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Psychiatric Comorbidity in Women with Chronic Pelvic Pain Samantha Meltzer-Brody and Jane Leserman CNS Spectrums / Volume 16 / Issue 02 / February 2011, pp 29 - 35 DOI: 10.1017/S1092852912000156, Published online: 26 March 2012
Link to this article: http://journals.cambridge.org/abstract_S1092852912000156 How to cite this article: Samantha Meltzer-Brody and Jane Leserman (2011). Psychiatric Comorbidity in Women with Chronic Pelvic Pain. CNS Spectrums, 16, pp 29-35 doi:10.1017/S1092852912000156 Request Permissions : Click here
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doi:10.1017/S10928529120001566
Review Article
Psychiatric Comorbidity in Women with Chronic Pelvic Pain Samantha Meltzer-Brody MD, MPH, and Jane Leserman, PhD
ABSTRACT
FOCUS POINTS
Chronic pain syndromes are often treatment
• History of prior abuse or trauma is associated with treatment refractory chronic pelvic pain (CPP). • Screening for psychiatric comorbidity, including posttraumatic stress disorder (PTSD) and major depression, in women with CPP is critical because it significantly impacts medical symptoms and health related functioning. • Women with vulvodynia-type CPP and comorbid depression or PTSD may benefit from a trial of lamotrigine.
refractory and pose an enormous burden of suffering for the individual. Chronic pelvic pain (CPP) is generally defined as noncyclic pain of at least 6 months duration and severe enough to require medical care or cause disability. CPP has been estimated to have a prevalence of 15% among women of reproductive age. Women are at increased risk for both major depression and chronic pain syndromes such
should include a thorough gynecologic exam
as CPP, and are more likely to report antecedent
and a full mental health assessment. Treatment
stressful events, have higher rates of physical
of CPP must include an integrated approach
and sexual abuse, and subsequently develop
targeted at both the psychiatric comorbidity
posttraumatic stress disorder. High rates of sex-
and pain symptoms. A multidisciplinary treat-
ual and physical abuse and other trauma have
ment team offers the best chance for success
been shown among women with CPP, includ-
with CPP, and it is critical to suggest psychiatric
ing symptoms of dyspareunia (pain during
treatment (psychopharmacology and/or psycho-
intercourse), dysmenorrhea (pain during men-
therapy) in addition to traditional medical and
struation), and vulvar pain. A detailed and com-
surgical approaches.
prehensive evaluation of the patient with CPP Dr. Meltzer-Brody and Dr. Leserman are faculty in the Department of Psychiatry at the University of North Carolina at Chapel Hill. Faculty Disclosures: Dr. Meltzer-Brody receives research support from AstraZeneca, the Foundation of Hope, and the NIH (Grant number K23MH085165). Dr. Leserman reports no affiliations with or financial interests in any organization that may pose a conflict of interest. Submitted for publication: November 3, 2010; Accepted for publication: December 20, 2010; First published online: February 1, 2011 . Corresponding Author: Samantha Meltzer-Brody, MD, MPH, Associate Professor, Director, UNC Perinatal Psychiatry Program, Campus Box, #7160, UNC Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514; Tel: 919-962-9766; E-mail [email protected]
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INTRODUCTION Chronic pain is often treatment refractory and poses an enormous burden of suffering for the individual. The experience of constant pain may be viewed as a severe stress that is associated with the development of psychopathology, including depressive disorders, anxiety disorders, substance dependence, and personality disorders.1-3 Women are at increased risk for both major depression and chronic pain syndromes, including chronic pelvic pain (CPP).4 Women have a two-fold increased prevalence of major depressive disorder (MDD) throughout their reproductive lifecycle. 5-8 Furthermore, women are also more likely to report antecedent stressful events, have higher rates of physical and sexual abuse, and subsequently develop posttraumatic stress disorder (PTSD).9-13 High rates of sexual and physical abuse and other trauma have been shown among women with CPP, including symptoms of dyspareunia (pain during intercourse) and dysmenorrhea (pain during menstruation), and vulvar pain.14-23 Thus, the assessment and treatment of women with CPP must include a careful evaluation of prior trauma history and current psychiatric comorbidity. We review the epidemiology of CPP and comorbid psychiatric illness, strategies for the evaluation and diagnosis of CPP from a biopsychosocial perspective, and non-surgical treatment interventions that address both the pain and psychological distress of this disorder.
