Intravesical drug delivery for dysfunctional bladder

The bladder is a hollow organ that can be treated locally by transurethral catheter for intravesical drug instillation or cystoscopy for intravesical drug injection. With advancing technology, local organ‐specific therapy and drug delivery is of expanding interest for treating dysfunctional bladder, including interstitial cystitis/bladder pain syndrome, overactive bladder and sterile hemorrhagic cystitis after chemotherapy or pelvic radiation. Intravesical therapy has shown varying degrees of efficacy and safety in treating interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with new modalities being developed. Intravesical (regional) therapy has several advantages than oral (systemic) therapy, including high local concentration and less systemic toxicity. In recent years, intravesical delivery of biotechnological products including neurotoxins and immunosuppressive agents, and delivery platform including liposomes has shown promise for lower urinary tract symptoms. This review considers the current status of intravesical therapy in dysfunctional bladder including interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with special attention to lipid based novel drug‐delivery.     

肉毒素联合膀胱灌注治疗间质性膀胱炎

目的:评价肉毒素注射联合肝素、利多卡因、碳酸氢钠膀胱灌注治疗间质性膀胱炎的疗效。方法:将20例间质性膀胱炎患者随机分为两组,联合组在麻醉下行膀胱内200 U肉毒素多点注射,3 d后行2%利多卡因8 mL、肝素37 500万U、5%碳酸氢钠5 mL膀胱灌注,每周1次,治疗周期1个月;透明质酸钠组膀胱灌注每周1次,治疗周期1个月,并对疗效进行随访。结果:随访1年,透明质酸钠组症状评分、问题评分、日排尿次数、最大膀胱容量指标较治疗前未发现明显改善(P0.05);联合组以上指标较治疗前均有明显改善(P0.05)。结论:肉毒素联合肝素、利多卡因、碳酸氢钠膀胱灌注治疗间质性膀胱炎,疗效明显优于透明质酸钠,该治疗方案值得进一步临床推广应用。     

THE ROLE OF URINARY POTASSIUM IN THE PATHOGENESIS AND DIAGNOSIS OF INTERSTITIAL CYSTITIS

Purpose

We determined whether intravesical potassium absorption in normal bladders correlates with increased sensory urgency, and corroborated the hypothesis that mucus is important in the regulation of epithelial permeability. We compared sensory nerve provocative ability of sodium versus potassium, and determined whether intravesical potassium sensitivity discriminates patients with interstitial cystitis from normal subjects and those with other sensory disorders of the bladder.

Materials and Methods

A total of 231 patients with interstitial cystitis and 41 normal subjects underwent intravesical challenge with 40 ml. water and then 40 ml. of 40 mEq./100 ml. potassium chloride. Subjective responses of urgency or pain stimulation were recorded on a scale of 0 to 5. In 19 normal subjects potassium absorption was measured at baseline, after injury of the bladder mucus with protamine, after heparin treatment to reverse mucus damage and then for a final time. These subjects simultaneously recorded the symptoms of sensory urgency and pain at baseline, after protamine and after heparin. Another group of normal volunteers underwent a challenge with sodium versus potassium to determine which cation was more provocative. Patients with bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH), detrusor instability, and acute and chronic urinary tract infection but no current infection were also evaluated for potassium sensitivity.

Results

Neither normal subjects nor patients with interstitial cystitis reacted to water administered intravesically. There was marked sensitivity to intravesical potassium in 75% of patients with interstitial cystitis versus 4% of controls (p <0.01). Only 1 patient with BPH responded to potassium and none of the 5 with chronic urinary tract infection responded. All 4 patients (100%) with a current acute urinary tract infection reacted positively to the potassium challenge. Of 16 patients with detrusor instability 25% responded. Normal subjects had minimal sensitivity to potassium before (11%) and markedly increased sensitivity after (79%) protamine treatment, and these symptoms were reversed by heparin in 42%. Potassium absorption directly correlated with symptoms (0.4, 3.0 and 1.3 mEq. before and after protamine, and after heparin reversal, respectively). In regard to sodium versus potassium provocation, potassium was far more provocative for causing urgency after protamine (10 versus 90%). Neither group underwent provocation before protamine.

