‘Don’t pee on that!’ Comparing environmental modification and medical management in cats with FIC

a Knowledge Summary by

Amelia Poole DipAVN DipFB CertVN(ECC) CertISFM(FN) RVN ^1*

¹Harper Adams University, Edgemond, Newport, TF10 8NB
^*Corresponding Author (amelia@rcvsknowledge.org)

Clinical scenario

A 4-year-old, male neutered cat is being presented for the third time for cystitis. After a thorough work up, a diagnosis of idiopathic cystitis has been made. The patient is already on a gastrointestinal prescription diet, and the owner does not want to change this. The owner asks if other treatments are available to reduce the occurrence of his clinical signs.

The evidence

The literature searches uncovered 13 papers that addressed pharmaceutical treatment for cats with feline idiopathic cystitis (FIC) and three papers addressing environmental modification as a treatment. Pharmaceutical treatments included oral preparations of non-steriodal anti-inflammotory Drugs (NSAIDS) (Dorsch et al., 2016), steroids (Osbourne et al., 1996), tricyclic antidepressants (Chew et al., 1998; Kruger et al., 2003; and Kraijer et al., 2003), glucosamine (Gunn-Moore and Shenoy, 2004) and prazosin (Reineke et al., 2017). Parenteral treatments include intravesical glycosaminoglycan (GAGs) (Bradley et al., 2013), pentosan polysulphate and lidocaine (Zezza et al., 2012) and subcutaneous pentosan polysulphate (Wallius et al., 2009). Of these studies, only one paper (Chew et al., 1998) found that long-term (12 months) use of amitriptyline successfully decreased clinical signs of recurrent cystitis in 9/15 cats treated, however this improvement was only apparent in the last 6 months. Three studies included environmental modification as a treatment option, which included the use of feline facial pheromones (FFPs) (Gunn-Moore and Cameron, 2004). The use of FFPs did not have a statistical difference in reoccurrence of signs when compared to the placebo, however there was a clinical difference shown, with those exposed to FFP having a reduced occurrence and reduced severity of FIC. A case study by Seawright et al. (2008) followed a case with environmental modification for an extended period of time, which showed that episodes of cystitis only occurred during extraordinary stressful situations such as building works. A study into multimodal environmental modification (Buffington et al., 2006) showed a resolution in signs for 75% for 10 months. Each study into environmental modifications had a number of uncontrollable variables due to each cat’s condition and environment, so further studies are required to confirm any success.

Summary of the evidence

Appraisal, application and reflection

A number of studies were identified due to the wide variables involved with searching for medication. However, each study focused on a different treatment, allowing for a wide range of results. There was no study that compared medical treatment alone to environmental treatment.

Only one study, Chew et al. (1998), identified medication as having an effect on reducing the occurrence of FIC. This was if the patients were treated with amitriptyline 10 mg/cat SID PO long-term. The study showed that the medication decreased the occurrence in 9/15 (60%) cats, and reduced haematuria and proteinuria in 100% of cats at the 12 month evaluation. However, the sample size of this study was small (n=15) and could have been impacted by a number of variables within the cat’s environment. The cessation of haematuria and proteinuria is a positive outcome for the treatment; however, it is not made clear if these patients were tested within the same time period. FIC being a self-limiting disease may indicate that the cats could have been asymptomatic at the time regardless of the treatment. 5 years later, Kruger et al. (2003) found that short-term administration (7 days) of amitriptyline had no statistical benefit over the reduction in pollakiuria and haematuria. Additionally, cats treated with amitriptyline had a faster recurrence rate when compared to the placebo. Much like the study by Chew et al. (1998) there were uncontrollable variables within the cat’s environment that could have contributed to these results.

Six of the studies focused specifically on cats with FIC that caused urethral obstruction and the reoccurrence of symptoms if treatment was given at the time of obstruction. Dorsch et al. (2016) identified that there was no significant difference between patients having meloxicam and a placebo for 5 days post obstruction, however due to the nature of the treatment for a urethral obstruction, this was given concurrently with a urinary catheter and fluid therapy, so credit of success cannot be given to one treatment alone. This study does not identify the cause of the obstruction, and whether patients had high amounts of urinary sediment, or inflammation. The measured outcome was a repeat urethral obstruction and does not record whether cats suffered with other generalised symptoms of FIC before becoming obstructed. This was a similar finding to Nivy et al. (2019) with the administration of phenoxybenzamine and alprazolam (n=51) with the addition of meloxicam (n=24). This study had the largest sample size, but no placebo control group, so the results cannot be contributed to any success.

