The Efficacy and Safety of Duloxetine in a Multidrug Regimen for Chronic Prostatitis/Chronic Pelvic Pain Syndrome

doi:10.1016/j.urology.2013.09.024

Urology

Volume 83, Issue 2, February 2014, Pages 400-405

https://doi.org/10.1016/j.urology.2013.09.024 Get rights and content

Objective

To evaluate the efficacy and safety of duloxetine hydrochloride in the treatment of patients affected by chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Methods

Thirty-eight CP/CPPS patients completed the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and International Index of Erectile Function-Erectile Function-5 (IIEF-5) questionnaires, uroflowmetry, and evaluation of psychologic status using Hamilton Anxiety Scale (HAM-A) and Hamilton Depression Scale (HAM-D). Patients were randomly assigned to 2 treatments groups. Treatment in group 1 consisted of a simultaneous oral administration of tamsulosin (0.4 mg/d, 60 mg/d), saw palmetto (320 mg/d), and duloxetine (60 mg/d). Treatment in group 2 consisted of tamsulosin (0.4 mg/d) and saw palmetto (320 mg/d). NIH-CPSI and IIEF-5 questionnaires, uroflowmetry, and evaluation of the psychological status were repeated at 16 weeks of follow-up.

Results

At 16 weeks, a significant improvement in NIH-CPSI pain subscore, NIH-CPSI quality of life subscore, and NIH-CPSI total score were observed in group 1 patients compared with those in group 2 (P <.01, respectively), together with a significant improvement in HAM-A and HAM-D scores (P <.01, respectively). Patients in group 2 showed a significant improvement in NIH-CPSI total score, in the urinary symptoms subscore, and in the HAM-A total score. No significant differences were observed in IIEF-5 scores in the 2 groups. Maximum flow rate significantly increased in both groups. In group 1, 20% of patients stopped the study due to adverse effects.

Conclusion

The use of duloxetine in a multimodal treatment with an α-blocker medication and a saw palmetto extract allowed better results in controlling clinical symptoms, psychologic status and quality of life patients affected by CP/CPPS.

Section snippets

Patients and Methods

The study was approved by the Institutional Review Board, and patients gave their written consent. All procedures were conducted in accordance with the Declaration of Helsinki.

Results

The treatments groups were well balanced in baseline characteristics. The mean (SD) age of patients in group 1 was 47 (13.0) years compared with 46.6 (12.2) years for patients in group 2. There was no difference in educational level or employment status between the 2 treatment groups. Mean duration of symptoms since diagnosis was 5.7 (8.1) years for patients in group 1 and 6.5 (7.3) years for patients in group 2. At 16 weeks of follow-up, we observed a significant amelioration, compared with

Comment

This study demonstrated that the addition of duloxetine hydrochloride to an α-blocker medication and a saw palmetto extract was superior in relieving pain and improving psychologic status and QoL compared with a conventional treatment including the 2 drugs alone in patients affected by CP/CPPS. Particularly, a combination treatment with duloxetine (60 mg/d), tamsulosin (0.4 mg/d), and saw palmetto (320 mg/d) was able to significantly improve the NIH-CPSI total score and subscores (pain, urinary

Conclusions

The inclusion of duloxetine hydrochloride in a multimodal treatment with an α-blocker medication and a saw palmetto extract allowed better results in controlling clinical symptoms, psychological status, and QoL in patients affected by CP/CPPS.

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Cited by (24)

