The Interactions Between Newer Antidepressants And Second-Generation Antipsychotics

Combinations of newer antidepressants and second-generation antipsychotics(SGAs) are frequently used in clinical.Newer antidepressants and SGAs are often used together in patients with concomitant psychotic and depressive symptoms, such as schizoaffective disorder or psychotic depression; Newer antidepressants may be used as an adjunctive strategy for the treatment of negative symptoms of schizophrenia; SGAs may be added to patients with refractory OCD and in those with treatment-resistant major depressive disorder. These two kinds of drug are extensively metabolized via the hepatic cytochrome P450 (CYP) system. Many new antidepressants are inhibitors of various CYPs, and may therefore impair the elimination of antipsychotic drugs metabolized via these isoforms, causing the pharmacokinetic interaction. For example, fluoxetine may increase the plasma drug concentration in different degrees of clozapine, risperidone and aripiprazole. Fluvoxamine may increase significantly the plasma drug concentration of clozapine and olanzapine, both mainly metabolized via the CYP1A2 enzyme. Combination may achieve better effect, but also may increase the risk. Clinicians should especially pay attention to these fatal adverse reactions, such as Torsade de pointes due to the prolonging of the QTc interval.