Curcumin as supportive therapy in depression

Major depressive disorder Major Depressive Disorder, MDD) is one of the most common psychosomatic disorders that shows a pronounced tendency to increase. In order to relieve the symptoms of depression, patients are prescribed different types of antidepressants, from monoamine oxidase inhibitors until serotonin reuptake inhibitors. Despite the wide availability of these substances, it is estimated that approximately 30% of patients do not respond to antidepressant therapy and 70% of patients fail to achieve complete remission (1).

A reduced concentration of monoamines, primarily serotonin, noradrenaline and dopamine, in the synaptic membrane of patients is often cited as the leading cause of depression.However, recent findings reveal a whole range of disorders accompanying major depressive disorder: from activation of inflammatory pathways, increased oxidative stress to increased activity of the pituitary-hypothalamic-adrenal axis (HPA) (2). Scientists are looking for new therapeutic approaches in the treatment of depression and, in this context, curcumin has been recognized as a molecule that shows promising results (1,3).

Curcumin is the main plant compound and the characteristic yellow pigment of turmeric powder, which is obtained by extracting the rhizome of the plant Curcuma longa.

Curcumin is the most active ingredient in turmeric and has been described as a substance with anti-inflammatory, antioxidant, immunomodulatory, pro-apoptotic and anti-proliferative effects (4,5).

More and more evidence supports the neuroprotective effect of curcumin, which is why it is being considered either as a monotherapy or as a supportive therapy in depression (6).

Kurkumin i depresija – klinička istraživanja

Research published in recent years has shown that pro-inflammatory cytokines and oxidative stress, among other things, underlie depression. Precisely because of its proven anti-inflammatory and antioxidant properties, curcumin represents an interesting and potentially successful therapy for depression.

• Učinak kurkumina na depresiju proučavan je u randomiziranoj, dvostruko-slijepoj, placebo-kontroliranoj studiji objavljenoj 2014. godine. 56 ispitanika s velikim depresivnim poremećajem je kroz razdoblje od 8 tjedana dobivalo ili kurkumin u dozi od 1 g (500 mg kurkumina dva puta dnevno) ili placebo. U početku studije zabilježeno je poboljšanje simptoma u obje skupine, međutim nakon 4. tjedna kurkumin je bio značajno učinkovitiji od placeba u poboljšanju simptoma depresije i anksioznosti. Dodatno, kod ispitanika s atipičnom depresijom zabilježen je još veći antidepresivni učinak kurkumina u usporedbi s placebom. Inače, atipičnu depresiju karakterizira „odgovor u raspoloženju”, tj. raspoloženje se popravlja kao odgovor na stvarni ili mogući pozitivni događaj te prekomjerno spavanje, značajno povećanje apetita, porast tjelesne mase i osjećaj težine i umora u rukama i nogama (2).
• A double-blind, placebo-controlled study published in 2015 looked at the use of curcumin as adjunctive therapy to antidepressants. 108 male subjects with MDD took 1000 mg of curcumin or placebo for a period of 6 weeks, along with standard therapy. The results showed a significant antidepressant effect of curcumin and pointed to its ability to improve the outcome of standard antidepressant therapy for major depressive disorder (7).
• The latest study on this topic published this year provided new evidence in support of curcumin as a supportive treatment for depression. In a double-blind, placebo-controlled study, 65 subjects aged 18 to 63 took up to 1,500 mg of curcumin daily or a placebo in addition to standard antidepressant therapy.After 12 weeks, a significant antidepressant contribution of curcumin to the therapy of major depressive disorder was established. Additionally, a greater antidepressant effect was recorded in men than in women (6).

Zanimljivo, istraživanja ukazuju na vremenski odmak djelovanja kurkumina – potrebno je i do nekoliko tjedana unosa da bi antidepresivni učinak kurkumina došao do izražaja što potvrđuje i meta-analiza 6 studija. Pokazalo se da kratkotrajna primjena kurkumina (kraće od 6 tjedana) ne pokazuje statistički značajno smanjene simptoma depresije, dok primjena dulja od 6 tjedana ima značajan antidepresivni učinak. Dodatno, analiza je pokazala kako kurkumin kao potporna terapija u liječenju depresije najbolje rezultate pokazuje kod osoba srednje dobi  (8).

Mechanism of action

Curcumin has a whole range of activities that can explain its effectiveness, which include:

• the strong anti-inflammatory effect of curcumin is manifested in the suppression of several inflammatory cytokines, such as TNF-α, interleukins (IL-1, -1β, -6 and -8) and cyclooxygenase-2 (COX-2). Additionally, curcumin has the ability to block inducible nitric oxide synthase (iNOS), thus reducing the release of pro-inflammatory NO (Figure 1).
• modulating the level of numerous neurotransmitters such as increasing the level of dopamine and serotonin and reducing the level of cortisol, which positively affects mood
• the neuroprotective action, i.e. the stimulation of neurogenesis of curcumin is well documented, and originates from the positive effect on the level of brain-derived neurotrophic factor (BDNF)
• inhibition of the enzyme monoamine oxidase, which normally catalyzes the breakdown of serotonin and other monoamine neurotransmitters
• stimulation of the body's antioxidant response by curcumin is manifested by its ability to increase the activity of enzymes that act as antioxidants such as superoxide dismutase and glutathione peroxidase (1, 6, 9, 10).

What can we conclude?

Major depressive disorder is a common disease in which, despite the wide availability of drugs, the percentage of complete cure is low, and the frequency of symptoms returning is high. Great efforts are being made to find new substances that will provide effective therapy for depression.

Research shows that curcumin, a polyphenol with strong anti-inflammatory and neuroprotective effects in a dose of 500-1500 mg per day can be effective as monotherapy or as supportive therapy in depression.

Author: Sandra Krstev Barać, M.Sc.

Literature:

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