Antipsihotici su temeljna terapija shizofrenije pa se cesto rabe i u više drugih poremećaja. Dok je monoterapija idealna, cesto je nedovoljna zbog složenosti simptoma i čestog komorbiditeta. Antipsihotici se stoga svakodnevno kombiniraju i s drugim antipsihoticima, kao i s ostalim psihijatrijskim i somatskim lijekovima te nastaje mogućnost interakcija. One mogu biti farmakodinamske (PD) i farmakokinetske (PK). Prve se zbivaju na razini receptora, ceste su, ali nedovoljno istražene, dok se o drugima mnogo zna te se lako utvrđuju jer dovode do promjene u koncentraciji lijekova. Najčešće nastaju zbog inhibicije ili indukcije metabolizma antipsihotika putem enzima CYP450 1A2, 2D6 i 3A4. Takve su interakcije posebice važne kod antipsihotika s malenom terapijskom širinom, poput klozapina, ili onih koji se razgrađuju samo putem jedne skupine enzima, kao, npr., kvetiapin. U posljednje vrijeme otkrivena je i važnost transportnog proteina, glikoproteina P, iako o tome zasad premalo znamo. Budući da su mnogi antipsihotici i brojni drugi lijekovi, supstrati, inhibitori ili induktori ovog transportera, možda ce interakcije na ovoj razini u budućnosti pomoći da razumijemo neke trenutačno neobjašnjive reakcije na lijekove. Interakcije mogu biti korisne ili štetne. Npr., mnogo studija pokazuje da je dodavanje aripiprazola određenim antipsihoticima poboljšalo metaboličke parametre te ublažilo hiperprolaktinemiju. Ovaj pregledni rad opisuje mehanizme nastanka najvažnijih interakcija s antipsihoticima te prikazuje različite kombinacije, od kontraindiciranih do sigurnih i potencijalno poželjnih. U svakom slučaju, individualni pristup, s pažljivim odmjeravanjem mogućih koristi i rizika u sklopu dobre suradnje s pacijentom, put je k najboljem ishodu liječenja.Antipsychotics are the cornerstone in the treatment of schizophrenia and are frequently used for several other mental disorders. Monotherapy with antipsychotics is strongly advised, but is often insufficient due to complex symptomatology and frequent comorbidities. Antipsychotics are commonly prescribed in combination with another antipsychotic, other psychotropic and somatic medications, which raises the risk for drug interactions (DIs). Those can be both pharmacodynamic (PD) and pharmacokinetic (PK). The former occur at the receptor level and are common but incompletely understood, while the latter are well-studied and easily verified by a change in the drug concentration. Those DIs mostly involve inhibition or induction of antipsychotic metabolism by hepatic CYP450 1A2, 2D6 and 3A4 enzymes. Drug interactions are particularly important for antipsychotics with a narrow therapeutic range, such as clozapine, or those that are extensively metabolized by a single pathway, such as quetiapine. The importance of an efflux protein, P-glycoprotein P (P-gp) is increasingly recognized but still poorly understood. Given that many agents, including antipsychotics, are substrates, inhibitors or inducers of P-gp, those DIs might have a role in unexplained drug reactions. DIs might be beneficial and harmful. For example, there is substantial evidence that aripiprazole addition to current antipsychotic regimen, due to its unique receptor profile, improves metabolic profiles and hyperprolactinemia. This review describes mechanisms of relevant DIs and provides information on different combinations, ranging from contraindicated to safe to potentially beneficial. Individualized treatment, careful consideration of risks and benefits, and a good therapeutic alliance, paves the way for best treatment outcome
