5-Hydroxytryptophan plus SSRIs for interferon-induced depression: synergistic mechanisms for normalizing synaptic serotonin.
Interferon-alpha (IFN) is widely used in the treatment of certain cancers and viral infections, including hepatitis C (HCV). Unfortunately, depression is a common side effect of IFN therapy, affecting approximately a third of HCV patients receiving IFN therapy. Studies have shown that selective serotonin reuptake inhibitors (SSRIs) can effectively treat IFN-induced depression in only 63-75% of cases. For the remaining percentage, depression often necessitates dose reduction of or discontinuation from IFN therapy. Emerging evidence indicates that IFN may cause depression by affecting brain serotonin. IFN has been shown to increase serotonin reuptake and to decrease serotonin synthesis. We hypothesize that SSRIs are not fully effective because they affect only serotonin reuptake, not serotonin synthesis, and that effective treatment must address both uptake and synthesis. 5-Hydroxytryptophan (5-HTP) effectively increases central nervous system synthesis of serotonin. It is the immediate precursor of serotonin and is widely available as a dietary supplement, which is well absorbed after an oral dose. Several double-blind studies have shown 5-HTP to be effective in the treatment of nondrug-induced depression. We hypothesize that patients who become depressed on IFN will respond to the synergistic combination of SSRIs plus 5-HTP.
Turner
Erick H
EH
Mental Health Division, Mood Disorders Research Center, Portland VA Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR 97239, USA. Erik.turner@med.va.gov
Blackwell
Aaron D
AD
D006916:5-Hydroxytryptophan / Q000378:metabolism / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001923:Brain Chemistry; D003863:Depression / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006526:Hepatitis C / Q000188:drug therapy / Q000523:psychology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D008954:Models, Biological; D012307:Risk Factors; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D013569:Synapses / Q000187:drug effects
D006916:5-Hydroxytryptophan; D000998:Antiviral Agents; D016898:Interferon-alpha; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors