- Email: [email protected]
An Open Clinical Trial of Venlafaxine Treatment of Fibromyalgia
Original Research Reports An Open Clinical Trial of Venlafaxine Treatment of Fibromyalgia MEGAN M. DWIGHT, M.D., LESLEY M. ARNOLD, M.D. HADLEY O’BRIEN, M.S.H.P.A., RAY METZGER, B.S. EMILY MORRIS-PARK, B.A., PAUL E. KECK, JR., M.D.
Of 15 patients with fibromyalgia who were first evaluated for the presence of Axis I psychiatric diagnoses by use of the Structured Clinical Interview for DSM-IV, 11 completed an open 8-week trial with the novel antidepressant venlafaxine. Six (55%) of 11 completers experienced a ⱖ50% reduction of fibromyalgia symptoms. The presence of lifetime psychiatric disorders, particularly depressive and anxiety disorders, predicted a positive response to venlafaxine. These findings suggest that it is important to assess for comorbid psychiatric disorders in patients with fibromyalgia and that venlafaxine may be helpful to some of these patients. (Psychosomatics 1998; 39:14–17)
F
ibromyalgia is a common condition that is often challenging to treat. Fibromyalgia occurs in about 2% of the general population of the United States.1 It is diagnosed in 5%–11% of patients in general medical and family practice clinics and occurs in 15%–20% of rheumatology outpatients.2–4 Although tricyclic antidepressants are moderately effective for some fibromyalgia patients, they have been used only in low doses.5–8 Their cardiovascular, antihistaminergic, and anticholinergic side effects may limit higher dose titration in patients who do not respond to lower doses. We conducted an open trial to assess whether venlafaxine, a potent inhibitor of both norepinephrine and serotonin reuptake,9 is well tolerated and efficacious in the treatment of fibromyalgia. METHODS Fifteen subjects, 18 years of age and older, with a diagnosis of fibromyalgia for ⱖ6 months were consecutively recruited by newspaper advertise14
ment for a medication trial. Exclusion criteria included untreated hypertension, suicidal or homicidal ideation, a history of hypomania/ mania or psychosis, current substance use disorder, pregnancy, lactation, or the use of antidepressants within 2 weeks before start of the study (4 weeks for fluoxetine). The subjects could not initiate any new treatments for fibromyalgia during the study, but diphenhydramine and chloral hydrate were allowed for insomnia. After providing written informed consent, all subjects were evaluated by using the Structured Clinical Interview for DSM-IV (SCID)10 and additional modules for irritable bowel syndrome, narcolepsy/cataplexy, Tourette’s disorder, migraine, fibromyalgia, and chronic fatigue Received September 17, 1996; revised December 4, 1996; accepted February 6, 1997. From the Division of Psychosomatic Research, Biological Psychiatry Program, Department of Psychiatry, University of Cincinnati, Ohio. Address reprint requests to Dr. Arnold, P.O. Box 670559, University of Cincinnati College of Medicine, Cincinnati, OH 45267. Copyright 䉷 1998 The Academy of Psychosomatic Medicine.
PSYCHOSOMATICS
Dwight et al.