Reineke et al. (2017) completed a longer-term study with the administration of prazosin (n=27) for 1 month following urethral obstruction. Follow-ups for 6 months post-treatment identified no statistical difference between the prazosin and placebo for a repeat urethral obstruction, or a reduction in the severity of clinical signs. Like the previous studies that test oral medication, the variables in the environment cannot be controlled, and may have contributed to the recurrence of clinical signs, alternatively the stress of giving medication on a daily basis could have also contributed to clinical signs.

Three studies focused on the administration of medication through intravesical means, one with intravesical GAGs (Bradley et al., 2013), pentosan polysulphate (Delille et al., 2016) and the other with intravesical sodium bicarbonate ± lidocaine (Zezza et al., 2012). Bradley et al. (2013) found that those treated with GAGs had a reduced recurrence of obstruction when compared to the placebo group (p=0.06), however the study size was small (n=14) and performed within a hospital environment with concurrent treatment of fluid therapy. When given intravesical pentosan polysulphate (Delille et al., 2016), obstructed cats suffered with repeat obstruction at the same rate as those with a placebo (p=1.00). Zezza et al. (2012) found no clinical benefit to the addition of lidocaine, however although the sample size was larger than Bradley et al. (2013), it was again restricted to hospitalised patients (n=26) with concurrent treatments of amoxicillin-clavulanic acid for 2 days before discharge.

Wallius et al. (2009) combined owner interviews with clinical examination for treatment with subcutaneous injections of pentosan polysulphate, treatment used in human interstitial cystitis. The sample size was small (n=18) and was made smaller due to two cats being euthanised due to their clinical signs during the study. No statistical difference was found between the treatment and the placebo, despite the differing variables within the cat’s environment.

Giving other treatment concurrently to medication was common in these studies. Those owners that participated in the studies were obviously keen to treat their cats, so tried all forms of treatment to alleviate symptoms. Although beneficial for the patient, is not helpful in regard to studies as any results cannot be related directly to the medication. This was the case with Gunn-Moore & Shenoy (2004) and grading the severity of FIC signs alongside the administration of N-acetylglucosamine (n=40). Participants for the study were recruited from those referred directly to the university so had an invested interest in the cat’s success. Although owner assessment suggested that those treated had a greater improvement, there was no significant difference, and it was identified that owners had concurrently increased the water intake of the cats during the study, probably leading to the improvement seen.

Controlled studies within the hospital took place with the administration of prednisolone UID for 10 days (Osbourne et al., 1996). Although this allows for variables to be controlled, it also introduces the variable of the patient being stressed in an unnatural environment, thus potentially increasing the chance of stress related signs. Osbourne showed that steroid treatment had no benefit for reducing the clinical signs of FIC (n=12), however the sample size was small and was only concentrating on the cessation of signs and not the rate of recurrence.

One study concentrated on environmental modification as a treatment (Buffington et al., 2006), with indoor cats (n=46). A change in environment showed a reduction in the reoccurrence of lower urinary tract signs (p<0.0001) and a general improvement in fearfulness (p<0.0002) and nervousness (p<0.0002). However, the environmental modification for each cat was varied, with a number of options being given to the owner. With a number of different variables, it cannot be identified if one was more successful than the other, or if a variety is required for success. There were also no concurrent control groups.

Seawright et al. (2008) reported on a single case control study of a patient treated with a range of medications for 3 weeks and environmental treatment long-term. The patient was assessed for 15 months and showed only one period of FIC signs, occurring due to a stressful event in the environment. This episode was self-resolving. This study indicates the effect the environment has on one cat suffering from FIC; however, it is only one case with a number of variables in place and cannot be taken as a treatment option for a larger population.

Feline facial pheromones were used in adjunction to environmental therapy for 12 cats for a duration of 6 months. Owners were asked to score their cats on a number of scales to identify not only signs of cystitis, but also signs of stress. Owners were given visual analogue scales and daily diaries to record, and although there was no statistical difference between the treatment period and the placebo period, there was a clinical difference, with reports showing a reduced severity and occurrence of FIC; however, those cats that were to experience stressful situations (such as building or moving house) were removed from the study so it is not known if this is an effective treatment during signs of stress.

There was one paper that tested alternative methods of treating FIC, a mix of medication, vitamins and a probiotic (Sofyan et al., 2019). The case report by Sofyan attributed the success of the cat being able to urinate post urethral obstruction to the probiotic. However, this was given concurrently with muscle relaxants and antibiotics. With no control study taking place, the evidence to support the probiotics success in this case is weak.

