Table 3.
Different characteristics and properties of antidepressants
| Medication | Metabolism | Elimination half-life (hours) | Onset after oral dose consumption | Commentsa |
|---|---|---|---|---|
| SSRIs | ||||
| Citalopram | CYP3A4, CYP2D6, and CYP2C19 to weakly active metabolites (desmethylcitalopram, didesmethylcitalopram) | 33–35 | 1–4 weeks | The highest protein binding among SSRIs; dose-related QTc prolongation |
| Escitalopram | CYP3A4, CYP2D6, and CYP2C19 to weakly active metabolites (S-desmethylcitalopram, S-didesmethylcitalopram) | 27–32 | Within a week | The least protein binding among SSRIs (56%) |
| Fluoxetine | CYP3A4, CYP2D6, and CYP2C9 to active metabolites (norfluoxetine) | Parent drug: 24–144; active metabolite: 96–384 | Within a week | Causes a decrease in appetite; activating agent; longest half-life among SSRIs |
| Paroxetine | CYP2D6 to non-active metabolites | 21–24 | Within a week | A weak anticholinergic agent; very high risk of sexual dysfunction; weight gain |
| Sertraline | CYP3A4, CYP2D6, and CYP2C19 to weakly active metabolites (desmethylsertraline) | 26 | Within a week | More GI disturbances including diarrhea than other SSRIs; variable oral bioavailability |
| SNRIs | ||||
| Duloxetine | CYP1A2 and CYP2D6 to inactive metabolites | 12 (8–17) | – | Should not be used in patients with substantial alcohol use or evidence of chronic liver disease due to an increase in LFTs |
| Venlafaxine | CYP2D6 to active metabolite (O-desmethylvenlafaxine) and inactive metabolites (N-desmethylvenlafaxine, N,O-didesmethylvenlafaxine) | Parent drug: 4; active metabolite: 11 | – | Dose-related increase in BP and heart rate |
| Desvenlafaxine | Mainly via hepatic conjugation; also, oxidation by CYP3A4 | 10–11 | – | – |
| Levomilnacipran | Hepatic to inactive metabolites | 12 | – | More potent effects on NE as compared to its 5-HT reuptake; the greatest risk of increasing BP among SNRIs |
Notes:
Most SSRIs are inhibitors of the CYP/CYP450 isoenzymes and can alter the blood levels of other medications. Among them, sertraline, citalopram, and escitalopram have the minimal effect on CYP450 enzyme system. Fluoxetine and paroxetine have the highest impact on CYP2D6 (interaction with tamoxifen), and fluvoxamine is potent inhibitor of CYP1A2. Among SNRIs, only duloxetine is a moderately potent inhibitor of CYP2D6 and the others do not have significant effect on CYP/CYP450 isoenzymes. SNRIs should not be used in patients who have received MAOIs in previous 2 weeks due to the risk of serotonin syndrome.
Abbreviations: SSRI, selective serotonin reuptake inhibitor; GI, gastrointestinal; SNRI, serotonin–norepinephrine reuptake inhibitor; LFT, liver function test; BP, blood pressure; QTc, corrected QT interval; NE, norepinephrine; MAOIs, monoamine oxidase inhibitors; HT, hydroxytryptamine.