Pharmacology Notes

Antipsychotics, typical

3

Plasma concentrations of both the antipsychotic and the TCA may increase. Additive adverse effects also possible.

Monitor for adverse effects.

Barbiturates

3

TCA metabolism increased.

Use with caution.

Carbamazepine

3

Variable effect on plasma TCA concentrations, ie amitriptyline, imipramine and nortriptyline decreased and clomipramine increased.

Unresponsive patients may need higher doses of TCAs. Observe for carbamazepine or clomipramine toxicity.

Cimetidine

3

TCA metabolism inhibited by cimetidine.

Use an alternative H2-receptor antagonist.

Clonidine

2

TCAs may reduce clonidine’s antihypertensive effect. On clonidine cessation, TCAs may worsen rebound hypertension.

Avoid combination.

Dextropropoxyphene

3

Doubles plasma doxepin concentration and adverse effects increased.

Use an alternative analgesic.

Fluconazole

2

Fluconazole increases amitriptyline and nortriptyline plasma levels, probably due to inhibition of CYP2C9 and CYP3A4 metabolism.

Avoid combination of TCA and fluconazole or monitor for TCA adverse effects.

MAOIs, irreversible nonselective

1

Serotonin syndrome and fatalities reported.

Avoid combination of MAOI and TCA. Care needed in changing between MAOI and TCA, especially clomipramine, 

Moclobemide

2

Serotonin syndrome reported with clomipramine and possible with other serotonergic TCAs.

Avoid combination of moclobemide and TCA. Care needed in changing between moclobemide and TCA, especially clomipramine,

NSAIDs

3

Increased risk of upper gastrointestinal tract bleeding when clomipramine and NSAID are coadministered. Patients with a history of peptic ulcer or oesophageal varices at most risk.

Monitor for evidence of gastrointestinal tract bleeding or use alternative analgesic or alternative antidepressant with minimal serotonergic effect.

Quinidine

2

Reduces TCA metabolism probably due to CYP2D6 inhibition.

Use alternative antidepressant.

SSRIs and nefazodone

2

Plasma TCA concentrations increased, especially with fluoxetine, fluvoxamine and paroxetine. Serotonin syndrome also possible especially with clomipramine.

Avoid combination of TCA and SSRI or nefazodone, except under specialist supervision. The interaction may vary with different SSRIs and may be less likely to occur with citalopram. Care needed in changing between TCA and SSRI or nefazodone, see Table 8.11.

Sympathomimetic amines, parenteral--directly acting: adrenaline, dopamine, isoprenaline, noradrenaline

2

Grossly exaggerated pressor response to adrenaline, phenylephrine and noradrenaline. Does not occur with indirectly acting sympathomimetics, eg isoprenaline or felypressin. Some reports of adrenergic effects, eg headache, dilated pupils, increased blood pressure with dental local anaesthetics (lignocaine with noradrenaline).

Avoid combination of TCA and parenteral sympathomimetics or use with great caution in patients taking TCAs. In anaphylaxis, benefit may outweigh risk.

Venlafaxine

2

Venlafaxine may increase plasma imipramine, clomipramine and nortriptyline concentration due to CYP2D6 inhibition.

Avoid combination of venlafaxine and imipramine, clomipramine or nortriptyline. Care needed in changing between venlafaxine and TCA, see Table 8.11.