Conclusions

Chronic diffusion of urinary potassium into the bladder interstitium may induce sensory symptoms, damage tissue and be a major toxic factor in the pathogenesis of interstitial cystitis. Intravesical potassium sensitivity is a reliable method for detecting abnormal epithelial permeability. It discriminates between patients with interstitial cystitis and normal subjects with intact epithelial function, and it is a useful diagnostic test for interstitial cystitis. Potassium sensitivity correlates with increased potassium absorption in normal subjects, and potassium is far more provocative than sodium. Potassium sensitivity is also present in acute urinary tract infection and occasionally detrusor instability but not in BPH or chronic urinary tract infections.     

Intravesical hyaluronic acid for interstitial cystitis/painful bladder syndrome: A comparative randomized assessment of different regimens

Objectives: To compare the clinical effectiveness of different regimens of intravesical hyaluronic acid instillation for patients with interstitial cystitis/painful bladder syndrome. Methods: A total of 60 patients (age 16–77 years) diagnosed with interstitial cystitis/painful bladder syndrome were enrolled in this prospective, randomized study. A total of 30 patients were assigned to receive four weekly intravesical instillations of 40 mg of hyaluronic acid followed by five monthly instillations (hyaluronic acid‐9 group). Another 30 patients received 12 intravesical instillations of 40 mg hyaluronic acid every 2 weeks (hyaluronic acid‐12 group). Symptomatic changes after hyaluronic acid treatments were assessed using Interstitial Cystitis Symptom and Problem Indexes, pain visual analog scale, functional bladder capacity, frequency and nocturia in voiding diary, maximum flow rate, voided volume, postvoid residual volume, and Quality of Life Index at 1, 3 and 6 months. Results: Of the 60 patients, 59 were evaluable at the end of the study. The Interstitial Cystitis Symptom Index, Interstitial Cystitis Problem Index and total score, pain visual analog scale, functional bladder capacity, maximum flow rate, and Quality of Life Index improved significantly after 6 months in both groups. The frequency and voided volume improved significantly only in the hyaluronic acid‐12 group. However, patients with moderate and marked improvement were clinically similar in both groups. The measured variables did not differ between the two groups over the course of the study. Conclusion: No significant difference was noted in the therapeutic effect between two hyaluronic acid instillation regimens for treatment of interstitial cystitis/painful bladder syndrome patients. Both groups showed significant improvement in symptom scores and Quality of Life Index.     

阿米替林联合透明质酸钠、肝素治疗间质性膀胱炎的临床疗效评价

目的探讨口服阿米替林联合膀胱灌注透明质酸钠、肝素治疗间质性膀胱炎/膀胱疼痛综合征（interstitial cystitis/painfulbladder syndrome,IC/PBS）的临床疗效和安全性。方法 24例IC/PBS患者行口服阿米替林联合膀胱灌注透明质酸钠、肝素治疗。麻醉下膀胱镜检查及水扩张后,诊断明确所有患者即开始口服阿米替林25mg/d,最大剂量75mg/d;同采用透明质酸40mg、肝素25 000U混合液膀胱灌注、每周1次,4次后改每月1次。观察治疗前及治疗后3、6个月的排尿次数、排尿量和Oleary saint问卷表评分（OLeary-Sant patient symptom/problem index scores,ICSI/ICPI）;盆腔疼痛及尿频评分（pelvic painand urgency frequency questionnaire,PUF）;第6月复查膀胱镜。结果 22例患者完成本研究,随访3、6月时,每日排尿次数明显减少,尤其是夜尿次数,平均每次尿量明显增加,ICSI、ICPI、PUF评分明显降低,差异有统计学意义（P〈0.001）;治疗6月与治疗3月相比差异除夜尿次数及PUF评分外,其他各项指标均无统计学意义（P〉0.05）。6月复查膀胱镜检查,19例黏膜下出血点消失或减轻,3例膀胱三角区炎性改变。结论阿米替林联合透明质酸钠、肝素治疗IC/PBS安全有效。     

Interstitial cystitis: bladder training with intravesical oxybutynin

PURPOSE: We assess the efficacy of intravesical administration of oxybutynin chloride in patients with interstitial cystitis. MATERIALS AND METHODS: The study included 36 women with a mean age of 45 years with a diagnosis of interstitial cystitis. Patients were treated with gradual intravesical instillation of saline oxybutynin solution (oxybutynin group) or gradual filling of simple saline (control group). Evaluation parameters consisted of symptom problem index, voids per day, volume per void, functional bladder capacity, volume at first sensation, cystometric bladder capacity and cystometric volume at first sensation. RESULTS: Statistically significant improvement of all evaluated parameters was found in both groups. When comparing the outcomes statistically significant improvement of parameters favored the oxybutynin group. CONCLUSIONS: Bladder training alone produces a satisfactory result by gradually expanding the bladder, and an additional statistically significant improvement is evident with intravesical oxybutynin.     