There is limited evidence in this research area, with treatments focusing on reducing inflammation or stress to reduce the clinical effects of FIC. This makes any research difficult, as to control variables cats have to be hospitalised, which increases the stress they experience. If not in the hospital, cats are then in their own home environment, where variables cannot be controlled, reducing the efficacy of the research by allowing other variables, meaning any success cannot be contributed to one treatment. Two of the randomised control studies showed a statistical difference between the treatment group and the placebo, these being MEMO and long-term amitriptyline, with the trial involving FFP not showing a statistical difference but a clinical difference. Two of the case reports based on environmental modification showed patient improvement, however their level of evidence is weak as they both have uncontrolled variables and cannot be repeated under the same conditions. It is clear from the variety of medical treatment options, that the true cause of FIC has not been identified. Further research is required to identify the true cause, to then make true comparisons.

Methodology Section

Search Strategy
Databases searched and dates covered:	CAB Abstracts on OVID interface (1973 – 2020 Week 21) PubMed accessed via the NCBI website (1910 – June 2020)
Search strategy:	CAB Abstracts: cat or cats or feline or felines or exp cats/ or exp felis/ cystitis or 'feline interstitial cystitis' or 'feline idiopathic cystitis' or FIC or 'Feline lower urinary tract disease' or FLUTD environment* or behaviour or behavior or enrich* or exp environment/ or exp animal behaviour/ drug* or medicat* or medicin* or pharmaceutical* or opioid* or NSAID or NSAIDs or 'non-steroidal anti-inflammatory' or 'non-steroidal anti inflammatories' or 'non-steroidal anti-inflammatory' or 'non-steroidal anti-inflammatories' or ‘nonsteroidal anti-inflammatory' or 'nonsteroidal anti inflammatories' or 'nonsteroidal anti-inflammatory' or 'nonsteroidal anti-inflammatories' or exp anti-inflammatory agents/ or exp non-steroidal anti-inflammatory agents/ or exp opioids/ 1 and 2 and (3 or 4) manag* or treat* or therap* or prevent* 5 and 6 PubMed: cat OR cats OR feline OR felines cystitis OR “feline interstitial cystitis” OR “feline idiopathic cystitis” OR FIC OR “Feline lower urinary tract disease” OR FLUTD environment OR environmental OR behaviour OR behavior OR enrichment drug OR medication OR medicine OR pharmaceutical OR opioid OR nsaid OR nsaids OR “non steroidal anti inflammatory” OR “non steroidal anti inflammatories” 1 AND 2 AND (3 OR 4) manage OR management OR treat OR treatment OR therapy OR therapeutic OR prevent OR prevention 5 AND 6
Dates searches performed:	03 Jun 2020

Exclusion / Inclusion Criteria
Exclusion:	No relevance to PICO question (e.g. co-morbidities, cause for urine infection) non-English paper, duplicates, diet
Inclusion:	Any study which involved cats with idiopathic cystitis and medication or environmental treatment. This included obstructed idiopathic cystitis if this was mentioned

Search Outcome
Database	Number of results	Excluded – Not relevant to PICO question	Excluded – Non-English language	Excluded – Conference abstract	Excluded – Duplicate	Excluded – Diet	Total relevant papers
CAB Abstracts	189	146	21	10	1	2	9
PubMed	315	292	3	1	9	3	7
Total relevant papers when duplicates removed							16

I work for RCVS Knowledge as a Project Officer: Quality Improvement and Vets Now as an ECC RVN.

