Is there any antidepressant from the selective serotonin reuptake inhibitor group (SSRI) or from ot

Fråga: Is there any antidepressant from the selective serotonin reuptake inhibitor group (SSRI) or from other new antidepressants that is preferable to a patient with depression and severe liver failure? Background: The question concerns a 51-year-old man, with ethylism and severe depression. He takes no drugs. He was recently admitted to hospital due to ascites, liver encephalopathy and leg edema. He was critically ill but survived. The questioner wants to administrate an antidepressant, if possible from the SSRI group, if the patient will accept the treatment.

Sammanfattning: It is nearly impossible to predict the pharmacokinetics of a certain antidepressant drug in a patient with liver cirrhosis. Data concerning the SSRIs are still sparse. It would therefore be preferable to choose a drug with documented use in liver failure, and for which Therapeutic Drug Monitoring can be performed, such as clomipramine.

Svar: The question concerning antidepressants and liver disease has been answered before in Drugline (1). In this document it is stated that tricyclic antidepressants (TCA) with a defined plasma concentration-effect relation could be used in patients with liver failure and that data concerning selective serotonin reuptake inhibitors (SSRI) were sparse.

In general it is difficult to give advice on drug treatment to patients with liver failure. Many factors, such as hepatic blood flow, liver enzyme activity and the binding of a drug to plasma proteins may affect the pharmacokinetics of a drug in a patient with liver cirrhosis (2). Decreased metabolism due to liver cirrhosis might lower the amount of toxic metabolites and thus decrease the risk of hepatotoxicity. Decreased metabolism might also increase the concentration of a parent compound, a compound that might be toxic in high concentrations.

There is also the aspect of altered pharmacodynamics especially with reference to hepatic encephalopathy and increased sensibility to sedation.

Therapeutic Drug Monitoring (TDM) of the parent compound and its possible metabolites is therefore suggested in patients with liver cirrhosis. TDM can be performed for several antidepressants at our lab at the division of Clinical Pharmacology, Huddinge University Hospital.

A guess would be that an antidepressant drug such as citalopram (Cipramil) might be possible to use. It has no farmacodynamic or farmacokinetic interactions with alcohol and binding to plasma proteins is less than 80%. The main metabolite of citalopram has no antidepressant effect (3). Another antidepressive agent that could be chosen is venlafaxine (Efexor). It has a low binding to plasma proteins (approximately 30%) and can be administrated to patients with severe liver failure, according to the same source (3). Administration of venlafaxine should start at the lowest possible dose, approximately less than 25% of the dose given to a patient with normal liver function, and then be switched to the depot form of the drug. Both citalopram and venlafaxine and its active metabolite can be measured at the department of Clinical Pharmacology.

Still, a better choice might be an antidepressant from the TCA group, with documented use in liver failure, such as clomipramine.