Alternate Occurrence of Allergic Disease and an Unusual Form of Interstitial Cystitis

Background : It has been postulated that interstitial cystitis can be induced by an allergy. This is partly based on the observation that many patients with interstitial cystitis also have allergic diseases. In this study, an allergic evaluation was conducted on patients with interstitial cystitis complicated by bronchial asthma, a typical allergic disease.
Methods : Clinical histories were obtained and biopsy specimens from the vesical walls of the study patients were examined histologically. Cutaneous tests and IgE radioallergosorbent tests (RAST) were performed. Further, intravesical provocation tests were carried out using IgE RAST-positive antigens, and histamine release assays were performed on the vesical biopsy specimens using anti-lgE antibodies.
Results : Five of 6 patients alternately exhibited symptoms of allergic disease and bladder symptoms. The eosinophil and mast cell counts in the vesical biopsy specimens of these 5 patients were increased. Furthermore, an intravesical provocation test performed using the IgE RAST-positive antigen was positive in 4 patients. The mean vesical biopsy specimen histamine release was 1 7.7% for patients with interstitial cystitis with bronchial asthma which was significantly higher than that for interstitial cystitis patients without bronchial asthma (8.9%) or the control group (4.5%). The prognosis of patients with interstitial cystitis with allergic complications was relatively good.
Conclusion : Patients with bronchial asthma exhibited hypersensitivity both generally and locally in the bladder. The alternation phenomenon was observed between the hypersensitive organs.     

Interstitial cystitis treated with intravesical doxorubicin

Three patients with interstitial cystitis diagnosed on the basis of clinical symptoms, classic endoscopic findings, and a typical histologic picture were treated with intravesical doxorubicin. All 3 patients showed remarkable improvement, as manifested by complete clearance of irritative bladder symptoms and healing of ulceration. Doxorubicin therefore may be the breakthrough drug for interstitial cystitis.     

Clinical and urodynamic experience with intravesical hyaluronic acid in painful bladder syndrome associated with interstitial cystitis

Introductionfew studies have been carried out on therapeutic options in patients with painful bladder syndrome associated with interstitial cystitis. The aim is to verify the safety and effectiveness of treatment with sodium hyaluronate through intravesical instillation in patients with painful bladder syndrome.Materials and methodsa series of 18 female patients is presented, with a mean age of 51 years and prior diagnosis of painful bladder syndrome, who were treated by means of the weekly infusion of an intravesical solution of 40 mg of sodium hyaluronate in sterile solution, over a period of eight weeks. The patients were examined clinically and urodynamically prior to their inclusion in the study and eight months after the instillations had concluded.Resultsthere was a statistically significant improvement in the urodynamic parameters and in the symptoms measured quantitatively by means of the questionnaire “Pelvic Pain and Urgency/Frequency” between the baseline situation and after the vesical instillation of sodium hyaluronate in patients with painful bladder syndrome. There was no toxicity arising from the treatment, given that no adverse effects were recorded in relation to it.Conclusionthe clinical use of intravesical hyaluronic acid in patients with painful bladder syndrome possibly associated with interstitial cystitis has been demonstrated. The clinical improvement is also associated both with increased bladder capacity and improved bladder sensitivity. Tolerance was excellent. Clinical tests that more profoundly evaluate the therapeutic potential of this drug in this type of patients are required.     

Prospective study of intravesical dimethyl sulfoxide in treatment of suspected early interstitial cystitis

The efficacy of intravesical instillations of dimethyl sulfoxide (DMSO) in the treatment of suspected early interstitial cystitis was investigated in a prospective study. Among 20 patients treated, complete symptomatic remissions were achieved in 3, partial symptomatic remissions were achieved in 16, and 1 had no symptomatic improvement. However, functional bladder capacities following treatment were increased by more than 25 per cent in only 4 cases. Among 16 patients who experienced symptomatic remissions and who have been followed for > four months, 14 had sustained remissions (mean follow-up eleven months) and 2 had unsustained remissions. Clinically apparent toxicity was minimal but transient elevation of the serum lactic acid dehydrogenase was occasionally observed during treatment. DMSO appears to be useful in the management of carefully selected patients with suspected early interstitial cystitis.     

