Studies and case reports have described increased tricyclic antidepressant levels with phenothiazines. There is currently evidence for this interaction between:
  • chlorpromazine and imipramine
  • flupentixol and imipramine or desipramine
  • fluphenazine and imipramine
  • haloperidol and desipramine
  • levomepromazine and nortriptyline
  • perphenazine and amitriptyline, imipramine, desipramine or nortriptyline
  • thioridazine and desipramine, imipramine or nortriptyline Further, antipsychotic levels may be raised or their clearance reduced by the tricyclics, and this has been seen with:
  • doxepin or nortriptyline and tiotixene
  • amitriptyline, imipramine or nortriptyline and chlorpromazine The concurrent use of antipsychotics and tricyclics has also resulted in extrapyramidal reactions and seizures (both groups of drugs lower the seizure threshold). Despite these reactions these drugs are widely used in combination, and a number of fixed-dose combinations have been marketed. Also note that additive QT-prolonging effects are possible with certain combinations, see drugs that prolong the QT interval.
    No action is needed but bear the interaction in mind in case of problems. Additive antimuscarinic adverse effects are also possible. See antimuscarinics.
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