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The Food and Drug Administration has approved the oral drug desipramine (NORPRAMIN and generics) since 1964 for a single indication: relief of depression symptoms.[1] This drug belongs to a class of medications called tricyclic antidepressants, which are commonly used to treat individuals who either have not benefited from or not tolerated other antidepressants.
Public Citizen’s Health Research Group has designated desipramine as a Limited Use drug.[2] For patients who need drug treatment...
The Food and Drug Administration has approved the oral drug desipramine (NORPRAMIN and generics) since 1964 for a single indication: relief of depression symptoms.[1] This drug belongs to a class of medications called tricyclic antidepressants, which are commonly used to treat individuals who either have not benefited from or not tolerated other antidepressants.
Public Citizen’s Health Research Group has designated desipramine as a Limited Use drug.[2] For patients who need drug treatment for major depression, selective serotonin reuptake inhibitors (SSRIs) like citalopram (CELEXA and generics) and fluoxetine (PROZAC and generics) are first-choice medications because they are safer and better tolerated than other classes of antidepressants.
Like other tricyclic antidepressants, desipramine has clinically important and potentially dangerous interactions with many other medications and some supplements. We discuss three main types of these interactions to help desipramine users and their caregivers recognize them.
Risk of cardiotoxicity[3],[4],[5]
Desipramine can potentially cause cardiotoxicity and should be used with extreme caution in patients with cardiovascular disease or a family history of sudden death or heart-rhythm disturbances.
The best evidence of impending desipramine toxicity is prolongation of the QT interval, which is a change in the electrical activity of the heart that can cause a fatal heart-rhythm disturbance called torsades de pointes, possibly leading to cardiac arrest and sudden death.
The risk of QT prolongation is increased when desipramine is taken concurrently (at the same time) with certain other medications that treat heart-rhythm disturbances, bacterial infections, cancer, depression, fungal infections and psychosis, among other conditions (see Table 1, bwlow, for oral examples of these drugs). Some of these drugs — particularly dronedarone (MULTAQ), levoketoconazole (RECORLEV) and thioridazine (generic only) — should not be taken concurrently with desipramine due to the substantial increased risk of cardiotoxicity.
Table 1: Examples of Oral Drugs That May Increase the Risk of QT Prolongation When Taken Concomitantly With Desipramine[6],[7]
| Generic Name | Brand Name(s)† | Drug Class |
|---|---|---|
| asenapine* | SAPHRIS | Antipsychotic |
| azithromycin* | ZITHROMAX | Antibiotic |
| chlorpromazine* | generic only | Antipsychotic |
| ciprofloxacin* | CIPRO | Antibiotic |
| clarithromycin* | generic only | Antibiotic |
| disopyramide* | NORPACE | Abnormal heart rhythm drug |
| dronedarone** | MULTAQ | Abnormal heart rhythm drug |
| erythromycin | E.E.S., E.E.S. 400, ERY-TAB, ERYC, ERYPED, ERYTHROCIN | Antibiotic |
| fingolimod | GILENYA, TASCENSO ODT | Multiple sclerosis drug |
| fluconazole | DIFLUCAN | Antifungal drug |
| levoketoconazole | RECORLEV | Cushing’s syndrome drug |
| nilotinib | TASIGNA | Cancer drug |
| ofloxacin* | generic only | Antibiotic |
| quinidine* | generic only | Abnormal heart rhythm drug |
| solifenacin* | VESICARE | Overactive bladder drug |
| sorafenib | NEXAVAR | Cancer drug |
| thioridazine** | generic only | Antipsychotic |
| venlafaxine* | EFFEXOR XR | Serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressant |
| voriconazole | VFEND | Antifungal drug |
| zolmitriptan* | ZOMIG | Triptan for migraine headaches |
†Brand-name combination products that contain other active ingredients were excluded.
*Designated as Limited Use by Worst Pills, Best Pills News
**Designated as Do Not Use by Worst Pills, Best Pills News
Risk of serotonin syndrome
Rare reports of serotonin syndrome — characterized by mental health changes (including agitation, confusion and hallucinations), autonomic instability (including rapid heartbeat, high blood pressure, high fever and sweating), neuromuscular changes (including tremor and muscle rigidity) or gastrointestinal symptoms (including nausea, vomiting and diarrhea) — have occurred when desipramine was taken alone.[8] The risk of this potentially life-threatening condition increases when desipramine is taken concomitantly with certain other drugs that also raise serotonin levels in the body on their own (see Table 2, below, for a list of examples). These drugs include certain opioids; lithium (LITHOBID and generics), which is used to treat bipolar disorder; monoamine oxidase (MAO) inhibitors, which are used to treat either depression or Parkinson’s disease; and other tricyclic antidepressants.
Because the risk of serotonin syndrome increases greatly when desipramine is taken with some of the medications listed in Table 2 — mainly the antibiotic linezolid (ZYVOX and generics), MAO inhibitors and the Parkinson’s disease drugs rasagiline (AZILECT and generics) and safinamide (XADAGO) — these drugs should never be taken concurrently with desipramine.
