A Case–Control Study of Erectile Dysfunction Among Men Diagnosed with Panic Disorder

Case Report A case–control study of erectile dysfunction among men diagnosed with panic disorder

WA Blumentals1*, A Gomez-Caminero1,*, RR Brown1, V Vannappagari2 and LJ Russo1

1Worldwide Epidemiology, GlaxoSmithKline Pharmaceuticals, Collegeville, Pennsylvania, USA; and 2Department of Epidemiology, University of North Carolina at Chapel Hill, McGavran-Greenberg Hall, Chapel Hill, North Carolina, USA

The association between panic disorder and erectile dysfunction (ED) among men was examined in the Integrated Healthcare Information Services National Managed Care Benchmark Database (IHCIS). The IHCIS is a fully de-identified, HIPAA compliant database and includes complete medical history for more than 17 million managed care lives; data from more than 30 US health plans, covering seven census regions; and patient demographics, including morbidity, age and gender. A total of 60 949 ED cases and 243 796 controls were included for analysis. Unconditional logistic regression analyses were first performed to assess the crude risk of ED, and adjusted risks of ED that accounted for comorbid conditions and comedications. A second set of analyses measured the crude and adjusted risks after restricting the patient population to men who were diagnosed with panic disorder at least 1 month prior to an ED diagnosis. In the first set of analyses, men with panic disorder were observed to have more than a two-fold increase in risk for ED (OR ¼ 2.29, 95% CI ¼ 2.03, 2.58). After adjusting for comorbid conditions, a 52% increase in risk of ED was observed (OR ¼ 1.52, 95% CI ¼ 1.34, 1.72). Following subsequent adjustment for comorbidities and comedications, a 33% increased risk of ED was detected (OR ¼ 1.33, 95% CI ¼ 1.17, 1.51). In the second set of analyses studying panic disorder that preceded ED, only a 13% higher risk was noted (OR ¼ 1.13, 95% CI ¼ 0.97, 1.31). However, after adjusting for comorbid conditions, a 25% reduction in risk was observed (OR ¼ 0.75, 95% CI ¼ 0.64, 0.88). A 35% risk reduction was seen after adjusting for comorbidities and comedications (OR ¼ 0.65, 95% CI ¼ 0.56, 0.77). International Journal of Impotence Research (2004) 16, 299–302. doi:10.1038/sj.ijir.3901147

