Tricyclic antidepressants + Colestyramine - Drug Interactions

Colestyramine causes a moderate fall in plasma levels ofimipramine. In vitro evidence suggests that amitriptyline,desipramine and nortriptyline are likely to be similarly affected. Onepatient who had an unusual gut pathology and depression controlled by doxepin became depressed again when colestyraminewas added.

Six depressed patients taking imipramine 75 to 150 mg,usually twice daily, were given colestyramine 4 g three times daily for 5 days. The plasma levels of imipramine fell by an average of 23 % (range 11 to 30%) and plasma levels of desipramine (the major metabolite) fell, although this was less consistent and said not to be statistically significant.

The effect of these reduced levels on control of depression was not assessed (See reference number 1)

A man whose depression was controlled with doxepin relapsed within a week of starting to take colestyramine 6 g twice daily. Within 3 weeks of increasing dosage separation of two drugs from 4 to 6 hrs his combined serum antidepressant levels (i.e. doxepin plus n-desmethyldoxepin) had risen from 39 to 81 nanograms/mL and his depression had improved. Reducing colestyramine dosage to a single 6-g dose daily, separated from doxepin by 15 hours, resulted in a further rise in his serum antidepressant levels to 117 nanograms/mL accompanied by relief of his depression (See reference number 2).

It seems almost certain that these tricyclics become bound to colestyramine (an anion-exchange resin) within gut, thereby reducing their absorption. An in vitro study(See reference number 3) with simulated gastric fluid found that,at pH 1, amitriptyline, desipramine, doxepin, imipramine and nortriptyline were approximately 79 to 90 % bound by colestyramine: at pH 4 they were 36 to 48 % bound and at pH 6.5 they were 62 to 76 % bound. In an earlier study,(See reference number 4)binding of these tricyclics at pH 1 had ranged from 76 to 100%.

The interaction between imipramine and colestyramine is established but of uncertain clinical importance because fall in plasma imipramine levels quoted above was only moderate (23%) and effects were not measured. The single case involving doxepin(See reference number 2) was unusual because patient had an abnormal gastrointestinal tract (hemigastrectomy with pyloroplasty and chronic diarrhoea). Nevertheless it would now be prudent to be alert for any evidence of a reduced antidepressant response if colestyramine is given concurrently. A simple way of minimising admixture of drugs in gut is to separate their administration. It is usually suggested that these drugs should be given 1 hour before or 4 to 6 hrs after colestyramine. There seems to be no direct clinical information about other tricyclics but in vitro studies suggest that amitriptyline,desipramine and nortriptyline probably interact like imipramine.

Spina E,Avenoso A, Campo GM, Caputi AP, Perucca E. Decreased plasma concentrations of imipramine and desipramine following cholestyramine intake in depressed patients. Ther Drug Monit (1994) 16, 432–4.

Geeze DS,Wise MG, Stigelman WH. Doxepin-cholestyramine interaction. Psychosomatics (1988) 29, 233–6.

Bailey DN. Effect of pH changes and ethanol on the binding of tricyclic antidepressants to cholestyramine in simulated gastric fluid. Ther Drug Monit (1992) 14,343–6.

Bailey DN,Coffee JJ, Anderson B, Manoguerra AS. Interactions of tricyclic antidepressants with cholestyramine in vitro. Ther Drug Monit (1992) 14, 339–42.