Importantly, concurrent use of desipramine with kratom or the dietary supplement St. John’s wort also raises the risk of serotonin syndrome.[9]
Table 2: Examples of Oral Drugs That Increase the Risk of Serotonin Syndrome When Used Concomitantly With Desipramine[10],[11]
| Generic Name | Brand Name(s)† | Drug Class |
|---|---|---|
| buspirone* | generic only | Antianxiety drug |
| desvenlafaxine* | PRISTIQ | SNRI antidepressant |
| duloxetine** | CYMBALTA | SNRI antidepressant |
| fluoxetine* | PROZAC | SNRI antidepressant |
| hydrocodone | HYSINGLA ER | Opioid |
| hydromorphone | DILAUDID | Opioid |
| isocarboxazid* | MARPLAN | MAO inhibitor |
| levomilnacipran* | FETZIMA | SNRI antidepressant |
| linezolid | ZYVOX | Antibiotic |
| lithium* | LITHOBID | Bipolar disorder drug |
| meperidine* | generic only | Opioid |
| methadone* | METHADOSE | Opioid for pain, opioid-use disorder |
| paroxetine* | PAXIL | SSRI antidepressant |
| phenelzine* | NARDIL | MAO inhibitor |
| rasagiline* | AZILECT | Parkinson’s disease drug |
| safinamide | XADAGO | Parkinson’s disease drug |
| selegiline* | EMSAM, ZELAPAR | MAO inhibitor |
| sertraline* | ZOLOFT | SNRI antidepressant |
| tramadol** | CONZIP, QDOLO | Opioid |
| tranylcypromine* | PARNATE | MAO inhibitor |
| ziprasidone** | GEODON | Antipsychotic |
†Brand-name combination products that contain other active ingredients were excluded.
*Designated as Limited Use by Worst Pills, Best Pills News
**Designated as Do Not Use by Worst Pills, Best Pills News
Risk of bleeding
Concomitant use of desipramine with the following drugs increases the risk of bleeding:
- Nonsteroidal anti-inflammatory drugs, such as aspirin (BAYER ASPIRIN, DURLAZA, ECOTRIN, VAZALORE and generics), ibuprofen (ADVIL, JUNIOR STRENGTH MOTRIN, MIDOL LIQUID GELS, MOTRIN IB, TAB-PROFEN and generics) and naproxen (ALEVE, ANAPROX DS, EC-NAPROSYN, NAPRELAN, NAPROSYN and generics)
- warfarin (JANTOVEN and generics)
What You Can Do
If you need to take desipramine to treat depression, share a list of all your medications and supplements with your doctor to avoid potential drug interactions. If you are taking a medication that interacts with desipramine, your doctor may ask you to stop or adjust the dosage of the interacting drug. Alternatively, your doctor may ask you to take another antidepressant or a different medication in place of the interacting drug. Do not take desipramine or any other tricyclic antidepressant concurrently with MAO inhibitors or within 14 days of stopping treatment with these medications.[12]
Do not stop taking desipramine suddenly, because doing so can cause withdrawal symptoms (including headache, malaise and nausea). Be aware that other drugs not mentioned in this article also may interact with desipramine.
Do not drink alcohol while taking desipramine, because doing so can increase the effects of alcohol and related adverse effects.
References
[1] Validus Pharmaceuticals LLC. Label: desipramine (NORPRAMIN). January 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=70b562ea-9f21-4e4a-b3ed-0590b2892f6a&type=display. Accessed July 12, 2023.
[2] Drug profile: desipramine (NORPRAMIN). January 2023. https://www.worstpills.org/monographs/view/62. Accessed July 12, 2023.
[3] Validus Pharmaceuticals LLC. Label: desipramine (NORPRAMIN). January 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=70b562ea-9f21-4e4a-b3ed-0590b2892f6a&type=display. Accessed July 12, 2023.
[4] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “desipramine.” Accessed July 12, 2023.
[5] Hirsch M, Birnbaum RJ. Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects. UpToDate. November 7, 2022.
[6] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “desipramine.” Accessed July 12, 2023.
[7] Validus Pharmaceuticals LLC. Label: desipramine (NORPRAMIN). January 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=70b562ea-9f21-4e4a-b3ed-0590b2892f6a&type=display. Accessed July 12, 2023.
[8] Validus Pharmaceuticals LLC. Label: desipramine (NORPRAMIN). January 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=70b562ea-9f21-4e4a-b3ed-0590b2892f6a&type=display. Accessed July 12, 2023.
[9] Wolters Kluwer Lexicomp. Drug interactions. https://www.wolterskluwer.com/en/solutions/lexicomp. Search term: “desipramine.” Accessed July 12, 2023.
[10] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “desipramine.” Accessed July 12, 2023.
[11] Validus Pharmaceuticals LLC. Label: desipramine (NORPRAMIN). January 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=70b562ea-9f21-4e4a-b3ed-0590b2892f6a&type=display. Accessed July 12, 2023.
[12] Validus Pharmaceuticals LLC. Label: desipramine (NORPRAMIN). January 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=70b562ea-9f21-4e4a-b3ed-0590b2892f6a&type=display. Accessed July 12, 2023.