syndrome.11 All subjects met operational criteria for fibromyalgia.11 Treatment response was measured by using the Hamilton Depression (Ham-D)12 and Hamilton Anxiety (Ham-A)13 scales; the McGill Pain Questionnaire;14 and 10cm visual analog self-report scales (revised from Carrette et al.8) that assessed pain, fatigue, sleep quality, feeling upon awakening, morning stiffness, and global assessment of fibromyalgia symptoms. A visual analog sum score was determined by adding the results of all individual scales. The Psychosocial Adjustment to Illness Scale–Self-Report (PAIS-SR)15 was given at entry and completion. Vital signs were monitored at Weeks 1, 2, 4, 6, and 8. The starting dose of venlafaxine ranged from 37.5 mg/d to 75 mg/d in divided doses and was titrated every 1–2 weeks in increments of 37.5 mg/d to 75 mg/d to the maximum tolerated by the subject but not greater than 375 mg/d. Differences between baseline and end of treatment (Week 8) measures on the Ham-D and Ham-A scales, the McGill Pain Questionnaire, the visual analog individual scales and sum score, and the PAIS-SR were analyzed by using the Wilcoxon Signed Rank Test. Possible predictors of response (age, gender, socioeconomic
TABLE 1. Patient a
1 2 3a 4 5a 6 7 8 9 10a 11 12 13 14 15
status, lifetime history of Axis I psychiatric disorder, and current Axis I psychiatric disorder) were tested by using the two-tailed Fisher’s exact test and the phi coefficient. Positive response was defined as 50% or greater improvement in both the McGill Pain Questionnaire and the visual analog sum score. RESULTS Of the 15 subjects completing the initial evaluation, all were Caucasian, and most were women (n⳱13), employed (n⳱11), and married (n⳱11), with a mean age of 48 years (standard deviation [SD]⳱6 years) (Table 1). Lifetime Axis I disorders, predominately depressive and anxiety disorders, were identified in 10 subjects (66%), of which 9 (60%) had current disorders (Table 1). Four subjects also reported histories of irritable bowel syndrome, three migraine, and two chronic fatigue syndrome. Eleven subjects (73%) completed the venlafaxine trial. The mean starting dose for completers was 68 (SDⳲ14) mg/d in divided doses with a mean final dose of 167 (SDⳲ76) mg/d and a range of 37.5 mg/d to 300 mg/d. Of the four noncompleters, three were noncompliant
Demographics and comorbidities of fibromyalgia patients Age
Gender
49 63 41 51 47 42 39 48 44 45 48 56 47 45 50
F M F F F F F M F F F F F F F
Current Comorbid Disorders MDD, Dysthymia, Panic disorder, IBS None Adjustment disorder, IBS GAD, Specific phobia None Dysthymia, Anxiety disorder NOS, Specific phobia None Specific phobia Dysthymia, IBS MDD, IBS, Migraine, CFS None Migraine Dysthymia, GAD, CFS None GAD, IBS, Migraine
Past Comorbid Disorders None None None MDD, Alcohol dependence None None None None MDD None None MDD None None MDD
Note: MDD⳱major depressive disorder; GAD⳱generalized anxiety disorder; IBS⳱irritable bowel syndrome; CFS⳱chronic fatigue syndrome; NOS⳱not otherwise specified. a Patient did not complete the study.
VOLUME 39 • NUMBER 1
• JANUARY–FEBRUARY 1998
15
Venlafaxine in Fibromyalgia
with visits, and one discontinued venlafaxine because of insomnia without a trial of sleep medication. The most common side effects reported by completers were insomnia (n⳱9), headache (n⳱6), constipation (n⳱5), fatigue (n⳱5), nausea (n⳱5), and dry mouth (n⳱5). Of the 3 completers who had insomnia that required adjunctive medication, 1 responded well to chloral hydrate (500 mg), and 2 responded partially to chloral hydrate (500 mg) with diphenhydramine (75 mg) and to diphenhydramine (50 mg), respectively. The average change of mean blood pressure was a reduction by 2.9 mmHg. Significant improvement from baseline to end of treatment was noted on the McGill Pain Questionnaire, the visual analog sum score, Ham-D and Ham-A scores, and in the PAIS-SR (Table 2). The individual visual analog scales of pain, fatigue, sleep quality, feeling upon awakening, and morning stiffness all showed significant improvement (Pⱕ0.01), as did the patients’ global assessment of fibromyalgia (Pⱕ0.02). Six (55%) of 11 completers had a positive response of fibromyalgia symptoms to venlafaxine, defined as 50% or greater reduction in both the McGill Pain Questionnaire and the visual analog sum scores. The presence of lifetime, but not current, Axis I disorders was correlated with a positive response (phi⳱0.828 and Pⱕ0.02). TABLE 2.