Oral pharmacological treatments for chronic prostatitis/chronic pelvic pain syndrome: A systematic review and network meta-analysis of randomised controlled trials
2022, eClinicalMedicine
Citation Excerpt :
In total, the search yielded 4752 articles. Following abstract screening and full-text reviews, 25 randomised controlled trials involving 3514 patients with CP/CPPS were included (Figure 1).9,24,26–48 Overall, the studies were conducted between 1999 and 2019.
Pharmacological treatments for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are empirically used. However, the quantitative comparative effectiveness and safety of multiple pharmacological treatments is lacking.
PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched from inception to March 22, 2022. Randomised controlled trials comparing two or more oral pharmacological treatments for patients with CP/CPPS were included. Title, abstract, and full-text screening were independently screened by four reviewers. Primary outcomes were efficacy (the National Institutes of Health Chronic Prostatitis Symptom Index [NIHCPSI] total score, pain score, urinary score, and quality of life score [QoL]) and safety (adverse events). This study was registered with PROSPERO, CRD42020184106.
25 studies (3514 patients) assessed 26 treatments. Low to very low quality evidence indicated that doxazosin (Mean difference [MD], –11.4, 95% Credible interval [CrI], –17.5 to –5.1) and the doxazosin, ibuprofen, and thiocolchicoside combination (MD, –11.6, CrI, –18.1 to –5.3) were significantly more effective than placebo in the NIHCPSI total score. Other NIHCPSI relative outcomes (pain, urinary, and QoL scores) showed a similar pattern. Low and very low quality evidence suggested that combination treatment including doxazosin, ibuprofen, and thiocolchicoside (odds ratios [OR], 3.2, CrI, 0.5 to 19.3) and the tamsulosin and dapoxetine combination (OR, 6.0, CrI, 0.7 to 67.3) caused more adverse events. In half of all comparisons regarding NIHCPSI pain scores and quality of life scores, heterogeneity was minimal or low. Heterogeneity was high in both NIHCPSI total symptom scores (I² = 78.0%) and pain scores (I² = 87. 0%) for tamsulosin versus placebo. There was also high heterogeneity in NIHCPSI urine scores for the combination of tamsulosin and ciprofloxacin versus tamsulosin (I² = 66.8%), tamsulosin and levofloxacin versus tamsulosin (I² = 93.3%), and tamsulosin versus placebo (I² = 83%).
Pharmacological treatments have little evidence supporting efficacy in CP/CPPS. Future studies could personalise therapy for individuals according to specific symptoms and identify non-pharmacological targets for CP/CPPS.
Dr Jiani Wu received funding for this project from the China Association for Science and Technology (2017QNRC001), the China Academy of Chinese Medical Sciences (ZZ13-YQ-027), and the National Natural Science Foundation of China (82105037).
The Overactive Pelvic Floor (OPF) and Sexual Dysfunction. Part 2: Evaluation and Treatment of Sexual Dysfunction in OPF Patients
2021, Sexual Medicine Reviews
Citation Excerpt :
Some authors suggest starting with diazepam suppositories and muscle relaxants, reserving botulinum toxin for more recalcitrant OPF.116 Local or systemic neuromodulatory medications, such as topical117 or systemic gabapentin118,119, tricyclic antidepressants,119–121 and serotonin–norepinephrine reuptake inhibitors122,123 are often used to address pain in CPP and GPPPD patients; as their effect is not directly targeting muscle function, we will not discuss them in detail. The evidence for vaginal diazepam is equivocal at best.
The assessment of pelvic floor muscle (PFM) overactivity is part of a comprehensive evaluation including a detailed history (medical, gynecological history/antecedent), appraisal of the psychosocial contexts of the patient, as well as a musculoskeletal and a neurological examination.
The aims of this article are to review (i) the assessment modalities evaluating pelvic floor function in women and men with disorders associated with an overactive pelvic floor (OPF), and (ii) therapeutic approaches to address OPF, with particular emphases on sexual pain and function.
We outline assessment tools that evaluate psychological and cognitive states. We then review the assessment techniques to evaluate PFM involvement including digital palpation, electromyography, manometry, ultrasonography, and dynamometry, including an overview of the indications, efficacy, advantages, and limitations of each instrument. We consider each instrument's utility in research and in clinical settings. We next review the evidence for medical, physiotherapy, and psychological interventions for OPF-related conditions.
Research using these assessment techniques consistently points to findings of high PFM tone among women and men reporting disorders associated with OPF. While higher levels of evidence are needed, options for medical treatment include diazepam suppositories, botulinum toxin A, and other muscle relaxants. Effective psychological therapies include cognitive behavioral therapy, couple therapy, mindfulness, and educational interventions. Effective physiotherapy approaches include PFM exercise with biofeedback, electrotherapy, manual therapy, and the use of dilators. Multimodal approaches have demonstrated efficacy in reducing pain, normalizing PFM tone, and improving sexual function. Multidisciplinary interventions and an integrative approach to the assessment and management of OPF using a biopsychosocial framework are discussed.
Although the efficacy of various intervention approaches has been demonstrated, further studies are needed to personalize interventions according to a thorough assessment and determine the optimal combination of psychological, physical, and behavioral modalities.
Padoa A, McLean, L, Morin M, et al. The Overactive Pelvic Floor (OPF) and Sexual Dysfunction. Part 2: Evaluation and Treatment of Sexual Dysfunction in OPF Patients. Sex Med 2021;9:76–92.
Interventions to chronic prostatitis/Chronic pelvic pain syndrome treatment. Where are we standing and what's next?
2019, European Journal of Pharmacology
Citation Excerpt :