Student at Harper Adams University

1. Bradley, A.M. & Lappin, M.R. (2013). Intravesical glycosaminoglycans for obstructive feline idiopathic cystitis: A pilot study. Journal of Feline Medicine and Surgery. 16(6): 504–6. DOI: https://doi.org/10.1177/1098612X13510918
2. Buffington, C.T., Westropp, J.L., Chew. D.J. & Bolus, R.R. (2006). Clinical Evaluation of Multimodal Environmental Modification (MEMO) in the management of cats with idiopathic cystitis. Journal of Feline Medicine and Surgery. 8(4): 261–8. DOI:https://doi.org/10.1016/j.jfms.2006.02.002
3. Chew, D.J., Buffington, C.A., Kendall, M.S., DiBartola, S.P. & Woodworth, B.E. (1998). Amitriptyline treatment for severe recurrent idiopathic cystitis in cats. Journal of the American Veterinary Medical Association. 213(9): 1282–6.
4. Delille, M., Fröhlich, L., Muller, R.S., Hartmann, K. & Dorsch, R. (2016). Efficacy of intravesical pentosan polysulphate Sodium in Cats With Obstructive Feline Idiopathic Cystitis. Journal of Feline Medicine and Surgery. 18(6): 492–500. DOI: https://doi.org/10.1177/1098612X15588934
5. Dorsch, R., Zellner, F., Schulz, B., Sauter-Louis, C. & Hartmann, K. (2016). Evaluation of Meloxicam for the Treatment of Obstructive Feline Idiopathic Cystitis. Journal of Feline and Medicine and Surgery. 18(11): 925–933. DOI: https://doi.org/10.1177/1098612X15621603
6. Gunn-Moore, D.A. & Shenoy, C.M. (2004). Oral Glucosamine and the Management of Feline Idiopathic Cystitis. Journal of Feline and Medicine and Surgery. 6(4): 219–25. DOI: https://doi.org/10.1016/j.jfms.2003.09.007
7. Gunn-Moore, D.A. & Cameron, M.E. (2004). A Pilot Study Using Synthetic Feline Facial Pheromone for the Management of Feline Idiopathic Cystitis. Journal of Feline and Medicine and Surgery. 6(3): 133–8. DOI: https://doi.org/10.1016/j.jfms.2004.01.006
8. Kraijer, M., Fink-Gremmels, J. & Nickel, R.F. (2003). The Short-Term Clinical Efficacy of Amitriptyline in the Management of Idiopathic Feline Lower Urinary Tract Disease: A Controlled Clinical Study. Journal of Feline and Medicine and Surgery. 5(3): 191–6. DOI: https://doi.org/10.1016/S1098-612X(03)00004-4
9. Kruger, J.M., Conway, T.S., Kaneene, J.B., Perry, R.L., Hagenlocker, E., Golombek, A. & Stuhler, J. (2003). Randomized Controlled Trial of the Efficacy of Short-Term Amitriptyline Administration for Treatment of Acute, Nonobstructive, Idiopathic Lower Urinary Tract Disease in Cats. Journal of the American Veterinary Medical Association. 222(6): 749–58. DOI: https://doi.org/10.2460/javma.2003.222.749
10. Nivy, R., Segev, G., Rimer, D., Bruchim, Y., Aroch, I. & Mazaki-Tovi, M. (2019). A Prospective Randomized Study of Efficacy of 2 Treatment Protocols in Preventing Recurrence of Clinical Signs in 51 Male Cats With Obstructive Idiopathic Cystitis. Journal of Veterinary Internal Medicine. 33(5): 2117–2123. DOI: https://doi.org/10.1111/jvim.15594
11. Osbourne, C.A., Kruger, J. M., Lulich, J.P., Johnston, G.R., Polzin, D.J., Ulrich, L.K. & Sanna, J. (1996). Prednisolone therapy of idiopathic feline lower urinary tract disease: A double-blind clinical study. The Veterinary Clinics of North America Small Animal Practice. 26(3): 563–9. DOI: https://doi.org/10.1016/S0195-5616(96)50085-9
12. Reineke, E.L., Thomas, E.K., Syring, R.S., Savini, J. & Drobatz, K.J. (2017). The effect of prazosin on outcome in feline urethral obstruction. Journal of Veterinary Emergency and Critical Care. 27(4): 387-96. DOI: https://doi.org/10.1111/vec.12611
13. Seawright, A., Casey, R., Kiddie, J., Murray, J., Gruffydd-Jones, T., Harvey, A., Hibbert, A. & Owen, L. (2008). A case of recurrent feline idiopathic cystitis: The control of clinical signs with behaviour therapy. Journal of Veterinary Behaviour. 3(1): 32–38. DOI: https://doi.org/10.1016/j.jveb.2007.09.008
14. Sofyan, M., Rosman, N., Krisnu, B. & Kamaludeen, J. (2019). Management of Feline Idiopathic Cystitis (FIC) Using Probiotic Combination Treatment. The Indian Veterinary Journal. 96(12): 20–22.
15. Wallius, B.M. & Tidholm, A.E. (2009). Use of Pentosan Polysulphate in Cats With Idiopathic, Non-Obstructive Lower Urinary Tract Disease: A Double-Blind, Randomised, Placebo-Controlled Trial. Journal of Feline Medicine and Surgery. 11(6): 409–12. DOI: https://doi.org/10.1016/j.jfms.2008.09.003
16. Zezza, L., Reusch, C.E. & Gerber, B. (2012). Intravesical Application of Lidocaine and Sodium Bicarbonate in the Treatment of Obstructive Idiopathic Lower Urinary Tract Disease in Cats. Journal of Veterinary Internal Medicine. 26(3): 526–31. DOI: https://doi.org/10.1111/j.1939-1676.2012.00911.x