Outcome measures in fibromyalgia patients at baseline and following 8 weeks of venlafaxine treatment MeanⴣSD
Outcome Measure McGill Pain Questionnaire Visual Analog Sum score Hamilton Depression score Hamilton Anxiety score Psychosocial Adjustment to Illness Scale
Baseline
Week 8
22.9Ⳳ8.32
11.8Ⳳ8.18*
41.5Ⳳ7.35
22.8Ⳳ13.8*
10.1Ⳳ4.72
5.45Ⳳ4.19**
13.5Ⳳ6.18
6.36Ⳳ4.20**
35.0Ⳳ22.7
25.0Ⳳ25.1***
*P ⬍ 0.01, **P ⬍ 0.02, ***P ⬍ 0.05.
16
No other factors analyzed were associated with response of symptoms to treatment. DISCUSSION AND CONCLUSIONS These preliminary data suggest that venlafaxine may be effective in alleviating the symptoms of fibromyalgia in some patients. Venlafaxine was well tolerated by most patients despite the report of persistent insomnia by some patients. Most patients completing the study reported an improved quality of sleep, an increased feeling of restfulness upon awakening, a decrease in daytime fatigue, decrease in pain and morning stiffness, and an improved global assessment of the fibromyalgia, as well as a significant improvement in their quality of life, as measured by the PAIS-SR. Hudson et al.16 have suggested that fibromyalgia is one of the “Affective Spectrum Disorders,” a group of medical, neurological, and psychiatric disorders that share a high comorbidity with depression and other affective spectrum disorders, and responds to antidepressant treatment. In support of this hypothesis, 7 subjects (47%) reported other comorbid affective spectrum disorders (migraine, irritable bowel syndrome, and chronic fatigue syndrome). Furthermore, lifetime history of Axis I psychiatric disorders, in particular depressive and anxiety disorders, were common and predicted response of fibromyalgia symptoms to venlafaxine. Although the lack of correlation of current Axis I disorders with treatment response may be attributable to sample size, Hudson et al.17 have noted that fibromyalgia patients more often present with a lifetime history of affective disorders than with current disorders. The findings from this study underscore the importance of assessing for lifetime psychiatric disorders when evaluating patients with fibromyalgia. Both norepinephrine and serotonin may play a role in the pathophysiology of fibromyalgia. Prior studies have suggested that blockade of both norepinephrine and serotonin reuptake is more effective in treating fibromyalgia than blockade of either neurotransmitter alone.18,19 The ability of venlafaxine to exert efPSYCHOSOMATICS
Dwight et al.
fects on both the noradrenergic and serotonergic systems may explain its effectiveness in this preliminary trial. There are several study limitations. The study was not controlled or blinded; therefore, the rate of placebo response cannot be determined. The homogeneity and small size of our sample limits our ability to determine predictors of response. Furthermore, subject recruitment by newspaper advertisement introduced selection bias in the subject group. A larger, more diverse sample of patients may allow us to examine additional factors that may predict response. Although the open nature of this explora-
tory study limits drawing firm conclusions about the efficacy of venlafaxine in the treatment of fibromyalgia, the results suggest that venlafaxine may be useful for the treatment of fibromyalgia patients with comorbid lifetime Axis I disorders. Controlled trials are needed to further examine this issue. The authors thank Stephen Strakowski, M.D., for his critical review of this manuscript and assistance with statistical analysis. This work was supported by an unrestricted educational grant from Wyeth-Ayerst and a grant from the Theodore and Vada Stanley Foundation Scholars Program.