EPIDEMIOLOGY OF CPP AND PSYCHIATRIC COMORBIDITY CPP is generally defined as noncyclic pain of at least 6 months duration, severe enough to require medical care or cause disability and occurring in locations such as the pelvis, anterior abdominal wall at or below the umbilicus, lower back, or buttocks.24 CPP has been estimated to have a prevalence of 15% among women of reproductive 25 years of age, accounts for 10% of gynecological consultations and 40% of diagnostic laparoscopies performed in general hospitals. 26,27 Many women with CPP fail to respond to treatment, relapse rates are high, and they utilize a disproportionate amount of health care resources.28 A population-based survey14 of 1,931 women in primary care practices documented that women with a history of childhood sexual abuse were more likely to report pelvic pain (23.5%) compared to those without abuse (11.2%). A recent
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survey29 of women presenting to a specialty pelvic pain referral clinic demonstrated that ~50% of women with CPP reported a history of sexual or physical abuse, and rates of reported trauma in this population were much higher than in national samples of women in the general population. In this study, 1 in 3 women with pelvic pain also had a positive screen for PTSD indicating a high degree of psychiatric comorbidity that may contribute to the patient’s perception and ability to cope with chronic pain.29 This is consistent with previous literature documenting an association of CPP with childhood and/or adult sexual abuse.30-36
Defining CPP One challenge in the evaluation and management of patients with CPP is the often false assumption that the pelvic pain can be linked with some form of obvious pathology or tissue damage.37 Because every structure in the pelvis and/or abdomen could play a role in the etiology of CPP, it is essential to think beyond the reproductive organs and consider other contributions, such as the peripheral and central nervous systems.38 Interestingly, a comprehensive review39 of over 100 articles on CPP concluded that there is no consensus on a definition of CPP, and that this deficiency reduces the ability to investigate causation and improve treatment. Historically, three different operational definitions of CPP have been described in the literature. Durational is any type of pelvic pain that has lasted >6 months. Anatomic is CPP that lacks apparent physical cause sufficient to explain the pain (usually meaning that laparoscopy disclosed minimal, if any, pathology). Affective-behavioral is pain accompanied by significantly altered physical activity, including work, recreation, libido, as well as disturbance of mood.40 Therefore, it may be very helpful to approach the diagnosis and treatment of CPP from a biopsychosocial perspective (Figure) in which psychological events, such as sexual abuse and trauma, interact with structural and physiological factors to produce symptoms. These complicated interactions determine how patients cope with their symptoms and how they respond to treatments, including psychological as well as surgical and medical interventions. Additionally, it remains unclear whether all types of CPP disorder are equally affected. Two studies have shown that women with vulvodynia (pain localized to the vulva) are less likely to have iLÀÕ>ÀÞÊÓ䣣
Review Article
psychologic disturbance, sexual and/or physical abuse history, severe pain, and other somatic complaints compared with women with other types of CPP. 41,42 The literature is divided as to whether or not vulvodynia, characterized by localized vulvar pain, should be considered a type of CPP or if it is a separate and distinct syndrome.41,42 Alternatively, women with diffuse, non-localized, pain conditions report more depression, anxiety, and severity of pain than women with more focused pain,43 and those with intermittent pain (cyclical, ie, with dysmenorrhea), have less psychologic distress and histories of abuse than those with continuous chronic pain.37 Leserman and colleagues 44 examined seven diagnostic subtypes of CPP and how the subtypes differed in trauma history and current health status. In particular, they noted that patients with diffuse abdominal/pelvic pain had more trauma and worse mental and physical health status compared with patients with vulvovaginal pain and cyclic pain.44 Because psychiatric comorbidity is so common in women with CPP, specifically MDD and PTSD, it is worthwhile to briefly describe some of
the neuroscience underlying the clinical presentation. The literature documents that comorbid major depressive illness or other psychiatric disturbance may alter the perception of pain and increase pain intensity while decreasing the ability to tolerate the pain.45 The neuroanatomic and neurochemical processes associated with depression, PTSD, and chronic pain have been a focus of study and it is worthwhile to briefly describe this literature. In regards to the neuroscience underlying MDD, the periaqueductal gray (PAG) is thought to be a central anatomic site in the pain modulation system. 46,47 The PAG serves as an anatomic relay from limbic forebrain and midbrain structures to the brainstem.48 These relay systems contain both serotonergic and noradrenergic neurons, important neurotransmitters in the regulation of mood and several of the neurovegetative and cognitive functions that are often altered in patients with depression. It is hypothesized that when there is a depletion of serotonin and/or norepinephrine, the PAG system loses its modulatory effect so that minor signals from the body are amplified and more attention and emotion are focused on them. This may partially
FIGURE.
Schematic of the biopsychosocial model of chronic pain syndromes Predisposing Factors
Prior Trauma
Moderating Variables
Symptom Occurence
Health Status and Treatment Response (Medical, Surgical, Psychological)
Genetics
Demographics (Age, Race, SES)
Traumatic Life Events
Coping Strategies
Response (Adequate/ Inadequate)
(Sexual and Physical Abuse, other Trauma)
Type of Chronic Pain Psychosocial Symptoms (Anxiety, PTSD, Depression)
Health Outcome Biological Mechanisms
Health Status (Functional Status, Somatic Symptoms, Pain, Health Care Use)
* Figure created by Dr. Meltzer-Brody and previously published in her chapter Meltzer-Brody S, Golden R. “Chronic Pain and Comorbid Mood Disorders.” The Physicians Guide to Depression and Bipolar Disorders. Permission obtained. Meltzer-Brody S, Leserman J. CNS Spectr. Vol 16, No 2. 2011.
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explain why patients with depression often have multiple somatic complaints.48 The hypothalamic pituitary adrenal axis (HPA) is also felt to be involved in the experience of chronic pain.49,50 It is believed that chronic stress caused by chronic pain leads to loss of negative glucocorticoid feedback on the HPA axis, resulting in downregulation of glucocorticoid receptors within the brain and peripheral nervous system. This downregulation may lead to depressed mood.47 The underlying neuroscience and neuroanatomical work associated with PTSD also points to dysregulation in limbic, paralimbic and prefrontal regions which are involved in the stress response and emotional processing, including alterations of HPA function, autonomic and adrenergic hyperactivity, and the generation of PTSD symptoms.5153 Abnormalities in prefrontal function have also been noted in those pain patients prone to catastrophizing.54
evaluation and treatment approach offers the best clinical practice. Steege and Zolnoun55 have documented that it is critical for the health care provider to also ask focused questions about the nature of the pelvic pain and in particular, pain during intercourse (dyspareunia). Including questions about sexual comfort as a routine part of every gynecologic visit helps to legitimize the subject and allows the woman to feel more comfortable voicing a concern.55
EVALUATION OF CPP
Psychotherapeutic Interventions Psychological intervention studies for the treatment of CPP are extremely limited. One study described a mild-moderate impact of psychological counseling paired with ultrasound scanning on the course of CPP. 56 A second, more recent study (N=17), 57 evaluated the feasibility, acceptability, and efficacy of interpersonal psychotherapy adapted for women with comorbid depression and CPP. Despite the small sample size, large effect sizes with significant improvements were found for depression severity and
The evaluation of a patient with suspected CPP should begin with a complete medical history and comprehensive physical and gynecologic examination of the patient. The differential diagnosis of CPP includes, but is not limited: endometriosis, musculoskeletal pain, irritable bowel syndrome, interstitial cystitis, pelvic adhesive disease, neuropathic pain, and vulvodynia. It is important to assess location, duration, and timing of the pelvic pain. For example, the clinician should thoroughly assess the location of the pelvic pain, and if possible, determine whether the pain is within the abdominal wall, pelvic viscera (uterus, ovaries, bladder and/or intestines), pelvic floor muscles and/or vulva. A determination of first onset of pain and relation of the pain to the menstrual cycle is critical, particularly if endometriosis or uterine disease is suspected. A review of the evolution of pain over time is also a key component of the exam. Specific guidelines for the gynecologic physical exam are carefully detailed by Steege and Zolnoun.55 Obtaining an abuse and trauma history and an assessment for PTSD are critical components of the comprehensive evaluation of patients with CPP because addressing comorbid psychiatric illness in this patient population may lead to improved patient outcomes. 29 Ideally, a comprehensive evaluation of the patient with pelvic pain should include a full mental health assessment as well as a thorough gynecologic exam. A multidisciplinary
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NON-SURGICAL TREATMENT OF CPP Given the significant rates of comorbid psychiatric illness in women with CPP, treatment must include a comprehensive approach targeted at both the psychiatric comorbidity and the pain symptoms. We review the relatively small literature on evidence-based treatment interventions including psychotherapy, psychopharmacologic, and alternative therapies (Table 1).
