Double Blind Trial of Duloxetine in Chronic Fatigue Syndrome (CFS)

• Brief Pain Inventory (BPI) [ Time Frame: at the time of the assessment ] [ Designated as safety issue: No ]
• Hospital Anxiety and Depression Scale (HADS) [ Time Frame: at the time of the assessment ] [ Designated as safety issue: No ]
• Clinical Global Impression of Severity (CGI-S) [ Time Frame: at the time of the assessment ] [ Designated as safety issue: No ]
• Patient Global Impression of Improvement (PGI-I) [ Time Frame: compared to baseline, at the time of the assessment ] [ Designated as safety issue: No ]
• Discontinuation rates [ Time Frame: at the time of the assessment ] [ Designated as safety issue: Yes ]
• treatment-emergent adverse events [ Time Frame: at the time of the assessment ] [ Designated as safety issue: Yes ]
• vital signs [ Time Frame: at the time of the assessment ] [ Designated as safety issue: Yes ]
• laboratory analyses [ Time Frame: at the time of the assessment ] [ Designated as safety issue: Yes ]

• Efficacy:
• Brief Pain Inventory (BPI)
• Hospital Anxiety and Depression Scale (HADS)
• Clinical Global Impression of Severity (CGI-S)
• Patient Global Impression of Improvement (PGI-I)
• Safety:
• Discontinuation rates
• treatment-emergent adverse events
• vital signs
• laboratory analyses

The purpose of this study is to determine the safety and efficacy of duloxetine compared with placebo for reducing fatigue in patients diagnosed with Chronic Fatigue Syndrome (CFS).

Chronic fatigue syndrome (CFS) is characterized by severe disabling fatigue of at least six months duration that cannot be fully explained by an identifiable medical condition . Pain symptoms are also a part of the diagnostic criteria for CFS, and include muscle pain, multi-joint pain, and headaches. The prevalence of CFS ranges from 0.007 to 2.8 % in the general adult population and 0.006 to 3.0% in primary care practice (2). Although most who receive a CFS diagnosis are 30-40 years of age, Caucasian, and female, CFS affects both women and men, adults and children, and all racial and socioeconomic classes.

Patients with CFS have 2-4 times the rate of depression and anxiety compared with the general population. CFS is also commonly comorbid with fibromyalgia, a disorder characterized by chronic widespread pain, tenderness, fatigue, sleep and mood disturbances. In some samples, 70% of patients with fibromyalgia also meet criteria for CFS. CFS and fibromyalgia are characterized by greater similarities than differences and may share pathophysiologic features. Like fibromyalgia, CFS is associated with chronic pain, sleep and mood disturbances. Because fibromyalgia responds to treatment with antidepressants, particularly the dual serotonin and norepinephrine reuptake inhibitors, including duloxetine, antidepressant trials in CFS are clearly needed.

• Drug: Duloxetine
  Duloxetine po 60-120 mg/day for 12 weeks
  Other Name: Cymbalta
• Drug: Placebo
  Sugar pill dose comparable to duloxetine
  Other Name: Sugar Pill

• Experimental: Duloxetine
  Duloxetine po 60-120 mg/day for 12 weeks
  Intervention: Drug: Duloxetine
• Placebo Comparator: Placebo
  Placebo comparator to Duloxetine
  Intervention: Drug: Placebo

Inclusion Criteria:

1. Female and male outpatients between 18-65 years of age.
2. Meet criteria for revised CDC definition of Chronic Fatigue Syndrome (CFS) (at least 6 months of persistent fatigue that substantially reduces the person's level of activity; 4 or more of the following symptoms that must occur with fatigue in a 6-month period: impaired memory or concentration, sore throat, tender glands, aching or stiff muscles, multijoint pain, new headaches, unrefreshing sleep, and post-exertional fatigue. Medical conditions that may explain the fatigue and psychiatric disorders, including eating disorders, psychotic disorders, bipolar disorder, melancholic depression, and substance abuse within 2 years of the onset of fatigue, are excluded).
3. Provision of written informed consent for participation in the trial.
4. Educational level and degree of understanding such that the patient can communicate intelligibly with the investigator and study staff.
5. Judged to be reliable and agree to keep all appointments for clinic visits, tests, and procedures required by the protocol.

Exclusion Criteria:

1. Current melancholic major depressive disorder, or a previous diagnosis of psychosis, eating disorder, or bipolar disorder.
2. History of substance abuse or dependence within the past year, excluding nicotine and caffeine.
3. A positive urine drug screen for any substance of abuse (may be retested if positive test was for a prescribed medication that was not washed out).
4. Women who are pregnant or breast feeding; women must test negative for pregnancy at Visit 1.
5. Women of childbearing potential who are not using a medically accepted means of contraceptive when engaging in sexual intercourse.
6. Patients who, in the opinion of the investigator, are treatment-refractory or whose response is likely to be compromised by existing or future disability compensation issues.
7. Serious unstable medical illness, including cardiovascular, hepatic, renal, respiratory, or hematologic illness, or other unstable medical or psychiatric conditions that in the opinion of the investigator would compromise participation or would likely lead to hospitalization during the duration of the study. Abnormal TSH concentrations (unless treatment for hypothyroidism has been stable for at least the past 3 months and the patient is clinically euthyroid).
8. Patients who have uncontrolled narrow-angle glaucoma.
9. Patients who have acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C).
10. Patients who are judged prior to randomization to be at suicidal risk by the clinical investigator.
11. Treatment with antidepressant medication within 14 days prior to randomization with the exception of fluoxetine, which cannot be used within 30 days prior to randomization. Potential need to use a MAOI during the study or within 2 weeks of discontinuation of study treatment.
12. Patients who have previously taken duloxetine
13. Patients who are taking any excluded medications that cannot be discontinued at Visit 1.
14. Treatment within the last 30 days with a drug that has not received regulatory approval at the time of study entry.
15. Known hypersensitivity to duloxetine or any of the inactive ingredients.