References
1. Wolfe F, Ross K, Anderson J, et al: The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum 1995; 38:19–27 2. Goldenberg DL, Simmus RW, Geiger A, et al: High frequency of fibromyalgia patients with chronic fatigue seen in a primary care practice. Arthritis Rheum 1990; 33:381–387 3. Skootsky SA, Jaeger B, Oye RD: Prevalence of myofascial pain in general internal medicine practice. West J Med 1989; 151:157–160 4. Wolfe F, Cathey M: Prevalence of primary and secondary fibrositis. J Rheumatol 1983; 26:817–825 5. Scudds RA, McCain GA, Rollman GB, et al: Improvements in pain responsiveness in patients with fibrositis after successful treatment with amitriptyline. J Rheumatol 1989; 16(suppl):S98–S103 6. Goldenberg DL, Felson DT, Dinerman H: A randomized controlled trial of amitriptyline and naproxen in the treatment of patients with fibromyalgia. Arthritis Rheum 1986; 29:1371–1377 7. Carrette S, McCain GA, Bell DA, et al: Evaluation of amitriptyline in primary fibrositis: a double-blind, placebo controlled study. Arthritis Rheum 1986; 29:655– 659 8. Carrette S, Bell MJ, Reynolds WJ, et al: Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia: a randomized, double-blind clinical trial. Arthritis Rheum 1994; 37:32–40 9. Preskorn SH: Antidepressant drug selection: criteria and options. J Clin Psychiatry 1994; 55:6–22
VOLUME 39 • NUMBER 1
• JANUARY–FEBRUARY 1998
10. First MB, Spitzer RL, Gibbon M, et al: Structured Clinical Interview for the DSM-IV Axis I Disorders— patient edition (SCID-I/P, version 2.0). New York, Biometrics Research Department, New York State Psychiatric Institute, 1995 11. Pope HG Jr, Hudson JI: A supplemental interview for forms of “affective spectrum disorder.” Int J Psychiatry Med 1991; 21:202–232 12. Hamilton M: A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23:56–62 13. Hamilton M: The assessment of anxiety disorders by rating. Br J Med Psychol 1959; 32:50–65 14. Melzack R: The McGill Pain Questionnaire: major properties and scoring methods. Pain 1975; 1:277–299 15. Derogatis LR: The Psychosocial Adjustment to Illness Scale self-report version. Baltimore, MD, Clinical Psychometric Research, 1990 16. Hudson JI, Pope HG: Fibromyalgia and psychopathology: is fibromyalgia a form of “affective spectrum disorder?” J Rheumatol 1989; 16(suppl 19):S15–S22 17. Hudson JI, Goldenberg DL, Pope HI, et al: Comorbidity of fibromyalgia with medical and psychiatric disorders. Am J Med 1992; 92:363–367 18. Cantini F, Bellandi F, Niccoli L, et al: Fluoxetine combined with cyclobenzaprine in the treatment of fibromyalgia (abstract). Minerva Med 1994; 85:97–100 19. Goldenberg DL, Mayskiy M, Mossey C, et al: A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia. Arthritis Rheum 1996; 39:1852–1859
17
Of 15 patients with fibromyalgia who were first evaluated for the presence of Axis I psychiatric diagnoses by use of the Structured Clinical Interview for DSM-IV, 11 completed an open 8-week trial with the novel antidepressant venlafaxine. Six (55%) of 11 completers experienced a ⱖ50% reduction of fibromyalgia symptoms. The presence of lifetime psychiatric disorders, particularly depressive and anxiety disorders, predicted a positive response to venlafaxine. These findings suggest that it is important to assess for comorbid psychiatric disorders in patients with fibromyalgia and that venlafaxine may be helpful to some of these patients. (Psychosomatics 1998; 39:14–17)
F
ibromyalgia is a common condition that is often challenging to treat. Fibromyalgia occurs in about 2% of the general population of the United States.1 It is diagnosed in 5%–11% of patients in general medical and family practice clinics and occurs in 15%–20% of rheumatology outpatients.2–4 Although tricyclic antidepressants are moderately effective for some fibromyalgia patients, they have been used only in low doses.5–8 Their cardiovascular, antihistaminergic, and anticholinergic side effects may limit higher dose titration in patients who do not respond to lower doses. We conducted an open trial to assess whether venlafaxine, a potent inhibitor of both norepinephrine and serotonin reuptake,9 is well tolerated and efficacious in the treatment of fibromyalgia. METHODS Fifteen subjects, 18 years of age and older, with a diagnosis of fibromyalgia for ⱖ6 months were consecutively recruited by newspaper advertise14
ment for a medication trial. Exclusion criteria included untreated hypertension, suicidal or homicidal ideation, a history of hypomania/ mania or psychosis, current substance use disorder, pregnancy, lactation, or the use of antidepressants within 2 weeks before start of the study (4 weeks for fluoxetine). The subjects could not initiate any new treatments for fibromyalgia during the study, but diphenhydramine and chloral hydrate were allowed for insomnia. After providing written informed consent, all subjects were evaluated by using the Structured Clinical Interview for DSM-IV (SCID)10 and additional modules for irritable bowel syndrome, narcolepsy/cataplexy, Tourette’s disorder, migraine, fibromyalgia, and chronic fatigue Received September 17, 1996; revised December 4, 1996; accepted February 6, 1997. From the Division of Psychosomatic Research, Biological Psychiatry Program, Department of Psychiatry, University of Cincinnati, Ohio. Address reprint requests to Dr. Arnold, P.O. Box 670559, University of Cincinnati College of Medicine, Cincinnati, OH 45267. Copyright 䉷 1998 The Academy of Psychosomatic Medicine.