TABLE.
Evidence-Based Treatment for CPP and Comorbid Depression and Anxiety Type of Treatment Modality Psychotherapy
Evidence Based Intervention Supportive counseling and ultrasound Interpersonal psychotherapy
Psychopharmacology
TCA, SSRI and SNRI antidepressant therapy Lamotrigine (anticonvulsant)
Alternative
Botulinum toxin injections Physical therapy Biofeedback
Meltzer-Brody S, Leserman J. CNS Spectr. Vol 16, No 2. 2011.
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social adjustment although pain interference remained unchanged.
address the psychological or emotional aspects of chronic pain, including vulvodynia, may affect the outcome.67 One psychopharmacologic option that targets symptoms of both pain and mood is lamotrigine. There is one study 69 of the efficacy of lamotrigine in the treatment of CPP with a focus on women with vulvodynia. In this open label study of 43 women with CPP (>60% with vulvodynia) recruited from a specialty pelvic pain clinic, significant reductions on all pain and mood measures were observed after 8 weeks of treatment as compared to baseline. In particular, women with vulvodynia-type CPP had robust reductions in pain and mood symptoms.69 These findings suggest that treatment with lamotrigine for patients with vulvodynia may be helpful in addressing both the pain and mood symptoms associated with this disorder.
Psychopharmacologic Interventions Although there have been recent advances in the treatment of comorbid psychiatric illness with chronic pain syndromes, the data on treatment specifically for CPP is limited. However, antidepressants are often used to treat patients with other chronic pain syndromes with varying degrees of success in terms of long term patient outcomes. 58 These pharmacologic agents target either serotonin and/or norepinephrine neurotransmitter levels, which as described above, both modulate descending pain pathways. Historically, the tricyclic antidepressants (TCAs), including amitriptyline, that primarily target the norepinephrine system have been widely used.59 The selective serotonin reuptake inhibitors (SSRIs) have also been shown to have modest efficacy in treating chronic pain, and more recently, the serotonin norepinephrine reuptake inhibitors (SNRIs) have shown strong potential as treatment for chronic pain disorders because of their dual action on both serotonin and norepinephrine.60-62 Antidepressants have shown some efficacy to treat both mood symptoms and to demonstrate analgesic properties independent of psychiatric effects in other chronic pain syndromes.60-62 Additionally, anticonvulsants (gabapentin, pregabalin, and lamotrigine), have been used to treat chronic pain syndromes. 63,64 Therefore, because many patients with CPP have comorbid depressive and anxiety symptoms, including MDD and PTSD, antidepressants and anticonvulsants have been tried as a treatment strategy with the goal of improving long term patient outcomes. In clinical practice, the TCAs, SSRIs, SNRIs, and anticonvulsants have all been used with modest success in the treatment of women with CPP. 58 However, evidence for the efficacy of antidepressants in the treatment of CPP has been less than optimal. There is one small double-blind study65 of the SSRI sertraline that did not demonstrate clinical significance. A second small open-label study66 with citalopram showed an improvement in depressive symptoms, and some improvement in pain intensity, but not pain disability in women with CPP.6 Vulvodynia type pelvic pain, a vulvar pain syndrome that may have a better response to intervention, has been routinely treated with the TCAs.67,68 It is critical to highlight that failure to
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ALTERNATIVE THERAPIES Because so few randomized controlled trials on the treatment of CPP have been conducted, there are multiple alternative therapies that are used, although often with limited data. Examples of alternative non-invasive treatments that have some evidence include physical therapy, biofeedback, and botulinum toxin injections. 70 The rationale for the use of physical therapy and biofeedback as treatment modalities for CPP, comes from the small literature documenting a higher frequency of positive pelvic musculoskeletal findings in CPP.71 Unrecognized musculoskeletal pain may be an important factor in the development of a state of general pain amplification, which may initiate and maintain idiopathic chronic pain disorders.72 Until significant progress is made in clarifying the multifactorial model of chronic pain pathogenesis, treatment of both overt and occult musculoskeletal pain generators represents a practical strategy for potentially decreasing the burden of CPP.71,72 The pelvis contains a complex musculature system that is often overlooked as a possible cause for pain, although it is recognized that relief of muscle spasm is associated with relief of pain symptoms.71 Therefore, after a diagnosis of possible pelvic floor spasm as a contribution to CPP has been made, physical therapy offers a lowrisk treatment option and has been documented as a non-invasive first line treatment for CPP. 71 Physical therapy provides a contract/relax treatment model that reduces the resting tone of the pelvic floor muscles and disrupts the spasm cycle, allowing for relief of pain. Adding in biofeedback 33
