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Amitriptyline; Clomipramine; Nortriptyline/Valproic Acid

This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.

Medical warning:

Moderate. These medicines may cause some risk when taken together. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

Valproic acid may slow down how quickly your liver processes your antidepressant.

What might happen:

The amount of antidepressant in your blood may increase and cause more side effects than normal.

What you should do about this interaction:

Let your healthcare professionals (e.g. doctor or pharmacist) know that you are taking these medicines together. If you experience weakness, tiredness, dizziness, irregular heartbeat, confusion, anxiety, nervousness, difficulty sleeping, or problems urinating, contact your doctor. It may be necessary to adjust the dose of your antidepressant.Your healthcare professionals may already be aware of this interaction and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.


1.Wong SL, Cavanaugh J, Shi H, Awni WM, Granneman GR. Effects of divalproex sodium on amitriptyline and nortriptyline pharmacokinetics. Clin Pharmacol Ther 1996 Jul;60(1):48-53.

2.Vandel S, Bertschy G, Jounet JM, Allers G. Valpromide increases the plasma concentrations of amitriptyline and its metabolite nortriptyline in depressive patients. Ther Drug Monit 1988;10(4):386-9.

3.Reif A, Leonhard C, Mossner R, Lesch KP, Fallgatter AJ. Encephalopathy and myoclonus triggered by valproic acid. Prog Neuropsychopharmacol Biol Psychiatry 2004 Sep;28(6):1061-3.

4.DeToledo JC, Haddad H, Ramsay RE. Status epilepticus associated with the combination of valproic acid and clomipramine. Ther Drug Monit 1997 Feb; 19(1):71-3.

5.Fehr C, Grunder G, Hiemke C, Dahmen N. Increase in serum clomipramine concentrations caused by valproate. J Clin Psychopharmacol 2000 Aug; 20(4):493-4.

6.Joseph AB, Wroblewski BA. Potentially toxic serum concentrations of desipramine after discontinuation of valproic acid. Brain Inj 1993 Sep-Oct;7(5):463-5.

7.Conforti D, Borgherini G, Fiorellini Bernardis LA, Magni G. Extrapyramidal symptoms associated with the adjunct of nortriptyline to a venlafaxine-valproic acid combination. Int Clin Psychopharmacol 1999 May; 14(3):197-8.

8.Fu C, Katzman M, Goldbloom DS. Valproate/nortriptyline interaction. J Clin Psychopharmacol 1994 Jun;14(3):205-6.

Selected from data included with permission and copyrighted by First Databank, Inc. This copyrighted material has been downloaded from a licensed data provider and is not for distribution, expect as may be authorized by the applicable terms of use.

CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

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