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Table 2 Overview of the route of metabolism, effects on enzymes, and transporters of psychoactive agents

From: Drug–Drug Interactions Between Direct-Acting Antivirals and Psychoactive Medications

Drug Enzyme Transporter References
Substrate Inhibitor Substrate Inhibitor
Benzodiazepines
 Alprazolam CYP3A4 (major) CYP3A4 (weak)    [38]
 Bromazepam CYP1A2 (major)
CYP3A4 (minor)
CYP2E1 (weak)    
 Brotizolam CYP3A4     
 Chlordiazepoxide CYP3A4 (major)     [39]
 Clobazam CYP2C19 (major)
CYP2B6 (minor)
CYP3A4 (minor)
CYP2D6 (moderate)
CYP2C19 (weak)
Inducer: CYP3A4 (weak)
P-gp   [40]
 Clorazepate CYP3A4 (major)     [41]
 Diazepam CYP3A4 (major)
CYP2C19 (major)
CYP1A2 (minor)
CYP2B6 (minor)
CYP2C9 (minor)
CYP2C19 (weak)
CYP3A4
   [42]
 Flurazepam CYP3A4 (major) CYP2E1 (weak)    [43]
 Lorazepam Conjugation (UGT)     
 Lormetazepam Conjugation (UGT)     
 Midazolam CYP3A4 (major)
CYP2B6 (minor)
CYP2C8 (weak)
CYP2C9 (weak)
CYP3A4 (weak)
   [44]
 Oxazepam UGT     
 Temazepam UGT (major)
CYP2B6 (minor)
CYP2C19 (minor)
CYP3A4 (minor)
CYP2C9 (minor)
    [45]
 Zolpidem CYP3A4 (major)
CYP1A2 (minor)
CYP2C19 (minor)
CYP2D6 (minor)
    [46]
 Zopiclone CYP3A4 (major)
CYP2C8 (minor)
    
Selective serotonin reuptake inhibitors (SSRIs)
 Citalopram CYP3A4 (major)
CYP2C19 (major)
CYP2D6 (minor)
CYP2D6 (weak)
CYP2C19 (weak)
CYP1A2 (weak)
CYP2B6 (weak)
   [47]
 Duloxetine CYP1A2 (major)
CYP2D6 (major)
CYP2D6 (moderate)    [48]
 Escitalopram CYP3A4 (major)
CYP2C19 (major)
CYP2D6 (weak)    [49]
 Fluoxetine CYP2C9 (major)
CYP2D6 (major)
CYP1A2 (minor)
CYP2B6 (minor)
CYP2C19 (minor)
CYP2E1 (minor)
CYP3A4 (minor)
CYP2D6 (strong)
CYP2C19 (moderate)
CYP1A2 (weak)
CYP2B6 (weak)
CYP2C9 (weak)
   [50]
 Fluvoxamine CYP2D6 (major)
CYP1A2 (major)
CYP2C19 (strong)
CYP1A2 (strong)
CYP2B6 (weak)
CYP2C9 (weak)
CYP2D6 (weak)
CYP3A4 (weak)
   [51]
 Paroxetine CYP2D6 (major) CYP2D6 (strong)
CYP2B6 (moderate)
CYP2C19 (weak)
CYP2C9 (weak)
CYP1A2 (weak)
   [52]
 Sertraline CYP2C19 (minor)
CYP3A4 (minor)
CYP2B6 (minor)
CYP2D6 (minor)
CYP2C9 (minor)
CYP2B6 (moderate)
CYP2C19 (moderate)
CYP2D6 (moderate)
CYP1A2 (weak)
CYP2C8 (weak)
CYP2C9 (weak)
   [53]
 Trazodone CYP3A4 (major)
CPY2D6 (minor)
   Inducer: P-gp  
 Venlafaxine CYP2D6 (major)
CYP3A4 (major)
CYP2C9 (minor)
CYP2C19 (minor)
CYP2B6 (weak)
CYP2D6 (weak)
CYP3A4 (weak)
   [54]
 Vortioxetine CYP2D6 (major)
CYP3A4/5 (major)
CYP2C9 (minor)
CYP2C19 (minor)
CYP2C8 (minor)
CYP2B6 (minor)
CYP2A6 (minor)
  P-gp (minor) P-gp (weak) [55]
Tricylic antidepressants (TCAs)
 Amitriptyline CYP2D6 (major)
CYP1A2 (minor)
CYP2B6 (minor)
CYP2C19 (minor)
CYP2C9 (minor)
CYP3A4 (minor)
CYP1A2 (weak)
CYP2C19 (weak)
CYP2C9 (weak)
CYP2D6 (weak)
CYP2E1 (weak)
P-gp   
 Clomipramine CYP1A2 (major)
CYP2C19 (major)
CYP2D6 (major)
CYP3A4 (minor)
CYP2D6 (moderate)    [56]
 Dosulepin COMT     
 Doxepin CYP2D6 (major)
CYP1A2 (minor)
CYP2C19 (minor)
CYP3A4 (minor)
    