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may allow the patient to work with concrete information regarding the adequacy of pelvic floor training, and provide an objective assessment of the changes in baseline tone and strength.71 Another alternative treatment strategy for CPP associated with vulvar and generalized pelvic pain is the use of botulinum toxin therapy. Limited case reports and other small studies have indicated that botulinum toxins used in the vulva may offer a benefit for 3–6 months after injection of botulinum toxin 20–40 U.73-76 In CPP and, specifically, pelvic floor muscle spasm, a greater number of women have been studied and a double blind, randomized controlled study has reported a significant reduction in pelvic floor pressures with significant pain reduction for some types of pelvic pain compared to baseline.73-76
5. Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003;289:3095-3105. 6. Weissman MM, Bland RC, Canino GJ, et al. Cross-national epi-Acknowledgements: demiology of major depression and bipolar disorder. JAMA. 1996;276:293-299. 7. Kessler RC, McGonagle KA, Swartz M, et al. Sex and depression in the National Comorbidity Survey. I: lifetime prevalence, chronicity and recurrence. J Affect Disord. 1993;29:85-96. 8. Soares CN, Zitek B. Reproductive hormone sensitivity and risk for depression across the female life cycle: a continuum of vulnerability? J Psychiatry Neurosci. 2008;33:331-343. 9. Breslau N, Davis GC, Andreski P, et al. Traumatic events and posttraumatic stress disorder in an urban population of young adults. Arch Gen Psychiatry. 1991;48:216-222. 10. Resnick H, Kilpatrick DG, Dansky B, et al. Prevalence of civilian trauma and posttraumatic stress disorder in a representative sample of women. J Consult Clin Psychology. 1993;61:984-991. 11. Green BL. Psychological research in traumatic stress: an update. J Traumatic Stress. 1994;7:341-362. 12. Breslau N, Davis GC, Andreski P, Peterson EL, Schultz LR. Sex differences in posttraumatic stress disorder. Arch Gen Psychiatry. 1997;54:1044-1048. 13. Norris FH. Epidemiology of trauma: frequency and impact of different potentially traumatic events on different demographic groups. J Consult Clin Psychology. 1992;60:409-418. 14. McCauley J, Kern DE, Kolodner K, Dill L, Schroeder AF, DeChant HK, et all. Clinical characteristics of women with a history of childhood abuse: unhealed wounds. JAMA. 1997;277:1362-1368. 15. Walker EA, Gelfand A, Katon WJ, et al. Adult health status of women with histories of childhood abuse and neglect. Am J Med. 1999;107:332-339. 16. Golding JM. 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Int J Obstetrics Gynaecology. 2004;111:1121-1127. 23. Leserman J, Li Z, Drossman DA, Hu YJB. Selected symptoms associated with sexual and physical abuse history among female patients with gastrointestinal disorders: the impact on subsequent health care visits. Psychol Med. 1998;28:417-425. 24. American College of Obstetricians and Gynecologists. Chronic pelvic Pain: ACOG practice bulletin no. 51. Obstet Gynecol. 2004;103:589-605. 25. Mathias SD, Kuppermann M, Liberman RF, Lipschutz RC, Steege JF. Chronic pelvic pain: Prevalence, health-related quality of life, and economic correlates. Obstet Gynecol. 1996;87:321-327. 26. Reiter RC. A profile of women with chronic pelvic pain. Clin Obstet Gynecol. 1990;33:130-136. 27. Howard FM. The role of laparoscopy in chronic pelvic pain: Promise and pitfalls. Obstet Gynecol Surv. 1993;48:357-387. 28. Drossman DA, Leserman J, Nachman G, Li Z, Gluck H, Toomey TC, Mitchell CM. Sexual and physical abuse in women with functional or organic gastrointestinal disorders. Ann Intern Med. 1990;113:828-833. 29. Meltzer-Brody S, Leserman J, Zolnoun D, et al. Trauma and posttraumatic stress disorder in women with chronic pelvic pain. Obstet Gynecol. 2007;4;109:902-908. 30. Lampe A, Solder E, Ennemoser A, et al. Chronic pelvic pain and previous sexual abuse. Obstet Gynecol. 2000;96:929-933. 31. Golding JM, Wilsnack SC, Learman. Prevalence of sexual assault history among women with common gynecologic symptoms. Am J Obstet Gynecol. 1998;179:1013-1019. 32. Walker EA, Katon W, Harrop-Griffiths J, et al. Relationship of chronic pelvic pain to psychiatric diagnoses and childhood sexual abuse. Am J Psychiatry. 1988;145:75-79. 33. Walker EA, Katon WJ, Neraas K, Jemlka RP, Massoth D. Dissociation in women with chronic pelvic pain. Am J Psychiatry. 1992;149:534-537. 34. Lechner ME, Vogel ME, Garcia-Shelton LM, Leichter JL, Steibel KR. 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CONCLUSION The relationship between CPP and comorbid psychiatric illness is complex. Comorbid psychiatric illness appears to alter both the individual’s perception of pain and ability to tolerate the pain. A careful biopsychosocial approach to the diagnosis and treatment of CPP in which psychological events, such as sexual abuse and trauma interact with structural and physiological factors to produce symptoms is warranted. Women with CPP have a significantly higher prevalence of histories of abuse, other trauma and comorbid PTSD and depression. Therefore, it is important that all women with pelvic pain have appropriate psychiatric screening for trauma and PTSD and other comorbid psychiatric illness. An integrative multidisciplinary approach offers the best chance for success with CPP; thus it is critical to suggest psychological treatment in addition to traditional and/ or alternative medical and surgical approaches. Psychotropic medications that have mood stabilizing properties may be helpful in the treatment of CPP. Furthermore, treatment of CPP should be specifically tailored based on the subtype of CPP, (ie, vulvodynia), as this may greatly influence the efficacy of a particular intervention. CNS
