Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.
Some products that may interact with this drug include: arbutamine, thyroid supplements, anticholinergic drugs (such as belladonna alkaloids), central-acting drugs to treat high blood pressure (such as clonidine, guanabenz).
Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Avoid taking MAO inhibitors (isocarboxazid, linezolid, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before and after treatment with this medication. Ask your doctor when to start or stop taking this medication.
Other medications can affect the removal of doxepin from your body, thereby affecting how doxepin works. These drugs include cimetidine, St. John's Wort, terbinafine, drugs to treat irregular heart rate (such as quinidine/propafenone/flecainide), antidepressants (such as SSRIs including paroxetine/fluoxetine/fluvoxamine). This is not a complete list.
Many drugs besides doxepin may affect the heart rhythm (QT prolongation in the EKG), including amiodarone, cisapride, dofetilide, pimozide, procainamide, quinidine, sotalol, macrolide antibiotics (such as erythromycin), among others. Therefore, before using doxepin, report all medications you are currently using to your doctor or pharmacist.
Tell your doctor or pharmacist if you are taking other products that cause drowsiness such as opioid pain or cough relievers (such as codeine, hydrocodone), alcohol, marijuana (cannabis), other drugs for sleep or anxiety (such as alprazolam, lorazepam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), or antihistamines (such as cetirizine, diphenhydramine).
Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain decongestants or ingredients that cause drowsiness. Ask your pharmacist about using those products safely.
Preliminary research has suggested that St. John’s wort (Hypericum perforatum) may reduce blood levels of the tricyclic antidepressant amitriptyline. This may have occurred because certain chemicals found in St. John’s wort activate liver enzymes that are involved in the elimination of some drugs. Until more is known, people taking tricyclic antidepressants should avoid St. John’s wort.
- Mai I, Schmider J, et al. Unpublished results, May, 1999. Reported in: Johne A, Brockmöller, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St. John's wort (Hypericum perforatum). Clin Pharmacol Ther 1999;66:338-45.
- Nebel A, Schneider BJ, Baker RK, Kroll DJ. Potential metabolic interaction between St. John's wortand theophylline [letter]. Ann Pharmacother 1999;33:502.
Brewed black tea (Camellia sinensis) has been reported to cause precipitation of amitriptyline and imipramine in a test tube. If this reaction occurred in the body, it could decrease absorption of these drugs. Until more is known, it makes sense to sePte ingestion of tea and tricyclic antidepressants by at least two hours.
- Lasswell WL Jr, Weber SS, Wilkins JM. In vitro interaction of neuroleptics and tricyclic antidepressants with coffee, tea, and gallotannic acid. J Pharm Sci 1984;73:1056-8.
A number of tricyclic antidepressants have been shown to inhibit enzymes that require coenzyme Q10 (CoQ10), a nutrient that is needed for normal heart function. It is therefore possible that CoQ10 deficiency may be a contributing factor to the cardiac side effects that sometimes occur with tricyclic antidepressants. Some practitioners advise patients taking tricyclic antidepressants to supplement with 30–100 mg of CoQ10 per day.
- Kishi T, Makino K, Okamoto T, Kishi H, Folkers K. Inhibition of myocardial respiration by psychotherapeutic drugs and prevention by coenzymeQ. In Y Yamamura, K Folkers, Y Ito, eds. Biomedical and Clinical Aspects of Coenzyme Q, Vol. 2. Amsterdam: Elsevier/North-Holland Biomedical Press,1980:139-54.
Combination of 6 grams per day L-tryptophan and 1,500 mg per day niacinamide (a form of vitamin B3) with imipramine has shown to be more effective than imipramine alone for people with bipolar disorder. These levels did not improve the effects of imipramine in people with depression. Lower amounts (4 grams per day of L-tryptophan and 1,000 mg per day of niacinamide) did show some tendency to enhance the effect of imipramine.
The importance of the amount of L-tryptophan was confirmed in other studies, suggesting that if too much L-tryptophan (6 grams per day) is used, it is not beneficial, while levels around 4 grams per day may make tricyclic antidepressants work better.
- Chouinard G, Young SN, Annable L, Sourkes TL. Tryptophan-nicotinamide, imipramine and their combination in depression. Acta Psychiatr Scand 1979;59:395-414.
- Walinder J, Skott A, Carlsson A, et al. Potentiation of the antidepressant action of clomipramine by tryptophan. Arch Gen Psychiatry 1976;33:1384-9.
- Shaw DM, MacSweeney DA, Hewland R, Johnson AL. Tricyclic antidepressants and tryptophan in unipolar depression. Psychol Med 1975;5:276-8.
Giving 10 mg per day each of vitamins B1, B2, and B6 to elderly, depressed persons already on tricyclic antidepressants improved their depression and ability to think more than placebo did. The subjects in this study were institutionalized, so it is unclear if these results apply to persons living at home.
- Bell IR, Edman JS, Morrow FD, et al. Brief communication: Vitamin B1, B2, and B6 augmentation of tricyclic antidepressant treatment in geriatric depression with cognitive dysfunction. J Am Coll Nutr 1992;11:159-63.
SAMe may improve the clinical response to imipramine (Tofranil®). In a double-blind trial, depressive symptoms decreased earlier in the people who received SAMe injections (200 mg per day) in combination with imipramine than in those who received imipramine with placebo injections. Oral supplementation with SAMe has demonstrated antidepressant activity, independent of its combination with imipramine.
- Berlanga C, Ortega-Soto HA, Ontiveros M, Senties H. Efficacy of S-adenosyl-L-methionine in speeding the onset of action of imipramine. Psychiatry Res 1992;44:257-62.
- Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: Meta-analysis of clinical studies. Acta Neurol Scand 1994;154(suppl):7-14.