 Imipramine CYP2C19 (major)
CYP2D6 (major)
CYP1A2 (minor)
CYP2B6 (minor)
CYP3A4 (minor)
CYP2D6 (moderate)
CYP1A2 (weak)
CYP2C19 (weak)
CYP2E1 (weak)
   
 Maprotiline CYP2D6 (major)     
 Nortriptyline CYP2D6 (major)
CYP1A2 (minor)
CYP2C19 (minor)
CYP3A4 (minor)
CYP2D6 (weak)
CYP2E1 (weak)
P-gp   
Other antidepressants
 Agomelatine CYP1A2
CYP2C9
CYP2C19
    
 Bupropion CYP2B6 (major)
CYP1A2 (minor)
CYP2A6 (minor)
CYP2C9 (minor)
CYP2D6 (minor)
CYP2E1 (minor)
CYP3A4 (minor)
CYP2D6 (strong)   OCT2  
 Mianserin CYP2D6     
 Mirtazapine CYP1A2 (major)
CYP2D6 (major)
CYP3A4 (major)
CYP2C9 (minor)
CYP1A2 (weak)    
 Moclobemide CYP2C19 (major)
CYP2D6 (minor)
CYP2C19 (moderate)
CYP1A2 (weak)
CYP2D6 (weak)
(MAO)
   
 St John’s wort   Inducer: CYP3A4
Inducer: CYP1A2 (possible various CYP enzymes)
   
Antipsychotics
 Aripiprazole CYP2D6 (major)
CYP3A4 (major)
    [57]
 Bromperidol CYP3A4
CYP2D6
    
 Clozapine CYP1A2 (major)
CYP2A6 (minor)
CYP2C19 (minor)
CYP2C9 (minor)
CYP2D6 (minor)
CYP3A4 (minor)
CYP2D6 (moderate)
CYP1A2 (weak)
CYP2C19 (weak)
CYP2C9 (weak)
CYP2E1 (weak)
CYP3A4 (weak)
   
 Flupentixol CYP2D6     
 Fluphenazine CYP2D6 (major)
CYP1A2
CYP1A2 (weak)
CYP2C9 (weak)
CYP2D6 (weak)
CYP2E1 (weak)
   
 Haloperidol CYP2D6 (major)
CYP3A4 (major)
CYP1A2 (minor)
CYP2D6 (moderate)    
 Lurasidone CYP3A4 (major) CYP3A4 (weak) P-gp   [58]
 Olanzapine CYP1A2 (major)
CYP2D6 (minor)
UGT
CYP1A2 (weak)
CYP2C19 (weak)
CYP2C9 (weak)
CYP2D6 (weak)
CYP3A4 (weak)
   [59]
 Paliperidone     P-gp (weak) [60]
 Perphenazine CYP2D6 (major)
CYP1A2 (minor)
CYP2C19 (minor)
CYP2C9 (minor)
CYP3A4 (minor)
CYP1A2 (weak)
CYP2D6 (weak)
   
 Pimozide CYP3A4 (major)
CYP1A2 (major)
CYP2D6 (major)
CYP2C19 (weak)
CYP2D6 (weak)
CYP2E1 (weak)
   
 Quetiapine CYP3A4 (major)
CYP2D6 (minor)
    
 Risperidone CYP2D6 (major)
CYP3A4 (minor)
CYP2D6 (weak) P-gp   
 Sertindole CYP2D6
CYP3A4
    
 Zuclopenthixol CYP2D6 (major)
CYP3A4 (minor)
    
  1. Note that most of these drugs have older registration files and, therefore, possible involvement of transporters and CYP enzymes may not be studied in sufficient detail per the current standards
  2. Information in this table was compiled from the following sources: European Medicines Association summary of product characteristics, US Food and Drug Administration prescribing information, and data from Lexicomp, available through http://www.uptodate.com (October 2015)
  3. Note: assignment of major/minor substrate status based on their clinically relevant drug interaction potential (http://www.uptodate.com)
  4. No information about hepatic metabolism and/or drug tranporters were available for: Flunitrazepam, loprazolam, nitrazepam,prazepam, lithium salts, chlorprothixene, fluspirilene, penfluridol, pericyazine, pipamperone, sulpiride, and tiapride
  5. COMT catechol-O-methyl transferase, CYP cytochrome P450, MAO monoamine oxidase, P-gp P-glycoprotein, UGT uridine diphosphate glucuronosyltransferase