Deep Vein Thrombosis Caused by Drug‐Induced Giant Bladder Diverticulum in Long‐Term Use of Antipsychotic Drugs: Case Report and Literature Review

ABSTRACT

Introduction

Bladder diverticulum rarely causes deep vein thrombosis (DVT) due to compression of leg veins. However, only a few cases have been reported to date. In this article, we report the first known case of DVT caused by a giant bladder diverticulum associated with long‐term use of antipsychotic medication.

Case Presentation

A male in his 40s with a 20‐year history of schizophrenia was admitted to the hospital with complaints of swelling and pain in the left lower extremity. He was diagnosed with drug‐induced urinary retention caused by antipsychotics, a giant bladder diverticulum, and DVT. The patient underwent urinary catheter placement and was treated with rivaroxaban. He has limited therapeutic options due to poor adherence to treatment and is currently undergoing intermittent replacement of the urinary catheter.

Conclusion

Patients taking antipsychotic medications must be aware of the risk of urinary retention and may be unable to choose optimal medical care.

Abbreviations

BPH

benign prostatic hyperplasia

CT

computed tomography

DVT

deep vein thrombosis

Summary.

• We report a rare case of deep vein thrombosis caused by compression of lower extremity veins due to a bladder diverticulum resulting from psychiatric disease.

1. Background

A bladder diverticulum is a herniation of the bladder mucosa that lacks muscle fibers in the bladder wall. The incidence of congenital diverticula is reported to be 1.7%. Most acquired bladder diverticula are associated with lower urinary tract disorders, such as benign prostatic hyperplasia (BPH) and bladder outlet obstruction. Treatment consists of improving urinary retention, the cause of increased bladder pressure, and resecting the bladder diverticulum.

2. Case Presentation

The patient was a male (age: 40s) with a 20‐year history of schizophrenia and no diagnosis of mental retardation. Despite speech difficulties, the patient did not have significant communication impairment and was able to perform social activities. Three days prior to his visit, he noticed painful swelling in the left lower leg. He was admitted to our hospital with a diagnosis of cellulitis. Upon arrival, he exhibited prominent redness, swelling, and severe pain from his left thigh to his toes. Contrast‐enhanced computed tomography (CT) scans (Figures 1 and 2) revealed constriction and narrowing of the bilateral common iliac veins at their confluence due to a large bladder diverticulum protruding on the left side. On CT, the residual urine volume in the true bladder cavity was approximately 740 mL, and the residual urine volume in the diverticulum was approximately 1020 mL. Additionally, thrombi were present in the left internal and external iliac veins, extending into the left thigh and leg veins. A left ureteral opening into a diverticulum, thinning of the left kidney, and a prostate volume of 19 mL were also indicated. He tested negative for thrombophilia and had no enlarged prostate. However, he had been treated with anticholinergic drugs (i.e., olanzapine and flunitrazepam) for a long time. In this case, there were no obvious obstructions of the urinary tract, such as stones or BPH. Conditions such as neurogenic bladder, abnormal blood glucose levels, and spinal cord injury were also ruled out. Based on this information, we diagnosed drug‐induced urinary retention resulting in a bladder diverticulum and deep vein thrombosis (DVT). On Day 1 of admission, we placed a urinary catheter and initiated the administration of rivaroxaban (30 mg). The patient was discharged on Day 18.

FIGURE 1.

A contrast computed tomography scan was performed at the L5 level upon admission. The examination revealed the presence of a protruding giant bladder diverticulum on the left side, which caused compression and stenosis of the confluence of the left common iliac vein (indicated by the arrow).

FIGURE 2.

A contrast computed tomography scan was performed at the sacral level upon admission. The examination revealed a hyperabsorptive zone extending from the left internal and external iliac veins to the left femoral vein and leg veins (indicated by the arrow). This finding suggested the presence of a fresh thrombus.

In an outpatient setting, the rivaroxaban dose was reduced to 15 mg. The patient received tamsulosin and distigmine bromide to improve urinary retention. Nonetheless, drug therapy did not restore urinary retention. Moreover, since the residual urine was > 700 mL, a urinary catheter was maintained in place. We attempted to change the medication for schizophrenia; however, the patient's condition worsened. We introduced self‐catheterization, but the patient failed to adhere to the replacement schedule, causing his residual urine to increase. We also attempted to educate the patient regarding the amount of water he should consume since he was drinking > 10 L per day. We suggested cystostomy, urinary diversion, and resection of the bladder diverticulum; nevertheless, the patient declined surgery. In collaboration with the patient's social worker, attending psychiatrist, and family members, we attempted to educate the patient about his medications and urinary drainage. However, on many days, he was unable to follow the instructions due to his mental state. The current treatment plan includes replacing permanent urinary catheters intermittently and continuing to administer rivaroxaban to prevent DVT recurrence. One year after disease onset, there has been no recurrence of DVT.