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McGraw Hill Publishers, New York. 2005;439-455. 59. Onghena P, van Houdenhove B. Antidepressant-induced analgesia in chronic non-malignant pain: a meta-analysis of 30 placebo-controlled studies. Pain. 1992;49:205-219. 60. Briley M. Clinical experience with dual action antidepressants in different chronic pain syndromes. Human Psychopharmacology. 2004;Suppl 1:S21-S25. 61. Detke MJ, Lu Y, Goldstein DJ, Hayes JR, Demitrack MA. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. J Clin Psychiatry. 2002;63:308-315. 62. Rowbotham MC, Goli V, Kunz NR, Lei D Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. Pain. 2004;110:697-706. 63. Finnerup NB, Sindrup SH, Jensen TS.The evidence for pharmacological treatment of neuropathic pain. Pain. 2010;150:573-581. 64. Kroenke K, Krebs EE, Bair MJ. Pharmacotherapy of chronic pain: a synthesis of recommendations from systematic reviews. Gen Hosp Psychiatry. 2009;31:206-219. 65. Engel CC, Walker EA, Engel Al, Bullis J, Armstrong A. A randomized, double-blind crossover trial of sertraline in women with chronic pelvic pain. J Psychosom Res. 1998;44:203-207. 66. Brown CS, Franks AS, Wan J, Ling FW. Citalopram in the treatment of women with chronic pelvic pain: an open-label trial. J Reprod Med. 2008;53:191-195. 67. Gunter J. Vulvodynia: new thoughts on a devastating condition. Obstet Gynecol Surv. 2007;62:812-819. 68. Haefner HK, Collins ME, Davis GD, et al. The vulvodynia guideline. J Low Genit Tract Dis. 2005;9:40-51. 69. Meltzer-Brody SE, Zolnoun D, Steege JF, Rinaldi KL, Leserman J. Open-label trial of lamotrigine focusing on efficacy in vulvodynia. J Reprod Med. 2009;54:171-178. 70. Vercellini P, Viganò P, Somigliana E, et al. Medical, surgical and alternative treatments for chronic pelvic pain in women: a descriptive review. Gynecol Endocrinol. 2009;25:208-221. 71. Tu FF, Holt J, Gonzales J, Fitzgerald CM. Physical therapy evaluation of patients with chronic pelvic pain: a controlled study. Am J Obstet Gynecol. 2008;198:272.e1-7. 72. Diatchenko L, Nackley AG, Slade GD, Fillingim RB, Maixner W. Idiopathic pain disorders: pathways of vulnerability. Pain. 2006;123:226-230. 73. Wissel J, Muller J, Dressnandt J, et al. Management of spasticity associated pain with botulinum toxin A. J Pain Symptom Manage. 2000;20:44-49. 74. Abbott J.The use of botulinum toxin in the pelvic floor for women with chronic pelvic pain-a new answer to old problems? J Minim Invasive Gynecol. 2009;16:130-135. 75. Jarvis S, Abbott J, Lenart M, Steensma A, Vancaille T. Pilot study of botulinum toxin type A in the treatment of chronic pelvic pain as associated with spasm of the levator ani muscles. Aust N Z J Obstet Gynaecol. 2004;44:46-50. 76. Abbott JA, Jarvis SK, Lyons SD, Thomson A, Vancaille TG. Botulinum toxin type A for chronic pain and pelvic floor spasm in women: a randomized controlled trial. Obstet Gynecol. 2006;108:915-923.
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Psychiatric Comorbidity in Women with Chronic Pelvic Pain Samantha Meltzer-Brody and Jane Leserman CNS Spectrums / Volume 16 / Issue 02 / February 2011, pp 29 - 35 DOI: 10.1017/S1092852912000156, Published online: 26 March 2012
Link to this article: http://journals.cambridge.org/abstract_S1092852912000156 How to cite this article: Samantha Meltzer-Brody and Jane Leserman (2011). Psychiatric Comorbidity in Women with Chronic Pelvic Pain. CNS Spectrums, 16, pp 29-35 doi:10.1017/S1092852912000156 Request Permissions : Click here
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doi:10.1017/S10928529120001566
Review Article
Psychiatric Comorbidity in Women with Chronic Pelvic Pain Samantha Meltzer-Brody MD, MPH, and Jane Leserman, PhD
ABSTRACT
FOCUS POINTS
Chronic pain syndromes are often treatment
• History of prior abuse or trauma is associated with treatment refractory chronic pelvic pain (CPP). • Screening for psychiatric comorbidity, including posttraumatic stress disorder (PTSD) and major depression, in women with CPP is critical because it significantly impacts medical symptoms and health related functioning. • Women with vulvodynia-type CPP and comorbid depression or PTSD may benefit from a trial of lamotrigine.
refractory and pose an enormous burden of suffering for the individual. Chronic pelvic pain (CPP) is generally defined as noncyclic pain of at least 6 months duration and severe enough to require medical care or cause disability. CPP has been estimated to have a prevalence of 15% among women of reproductive age. Women are at increased risk for both major depression and chronic pain syndromes such
should include a thorough gynecologic exam
as CPP, and are more likely to report antecedent
and a full mental health assessment. Treatment
stressful events, have higher rates of physical
of CPP must include an integrated approach
and sexual abuse, and subsequently develop
targeted at both the psychiatric comorbidity
posttraumatic stress disorder. High rates of sex-
and pain symptoms. A multidisciplinary treat-
ual and physical abuse and other trauma have
ment team offers the best chance for success
been shown among women with CPP, includ-
with CPP, and it is critical to suggest psychiatric
ing symptoms of dyspareunia (pain during
treatment (psychopharmacology and/or psycho-
intercourse), dysmenorrhea (pain during men-
therapy) in addition to traditional medical and
struation), and vulvar pain. A detailed and com-
surgical approaches.
