Iako su antidepresivi kao skupina lijekova
raspoloživi više od 45 godina, još ne znamo sve o njihovu terapijskom
djelovanju. Antidepresivi se propisuju za bilo koju
od tri faze liječenja depresije ili anksioznih poremećaja, tj. za
terapiju akutne bolesti, terapiju održavanja i profilaktičku terapiju.
Cilj terapije akutne faze bolesti (prvih nekoliko tjedana)
jest eliminirati ili ublažiti simptome aktivne depresivne epizode.
Cilj terapije održavanja je spriječiti relaps nakon ublažavanja
simptoma tijekom najmanje šest mjeseci. Cilj profilaktičke
terapije je spriječiti ponovno pojavljivanje nove depresivne
epizode. Razlike u selektivnosti i intenzitetu inhibicije
ponovne pohrane monoamina, kao i u afinitetima za različite
neurotransmitorske receptore mogu objasniti razlike u
kliničkoj učinkovitosti i profilu nuspojava raspoloživih antidepresiva.
Usprkos velikim sličnostima u biološkim mehanizmima
djelovanja, selektivni inhibitori ponovne pohrane serotonina
(SIPPS) heterogena su skupina lijekova. Inhibicija transportera
serotonina uobičajeni je mehanizam djelovanja svih
selektivnih inhibitora ponovne pohrane serotonina (fluvoksamin,
fluoksetin, sertralin, paroksetin, citalopram, escitalopram)
i vjerojatno zasluæna za sličnosti između tih različitih
lijekova. Razlike u svojstvima vezanja na druge neuroreceptore
i subreceptore, kao i inhibicija citokroma vjerojatnije su
zaslužne za kliničke razlike između različitih selektivnih
inhibitora ponovne pohrane serotonina glede učinkovitosti,
profila nuspojava i interakcija s drugim lijekovima. Isto se
odnosi na selektivne inhibitore ponovne pohrane noradrenalina
(maprotilin, reboksetin) i neke druge skupine antidepresiva.
Liječnici trebaju biti upoznati s prednostima, ograničenjima
i problemima algoritma te rabiti individualni pristup antidepresivima
kako bi povećali učinkovitost (efikasnost) liječenja,
smanjili nuspojave (veća efektivnost) i ostvarili bolji cost-benefit
omjer (eficijentnost).Although antidepressants as a class have
been available for over 45 years we have still have lots of gaps
in our knowledge about their therapeutic mechanisms. Antidepressants
should be prescribed for any of the three phases of
treatment of depression or anxiety disorders described as
acute, maintenance and prophylactic treatment. The goal of
acute treatment (first several weeks) is to eliminate or alleviate
the symptoms of an active depressive episode. The goal of
maintenance treatment is to prevent a relapse into the index
episode after the alleviation of symptoms during at least six
months. The goal of prophylactic treatment is to prevent the
future reoccurrence of new depressive episodes. Differences in
the selectivity and intensity of inhibition of monoamine neuronal
reuptake transporters as well as in affinities for various neurotransmitter
receptors may explain the differences in clinical efficacy,
effectiveness, efficiency and side-effect profiles of the
available antidepressants. In spite of broad similarities in their
biological mechanisms of action, selective serotonin reuptake
inhibitors (SSRIs) are a heterogenous medication class. Serotonin
transporter inhibition is the common mechanism of action
of all SSRIs (fluvoxamine, fluoxetine, sertraline, paroxetine,
citalopram, escitalopram) and probably responsible for what
these different medications have in common. Differences in
binding properties to other neuroreceptor and subreceptor sites
as well as in the degree of inhibition of cytochrome enzymes
more likely account for the clinical differences observed
between different SSRIs in efficacy, side-effect profiles and drug
interactions. It is the same case with selective noradrenaline
reuptake inhibitors (maprotiline, reboxetine) and some other
antidepressant classes. Clinicians should be aware of advantages,
limitations, and problems of algorithms and use ”individualized
antidepressant medication” approach for improved
treatment efficacy with fewer adverse effects (higher effectiveness)
and better cost-benefit ratio (higher efficiency)