3. Discussion

Bladder diverticulum is a hernia of the bladder mucosa that lacks muscle fibers in the bladder wall. Congenital bladder diverticula occur in 1.7% of cases [1] and are often associated with vesicoureteral reflux disease [2]. Most acquired bladder diverticula are associated with lower urinary tract disorders, such as BPH and bladder outlet obstruction. They occur most frequently in elderly men, most are asymptomatic, and develop in 1%–8% of patients with BPH [3]. The most common sites of diverticula are above and lateral to the ureteral opening [4]; in some cases, the ureteral opening opens into the diverticulum.

The treatment consists of improving urinary retention and resecting the bladder diverticula. Urinary retention treatment may include medication, BPH treatment (e.g., transurethral resection of the prostate), and release of urinary tract obstruction (e.g., urethral catheterization) or bladder fistula. For frail patients who are unsuitable for prolonged surgery, transurethral removal of the bladder diverticula may be an option [5]. Clayman et al. reported on the postoperative course of six patients who underwent transurethral radiofrequency therapy [6]; five of those had no diverticulum. Diverticulectomy is commonly performed by laparotomy or laparoscopy, using either an extraperitoneal or an intraperitoneal approach [7, 8]. In the present case, the patient had urinary retention with no point of obstruction. Therefore, we chose to insert a urethral catheter following medical therapy.

Thus far, only six cases of giant bladder DVT have been reported [9, 10, 11, 12, 13, 14] (Table 1). Two of those [12, 13] involved patients with congenital diverticulum and vesicoureteral reflux disease who underwent open vesicoureteral diverticulectomy and vesicoureteral neo‐anastomosis at birth. One case [10] had a reason unknown. The remaining three cases [9, 11, 14] involved males who had undergone or were scheduled to undergo transurethral resection of the prostate due to BPH as the primary disease. To our knowledge, there have been no reports of bladder diverticulum or DVT caused by drug‐induced urinary retention due to psychiatric disorders.

TABLE 1.

Reported cases of DVT due to bladder diverticulum (including this case).

Case no.	Author, year of publication	Age of patient	Sex	Primary disease	Location of compressed blood vessel	Surgical procedure
1	Gupta et al. [9]	79 years	Male	BPH	Left common femoral vein; left external and left common iliac veins	TURP
2	Jepson et al. [10]	57 years	Male	None reported	None reported	Open bladder diverticulectomy; vesicoureteral neo‐anastomosis
3	Wang et al. [11]	71 years	Male	BPH	Left external iliac vein	Laparoscopic bladder diverticulectomy; TURP
4	Valadez et al. [12]	5 months	Male	Congenital	None reported	Open bladder diverticulectomy; vesicoureteral neo‐anastomosis
5	Miller et al. [13]	5 weeks	Male	Congenital	Left external iliac vein	Open bladder diverticulectomy; vesicoureteral neo‐anastomosis
6	Zimmermann et al. [14]	73 years	Male	BPH	Right common and right shallow femoral veins	Not implemented (Bladder diverticulectomy + TURP planned)
7	Sato et al. [15] (this article)	45 years	Male	Schizophrenia	Left internal and external iliac veins, Left thigh and leg veins	Not implemented

Abbreviations: BPH, benign prostatic hyperplasia; DVT, deep vein thrombosis; TURP, transurethral resection of the prostate.

Antipsychotic drugs inhibit the contraction of the bladder's smooth muscle by blocking muscarinic receptors. This increases the risk of urinary retention. Uekusa et al. examined the number of urinary retention occurrences and the odds ratio associated with antipsychotic drugs in Japan using a Japanese database of adverse drug event reports [16]. Of the 887,704 total reports, 4653 cases (0.52%) involved urinary retention, suggesting that olanzapine affects urinary retention. Among the drugs used in this case, olanzapine had an odds ratio of 2.58 (95% confidence interval: 1.905–3.486). Flunitrazepam was also reported to exert anticholinergic effects; however, the odds ratio of 1.23 (95% confidence interval: 0.711–2.118) was not statistically significant.

In this case, the urinary retention caused by the psychiatric drug is complicating the treatment of the bladder diverticulum. Firstly, the bladder wall becomes irreversibly thickened due to a prolonged course of urinary retention. Secondly, if the patient's symptoms are stable with the current prescription, changing the medication is difficult due to the risk of exacerbating the symptoms. Thirdly, the patient lacks awareness of the disease and may not adhere to treatment. In this case, attempts to educate the patient regarding urinary techniques and lifestyle changes often fail. He had not been diagnosed with mental retardation, and had not undergone a thorough examination. Therefore, we could not confirm that his intellectual disability was solely due to schizophrenia. Given the difficulty of curative treatment, preventing DVT recurrence is paramount. This task requires maintaining unobstructed urinary catheterization and preventing diverticular distention.

4. Conclusion

To our knowledge, this is the first reported case of DVT caused by a giant bladder diverticulum associated with long‐term antipsychotic use. Clinicians should be aware of the potential for urinary retention in patients on such medications. It is important to understand that some patients with psychiatric conditions may face challenges in adhering to treatment due to factors such as impaired insight or fluctuating mental status. Regular post‐void residual assessments or urology referrals may help prevent serious complications like DVT.

Ethics Statement

The authors have nothing to report.

Consent

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.