Prilikom odabira antidepresiva neophodno je poznavati mehanizam djelovanja antidepresiva jer o njemu ovisi učinak lijeka na određene simptome, ali i nastanak neželjenih reakcija. Stoga biramo antidepresiv ciljano prema simptomima koje želimo ublažiti (Nutt, 2008), u idealnom slučaju posve izbrisati, te o nuspojavama koje svakako želimo izbjeći.
Postoji široki raspon odgovora na terapiju antidepresivima. Odgovor može biti potpuna remisija, poboljšanje, bez promjene, ili čak pogoršanje simptoma, koje se također zapaža u nekih osoba liječenih antidepresivima. Obzirom je poremećaj neurotransmisije monoamina utvrđen u brojnim psihičkim poremećajima, antidepresivi se primjenjuju i u brojnim drugim poremećajima, što prikazuje tablica 1.

U liječenju OKPa (opsesivno-kompulzivnog poremećaja) i paničnog poremećaja neophodna je snažna blokada serotoninskog transportera, koja se postiže samo vrlo potentnim inhibitorima ponovne pohrane serotonina (Richelson, 2001). Stoga su serotonergički antidepresivi učinkoviti u liječenju OKPa, ali nisu u liječenju ADHD, dok je obrnut slučaj za noradrenergičke antidepresive (Hamon i Bourgoin, 2006). S druge strane, postoje brojni dokazi da je u depresiji disfunkcionalan i serotoninski, i noradrenergički i dopaminski sustav, te se stoga u terapiji depresivnog poremećaja primijenjuju antidepresivi koji djeluju na sva tri monoaminska sustava. Međutim, iako se depresivni poremećaj, po klasifikaciji, smatra jedinstvenim poremećajem, klinička slika je vrlo raznolika. Danas znamo da svi antidepresivi nisu jednako učinkoviti na sve simptome depresivnog poremećaja, što prikazuje slika 1.

Stoga, ovisno o ciljnim simptomima, odabiremo i antidepresive. Dok je poremećaj i serotonina i noradrenalina i dopamina utvrđen u sniženom raspoloženju, ostali simptomi povezuju se s poremećajem nekog od navedenih monoamina. Stoga danas odabiremo antidepresiv s ciljem djelovanja na dominantne simptome. Također, biramo antidepresiv i prema nuspojavama koje želimo izbjeći, odnosno, u želji da umanjimo nuspojave koje bolesnik već ima, što je prikazano u tablici 2.

Bitno je voditi računa i o komorbiditetu, koji je vrlo često prisutan u depresivnih bolesnika. Naime, iako je depresivni poremećaj prema klasifikaciji psihijatrijski poremećaj, bolje bi mu odgovarao naziv „multisistemski poremećaj" (McIntyre, 2010).

Također se primjenjuju kombinacije antidepresiva s različitim mehanizmima djelovanja, a u cilju poboljšanja učinkovitosti na što veći broj simptoma depresije, što prikazuje tablica 3.

Stječe se dojam da se antidepresivi u kliničkoj praksi često kombiniraju, a da o tome ima malo podataka u literaturi. Gore navedene studije uglavnom su otvorene, uključuju mali broj bolesnika, uglavnom rezistentnih na monoterapiju. Količina dokaza je premala da bi se donio zaključak da su te kombinacije uistinu sigurne i djelotvorne.

U svakom slučaju, kod primjene kombinirane antidepresivne terapije mora se pridržavati dva pravila:

1) Uvijek se kombiniraju lijekovi s različitim, ali komplementarnim mehanizmima djelovanja,

2) Ne kombiniraju se lijekovi kod kojih očekujemo farmakokinetske interakcije.

Danas vrlo dobro znamo da ne postoji jedinstven uzrok depresivnog poremećaja, već mnogo nepovoljnih čimbenika djeluje sinergistički. Ako imamo na raspolaganju više antidepresiva različitih mehanizama djelovanja, veća je vjerojatnost da ćemo moći utjecati na poremećaj koji se dogodio u pojedinog bolesnika, a koji ne mora biti isti kao u nekog drugog bolesnika.

Svi antidepresivi su učinkoviti u određenog dijela bolesnika. Općenito se smatra da se odluka o promjeni terapije donosi nakon 4 do 6 tjedana terapije (McIntyre i sur, 2010), kada se terapija može promijeniti, kombinirati, ili se može povisiti doza. Cilj liječenja je remisija.

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