Intravesical electromotive drug administration for the treatment of non-infectious chronic cystitis

Seventeen patients with non-infectious chronic cystitis (NICC) (9 with interstitial cystitis, 6 patients with radiation cystitis, 1 with chemocystitis and 1 with lupoid cystitis) were treated with electromotive administration of intravesical lidocaine and dexamethasone followed by hydrodistension of the bladder. Complete resolution of symptoms for an average of 7.5 months was observed in 11 patients (65%), partial improvement in 4 (23.5%). In this series no complications occurred. Electromotive drug administration (EMDA) and cystodistension were well tolerated by all patients. The treatment was performed on an outpatient basis, thus reducing therapeutic costs. The results presented demonstrate that the combination of EMDA and bladder hydrodistension is an effective first-line treatment for NICC patients. EDITORIAL COMMENT: Electromotive drug administration is a new therapy being evaluated by these researchers for non-infectious chronic cystitis (interstitial and radiation-induced cystitis). Traditional drugs and hydrodistension are used with the addition of this new modality. Randomized controlled trials are necessary to see if the initially good results of 65% cure can be confirmed.     

Intravesical instillation of resiniferatoxin for the patients with interstitial cystitis

Although hydrodistention of the bladder is accepted as the initial treatment for patients with interstitial cystitis (IC), second-line treatment for worsening symptoms is not concretely established. Resiniferatoxin (RTX) desensitizes bladder afferent c-fibers and its intravesical instillation is effective for patients with detrusor overactivity. We studied the clinical relevance of intravesical treatment with RTX for patients with IC. The treatment was performed for 3 patients with incomplete improvement after hydrodistention. All 3 patients were free of bladder pain posttreatment and had slight improvement of the maximum voided volume. Though RTX treatment requires general anesthesia against severe bladder pain it is effective for selected patients with interstitial cystitis and can be potentially used as one of the treatment options.     

吡柔比星(THP)膀胱灌注预防腺性膀胱炎术后复发的疗效观察

目的 评价吡柔比星(THP)膀胱灌注预防腺性膀胱炎术后复发的疗效。方法 对30例腺性膀胱炎患者行经尿道汽化电切术,术后定期应用THP(40mg/50ml)膀胱内灌注化疗。结果 30例患者随访5～20个月,平均14.5个月,3例复发(10％)。未见有全身性药物不良反应,仅2例血白细胞降至3000个/ml。结论THP膀胱灌注预防腺性膀胱炎术后复发疗效满意,病人耐受性好,副作用小。     

碱化利多卡因膀胱灌注治疗氯胺酮相关性膀胱炎

目的 探讨碱化利多卡因膀胱灌注扩张治疗氯胺酮相关性膀胱炎的临床价值.方法 2008-2009年收治氯胺酮相关性膀胱炎7例.男6例,女1例.平均年龄26(19～38)岁.其中复发病例3例共10次.患者均有氯胺酮滥用史,伴有严重尿频、尿急、尿痛等下尿路症状(LUTS);白天排尿间隔时间(20±15)min,夜尿12～20次,每次尿量(50±15)ml.B超检查示膀胱壁增厚、容积缩小;上尿路积水3例.尿动力学检查功能性膀胱容量平均50(20～100)ml,Qmax3.7～10.8 ml/s,残余尿量0～24 ml.膀胱感觉敏感性增高、顺应性下降3例.蛛网膜下腔加硬膜外麻醉下行膀胱镜检查术,见膀胱黏膜呈广泛出血样改变.患者均在麻醉下行膀胱水压扩张、术后留置硬膜外导管镇痛和2%碳酸利多卡因20 ml加5%碳酸氧钠10 ml膀胱灌注并口服清除氧自由基药物等综合治疗.结果 2例膀胱活检提示慢性炎症伴肉芽肿样增生改变.膀胱灌注治疗7～10 d后患者LUTS均明显改善,膀胱容量平均(150±30)ml,排尿间隔(85±25)min,Qmax(11.5±3.8)ml/s,夜尿3～5次.3例复发者重复上述治疗.平均随访7(2～17)个月,患者症状均明显好转,每次排尿量平均(250±80)ml,夜尿0～2次.结果 麻醉状态下以碱化利多卡因膀胱灌注扩张能迅速、有效地增加膀胱容量,改善LUTS,是治疗氯胺酮相关性膀胱炎一种简单有效的方法.     

