Psychosomatics 39:14-17, February 1998
© 1998 The Academy of Psychosomatic Medine
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., and
Paul E. Keck, Jr., M.D.
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.
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ABSTRACT
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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  50% 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.
Key Words: Venlafaxine • Fibromyalgia • Antidepressant
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INTRODUCTION
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Fibromyalgia 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.
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METHODS
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Fifteen subjects, 18 years of age and older, with a diagnosis of fibromyalgia for 6 months were consecutively recruited by newspaper advertisement 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 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 10-cm 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 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.
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RESULTS
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Of the 15 subjects completing the initial evaluation, all were Caucasian, and most were women (n=13), employed (n=11), and married (n=11), 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 (SD±14) mg/d in divided doses with a mean final dose of 167 (SD±76) mg/d and a range of 37.5 mg/d to 300 mg/d. Of the four noncompleters, three were noncompliant 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 (n=9), headache (n=6), constipation (n=5), fatigue (n=5), nausea (n=5), and dry mouth (n=5). 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 (P 0.01), as did the patients' global assessment of fibromyalgia (P0.02).
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 (phi=0.828 and P0.02). No other factors analyzed were associated with response of symptoms to treatment.
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DISCUSSION AND CONCLUSIONS
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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 effects 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 exploratory 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.
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ACKNOWLEDGMENTS
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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.
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ABSTRACT
INTRODUCTION