Significant improvement was observed in NIH–CPSI, HAD and SF-MPQ after treatment with duloxetine hydrochloride combined with doxazosin compared with doxazosin alone and doxazosin + sertraline group. Duloxetine hydrochloride was also tested in combination with an alpha-blocker and a saw palmetto extract that proved to be efficacious in improving NIH–CPSI sub scores such as depression, QoL and pain symptoms when compared with the effectiveness of these 2 drugs alone (Giannantoni et al., 2014). Psychological factors are closely associated with CP/CPPS (Riegel et al., 2014) and symptoms result from an interaction between psychologic factors and dysfunction in the immune and neurologic abnormalities (Pontari and Ruggieri, 2008).
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a frustrating syndrome. The pathogenesis and state of the art treatment of CP/CPPS are not known. A wide variety of therapies including anti-inflammatories, antibiotics, alpha-blockers, neuropathic pain modulators, and 5α-reductase inhibitors are in practice. These treatment strategies focus on alleviating symptoms in specific domains without treating root-cause and therapeutic outcome is far from satisfactory. We review the literature on current pharmacological treatments for CP/CPPS in detail and suggest future perspectives to modify the treatment strategies. We suggest that introducing novel treatment strategies such as gene editing, and T_regs expressing chimeric receptors may improve the treatment outcomes by inducing immune tolerance and controlling expression of pro-inflammatory cytokines.
Therapeutic strategies for the treatment of chronic prostatitis / chronic pelvic pain syndrome
2016, Revista Internacional de Andrologia
La prostatitis crónica/síndrome de dolor pélvico crónico es una enfermedad con una repercusión sobre la calidad de vida que en ocasiones es equiparable a la de los pacientes con infarto de miocardio, diabetes mellitus, etc. Durante años, la terapia médica estándar se ha realizado con antiinflamatorios no esteroideos, alfa-bloqueantes y antibióticos.
Con el objetivo de analizar las alternativas terapéuticas existentes en la actualidad se ha llevado a cabo una búsqueda bibliográfica en PubMed de los artículos publicados hasta marzo del 2014, encontrando diversas terapias para el tratamiento de la prostatitis crónica/síndrome de dolor pélvico crónico como modificaciones en los estilos de vida, fitoterapia, extractos bacterianos orales inmunoestimulantes, acupuntura, terapia miofascial y biofeedback, terapias neuromoduladoras, ondas de choque extracorpóreas, fármacos con efecto sobre el sistema nervioso central y periférico, terapias cognitivo-conductuales y terapias térmicas.
Aunque muchos de estos estudios muestran a priori unos resultados satisfactorios, son necesarios ensayos clínicos controlados y aleatorizados con el objetivo de determinar la efectividad real así como la durabilidad de estos tratamientos en el tiempo.
The chronic prostatitis/chronic pelvic pain syndrome is a disease with an impact on quality of life which is sometimes comparable to that of patients with myocardial infarction, diabetes mellitus, etc. For years, the standard medical therapy was performed with non steroidal anti-inflammatory, alpha-blockers and antibiotics.
In order to analyze existing therapeutic alternatives at the moment, a comprehensive literature search in PubMed database was conducted for articles published up to March 2014 data, founding several therapies for the treatment of chronic prostatitis/chronic pelvic pain syndrome as changes in lifestyle, herbal medicine, oral immunostimulant bacterial extracts, acupuncture, myofascial therapy and biofeedback, neuromodulatory therapies, extracorporeal shockwave, medications known to affect the central and peripheral nervous system, cognitive-behavioral therapies and thermal therapies.
Although many of these studies show a priori satisfactory results, controlled randomized clinical trials are necessary to determine the actual effectiveness and durability of these treatments over time.
Assessing psychological factors, social aspects and psychiatric co-morbidity associated with Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) in men - A systematic review
2014, Journal of Psychosomatic Research
Citation Excerpt :
All of the aforementioned results suggest that CP/CPPS is associated with a remarkable impairment in QoL. An increase in QoL is, therefore, an important therapeutic goal: Research on antibiotics, adrenoceptor antagonists, anti-inflammatory drugs, sodium, alpha-receptor antagonists and SSRI shows an increased QoL after treatment [57,71–78]. The effect was not, however, always stable over time without treatment.
Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a chronic pain disease with high prevalence rates and substantial health care costs. An interdisciplinary classification system is commonly used (UPOINT) which includes psychosocial factors. Nevertheless, psychosocial influences on CP/CPPS only recently became a research focus. Therefore, we aimed to synthesize the existing data and to identify further research topics. Then, based on our results, diagnosis and treatment can be improved.
In a systematic review conducted according to the PRISMA reporting guidelines we searched different databases (MEDLINE, EMBASE, PsychINFO) using the broad search terms “chronic pelvic pain syndrome AND men”. Two raters independently screened the literature and assessed the risk of bias.
We included 69 original research articles which considered psychosocial variables. We found studies investigating different psychosocial factors (pain catastrophizing, stress, personality factors, social aspects), co-morbid psychiatric disorders (depression, anxiety and trauma-related disorders, somatization disorder, substance abuse) and Quality of Life (QoL). In addition, there is a high risk of bias in most studies e.g. concerning the study design or the measures.
There is evidence suggesting that psychological factors are important in understanding CP/CPPS. However, research concentrated on a few aspects while the others were not covered adequately. We found evidence of a higher number of psychosocial factors and psychiatric co-morbidities than is currently included in the UPOINT system. More high quality research is needed to understand the interplay of psychosocial factors in CP/CPPS. Furthermore, these factors should be incorporated into treatment approaches.
Biopsychosocial approach to male chronic pelvic pain syndrome: Recent treatments and trials
2024, Sexual Medicine Reviews

