental Health Nurse Practitioner Program at Duke University School of Nursing in Durham, North Carolina. “It may not present until they start to have secondary symptoms, for example, anxiety, difficulty sleeping, and panic,” Scott said.

“We typically treat some of those symptoms, and then do a consult with urology,” he said, also pointing to the important role NPs play: first point of contact, screening, and partnering with other medical professionals to rule out UTI and obtain a ketamine cystitis diagnosis.

Beth Kuzma, DNP, FNP-BC, assistant dean of Advanced Practice Academic Programs, and a clinical professor of Health Behavior and Clinical Sciences at the University of Michigan School of Nursing in Ann Arbor, agreed, noting the need for initial ketamine assessment at the adolescent and adult primary care levels.

“Specialists are great at what they do, but they see things through a very focused, deep lens. If something crosses different domains and appears to fall outside this scope, they’re not looking at it, which is why primary care should be assessing this,” said Kuzma.

She explained that NP’s education focuses on holistic care. NPs also excel at care coordination, especially at the primary level.

“That’s where we can look at that patient, establish a relationship and create trust so they’ll share what they’re actually doing,” she said.

Lack of Standardized Treatment

Given its heterogeneous nature, treatment for ketamine cystitis is mostly supportive and fragmented, relying on multidisciplinary behavioral and pharmacologic interventions to address secondary symptoms. Robust evidence supporting effective treatment is also limited, with one exception: total abstinence.

“These patients are in a vicious cycle of really severe symptoms. The frequency is extreme. The pain is extreme,” said Anjana Shah, APRN, FNP-BC, a family and urology NP in the Department of Urology at UTSouthwestern Medical Center in Dallas. “They often use ketamine for pain and psychiatric symptoms, so they’re chasing the bladder pain. But the key is to abstain from ketamine in the first place, although it’s hard to convince them to stop,” she said.

The goal of treatment is to halt any bladder damage that has already occurred from progressing further, damage that is often irreversible. “It’s a chemical injury that looks like a burn,” said Shah. “Any reintroduction of ketamine is going to continue to cause more damage,” she said, also noting that the entire urinary tract as well as the liver can be affected.

Shah underscored the need for early recognition and screening, emphasizing that by the time patients are seen by urology or addiction psychiatry specialists, the opportunity to reverse bladder damage might have already passed.

NPs, Primary Care at the Frontlines

NPs and primary care doctors operate on the frontlines of medicine, which is another reason why awareness of the etiology of unclear urology symptoms, pain, and dissociation, as well as the confluence of other severe symptoms, is so important.

Lem said the key is to gain patient trust, inquire about ketamine use, and understand that patients who become dependent on ketamine and develop ketamine cystitis are not drug-seeking when they look for help or continue to escalate doses, but rather, are trying to work through and alleviate associated symptoms.

It’s also important to distinguish between ketamine used in supervised, therapeutic settings and ketamine used for recreational purposes.

“This condition is about dose and exposure, how much and how often patients use ketamine,” said Lem. “It’s an increasingly important issue, and providers need to make sure they can recognize it.”

Okroi, Kuzma, Scott, and Shah reported having no financial disclosures of interest.

Liz Scherer is an independent health and medical journalist who frequently reports on ketamine and other psychedelics in the US, Canada, and EU.