5-Hydroxytryptophan plus SSRIs for interferon-induced depression: Synergistic mechanisms for normalizing synaptic serotonin

Abstract

Summary Interferon-a (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.

Serotonin a la carte: Supplementation with the serotonin precursor 5-hydroxytryptophan

“…In particular, exogenous administration of IFN-a has been shown to cause depression in some patients (Musselman et al, 2001;Hauser et al, 2002;Loftis & Hauser, 2004). This IFN-induced depression has been attributed to the activation of the cytokine network (i.e., IFN-g) and IDO, resulting in perturbations of the serotonergic system (Menkes & MacDonald, 2000;Bonaccorso et al, 2002;Capuron et al, 2003;Turner & Blackwell, 2005). In agreement with these findings, IFN-a treatment increases the kynurenine-to-tryptophan ratio, which estimates the activity of IDO, suggesting potentiated 5-HTP and serotonin catabolism (Bonaccorso et al, 2002).…”

“…Thus, IFN-a may induce depression by a serotonergic-related mechanism (Schaefer et al, 2003;Wichers & Maes, 2004). To the extent that this is the mechanism for IFN-induced depression, it should be treatable with exogenous 5-HTP (Menkes & MacDonald, 2000;Turner & Blackwell, 2005).…”

Interferon-induced depressive illness in hep C patients responds to SSRI antidepressant treatments

“…Other workers have also reported similar high success rates in the treatment of depression following INF- therapy, with Turner and Blackwell (2005) reporting effective response in up to 75% and Lang et al 78.5% (2003). Both Schramm et al (2000) and Hauser (2004) also reported almost 100% success in their series.…”

Depression and pegylated interferon-based hepatitis C treatment

“…The fact that SSRIs sometimes are not efficacious, especially in a prophylactic role, can probably be explained by the fact that IFN not only increases serotonin re-uptake but also decreases serotonin synthesis. 85 Overall, more studies are needed to establish the role of SSRIs and SNRIs in the prevention and treatment of depression and their effectiveness in compliance and SVR rates. Psychiatric evaluation is mandatory when suicidal ideation becomes evident and treatment should be discontinued in such cases.…”