View all citing articles on Scopus

: Financial Disclosure: The authors declare that they have no relevant financial interests.

View full text

Prostatic Diseases and Male Voiding DysfunctionThe Efficacy and Safety of Duloxetine in a Multidrug Regimen for Chronic Prostatitis/Chronic Pelvic Pain Syndrome

Objective

Methods

Results

Conclusion

Section snippets

Patients and Methods

Results

Comment

Conclusions

Urology

J Psychosom Res

Urology

J Allergy Clin Immunol

Psychosomatics

Pain

NIH consensus definition and classification of prostatitis

JAMA

Chronic prostatitis: management strategies

Drugs

Mental health diagnoses in patients with interstitial cystitis/painful bladder syndrome and chronic prostatitis/chronic pelvic pain syndrome: a case/control study

J Urol

Mechanisms in prostatitis/chronic pelvic pain syndrome

J Urol

New treatments for chronic prostatitis/chronic pelvic pain syndrome

Nat Rev Urol

Italian version of the National Institutes of Health Chronic Prostatitis Symptom Index

Eur Urol

The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction

Urology

The assessment of anxiety states by ratings

Brit J Med Psychol

A rating scale for depression

J Neurol Neurosurg Psychiatry

Prostatic Diseases and Male Voiding Dysfunction
The Efficacy and Safety of Duloxetine in a Multidrug Regimen for Chronic Prostatitis/Chronic Pelvic Pain Syndrome