Selective serotonin reuptake inhibitors liver

Kobayashi K, Yamamoto T, Chiba K, et al. The effects of selective serotonin reuptake inhibitors and their metabolites on S-mephenytoin 4 -hydroxylase activity in human liver-microsomes. Br J Cbn Pharmacol 1995 40 481 -85. 

Belpaire FM, Wijnant P, Temmerman A, et al. The oxidative metabolism of metoprolol in human liver microsomes-inhibition by the selective serotonin reuptake inhibitors. Eur J Clin Pharmacol 1998 54 261-264. 

These selective serotonin reuptake inhibitors (SSRIs) include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and, most recently, escitalopram (Lexapro see the appendix). These drugs block the removal of the neurotransmitter serotonin from the synaptic cleft. A number of other antidepressants are potent nonselective serotonin reuptake inhibitors (NSRIs). These include the atypical venlafaxine (Effexor) and the tricyclic clomipramine (Anafra-nil). Nefazodone (Serzone) has been withdrawn from the market due to liver damage. 

Phenytoin, a liver enzyme inducer, decreases serum levels of TCAs (especially desipramine and clomipramine). An increase in serum levels of nortriptyline and trazodone has also been reported. In these cases, the net effect of enzyme induction (by phenytoin) and enzyme inhibition (by TCAs) seem to be in favor of the inhibitory effects. Carbamazepine also induces liver enzymes, with a consequent reduction in serum levels of TCAs (amitriptyline, desipramine, doxepin, and nortriptyline). These effects of carbamazepine have not been observed with clomipramine, but have been reported with selective serotonin reuptake inhibitors (SSRIs). 

Sertraline, at its usual effective dose of 50 mg/day, has been found to cause less pronounced modifications in plasma concentrations of tricyclic antidepressants (TCAs) as compared with other selective serotonin reuptake inhibitors (SSRIs) (mainly studies with fluoxetine, fluvoxamine, and paroxetine). However, since inhibition of the hepatic enzyme CYP2D6 is dose-dependent, significant increase in plasma concentration of TCAs may occur when higher doses of sertraline are administered. Acute liver damage possibly related to sertraline and venlafaxine ingestion has been reported. 

Hemeryck, A. De Vriendt, C. Belpaire, F.M. Effect of selective serotonin reuptake inhibitors on the oxidative metabolism of propafenone in vitro studies using human liver microsomes. J. Clin. Psychopharmacol. 2000, 20, 428 34. 

Hemeryck A, De Vriendt C, Belpaire FM. Inhibition of CYP2C9 by selective serotonin reuptake inhibitors in vitro studies with tolbutamide and (S)-warfarin usii human liver mi-crosomes. EurJ Clin Pharmacol (1999) 54,947-51. 

Rasmussen BB, Maenpaa J, Pelkonen O, Loft S, Poulsen HE, Lykkesfeldt J, Brosen K. Selective serotonin reuptake inhibitors and theophylline metabolism in human liver microsomes potent inhibition by fluvoxamine. BrJ Clin Pharmacol (1995) 39, 151-9. 

Post-2000 Renal rhabdomyolysis with the statin, cerivastin cardio-toxicity with the COX-2 inhibitor, rofecoxib and liver damage with the selective serotonin and norepinephrine reuptake inhibitor, atomoxetine. 

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