Introduction in the development and maintenance of sexual dysfunction.1 Kaplan3 found a high prevalence of panic disorder Approximately 5–20% of men are estimated to have among patients with active sexual aversion, but the moderate–to-severe erectile dysfunction (ED) and up study did not look into the association between ED 1 to 70% of them are not treated. The prevalence of and panic disorder. Sbrocco et al,4 in their case ED also varies depending on the age of study report involving three men with panic disorder participants, from 2 to 9% in men younger than and ED hypothesized that there is a significant over- 40 y; 10–71% among men older than 70 y to 18–86% lap between panic disorder symptoms and sexual 2 among men older than 86 y. Variability in the arousal sensations, which may lead to sexual prevalence of ED may reflect differences in defini- avoidance in patients with panic disorder. In their 1,2 tions, methodology, and study populations. assessment of 35 patients with erectile difficulties The long-standing psychological assumption is they found that three patients also had panic that anxiety and sexual arousal are mutually disorder. For these three cases, retrospective reports inhibitive and that chronic anxiety is important indicated that the erectile problems were preceded by panic attacks. Nevertheless, these were case reports and thus can be viewed as a preliminary study requiring additional research. 5 *Correspondence: WA Blumentals, PhD, 5421 Balsam Figueira et al retrospectively assessed the sexual Place, #203 Mason, OH 45040, USA. function and sexual history of 30 patients with E-mail: [email protected] social phobia and 28 patients with panic disorder. Received 16 June 2003; revised 9 August 2003; accepted 8 A semistructured interview was used to make the September 2003 diagnosis of panic disorder and social phobia. Panic disorder and ED WA Blumentals et al 300 Participants were interviewed to collect informa- tics, psychotropics, central nervous system depres- tion on sexual history. Panic disorder patients sants, and narcotic analgesics; benign prostatic reported a significantly higher number of sexual hyperplasia, prostate cancer, hypertension, depres- disorders as compared to social phobia participants sion, diabetes, diabetic neuropathy, hyperlipidemia, (21/28 vs 10/30). Sexual aversion disorder was most multiple sclerosis, Parkinson’s disease, spinal cord frequently found in panic disorder patients (12/28) injury, and renal failure. Among men diagnosed and premature ejaculation was most common in the with panic disorder, those patients with the follow- social phobia group (9/19). Out of the 14 male ing were excluded: acute stress reaction, transient patients with panic disorder and sexual disorders, adjustment reaction, neurasthenia, psychophysiolo- one reported ED. The study had a small sample size, gical disorders, and separation anxiety. These con- the problem of recall bias, and only one patient with ditions could potentially exacerbate the true both panic disorder and ED. Hence, it is difficult to association between panic disorder and ED. draw any conclusions about the relationship between 6 the two. Okulate et al studied the prevalence and Analysis predictors of ED among 829 