Liver disease caused by clomipramine/lithium? Cross reaction between different tricyclic antidepres

Fråga: Liver disease caused by clomipramine/lithium? Cross reaction between different tricyclic antidepressants?

A 43-year-old woman with a bipolar affective psychosis is being treated with lithium and clomipramine, which recently was added. The dose of clomipramine is 150 mg since June 25. The patient has now symptoms such as nausea, tiredness and dark coloured urine, which has appeared for several months. On August 8, the aminotransferases were: ALAT 4.1, ASAT 1.45, GT 2.11, ALP normal.

Sammanfattning: Lithium has rarely been associated with liver toxicity, such as an increase of aminotransferases. Tricyclic antidepressant drugs can cause liver toxicity in a small per cent of treated patients. No difference between different tricyclics has been documented in the literature.

Svar: Literature concerning liver toxicity and lithium is very poor (1,2). An earlier Drugline document found no information in the literature on this matter. A single report was found in an updated literature search (3). A 26-year-old man treated with lithium and perphenazine had elevated liver enzymes thought to be caused by the phenothiazine. Due to this he remained on lithium for 2.5 months while perphenazine was withdrawn. When lithium finally was withdrawn his ALAT and ASAT returned to normal. The patient went through two dechallenge tests and at both occasions the liver enzymes increased followed by a decrease when lithium was withdrawn.

The Swedish Adverse Drug Reactions Advisory Committee (SADRAC) has until now received 4 reports of liver reaction in connection to lithium (transaminases, ALP/GT increased 2, mixed liver reaction 2). In one of the former cases (ALP/GT increased)the patient was also treated with citalopram and in one of the latter cases (mixed liver reaction) the patient was also treated with lofepramine. During the combination a heavy increase of bilirubin, alkalic phosphatases, glutamyltransferases, ALAT and ASAT was seen. No influence on the liver values could be seen when the patient took lithium or lofepramine on its own.

Questions concerning tricyclic antidepressants and liver toxicity have been investigated at several occasions (4-6). In most of the cases the liver toxicity has been of a cholestatic type but hepatocellular necrosis has been described.

It has not been stated in the literature whether there is a difference between the different tricyclic antidepressant agents regarding liver toxicity. Cross reactions can occur.

According to SADRAC, clomipramine, amitriptyline and lofepramine are the drugs in this group, most often associated with liver affection. When comparing sales figures the same drugs are the most frequently prescribed among tricyclics.