PSYCHOSOMATICS
Dwight et al.
syndrome.11 All subjects met operational criteria for fibromyalgia.11 Treatment response was measured by using the Hamilton Depression (Ham-D)12 and Hamilton Anxiety (Ham-A)13 scales; the McGill Pain Questionnaire;14 and 10cm visual analog self-report scales (revised from Carrette et al.8) that assessed pain, fatigue, sleep quality, feeling upon awakening, morning stiffness, and global assessment of fibromyalgia symptoms. A visual analog sum score was determined by adding the results of all individual scales. The Psychosocial Adjustment to Illness Scale–Self-Report (PAIS-SR)15 was given at entry and completion. Vital signs were monitored at Weeks 1, 2, 4, 6, and 8. The starting dose of venlafaxine ranged from 37.5 mg/d to 75 mg/d in divided doses and was titrated every 1–2 weeks in increments of 37.5 mg/d to 75 mg/d to the maximum tolerated by the subject but not greater than 375 mg/d. Differences between baseline and end of treatment (Week 8) measures on the Ham-D and Ham-A scales, the McGill Pain Questionnaire, the visual analog individual scales and sum score, and the PAIS-SR were analyzed by using the Wilcoxon Signed Rank Test. Possible predictors of response (age, gender, socioeconomic
TABLE 1. Patient a
1 2 3a 4 5a 6 7 8 9 10a 11 12 13 14 15
status, lifetime history of Axis I psychiatric disorder, and current Axis I psychiatric disorder) were tested by using the two-tailed Fisher’s exact test and the phi coefficient. Positive response was defined as 50% or greater improvement in both the McGill Pain Questionnaire and the visual analog sum score. RESULTS Of the 15 subjects completing the initial evaluation, all were Caucasian, and most were women (n⳱13), employed (n⳱11), and married (n⳱11), with a mean age of 48 years (standard deviation [SD]⳱6 years) (Table 1). Lifetime Axis I disorders, predominately depressive and anxiety disorders, were identified in 10 subjects (66%), of which 9 (60%) had current disorders (Table 1). Four subjects also reported histories of irritable bowel syndrome, three migraine, and two chronic fatigue syndrome. Eleven subjects (73%) completed the venlafaxine trial. The mean starting dose for completers was 68 (SDⳲ14) mg/d in divided doses with a mean final dose of 167 (SDⳲ76) mg/d and a range of 37.5 mg/d to 300 mg/d. Of the four noncompleters, three were noncompliant
Demographics and comorbidities of fibromyalgia patients Age
Gender
49 63 41 51 47 42 39 48 44 45 48 56 47 45 50
F M F F F F F M F F F F F F F
Current Comorbid Disorders MDD, Dysthymia, Panic disorder, IBS None Adjustment disorder, IBS GAD, Specific phobia None Dysthymia, Anxiety disorder NOS, Specific phobia None Specific phobia Dysthymia, IBS MDD, IBS, Migraine, CFS None Migraine Dysthymia, GAD, CFS None GAD, IBS, Migraine
Past Comorbid Disorders None None None MDD, Alcohol dependence None None None None MDD None None MDD None None MDD
Note: MDD⳱major depressive disorder; GAD⳱generalized anxiety disorder; IBS⳱irritable bowel syndrome; CFS⳱chronic fatigue syndrome; NOS⳱not otherwise specified. a Patient did not complete the study.
