This is a preliminary, double-blind clinical trail aimed to investigate whether the combination of fluoxetine with ATP or phosphocreatine has a rapid antidepressant effect. 42 patients with major depressive disorder (Hamilton Depression Rating Scale (HAMD) score >= 20) will be recruited and divided into 3 groups randomly. This study involves two periods. In the first period, one group will be treated with fluoxetine and placebo, one with fluoxetine and ATP, and one with fluoxetine and phosphocreatine for 2 weeks. Placebo, ATP and phosphocreatine will be given intravenously, and fluoxetine orally. In the second period, each patient will be only given fluoxetine for 4 weeks.

Inclusion Criteria:

• 18-65 year-old male or female
• Major depressive disorder diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
• Hamilton depression rating scale score >= 20 at screening
• Written informed consent

Exclusion Criteria:

• Participants of other clinical trials in recent 4 weeks
• Suicidal idea or action that requires hospitalization
• Post Traumatic Stress Syndrome in recent 6 months
• Secondary depression, or have a direct familial history of schizophrenia
• Diseases that prevent from appropriate expression of depressive emotion
• Psychiatric disorders including bipolar disorder and schizophrenia
• Severe heart, kidney, lung or liver diseases that require hospitalization
• Diabetes
• Neurologic disease (eg., epilepsy, infarct, multiple sclerosis, brain tumor)
• Inflammatory disease including autoimmune disease
• Taking anti-inflammatory medication
• Taking antiarrhythmic drugs, antidiabetic agents or tryptophan
• Substance abuse or dependence history in recent 6 months
• Pregnant or having plan to be pregnant