prehensive evaluation of the patient with CPP Dr. Meltzer-Brody and Dr. Leserman are faculty in the Department of Psychiatry at the University of North Carolina at Chapel Hill. Faculty Disclosures: Dr. Meltzer-Brody receives research support from AstraZeneca, the Foundation of Hope, and the NIH (Grant number K23MH085165). Dr. Leserman reports no affiliations with or financial interests in any organization that may pose a conflict of interest. Submitted for publication: November 3, 2010; Accepted for publication: December 20, 2010; First published online: February 1, 2011 . Corresponding Author: Samantha Meltzer-Brody, MD, MPH, Associate Professor, Director, UNC Perinatal Psychiatry Program, Campus Box, #7160, UNC Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514; Tel: 919-962-9766; E-mail [email protected]
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INTRODUCTION Chronic pain is often treatment refractory and poses an enormous burden of suffering for the individual. The experience of constant pain may be viewed as a severe stress that is associated with the development of psychopathology, including depressive disorders, anxiety disorders, substance dependence, and personality disorders.1-3 Women are at increased risk for both major depression and chronic pain syndromes, including chronic pelvic pain (CPP).4 Women have a two-fold increased prevalence of major depressive disorder (MDD) throughout their reproductive lifecycle. 5-8 Furthermore, women are also more likely to report antecedent stressful events, have higher rates of physical and sexual abuse, and subsequently develop posttraumatic stress disorder (PTSD).9-13 High rates of sexual and physical abuse and other trauma have been shown among women with CPP, including symptoms of dyspareunia (pain during intercourse) and dysmenorrhea (pain during menstruation), and vulvar pain.14-23 Thus, the assessment and treatment of women with CPP must include a careful evaluation of prior trauma history and current psychiatric comorbidity. We review the epidemiology of CPP and comorbid psychiatric illness, strategies for the evaluation and diagnosis of CPP from a biopsychosocial perspective, and non-surgical treatment interventions that address both the pain and psychological distress of this disorder.
EPIDEMIOLOGY OF CPP AND PSYCHIATRIC COMORBIDITY CPP is generally defined as noncyclic pain of at least 6 months duration, severe enough to require medical care or cause disability and occurring in locations such as the pelvis, anterior abdominal wall at or below the umbilicus, lower back, or buttocks.24 CPP has been estimated to have a prevalence of 15% among women of reproductive 25 years of age, accounts for 10% of gynecological consultations and 40% of diagnostic laparoscopies performed in general hospitals. 26,27 Many women with CPP fail to respond to treatment, relapse rates are high, and they utilize a disproportionate amount of health care resources.28 A population-based survey14 of 1,931 women in primary care practices documented that women with a history of childhood sexual abuse were more likely to report pelvic pain (23.5%) compared to those without abuse (11.2%). A recent
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survey29 of women presenting to a specialty pelvic pain referral clinic demonstrated that ~50% of women with CPP reported a history of sexual or physical abuse, and rates of reported trauma in this population were much higher than in national samples of women in the general population. In this study, 1 in 3 women with pelvic pain also had a positive screen for PTSD indicating a high degree of psychiatric comorbidity that may contribute to the patient’s perception and ability to cope with chronic pain.29 This is consistent with previous literature documenting an association of CPP with childhood and/or adult sexual abuse.30-36
Defining CPP One challenge in the evaluation and management of patients with CPP is the often false assumption that the pelvic pain can be linked with some form of obvious pathology or tissue damage.37 Because every structure in the pelvis and/or abdomen could play a role in the etiology of CPP, it is essential to think beyond the reproductive organs and consider other contributions, such as the peripheral and central nervous systems.38 Interestingly, a comprehensive review39 of over 100 articles on CPP concluded that there is no consensus on a definition of CPP, and that this deficiency reduces the ability to investigate causation and improve treatment. Historically, three different operational definitions of CPP have been described in the literature. Durational is any type of pelvic pain that has lasted >6 months. Anatomic is CPP that lacks apparent physical cause sufficient to explain the pain (usually meaning that laparoscopy disclosed minimal, if any, pathology). Affective-behavioral is pain accompanied by significantly altered physical activity, including work, recreation, libido, as well as disturbance of mood.40 Therefore, it may be very helpful to approach the diagnosis and treatment of CPP from a biopsychosocial perspective (Figure) in which psychological events, such as sexual abuse and trauma, interact with structural and physiological factors to produce symptoms. These complicated interactions determine how patients cope with their symptoms and how they respond to treatments, including psychological as well as surgical and medical interventions. Additionally, it remains unclear whether all types of CPP disorder are equally affected. Two studies have shown that women with vulvodynia (pain localized to the vulva) are less likely to have iLÀÕ>ÀÞÊÓ䣣
Review Article
psychologic disturbance, sexual and/or physical abuse history, severe pain, and other somatic complaints compared with women with other types of CPP. 41,42 The literature is divided as to whether or not vulvodynia, characterized by localized vulvar pain, should be considered a type of CPP or if it is a separate and distinct syndrome.41,42 Alternatively, women with diffuse, non-localized, pain conditions report more depression, anxiety, and severity of pain than women with more focused pain,43 and those with intermittent pain (cyclical, ie, with dysmenorrhea), have less psychologic distress and histories of abuse than those with continuous chronic pain.37 Leserman and colleagues 44 examined seven diagnostic subtypes of CPP and how the subtypes differed in trauma history and current health status. In particular, they noted that patients with diffuse abdominal/pelvic pain had more trauma and worse mental and physical health status compared with patients with vulvovaginal pain and cyclic pain.44 Because psychiatric comorbidity is so common in women with CPP, specifically MDD and PTSD, it is worthwhile to briefly describe some of
the neuroscience underlying the clinical presentation. The literature documents that comorbid major depressive illness or other psychiatric disturbance may alter the perception of pain and increase pain intensity while decreasing the ability to tolerate the pain.45 The neuroanatomic and neurochemical processes associated with depression, PTSD, and chronic pain have been a focus of study and it is worthwhile to briefly describe this literature. In regards to the neuroscience underlying MDD, the periaqueductal gray (PAG) is thought to be a central anatomic site in the pain modulation system. 46,47 The PAG serves as an anatomic relay from limbic forebrain and midbrain structures to the brainstem.48 These relay systems contain both serotonergic and noradrenergic neurons, important neurotransmitters in the regulation of mood and several of the neurovegetative and cognitive functions that are often altered in patients with depression. It is hypothesized that when there is a depletion of serotonin and/or norepinephrine, the PAG system loses its modulatory effect so that minor signals from the body are amplified and more attention and emotion are focused on them. This may partially
FIGURE.