Nigerian military men ranging in age from 18 to 69 y. ED was assessed using the International Index of Erectile Function Ques- All risk analyses were performed utilizing uncondi- tionnaire; and the Patient Health Questionnaire was tional logistic regression models with SASs statis- used to screen for depression, alcohol abuse, and tical software. Two sets of analyses were performed. panic disorder (based on DSM-IV criteria). A total of The first set did not consider when panic disorder 329 out of 829 men (40%) had ED, and 10/829 (1%) was diagnosed in relation to the ED diagnosis date, had panic disorder. Of the 329 men with ED, two had and the second set of analyses was restricted to men panic disorder. Multivariate analysis indicated that with a diagnosis of panic disorder at least 1 month panic disorder was not a predictor of ED. However, before a diagnosis of ED. In both sets of analyses, since only two men experienced panic disorder and crude and adjusted odds ratios were computed. ED, no conclusions can be reached from this analysis. The adjusted odds ratios were based on models This study seeks to better understand the magni- that adjusted for all likely disease comorbidities; tude of association between panic disorder and ED and subsequently, comorbidities and comedications. and attempts to elucidate any causal link that may exist between the two disorders. Results Materials and methods As seen in Table 1, the mean age of cases in the first set of analyses was 51.6 y compared to a mean age of A case–control study was conducted to assess the relationship between panic disorder and ED among patients observed in the Integrated Healthcare Table 1 Descriptive characteristics of the cases and controls— Information Services National Managed Care Bench- first set of analyses mark Database (IHCIS) from January 1, 1997 through Study population Cases Controls March 31, 2002.. (n ¼ 304 745) (n ¼ 60 949) (n ¼ 243 796)

Cases Age at ED diagnosis Mean age in y (s.d.) 51.6 (11.5) 56.6 (11.4) Panic disorder 427 (0.7%) 750 (0.3%) A total of 427 patients with panic disorder and ED Cigarette smokers 2076 (3.4%) 4751 (1.9%) were identified based on ICD-9 diagnosis codes in Prostate cancer 4014 (6.6%) 9013 (3.7%) Hypertension 23 316 (38.3%) 89 928 (36.9%) the IHCIS, of which only 210 had the panic disorder Depression 2235 (3.7%) 4113 (1.7%) diagnosis at least 1 month prior to the ED diagnosis. Diabetes 11 190 (18.4%) 34 194 (14.0%) Diabetic neuropathy 1509 (2.5%) 3301 (1.4%) Hyperlipidemia 24 026 (39.4%) 82 781 (34.0%) Controls Multiple sclerosis 288 (0.5%) 544 (0.2%) Parkinson’s disease 215 (0.4%) 1138 (0.5%) Spinal cord injury 703 (1.2%) 2297 (0.9%) Controls. were matched to cases using a 5-y window Renal failure 813 (1.3%) 3530 (1.4%) on age, where the age of a case was determined at ED Diuretic users 5578 (9.2%) 22 326 (9.2%) diagnosis date. Four times the number of cases were Psychotropic users 8718 (14.3%) 23 073 (9.5%) Central nervous system 74 (0.1%) 298 (0.1%) selected, and thus 243 796 controls were included depressant users for analyses. Narcotic analgesic users 16 567 (27.2%) 44 600 (18.3%) Potential confounding variables included age at ED diagnosis; cigarette smoking; ever use of diure- s.d. ¼ standard deviation.

