Table 3.
Novel antidepressant treatment targets and strategies.
| Intervention | Antidepressant efficacy | Referencea |
|---|---|---|
| Cyclo-oxygenase-2 (COX-2) inhibition (e.g., celecoxib) | In a 6-week double-blind, placebo-controlled trial, the combination of fluoxetine + celecoxib (n = 20) showed superiority over fluoxetine + placebo (n = 20), as measured using the Hamilton Depression Rating Scale. | Myint et al., 2007; Muller and Schwarz, 2008; Nery et al., 2008; Song et al., 2009; Akhondzadeh et al., 2009 |
| Suppression of SAPK/MAPK and/or JAK/STAT signaling components | Administration of a p38 MAP kinase inhibitor resulted in an attenuation of proinflammatory cytokines in the hippocampus and improved spatial memory on the Y-maze. | Malemud and Miller, 2008; Munoz et al., 2007; Loftis et al., 2009 |
| TNF-α inhibition/antagonism (e.g., adalimumab, etanercept, and infliximab) | A limited number of clinical trials and open-label studies suggest that TNF-α antagonists may reduce depressive symptoms, in particular fatigue, and improve quality of life. | Jiang et al., 2008; Soczynska et al., 2009 |
| Melatonin | Pre-clinical and clinical data show that melatonin reduces adhesion molecules and proinflammatory cytokines (e.g., IL-6, IL-8 and TNF-α). Using an unpredictable chronic stress model in mice, melatonin counteracted the stress-induced degradation of coat and decrease in grooming behavior in the splash test Melatonin treatment also decreased corticosterone levels, similar to the decreases observed following imipramine treatment. | Detanico et al., 2009; Maldonado et al., 2009 |
| Probiotics (e.g., Bifidobacteria) | Rats receiving probiotic treatment showed no significant differences on the FST, as compared to controls. However, probiotic treatment resulted in a reduction of IFN-γ, TNF-α, and IL-6 following mitogen stimulation of whole blood cultures. | Desbonnet et al., 2008 |
| Curcumin | In chronically stressed rats, curcumin treatment increased hippocampal neurogenesis (similar to imipramine treatment) and prevented stress-induced decreases in hippocampal serotonin receptor mRNA and BDNF protein levels. | Xu et al., 2007 |
| Ethyl-eicosapentaenoate (EPA) | In a rat olfactory bulbectomy model of depression, EPA significantly attenuated behavioral changes in the open field test and improved spatial memory, as compared to control rats. EPA treatment additionally resulted in a reduction of IL-1β and corticosterone levels. | Song et al., 2009 |
| Folic acid | A clinical study comparing fluoxetine+folic acid (n=14) with fluoxetine+placebo (n=13) found that patients receiving folate supplementation had significantly lower depression rating scale scores after 6 weeks of treatment. | Resler et al., 2008 |
| Psychotherapy (e.g., cognitive behavioral therapy and mindfulness interventions) | In a study comparing mindfulness meditation, cognitive behavioral therapy and education, patients with recurrent depression benefited from mindfulness meditation; in a separate group, IL-6 production was decreased following cognitive behavioral therapy in patients with depressive symptoms. | Fazzino et al., 2009; Zautra et al., 2008 |
| Vaccination (e.g., immunization with CNS-related antigens as a therapeutic means for treating depression) | In rats, immunization with a modified peptide [i.e., a segment of myelin basic protein (MBP)] resulted in the amelioration of anhedonia but no treatment effect was seen on the FST. Vaccination also resulted in significantly higher BDNF expression in hippocampus and increased cell proliferation. | Lewitus et al., 2009 |
a
Additional supporting references are provided for studies not specifically summarized under “Antidepressant efficacy”.