Schematic of the biopsychosocial model of chronic pain syndromes Predisposing Factors
Prior Trauma
Moderating Variables
Symptom Occurence
Health Status and Treatment Response (Medical, Surgical, Psychological)
Genetics
Demographics (Age, Race, SES)
Traumatic Life Events
Coping Strategies
Response (Adequate/ Inadequate)
(Sexual and Physical Abuse, other Trauma)
Type of Chronic Pain Psychosocial Symptoms (Anxiety, PTSD, Depression)
Health Outcome Biological Mechanisms
Health Status (Functional Status, Somatic Symptoms, Pain, Health Care Use)
* Figure created by Dr. Meltzer-Brody and previously published in her chapter Meltzer-Brody S, Golden R. “Chronic Pain and Comorbid Mood Disorders.” The Physicians Guide to Depression and Bipolar Disorders. Permission obtained. Meltzer-Brody S, Leserman J. CNS Spectr. Vol 16, No 2. 2011.
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explain why patients with depression often have multiple somatic complaints.48 The hypothalamic pituitary adrenal axis (HPA) is also felt to be involved in the experience of chronic pain.49,50 It is believed that chronic stress caused by chronic pain leads to loss of negative glucocorticoid feedback on the HPA axis, resulting in downregulation of glucocorticoid receptors within the brain and peripheral nervous system. This downregulation may lead to depressed mood.47 The underlying neuroscience and neuroanatomical work associated with PTSD also points to dysregulation in limbic, paralimbic and prefrontal regions which are involved in the stress response and emotional processing, including alterations of HPA function, autonomic and adrenergic hyperactivity, and the generation of PTSD symptoms.5153 Abnormalities in prefrontal function have also been noted in those pain patients prone to catastrophizing.54
evaluation and treatment approach offers the best clinical practice. Steege and Zolnoun55 have documented that it is critical for the health care provider to also ask focused questions about the nature of the pelvic pain and in particular, pain during intercourse (dyspareunia). Including questions about sexual comfort as a routine part of every gynecologic visit helps to legitimize the subject and allows the woman to feel more comfortable voicing a concern.55
EVALUATION OF CPP
Psychotherapeutic Interventions Psychological intervention studies for the treatment of CPP are extremely limited. One study described a mild-moderate impact of psychological counseling paired with ultrasound scanning on the course of CPP. 56 A second, more recent study (N=17), 57 evaluated the feasibility, acceptability, and efficacy of interpersonal psychotherapy adapted for women with comorbid depression and CPP. Despite the small sample size, large effect sizes with significant improvements were found for depression severity and
The evaluation of a patient with suspected CPP should begin with a complete medical history and comprehensive physical and gynecologic examination of the patient. The differential diagnosis of CPP includes, but is not limited: endometriosis, musculoskeletal pain, irritable bowel syndrome, interstitial cystitis, pelvic adhesive disease, neuropathic pain, and vulvodynia. It is important to assess location, duration, and timing of the pelvic pain. For example, the clinician should thoroughly assess the location of the pelvic pain, and if possible, determine whether the pain is within the abdominal wall, pelvic viscera (uterus, ovaries, bladder and/or intestines), pelvic floor muscles and/or vulva. A determination of first onset of pain and relation of the pain to the menstrual cycle is critical, particularly if endometriosis or uterine disease is suspected. A review of the evolution of pain over time is also a key component of the exam. Specific guidelines for the gynecologic physical exam are carefully detailed by Steege and Zolnoun.55 Obtaining an abuse and trauma history and an assessment for PTSD are critical components of the comprehensive evaluation of patients with CPP because addressing comorbid psychiatric illness in this patient population may lead to improved patient outcomes. 29 Ideally, a comprehensive evaluation of the patient with pelvic pain should include a full mental health assessment as well as a thorough gynecologic exam. A multidisciplinary
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NON-SURGICAL TREATMENT OF CPP Given the significant rates of comorbid psychiatric illness in women with CPP, treatment must include a comprehensive approach targeted at both the psychiatric comorbidity and the pain symptoms. We review the relatively small literature on evidence-based treatment interventions including psychotherapy, psychopharmacologic, and alternative therapies (Table 1).
TABLE.
Evidence-Based Treatment for CPP and Comorbid Depression and Anxiety Type of Treatment Modality Psychotherapy
Evidence Based Intervention Supportive counseling and ultrasound Interpersonal psychotherapy
Psychopharmacology
TCA, SSRI and SNRI antidepressant therapy Lamotrigine (anticonvulsant)
Alternative
Botulinum toxin injections Physical therapy Biofeedback
Meltzer-Brody S, Leserman J. CNS Spectr. Vol 16, No 2. 2011.