The use of dimethyl sulfoxide in the treatment of intractable urinary frequency

Intravesical instillation of dimethyl sulfoxide (DMSO) was used in the treatment of patients with intractable urinary frequency due to chronic prostatitis, chronic cystitis, tuberculous contracted bladder and interstitial cystitis. Before the application of this therapy, all 4 patients were examined carefully to rule out cases of acute infectious diseases of the urinary tract, active urinary tuberculosis, neurogenic bladder and carcinoma in situ of the bladder. Three of the four patients achieved an excellent response both subjectively and objectively. In the United States, intravesical instillation of DMSO had already been established as the specific method in the treatment of interstitial cystitis and no side effects have been reported so far. Therefore, we recommend the use of intravesical instillation of DMSO more commonly in various forms of intractable urinary frequency.     

Beneficial effects of suplatast tosilate (IPD-1151T) in a rat cystitis model induced by intravesical hydrochloric acid

OBJECTIVE: To examine the effects of suplatast tosilate (IPD-1151T), a Th2 cytokine inhibitor recently recognized to improve the symptoms in patients with interstitial cystitis (IC), in a rat model of HCl-induced chronic cystitis, to elucidate the possible mechanisms by which the drug improves the symptoms of IC. MATERIALS AND METHODS: Chronic cystitis was induced by intravesical instillation of 0.2 mL of 0.4 m HCl in female adult rats. After a once-daily oral administration of IPD-1151T (0.1-100 mg/kg) or prednisolone (5 mg/kg) for 7 days, cystometry was performed under urethane anaesthesia. The bladder from HCl-induced cystitis rats was also assessed histopathologically. RESULTS: On cystometrography there was frequent voiding in cystitis rats. Administration of IPD-1151T for 7 days after intravesical HCl instillation dose-dependently increased the micturition volume and intercontraction intervals. Treatment with prednisolone had similar therapeutic effects. Histological analyses in the bladder from cystitis rats revealed oedema and infiltration of inflammatory cells such as mast cells and eosinophils in the lamina propria and the transitional epithelial thickening. These histological changes and the number of mast cells and eosinophils were reduced by administration of IPD-1151T or prednisolone. CONCLUSION: The present results indicate that IPD-1151T improves bladder function and pathological changes in HCl-induced cystitis rats, as previously observed in patients with IC. The rat cystitis model induced by HCl could provide useful information for studying proposed therapies for IC which might involve T cell-dependent inflammatory responses as one of its potential pathophysiologies.     

Recent developments of intravesical therapy of painful bladder syndrome/interstitial cystitis: a review

PURPOSE OF REVIEW: Painful bladder syndrome/interstitial cystitis is a chronic sterile inflammatory disease of the bladder of unknown cause. It is characterized by bladder pain, urinary frequency, urgency, and nocturia. Although there are plenty of theories, the cause of the condition remains obscure. An abundance of treatments has been suggested, but very few have been subjected to proper controlled trials. This review focuses on the recently published literature on intravesical therapy strategies in painful bladder syndrome/interstitial cystitis. RECENT FINDINGS: Bladder irrigation with different agents has been used during years in an attempt to treat painful bladder syndrome/interstitial cystitis. The background for this is the existing theories about urothelial dysfunction. The 'traditional' agent for glycosaminoglycan substitution is hyaluronic acid. Often used are heparin and dimethyl sulfoxide, the actions of which are not quite clear but supposedly on an anti-inflammatory basis. Other agents for intravesical treatment are Bacillus Calmette-Guerin vaccine and botulinum toxin, and some recent studies have pointed to resiniferatoxin and RDP58. SUMMARY: Painful bladder syndrome/interstitial cystitis persists as a challenging syndrome in urology. Intravesical instillation therapy has basically not changed during the last few years, although some studies have disconfirmed some regimens. Intensive research may hopefully result in more effective treatments in the future.     