International Journal of Impotence Research Panic disorder and ED WA Blumentals et al 301 Table 2 Association between panic disorder and ED—first set of Table 3 Descriptive characteristics of the cases and controls— analysesa second set of analyses

Association OR (95% CI) Study population Cases Controls (n ¼ 304 518) (n ¼ 60 722) (n ¼ 243 796) Model 1: Panic disorder and ED (crude) 2.29 (2.03, 2.58) Model 2: Panic disorder and ED (adjusted 1.52 (1.34, 1.72) Age at ED diagnosis for disease risk factors) Mean age in y (s.d.) 51.6 (11.5) 56.6 (11.4) Model 3: Panic disorder and ED (adjusted 1.33 (1.17, 1.51) Panic disorder 210 (0.3%) 750 (0.3%) for disease risk factors and medications) Cigarette smokers 2063 (3.4%) 4751 (1.9%) Prostate cancer 3991 (6.6%) 9013 (3.7%) a Model 2 is adjusted for: age at ED index date, cigarette smoking, Hypertension 23 217 (38.2%) 89 928 (36.9%) Depression 2172 (3.6%) 4113 (1.7%) benign prostatic hyperplasia, prostate cancer, hypertension, Diabetes 11 162 (18.4%) 34 194 (14.0%) depression, diabetes, diabetic neuropathy, hyperlipidemia, multiple sclerosis, Parkinson’s disease, spinal cord injury, and renal Diabetic neuropathy 1505 (2.5%) 3301 (1.4%) failure. Hyperlipidemia 23 907 (39.4%) 82 781 (34.0%) Model 3 is adjusted for the same variables as in Model 2, and also Multiple sclerosis 288 (0.5%) 544 (0.2%) use of: diuretics, psychotropics, central nervous system depres- Parkinson’s disease 211 (0.3%) 1138 (0.5%) Spinal cord injury 701 (1.2%) 2297 (0.9%) sants, and narcotic analgesics. Renal failure 811 (1.3%) 3530 (1.4%) Diuretic users 5550 (9.1%) 22 326 (9.2%) Psychotropic users 8589 (14.1%) 23 073 (9.5%) 56.6 y among controls. A slightly higher proportion Central nervous system 72 (0.1%) 298 (0.1%) of cases were diagnosed with panic disorder (0.7%), depressant users while 0.3% of controls had panic disorder. Indeed, Narcotic analgesic users 16 471 (27.1%) 44 600 (18.3%) more cases were prescribed psychotropics than controls (14 vs 9%). Similarly, more patients with s.d. ¼ standard deviation. ED had hyperlipidemia and were prescribed narcotic analgesics compared to controls (39 vs 34%) and (27 vs 18%), respectively. (Table 1) Table 4 Association between panic disorder and ED—second set The goal of the initial analyses was to determine of analysesa the magnitude of association between lifetime Association OR (95% CI) history of panic disorder and current ED. Table 2 illustrates that the crude analysis revealed a more Model 1: Panic disorder and ED (crude) 1.13 (0.97, 1.31) than two-fold increase in risk of ED among men with Model 2: Panic disorder and ED (adjusted 0.75 (0.64, 0.88) panic disorder vs men without panic disorder for disease risk factors) (OR ¼ 2.29, 95% CI ¼ 2.03, 2.58). After adjusting for Model 3: Panic disorder and ED (adjusted 0.65 (0.56, 0.77) the following variables and comorbidities: age at ED for disease risk factors and medications) index date, cigarette smoking, benign prostatic a hyperplasia, prostate cancer, hypertension, depres- Model 2 is adjusted for: age at ED index date, cigarette smoking, benign prostatic hyperplasia, prostate cancer, hypertension, sion, diabetes, diabetic neuropathy, hyperlipidemia, depression, diabetes, diabetic neuropathy, hyperlipidemia, multi- multiple sclerosis, Parkinson’s disease, spinal cord ple sclerosis, Parkinson’s disease, spinal cord injury, and renal injury, and renal failure, the risk remained 52% failure. higher comparing men with a history of panic Model 3 is adjusted for the same variables as in Model 2, and also disorder to those without (OR ¼ 1.52, 95% use of: diuretics, psychotropics, central nervous system depressants, and narcotic analgesics. CI ¼ 1.34, 1.72). Following control for the use of diuretics, psychotropics, central nervous system depressants, and analyses (Table 1). Once again, more cases received narcotic analgesics (in addition to the aforementioned psychotropics (14 vs 9%) and narcotic analgesics (27 variables and comorbidities) the risk further decreased vs 18%); while more cases were diagnosed with such that men with panic disorder were 33% more diabetes and hyperlipidemia (18 vs 14%) and (39 vs likely to developed ED compared to men without panic 34%), respectively (Table 3). disorder (OR ¼ 1.33, 95% CI ¼ 1.17, 1.51). (Table 2) The crude analysis (Table 4) indicated a trend In order to establish temporality, and thus the towards a 13% increase in risk for ED among men potential for a causal link between panic disorder with panic disorder compared to no panic disorder, and ED, men with a panic disorder diagnosis from 1 however this was not statistically significant month prior to an ED diagnosis to any later time (OR ¼ 1.13, 95% CI ¼ 0.97, 1.31). After adjusting for were excluded from the first set of analyses the same disease risk factors as in the first analysis, (n ¼ 217). An additional 10 patients without panic however, a 25% reduction in risk of ED was detected disorder were excluded after we were unable to (OR ¼ 0.75, 95% CI ¼ 0.64, 0.88). An even more ascertain their ED diagnoses. pronounced protective effect was observed after The mean age and distribution of risk factors controlling for disease risk factors and comedica- among cases and controls (Table 3) remained tions. Specifically, a 35% decrease in risk of ED relatively unchanged compared to the first set of was noted among men with panic disorder vs no

