MDD is a common debilitating psychiatric disorder that affects nearly 16% to 20% of the

population in both developed and developing nations.1,2 According to the World Health
Organization, by the year 2020, major depression will become the second most prevalent
cause of illness-induced disability worldwide.3,4 About 1 in 10 Americans report symptoms of
depression, and this illness is responsible for the majority of almost 40,000 suicides per year
in the United States. Depressed mood, anhedonia, and reduced energy levels are believed
to be the core symptoms of depression, and presence of at least 2 of these symptoms is
required for a confirmatory diagnosis of an individual suffering from MDD.

Antidepressants, ranging from monoamine oxidase inhibitors to recently developed selective

serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors, are prescribed
for alleviating the symptoms of depression. Ironically, in spite of the availability of these
blockbuster molecules, as many as 30% of MDD patients do not even respond to these drug
therapies in the first place, and the remaining 70% fail to achieve complete remission.5 Even
when they provide some benefit, these drugs are truly only effective and safe in the short
term. When taken long term, these synthetic antidepressants often associate with a plethora
of side effects including sedation, weight gain, physical sensations of numbness or pain, and
a propensity for abuse.

The role of immune activation in MDD was for the first time reported more than 20 years
ago,6and since then, it has become apparent that chronic inflammation plays a major role in
this psychiatric illness.7 Meta-analyses of studies have revealed that increased peripheral
blood levels of various cytokines, interleukin-6, tumor necrosis factor-alpha, and C-reactive
protein are some of the key biomarkers of increased inflammation in depressed
patients,8,9 and significant associations have been found between blood concentrations of
these biomarkers and the severity of depression in individuals suffering from
MDD.10,11 Inflammatory cytokines also interact with mitochondria to increase the reactive
oxygen species production, which in turn increases cytokine expression.12 Taken together,
these scientific findings clearly suggest that any treatment approach that can effectively
combat inflammation and oxidative stress can have significant influence in alleviating MDD
symptoms. Not surprisingly, there is an imperative need to develop novel approaches for the
identification of more efficacious and safe drugs for the treatment of major depression.

The present study by Lopresti and colleagues is clearly a significant step forward in this
direction because the authors have undertaken first ever, randomized, double-blind, placebo-
controlled clinical trial to demonstrate that curcumin, the active compound in turmeric
(Curcuma longa), has a significant antidepressive effect vis-à-vis placebo treatment in
individuals suffering from MDD. These results also support a previous study that
demonstrated that curcumin was equally effective as the pharmaceutical antidepressant
fluoxetine (Prozac) for the treatment of depression.13 One of the most provocative aspects of
this study was that curcumin treatment not only benefitted patients with major depression,
but it significantly enhanced antidepressant and anxiolytic efficacy in people with atypical
depression—a condition that involves much higher levels of inflammation and is much more
difficult to treat.

Another important point worth noting about this study was that the researchers used a very
specific type of curcumin, BCM-95, which has unique specifications, including high
absorption and inclusion of turmeric essential oil not found in standard curcumin. Therefore,
one must be cautious that the results may not be reproducible when using other forms of
curcumin.