Can desipramine be taken with Sertraline? (+1 interaction)

In this article, we will answer the question “Can desipramine be taken with Sertraline?”. We will discuss the potential interaction between desipramine and Sertraline, the possible mechanism behind the interaction and what research has to say in this regard. We will also discuss the side effects associated with their use and precautions that should be taken by an individual taking both medications.

Can Desipramine be taken with Sertraline?

Desipramine may be taken with Sertraline. However, the concomitant use of both medications should be under constant medical supervision. You may need dose adjustments of both medications to use them safely.

Sertraline (also known as Zoloft) is an antidepressant belonging to the class of selective serotonin reuptake inhibitors (SSRIs) and is approved by the FDA for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder (OCD), panic disorder (PD), posttraumatic stress disorder (PTSD), social anxiety disorder (SAD) and premenstrual dysphoric disorder (PMDD) (1).

Sertraline has been used ‘off-label’ for the treatment of bulimia nervosa (BN), binge eating disorder, body dysmorphic disorder, premature ejaculation and generalised anxiety disorder (GAD) (2).

Desipramine (also known as Norpramin) is a tricyclic antidepressant (TCA) that is approved by the FDA for the treatment of depression. It can be used as a monotherapy or as an adjunct to other antidepressant medications (3).

Desipramine has been used ‘off-label’ for the management of bulimia nervosa (BN), overactive bladder, irritable bowel syndrome, neuropathic pain, attention deficit hyperactivity disorder (ADHD) and postherpetic neuralgia. However, it is not considered a first-line drug in the treatment of depressive illnesses due to its side effects (4).

Desipramine and Sertraline may be prescribed with utmost caution in situations where the illness cannot be managed by one medication alone and the benefits outweigh the risks of the combination.

What are the potential interactions between Desipramine and Sertraline?

The potential interactions that may occur as a result of the combination of Desipramine and Sertraline, and their possible mechanisms are as follows:

Effect Interaction Mechanism

Potentiation of the therapeutic effect of Desipramine

If both medications are taken together, there may be a risk of increased effect of Desipramine as Sertraline can increase the plasma concentrations of some TCAs. Sertraline tends to inhibit the CYP450 2D6 enzyme, which is responsible for the metabolism of Desipramine and other TCAs. This causes hindrance in the elimination of Desipramine and hence an increase in the plasma concentration of the drug. This can lead to increased therapeutic effects and side effects.

Risk of developing serotonin syndrome

When TCAs including Desipramine are used concomitantly with SSRIs, there is a risk of the occurrence of a rare side effect known as the serotonin syndrome. Although Desipramine is considered to selectively act on norepinephrine reuptake, it may also mildly inhibit serotonin reuptake. This can cause the occurrence of serotonin syndrome if Desipramine is used with Sertraline.

Any individual taking this combination should be closely monitored for the occurrence of undesirable symptoms. Keep in mind that not everyone taking the medication will experience these interactions, but individuals prescribed should be monitored closely for the symptoms of Desipramine toxicity or serotonin syndrome.

What does research suggest?

Clinical evidence and studies have reported the use of and in some cases the interaction of Desipramine with Sertraline.

A case study of a 50-year-old woman was reported with the interaction of Sertraline and Desipramine. The patient was treated with both medications for MDD and residual dysphoria. The plasma concentrations of Desipramine increased by almost 50% by the end of one week of concomitant treatment with Sertraline (5).

A study assessing the interaction between Desipramine and the SSRIs, Paroxetine and Sertraline, reported that Sertraline was not as potent an inhibitor as Paroxetine. Sertraline and Desipramine were administered in doses of 50mg/each. The concentration of Desipramine was found to increase by 44% after the administration of Sertraline (6).

Another research study assessing the effect of Sertraline on the pharmacokinetics of Desipramine and Imipramine concluded that due to the inhibition of CYP2D6 enzyme by Sertraline the concentrations of the TCAs may increase and cause side effects. The study stated that if the combination is to be used, the doses of TCAs should be lowered (7).

A research study on the effects of coadministration of Desipramine with Sertraline or Fluoxetine on healthy male volunteers was published. It reported that the concentration of individuals given Sertraline and Desipramine showed a 31% increase in Desipramine concentrations while individuals receiving Fluoxetine showed a much greater interaction (8).

What are the side effects of using Desipramine with Sertraline?

If Desipramine is used with Sertraline then the individual receiving treatment should be monitored for the following side effects:

  • Sedation
  • Dry mouth
  • Constipation
  • Urinary retention
  • Blurred vision
  • Muscle tension
  • Confusion
  • Shivering
  • Hallucinations
  • Tremors
  • Hypertension
  • Tachycardia
  • Excessive sweating
  • High fever
  • Altered consciousness
  • Irritability
  • Agitation

Keep in mind that not all individuals receiving the combination of Desipramine and Sertraline will experience these side effects. However, if you do experience such symptoms which do not resolve or get worse, you should contact your healthcare provider for guided medical assistance.

What to do if you are prescribed Desipramine with Sertraline?

If your healthcare provider has prescribed Desipramine and Sertraline simultaneously for your depressive illness, there is no need to worry. The combination is prescribed only when the benefits outweigh the risks.

Your healthcare provider will schedule regular follow-up appointments to assess your condition and make adjustments to your regimen. Make sure to never skip the follow-up appointments and keep open communication with your healthcare provider regarding your symptoms.

You should also closely monitor your symptoms and if you feel anything out of the ordinary, you should contact your healthcare provider for advice.

You should also avoid alcohol because it may hinder the elimination of Sertraline, increasing its concentrations, and subsequently also increasing the concentrations of Desipramine.

To the best of my knowledge and according to scientific research, Desipramine can be taken with Sertraline. However, there is a risk of a potential interaction between both medications so the combination should be used only when necessary and under constant monitoring by a healthcare provider.

In my opinion, you should not take any medication without the prescription of your healthcare provider and should monitor yourself closely for the occurrence of side effects. In case of the development of uncomfortable symptoms or side effects, it is advised to seek medical assistance.

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The Food and Drug Administration (FDA). HIGHLIGHTS OF PRESCRIBING INFORMATION. ZOLOFT® (sertraline hydrochloride) tablets, for oral use. Available from: 


Singh HK, Saadabadi A. Sertraline. [Updated 2023 Feb 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:


The Food and Drug Administration (FDA). HIGHLIGHTS OF PRESCRIBING INFORMATION. NORPRAMIN® (desipramine hydrochloride) tablets, for oral use. Available from: 


Maan JS, Rosani A, Saadabadi A. Desipramine. [Updated 2023 Aug 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:


Barros J, Asnis G. An interaction of sertraline and desipramine. The American Journal of Psychiatry. 1993 Nov.


Alderman J, Preskorn SH, Greenblatt DJ, Harrison W, Penenberg D, Allison J, Chung M. Desipramine pharmacokinetics when coadministered with paroxetine or sertraline in extensive metabolizers. Journal of clinical psychopharmacology. 1997 Aug 1;17(4):284-91.


Kurtz DL, Bergstrom RF, Goldberg MJ, Cerimele BJ. The effect of sertraline on the pharmacokinetics of desipramine and imipramine. Clinical Pharmacology & Therapeutics. 1997 Aug;62(2):145-56.


Preskorn SH, Alderman J, Chung M, Harrison W, Messig M, Harris S. Pharmacokinetics of desipramine coadministered with sertraline or fluoxetine. Journal of clinical psychopharmacology. 1994 Apr 1;14(2):90-8.

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