International Journal of Impotence Research Panic disorder and ED WA Blumentals et al 302 panic disorder (OR ¼ 0.65, 95% CI ¼ 0.56, 0.77) alternative lipid-lowering drugs of the same or a (Table 4). different class can resolve the problem.9 The use of administrative data of this type carries some limitations. The IHCIS database represents Discussion those who have sought treatment for panic disorder and ED. It is possible to have an ascertainment bias whereby the type of patient likely to seek care We wanted to test the long-held belief that anxiety for a panic attack is also more likely to be suffering and sexual arousal are mutually inhibitive and that from ED. We are not aware, however, of any chronic anxiety is key in sexual dysfunction. The evidence that can confirm this occurrence. Finally, results of our study suggest that this may be true, the sensitivity of the diagnosis of both panic although it appears unlikely that the association is disorder and ED is not known. Therefore, there very strong. may be misclassification of true ED cases as To our knowledge, the present study may be the controls. This misclassification is likely to be only case–control study to look at ED risk among nondifferential with respect to panic disorder which men diagnosed with panic disorder. Indeed, we would dilute a positive result. could not find published studies that had attempted Among psychiatric disorders, the association to establish an association between the two dis- between depression and ED is well known. orders. Case reports have suggested a potential Feldman et al10 observed that the age-adjusted association and theories hypothesizing the biologi- probability of ED was 25% for even mildly cal mechanism have been proposed, yet there is no depressed men. At the same time, however, there conclusive evidence to corroborate either the theory are very few epidemiological studies that have or possible association. Our study was specifically looked at the relationship between panic disorder designed to assess the magnitude of risk after and ED. The results of this study confirm that the adjusting for potential comorbidities and comedica- prevalence of panic disorder is very small among ED tions and to determine potential causation. The first patients, but also provide an estimate of the set of analyses provided a cross-sectional view of the magnitude of the risk. Given that a rather strong relationship between ED and panic disorder. That is, protective effect for ED was observed after adjusting the analyses were conducted without regard to the for other risk factors and medications, further time panic disorder was diagnosed in relation to the studies are necessary to understand which specific ED diagnosis. The study data demonstrate a con- treatment(s) may contribute to the risk decline sistent increase in risk for ED, even after adjusting among men with panic disorder. Additional next for other disease risk factors and comedications. steps include a study of ED as a predictive factor for The second set of analyses restricted panic panic disorder. disorder patients to having a diagnosis at least 1 month before an ED diagnosis. While such a restriction could introduce selection bias, it also provided the best way to see whether a temporal References relationship existed between the two disorders. In fact, the crude model indicated only a small increase 1 Kubin M, Wagner G, Fugl-Meyer AR. Epidemiology of erectile in risk. Our study found that 0.3% of all ED cases dysfunction. Int J Impot Res 2003; 15: 63–71. had panic disorder, and this is similar to the 2 Prins J et al. Prevalence of erectile dysfunction: a systematic Nigerian study which showed that only 0.6% of review of population-based studies. Int J Impot Res 2002; 14: men with ED had panic disorder.6 Hence, the 422–432. 3 Kaplan H. Sexual Aversion, Sexual Phobias and Panic relationship between panic disorder and ED may Disorder. Brunner/Mazel: New York, 1987. likely be quite minimal. 4 Sbrocco T, Weisberg RB, Barlow DH, Carter MM. The Interestingly, a protective effect was observed after conceptual relationship between panic disorder and male controlling for disease risk factors including medi- erectile dysfunction. J Sex Marital Ther 1997; 23: 212–220. 5 Figueira I, Possidente E, Marques C, Hayes K. Sexual cations. It is hypothesized that treatment for some of dysfunction: a neglected complication of panic disorder and the more vascular and endocrine causes of ED may social phobia. Arch Sex Behav 2001; 30: 369–377. help account for the protective effect. Because men 6 Okulate G, Olayinko O, Dogunro AS. Erectile dysfunction: with panic disorder seek treatment for what is often prevalence and relationship to depression, alcohol abuse and perceived as a cardiovascular condition, it is panic disorder. General Hosp Psychiatry 2003; 25: 209–213. 7 Pedersen TR, Faergeman O. Simvastatin seems unlikely to possible that early diagnosis and treatment of cause impotence (letter). Br Med J 1999; 318: 192. hypertension and hyperlipidemia may contribute 8 Halkin A, Lossos IS, Mevaorach D. HMG-CoA reductase to the reduced risk among those with panic. ED has inhibitor-induced impotence (letter). Ann Pharmacother not been reported in the major randomized double- 1996; 30: 192. blind trials of lipid-lowering therapy.7 And although 9 Jackson G. Simvastatin and impotence. Br Med J 1997; 315: 31. 8 10 Feldman HA et al. Impotence and its medical and psychoso- Halkin et al suggested that ED is a class effect of cial correlates: results of the Massachusetts Male Aging Study. statins, another report suggested that switching to J Urol 1994; 151: 54–61.

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