VOLUME 39 • NUMBER 1
• JANUARY–FEBRUARY 1998
15
Venlafaxine in Fibromyalgia
with visits, and one discontinued venlafaxine because of insomnia without a trial of sleep medication. The most common side effects reported by completers were insomnia (n⳱9), headache (n⳱6), constipation (n⳱5), fatigue (n⳱5), nausea (n⳱5), and dry mouth (n⳱5). Of the 3 completers who had insomnia that required adjunctive medication, 1 responded well to chloral hydrate (500 mg), and 2 responded partially to chloral hydrate (500 mg) with diphenhydramine (75 mg) and to diphenhydramine (50 mg), respectively. The average change of mean blood pressure was a reduction by 2.9 mmHg. Significant improvement from baseline to end of treatment was noted on the McGill Pain Questionnaire, the visual analog sum score, Ham-D and Ham-A scores, and in the PAIS-SR (Table 2). The individual visual analog scales of pain, fatigue, sleep quality, feeling upon awakening, and morning stiffness all showed significant improvement (Pⱕ0.01), as did the patients’ global assessment of fibromyalgia (Pⱕ0.02). Six (55%) of 11 completers had a positive response of fibromyalgia symptoms to venlafaxine, defined as 50% or greater reduction in both the McGill Pain Questionnaire and the visual analog sum scores. The presence of lifetime, but not current, Axis I disorders was correlated with a positive response (phi⳱0.828 and Pⱕ0.02). TABLE 2.
Outcome measures in fibromyalgia patients at baseline and following 8 weeks of venlafaxine treatment MeanⴣSD
Outcome Measure McGill Pain Questionnaire Visual Analog Sum score Hamilton Depression score Hamilton Anxiety score Psychosocial Adjustment to Illness Scale
Baseline
Week 8
22.9Ⳳ8.32
11.8Ⳳ8.18*
41.5Ⳳ7.35
22.8Ⳳ13.8*
10.1Ⳳ4.72
5.45Ⳳ4.19**
13.5Ⳳ6.18
6.36Ⳳ4.20**
35.0Ⳳ22.7
25.0Ⳳ25.1***
*P ⬍ 0.01, **P ⬍ 0.02, ***P ⬍ 0.05.
16
No other factors analyzed were associated with response of symptoms to treatment. DISCUSSION AND CONCLUSIONS These preliminary data suggest that venlafaxine may be effective in alleviating the symptoms of fibromyalgia in some patients. Venlafaxine was well tolerated by most patients despite the report of persistent insomnia by some patients. Most patients completing the study reported an improved quality of sleep, an increased feeling of restfulness upon awakening, a decrease in daytime fatigue, decrease in pain and morning stiffness, and an improved global assessment of the fibromyalgia, as well as a significant improvement in their quality of life, as measured by the PAIS-SR. Hudson et al.16 have suggested that fibromyalgia is one of the “Affective Spectrum Disorders,” a group of medical, neurological, and psychiatric disorders that share a high comorbidity with depression and other affective spectrum disorders, and responds to antidepressant treatment. In support of this hypothesis, 7 subjects (47%) reported other comorbid affective spectrum disorders (migraine, irritable bowel syndrome, and chronic fatigue syndrome). Furthermore, lifetime history of Axis I psychiatric disorders, in particular depressive and anxiety disorders, were common and predicted response of fibromyalgia symptoms to venlafaxine. Although the lack of correlation of current Axis I disorders with treatment response may be attributable to sample size, Hudson et al.17 have noted that fibromyalgia patients more often present with a lifetime history of affective disorders than with current disorders. The findings from this study underscore the importance of assessing for lifetime psychiatric disorders when evaluating patients with fibromyalgia. Both norepinephrine and serotonin may play a role in the pathophysiology of fibromyalgia. Prior studies have suggested that blockade of both norepinephrine and serotonin reuptake is more effective in treating fibromyalgia than blockade of either neurotransmitter alone.18,19 The ability of venlafaxine to exert efPSYCHOSOMATICS
Dwight et al.
