Clinically relevant interactions between newer antidepressants and second-generation antipsychotics.
BACKGROUND
Combinations of newer antidepressants and second-generation antipsychotics (SGAs) are frequently used by clinicians. Pharmacokinetic drug interaction (PK DI) and poorly understood pharmacodynamic (PD) drug interaction (PD DI) can occur between them.


METHODS
This paper comprehensively reviews PD DI and PK DI studies.


CONCLUSIONS
More PK DI studies are needed to better establish dose correction factors after adding fluoxetine and paroxetine to aripiprazole, iloperidone and risperidone. Further PK DI studies and case reports are also needed to better establish the need for dose correction factors after adding i) fluoxetine to clozapine, lurasidone, quetiapine and olanzapine; ii) paroxetine to olanzapine; iii) fluvoxamine to asenapine, aripiprazole, iloperidone, lurasidone, olanzapine, quetiapine and risperidone; iv) high sertraline doses to aripiprazole, clozapine, iloperidone and risperidone: v) bupropion and duloxetine to aripiprazole, clozapine, iloperidone and risperidone; and vi) asenapine to paroxetine and venlafaxine. Possible beneficial PD DI effects occur after adding SGAs to newer antidepressants for treatment-resistant major depressive and obsessive-compulsive disorders. The lack of studies combining newer antidepressants and SGAs in psychotic depression is worrisome. PD DIs between newer antidepressants and SGAs may be more likely for mirtazapine and bupropion. Adding selective serotonin reuptake inhibitors and SGAs may increase QTc interval and may very rarely contribute to torsades de pointes.
University of Messina, Policlinico Universitario, Department of Clinical and Experimental Medicine , Via Consolare Valeria, 98125 Messina , Italy +39 090 2213647 ; +39 090 2213300 ; espina@unime.it.
Edoardo
E
Spina
Jose
J
de Leon
D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism; D004347:Drug Interactions; D004351:Drug Resistance; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000009:adverse effects; D006801:Humans; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy / Q000378:metabolism; D057285:Precision Medicine
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents