Curcumin as supportive therapy in depression

Veliki depresivni poremećaj (engl. Major Depressive Disorder, MDD) jedan je od najčešćih psihosomatskih poremećaja koji pokazuje izraženu tendenciju porasta. U svrhu olakšanja simptoma depresije pacijentima se pripisuju različite vrste antidepresiva, od monoamine oxidase inhibitors do 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).

Kao vodeći uzrok depresije često se navodi smanjena koncentracija monoamina, ponajprije serotonina, noradrenalina i dopamina u sinaptičkoj membrani oboljelih. Međutim, novija saznanja otkrivaju cijeli niz poremećaja koje prate veliki depresivni poremećaj: od aktivacije upalnih puteva, povećanog oksidacijskog stresa do povećane aktivnosti osi hipofiza-hipotalamus-nadbubrežna žlijezda (HPA) (2). Znanstvenici su u potrazi za novim terapeutskim pristupima u liječenju depresije te je, u tom kontekstu,  prepoznat kurkumin kao molekula koja pokazuje obećavajuće rezultate (1,3).

Kurkumin je glavni biljni spoj i karakteristični žuti pigment praha kurkume koji se dobiva ekstrakcijom rizoma biljke Curcuma longa.

Kurkumin je najaktivniji sastojak kurkume i opisan je kao supstanca s protuupalnim, antioksidacijskim, imunomodulatornim, pro-apoptotskim i antiproliferatornim djelovanjem (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
• neuroprotektivno djelovanje odnosno poticanje neurogeneze kurkumina dobro je dokumentirano, a potječe iz pozitivnog  učinka na razinu moždanog neurotrofnog čimbenika (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?

Veliki depresivni poremećaj je česta bolest kod koje je, unatoč širokoj dostupnosti lijekova, postotak potpunog izlječenja nizak, a učestalost vraćanja simptoma visok.  Veliki napori ulažu se u pronalazak novih supstanci koji će pružiti učinkovitu terapiju za depresiju.

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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