In this trial, participants will be randomly assigned to receive either fluoxetine or placebo. Treatment will consists of two phases (acute treatment and maintenance). In the acute treatment phase, participants will receive fluoxetine or placebo daily for 12 weeks. Participants will be followed every 2 weeks. In the Maintenance phase, participants showing significant improvement after 12 weeks may continue treatment for an additional 6 months. In this phase, participants are followed every 4 weeks.

Participants who do not improve during the acute treatment phase may receive open fluoxetine, or another appropriate medication, for 3 months.

Inclusioin Criteria:

• Meets DSM-IV criteria for depersonalization disorder in the last month

Exclusion Criteria:

• Prior or concurrent bio- or chemotherapy or
• Use of any of the following within 2 weeks prior to study entry: antipsychotics, anticonvulsants, stimulants, barbiturates, lithium, benzodiazepines, or antidepressants
• Use of MAO inhibitors or investigational drugs within 4 weeks prior to study entry
• History of fluoxetine use at a dose of 10 mg or more for at least 6 weeks duration
• Hematologic, hepatic, renal, cardiovascular, pulmonary, metabolic, endocrine, systemic, or gastrointestinal disease
• History of mental disorders
• Current substance abuse
• Current eating disorder
• Current clinically unstable suicidal ideation
• Unstable medical illness
• Clinically unstable
• Clinically important abnormalities in lab tests or physical exams
• History of seizure disorders or abnormal electroencephalogram
• Hypersensitivity or severe side effects to fluoxetine
• Pregnancy or breast-feeding. Women of child-bearing potential must use effective contraception