Desipramine Side Effects: What to Expect and When to Call Your Doctor

Desipramine (Norpramin) is a tricyclic antidepressant with a well-documented side effect profile. While it tends to have fewer anticholinergic and sedating side effects than other TCAs, it still carries significant risks — including serious cardiac and CNS effects that require awareness and monitoring. This guide covers what to expect when starting desipramine, which side effects typically resolve on their own, and which symptoms require immediate medical attention.

Boxed Warning: Suicidality in Young Patients

Desipramine, like all antidepressants, carries an FDA boxed warning (the most serious type of warning) regarding an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults up to age 24. This risk is highest in the first few months of treatment and when the dose is changed. If you or someone you know is taking desipramine and experiencing new or worsening thoughts of self-harm, call 911 or contact the 988 Suicide and Crisis Lifeline immediately.

Common Side Effects (Usually Manageable)

These side effects are common, especially when starting desipramine or increasing the dose. They often improve over time as your body adjusts:

Dry mouth: One of the most common anticholinergic effects. Sipping water frequently, chewing sugar-free gum, and maintaining good dental hygiene can help.

Constipation: Increase fluid and fiber intake. Talk to your doctor if it becomes severe.

Drowsiness/sedation: Less common with desipramine than other TCAs. If it occurs, taking desipramine at bedtime may help.

Insomnia: Desipramine can actually be activating (rather than sedating) and may cause insomnia in some patients. Taking it in the morning rather than at bedtime may reduce this.

Dizziness/lightheadedness: Often from orthostatic hypotension (blood pressure drop when standing). Rise slowly from sitting or lying positions.

Nausea: Taking desipramine with food can help reduce stomach upset.

Tremors: Fine hand tremors can occur. These usually improve with time or dose adjustment.

Blurred vision: Due to anticholinergic effects. Usually mild and temporary.

Sweating (diaphoresis): Related to noradrenergic effects. Can persist with long-term use.

Sexual dysfunction: Impaired arousal or orgasm can occur. Discuss with your doctor if this is affecting your quality of life.

Serious Side Effects: Call Your Doctor Right Away

The following side effects require prompt medical attention. Do not wait to see if they resolve on their own:

Heart palpitations, irregular heartbeat, or fainting: Desipramine can cause QT prolongation and cardiac arrhythmias. Any changes in heart rhythm should be evaluated immediately.

Severe orthostatic hypotension: Sudden, severe dizziness or fainting when standing — especially dangerous in elderly patients.

Seizures: Desipramine lowers the seizure threshold. Any new-onset seizure requires immediate emergency care.

Signs of serotonin syndrome: Agitation, confusion, rapid heart rate, high fever, muscle rigidity, or twitching — especially if you recently started or changed medications.

Eye pain, sudden vision changes, or redness in the eyes: May indicate angle-closure glaucoma, a medical emergency.

Unusual bruising, bleeding, or purple/red spots under the skin: May indicate a blood disorder such as agranulocytosis or thrombocytopenia.

Jaundice (yellowing of skin or eyes), abdominal pain, dark urine: May indicate hepatitis or liver injury.

High fever, confusion, stiff muscles, fast heart rate: Signs of neuroleptic malignant syndrome or severe serotonin syndrome — call 911.

Desipramine Side Effects vs. Other TCAs

Compared to other tricyclic antidepressants, desipramine tends to cause less sedation, less weight gain, and fewer anticholinergic effects (dry mouth, constipation, urinary retention). This is because it is a secondary amine TCA with the weakest antihistamine and anticholinergic activity of the class. However, it is the most noradrenergic TCA, which means it is more likely to cause insomnia, sweating, and tachycardia than its peers.

One important caveat: desipramine has a higher death rate in overdose compared to most other antidepressants. This makes it critical to dispense only the smallest practical quantity to patients with any history of suicidal ideation, and to ensure safe storage at home.

Tips for Managing Common Side Effects

Take desipramine with food to reduce nausea

If insomnia occurs, ask your doctor about switching to morning dosing

Rise slowly from bed or chairs to reduce dizziness from orthostatic hypotension

Stay well-hydrated and increase fiber intake to address dry mouth and constipation

Avoid alcohol — combining it with desipramine increases CNS depression risk and can be dangerous

Also review our guide on desipramine drug interactions to understand which other medications may worsen these side effects.