Clinical experience with multiagent intravesical therapy in interstitial cystitis patients unresponsive to single-agent therapy

Summary A total of 25 patients with the diagnosis of interstitial cystitis (IC) were involved in this study. All patients had been previously diagnosed with interstitial cystitis and had received treatment with single intravesical agents. Patients were divided into two groups according to their bladder capacity. The bladder capacity was >350 ml in group I patients and <350 ml in group II patients. For our study, dimethylsulfoxide (DMSO), methylprednisolone, and heparin sulfate were given every week for a total of 6 weeks. When symptoms recurred, supportive oral pharmacotherapy consisting of anticholinergics and/or tricyclic antidepressants was given. Under anesthesia, patients in group I showed a 99% increase in their bladder capacity; whereas those in group II showed an increase of only 19%. Cystoscopically, Hunner's ulcers were present in 60% of the group II patients but were seen in only 5% of the group I patients. Histopathological examination showed that the inflammatory changes were more frequent and severe in group II than in group I. Mast-cell hyperplasia was present in 100% of the patients in group II, versus only 61% of those in group I. A total of 23 patients (92%) achieved an initial remission averaging 8.1 months. In all, 9 patients (35%) had 1 or more relapses, and all achieved a subsequent remission averaging 8 months. By this combined multiagent approach, the majority of patients with IC obtained relief from their incapacitating symptoms and were socially rehabilitated.     

Measuring the success of combined intravesical dimethyl sulfoxide and triamcinolone for treatment of bladder pain syndrome/interstitial cystitis

Introduction and hypothesis

The purpose of this study was to investigate change in bladder capacity as a measure of response to combined intravesical dimethyl sulfoxide (DMSO) and triamcinolone instillations for the treatment of newly diagnosed bladder pain syndrome/interstitial cystitis (BPS/IC).

Methods

141 newly diagnosed women were identified retrospectively. 79 were treated with weekly DMSO/triamcinolone instillations. Change in bladder capacity with bladder retrofill, daytime urinary frequency, nocturia episodes per night, and Likert scale symptom scores were reviewed. Wilcoxon signed-rank tests, Wilcoxon rank-sum tests, Spearman’s rank correlations, COX regression analysis, and a Kaplan-Meier survival curve were performed.

Results

Significant changes (median (25^th-percentile to 75^th-percentile) were noted for bladder capacity (75 mL (25 to 130 mL), p?<?0.0001), inter-void interval (0 hrs (0 to 1 hour), p?<?0.0001), nocturia episodes per night (?1 (?2 to 0), p?<?0.0001), and aggregate Likert symptom scores (?2 points (?5 to 0), p?<?0.0001). Percent change in bladder capacity correlated positively with percent change in inter-void interval (p?=?0.03) and negatively with percent changes in nocturia (p?=?0.17) and symptom scores (p?=?0.01). Women without detrusor overactivity (DO) had greater percent changes in capacity than women with DO (62.5 % vs. 16.5 %, p?=?0.02). 61.3 % of patients were retreated with a 36 weeks median time to retreatment and no difference in time to retreatment based upon DO. Greater capacity was protective against retreatment (hazard ratio?=?0.997 [95 % CI 0.994,0.999], p?=?0.02).

Conclusions

Percent change in bladder capacity is a useful objective measure of response to intravesical DMSO/triamcinolone for newly diagnosed BPS/IC. Clinical outcomes do not differ based upon presence of DO.     

Use of amitriptyline in the treatment of interstitial cystitis

A total of 25 patients with interstitial cystitis who had failed standard therapy with hydrodistension of the bladder during anesthesia and intravesical dimethyl sulfoxide instillation underwent treatment with the tricyclic antidepressant amitriptyline. The initial dosage of 25 mg. before bed was increased gradually during a 3-week period to 75 mg. at bedtime. Of the patients 20 were able to tolerate the medication for a minimum of 3 weeks and could be evaluated for response. A significant improvement was noted in pain and daytime frequency. Of 9 patients 8 experienced relief of dyspareunia and 11 of 19 reported diminished urinary urgency. Eight patients have experienced virtual total remission of symptoms and have been on the drug for 4 to 28 months. It appears reasonable to consider the use of amitriptyline in patients with interstitial cystitis refractory to standard therapy.