Double Blind Trial of Duloxetine in Chronic Fatigue Syndrome

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.

Inclusion Criteria:

1. Female and male outpatients between 18-65 years of age.

2. Meet criteria for revised Center for Disease Control (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
thyroid stimulating hormone (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 monoamine oxidase inhibitor (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.