fects on both the noradrenergic and serotonergic systems may explain its effectiveness in this preliminary trial. There are several study limitations. The study was not controlled or blinded; therefore, the rate of placebo response cannot be determined. The homogeneity and small size of our sample limits our ability to determine predictors of response. Furthermore, subject recruitment by newspaper advertisement introduced selection bias in the subject group. A larger, more diverse sample of patients may allow us to examine additional factors that may predict response. Although the open nature of this explora-
tory study limits drawing firm conclusions about the efficacy of venlafaxine in the treatment of fibromyalgia, the results suggest that venlafaxine may be useful for the treatment of fibromyalgia patients with comorbid lifetime Axis I disorders. Controlled trials are needed to further examine this issue. The authors thank Stephen Strakowski, M.D., for his critical review of this manuscript and assistance with statistical analysis. This work was supported by an unrestricted educational grant from Wyeth-Ayerst and a grant from the Theodore and Vada Stanley Foundation Scholars Program.
References
1. Wolfe F, Ross K, Anderson J, et al: The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum 1995; 38:19–27 2. Goldenberg DL, Simmus RW, Geiger A, et al: High frequency of fibromyalgia patients with chronic fatigue seen in a primary care practice. Arthritis Rheum 1990; 33:381–387 3. Skootsky SA, Jaeger B, Oye RD: Prevalence of myofascial pain in general internal medicine practice. West J Med 1989; 151:157–160 4. Wolfe F, Cathey M: Prevalence of primary and secondary fibrositis. J Rheumatol 1983; 26:817–825 5. Scudds RA, McCain GA, Rollman GB, et al: Improvements in pain responsiveness in patients with fibrositis after successful treatment with amitriptyline. J Rheumatol 1989; 16(suppl):S98–S103 6. Goldenberg DL, Felson DT, Dinerman H: A randomized controlled trial of amitriptyline and naproxen in the treatment of patients with fibromyalgia. Arthritis Rheum 1986; 29:1371–1377 7. Carrette S, McCain GA, Bell DA, et al: Evaluation of amitriptyline in primary fibrositis: a double-blind, placebo controlled study. Arthritis Rheum 1986; 29:655– 659 8. Carrette S, Bell MJ, Reynolds WJ, et al: Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia: a randomized, double-blind clinical trial. Arthritis Rheum 1994; 37:32–40 9. Preskorn SH: Antidepressant drug selection: criteria and options. J Clin Psychiatry 1994; 55:6–22
VOLUME 39 • NUMBER 1
• JANUARY–FEBRUARY 1998
10. First MB, Spitzer RL, Gibbon M, et al: Structured Clinical Interview for the DSM-IV Axis I Disorders— patient edition (SCID-I/P, version 2.0). New York, Biometrics Research Department, New York State Psychiatric Institute, 1995 11. Pope HG Jr, Hudson JI: A supplemental interview for forms of “affective spectrum disorder.” Int J Psychiatry Med 1991; 21:202–232 12. Hamilton M: A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23:56–62 13. Hamilton M: The assessment of anxiety disorders by rating. Br J Med Psychol 1959; 32:50–65 14. Melzack R: The McGill Pain Questionnaire: major properties and scoring methods. Pain 1975; 1:277–299 15. Derogatis LR: The Psychosocial Adjustment to Illness Scale self-report version. Baltimore, MD, Clinical Psychometric Research, 1990 16. Hudson JI, Pope HG: Fibromyalgia and psychopathology: is fibromyalgia a form of “affective spectrum disorder?” J Rheumatol 1989; 16(suppl 19):S15–S22 17. Hudson JI, Goldenberg DL, Pope HI, et al: Comorbidity of fibromyalgia with medical and psychiatric disorders. Am J Med 1992; 92:363–367 18. Cantini F, Bellandi F, Niccoli L, et al: Fluoxetine combined with cyclobenzaprine in the treatment of fibromyalgia (abstract). Minerva Med 1994; 85:97–100 19. Goldenberg DL, Mayskiy M, Mossey C, et al: A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia. Arthritis Rheum 1996; 39:1852–1859
17