Desipramine, sold under the brand name Norpramin, is a medication belonging to a class known as tricyclic antidepressants (TCAs). First approved by the U.S. Food and Drug Administration (FDA) in 1964, it was derived from the first-ever TCA, imipramine. As a secondary amine TCA, desipramine functions by inhibiting the reuptake of neurotransmitters, primarily norepinephrine and to a lesser extent serotonin, in the brain. This action helps restore the balance of these natural substances, which is thought to be a key factor in regulating mood.
FDA-Approved Use: Treating Major Depressive Disorder
The primary, and FDA-approved, use for desipramine is the treatment of major depressive disorder in adults. While effective, it is not typically a first-choice antidepressant today due to its side effect profile compared to newer classes of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs).
For adults with depression, a healthcare provider will determine the appropriate starting dose, which can vary based on individual needs. Dosage adjustments may be made over time depending on how a patient responds to the medication and any side effects experienced. In some situations, higher daily amounts might be used, often requiring close medical supervision. It is important to note that the full therapeutic benefit may take several weeks to manifest, so patients should continue treatment as prescribed even if initial changes are not dramatic.
Common Off-Label Uses of Desipramine
In addition to its approved use for depression, prescribers may use desipramine off-label for several other conditions based on clinical judgment. Off-label use is the practice of prescribing a drug for a different purpose than the one for which it was originally approved.
Neuropathic Pain Conditions
Desipramine is occasionally prescribed for chronic neuropathic pain, which is pain caused by nerve damage. Conditions such as painful diabetic neuropathy and postherpetic neuralgia are often treated with this medication. For neuropathic pain, desipramine may be effective at amounts lower than those used for depression, which may help minimize side effects. Its analgesic effect is thought to involve different mechanisms than its antidepressant action, such as inhibition of sodium channels in nerve membranes. While some studies show benefit, the evidence is of relatively low quality compared to other treatments, suggesting it may be a better option for patients who have not found relief from first-line medications.
Attention-Deficit/Hyperactivity Disorder (ADHD)
Desipramine has been investigated for the treatment of ADHD, especially in children and adolescents, and has shown some short-term effectiveness in reducing core symptoms. It is not considered a first-line treatment, and its use requires careful monitoring for potential cardiovascular side effects, such as increased heart rate and blood pressure. Safety data in pediatric patients is not as robust as for other ADHD medications, and its use in this population is rare.
Bulimia Nervosa
As an adjunct therapy to cognitive behavioral interventions, desipramine may be used to help reduce binge-eating episodes in patients with bulimia nervosa. Clinical trial data on this use is limited, and side effects sometimes limit its long-term usefulness compared to SSRIs.
Irritable Bowel Syndrome (IBS)
Due to its anticholinergic properties, desipramine can be used to treat global symptoms of IBS, especially in patients with the diarrhea-predominant form (IBS-D), by improving urgency and diarrhea. The appropriate amount for IBS is typically started low and adjusted based on how well it works and how well the patient tolerates it.
Desipramine vs. Other Tricyclic Antidepressants
Not all tricyclic antidepressants are the same. Their chemical structure influences their effectiveness and side effect profiles. Desipramine is a secondary amine, meaning it is more selective for norepinephrine reuptake inhibition compared to tertiary amines like amitriptyline, which have a broader effect on both serotonin and norepinephrine.
| Feature | Desipramine (Norpramin) | Amitriptyline (Elavil) | Imipramine (Tofranil) |
|---|---|---|---|
| Mechanism | Primarily inhibits norepinephrine reuptake. | Inhibits both norepinephrine and serotonin reuptake. | Inhibits both norepinephrine and serotonin reuptake. |
| Sedative Effects | Less sedating compared to other TCAs. | More likely to cause sleepiness. | Can cause sleepiness. |
| Anticholinergic Effects | Fewer anticholinergic side effects (e.g., dry mouth, constipation). | More pronounced anticholinergic effects. | Can cause anticholinergic side effects. |
| Off-Label Uses | Neuropathic pain, ADHD, bulimia nervosa, IBS. | More commonly used for nerve pain and migraine prevention. | Also used for bedwetting in children. |
Important Considerations and Risks
Taking desipramine requires careful consideration of its potential side effects and interactions. Patients should be closely monitored throughout treatment.
Side Effects
While generally better tolerated in terms of sedation than some other TCAs, desipramine still has a significant side effect profile. Common side effects include:
- Dry mouth
- Constipation
- Drowsiness or fatigue
- Blurred vision
- Difficulty urinating
- Dizziness
- Changes in appetite or weight
- Nausea
More serious side effects can also occur, and any concerning symptoms should be reported to a doctor immediately. Serious risks include:
- Cardiovascular Effects: Heart rhythm changes, including prolongation of the QT interval, require careful monitoring, especially in hospitalized patients or those with pre-existing heart conditions.
- Suicidal Thoughts: A black box warning indicates an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults starting on antidepressants, including desipramine.
- Serotonin Syndrome: A rare but potentially life-threatening condition caused by an excess of serotonin. Risk is higher when taken with other serotonergic drugs.
Contraindications and Precautions
Desipramine is not suitable for everyone. Major contraindications include:
- Concurrent use with monoamine oxidase inhibitors (MAOIs), with a required washout period.
- Acute recovery phase following a heart attack.
- Hypersensitivity to desipramine or other dibenzazepines.
Special caution is advised for patients with a history of cardiovascular disease, angle-closure glaucoma, urinary retention, seizures, or thyroid disease. It should also be used carefully in older adults, who are more susceptible to side effects like confusion and orthostatic hypotension.
Conclusion: The Niche of Desipramine in Modern Medicine
Desipramine is an older but still valuable medication in the pharmacologic toolkit, primarily used for major depressive disorder and a variety of off-label conditions. Its role has shifted over time due to the introduction of newer antidepressants with fewer side effects. As a tricyclic antidepressant, its specific mechanism focusing heavily on norepinephrine provides a therapeutic option for patients who have not responded to other medications. For off-label applications, such as neuropathic pain, it may provide relief, sometimes at lower, better-tolerated amounts. However, its use requires careful consideration of its side effect profile, particularly the risks associated with cardiovascular health and suicidality. Ultimately, desipramine remains a second or third-line option that can provide significant benefit for the right patient, under the close supervision of a healthcare provider.
Where to find authoritative information
For more in-depth information and up-to-date patient guidance on desipramine, the FDA's website is a reliable resource, including the official Medication Guide for antidepressants.(https://www.fda.gov/drugs/drug-safety-and-availability/medication-guides-antidepressants-children-and-adolescents)
Important Safety Note
This article is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read here.