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social adjustment although pain interference remained unchanged.
address the psychological or emotional aspects of chronic pain, including vulvodynia, may affect the outcome.67 One psychopharmacologic option that targets symptoms of both pain and mood is lamotrigine. There is one study 69 of the efficacy of lamotrigine in the treatment of CPP with a focus on women with vulvodynia. In this open label study of 43 women with CPP (>60% with vulvodynia) recruited from a specialty pelvic pain clinic, significant reductions on all pain and mood measures were observed after 8 weeks of treatment as compared to baseline. In particular, women with vulvodynia-type CPP had robust reductions in pain and mood symptoms.69 These findings suggest that treatment with lamotrigine for patients with vulvodynia may be helpful in addressing both the pain and mood symptoms associated with this disorder.
Psychopharmacologic Interventions Although there have been recent advances in the treatment of comorbid psychiatric illness with chronic pain syndromes, the data on treatment specifically for CPP is limited. However, antidepressants are often used to treat patients with other chronic pain syndromes with varying degrees of success in terms of long term patient outcomes. 58 These pharmacologic agents target either serotonin and/or norepinephrine neurotransmitter levels, which as described above, both modulate descending pain pathways. Historically, the tricyclic antidepressants (TCAs), including amitriptyline, that primarily target the norepinephrine system have been widely used.59 The selective serotonin reuptake inhibitors (SSRIs) have also been shown to have modest efficacy in treating chronic pain, and more recently, the serotonin norepinephrine reuptake inhibitors (SNRIs) have shown strong potential as treatment for chronic pain disorders because of their dual action on both serotonin and norepinephrine.60-62 Antidepressants have shown some efficacy to treat both mood symptoms and to demonstrate analgesic properties independent of psychiatric effects in other chronic pain syndromes.60-62 Additionally, anticonvulsants (gabapentin, pregabalin, and lamotrigine), have been used to treat chronic pain syndromes. 63,64 Therefore, because many patients with CPP have comorbid depressive and anxiety symptoms, including MDD and PTSD, antidepressants and anticonvulsants have been tried as a treatment strategy with the goal of improving long term patient outcomes. In clinical practice, the TCAs, SSRIs, SNRIs, and anticonvulsants have all been used with modest success in the treatment of women with CPP. 58 However, evidence for the efficacy of antidepressants in the treatment of CPP has been less than optimal. There is one small double-blind study65 of the SSRI sertraline that did not demonstrate clinical significance. A second small open-label study66 with citalopram showed an improvement in depressive symptoms, and some improvement in pain intensity, but not pain disability in women with CPP.6 Vulvodynia type pelvic pain, a vulvar pain syndrome that may have a better response to intervention, has been routinely treated with the TCAs.67,68 It is critical to highlight that failure to
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ALTERNATIVE THERAPIES Because so few randomized controlled trials on the treatment of CPP have been conducted, there are multiple alternative therapies that are used, although often with limited data. Examples of alternative non-invasive treatments that have some evidence include physical therapy, biofeedback, and botulinum toxin injections. 70 The rationale for the use of physical therapy and biofeedback as treatment modalities for CPP, comes from the small literature documenting a higher frequency of positive pelvic musculoskeletal findings in CPP.71 Unrecognized musculoskeletal pain may be an important factor in the development of a state of general pain amplification, which may initiate and maintain idiopathic chronic pain disorders.72 Until significant progress is made in clarifying the multifactorial model of chronic pain pathogenesis, treatment of both overt and occult musculoskeletal pain generators represents a practical strategy for potentially decreasing the burden of CPP.71,72 The pelvis contains a complex musculature system that is often overlooked as a possible cause for pain, although it is recognized that relief of muscle spasm is associated with relief of pain symptoms.71 Therefore, after a diagnosis of possible pelvic floor spasm as a contribution to CPP has been made, physical therapy offers a lowrisk treatment option and has been documented as a non-invasive first line treatment for CPP. 71 Physical therapy provides a contract/relax treatment model that reduces the resting tone of the pelvic floor muscles and disrupts the spasm cycle, allowing for relief of pain. Adding in biofeedback 33
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may allow the patient to work with concrete information regarding the adequacy of pelvic floor training, and provide an objective assessment of the changes in baseline tone and strength.71 Another alternative treatment strategy for CPP associated with vulvar and generalized pelvic pain is the use of botulinum toxin therapy. Limited case reports and other small studies have indicated that botulinum toxins used in the vulva may offer a benefit for 3–6 months after injection of botulinum toxin 20–40 U.73-76 In CPP and, specifically, pelvic floor muscle spasm, a greater number of women have been studied and a double blind, randomized controlled study has reported a significant reduction in pelvic floor pressures with significant pain reduction for some types of pelvic pain compared to baseline.73-76
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CONCLUSION The relationship between CPP and comorbid psychiatric illness is complex. Comorbid psychiatric illness appears to alter both the individual’s perception of pain and ability to tolerate the pain. A careful biopsychosocial approach to the diagnosis and treatment of CPP in which psychological events, such as sexual abuse and trauma interact with structural and physiological factors to produce symptoms is warranted. Women with CPP have a significantly higher prevalence of histories of abuse, other trauma and comorbid PTSD and depression. Therefore, it is important that all women with pelvic pain have appropriate psychiatric screening for trauma and PTSD and other comorbid psychiatric illness. An integrative multidisciplinary approach offers the best chance for success with CPP; thus it is critical to suggest psychological treatment in addition to traditional and/ or alternative medical and surgical approaches. Psychotropic medications that have mood stabilizing properties may be helpful in the treatment of CPP. Furthermore, treatment of CPP should be specifically tailored based on the subtype of CPP, (ie, vulvodynia), as this may greatly influence the efficacy of a particular intervention. CNS
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