Is desipramine (tricyclic antidepressant) only used for treating depression?

Desipramine: Beyond Depression

No, desipramine is not used only for depression—it has well-established efficacy for neuropathic pain and is used off-label for several other conditions. 1, 2

FDA-Approved Indication

• Desipramine is FDA-approved specifically and solely for the treatment of depression 1
• However, FDA approval does not limit clinical use to this single indication

Primary Off-Label Use: Neuropathic Pain

Desipramine is a first-line coanalgesic for cancer-related and non-cancer neuropathic pain. 2

Mechanism and Efficacy

• The analgesic effect is independent of antidepressant activity—pain relief occurs at lower doses (10-150 mg nightly) than required for depression treatment and with earlier onset of action 2
• Pain relief is mediated through blockade of norepinephrine reuptake, not mood elevation 3
• Desipramine demonstrated significant pain relief in postherpetic neuralgia, with 12 of 19 patients reporting at least moderate relief versus 2 with placebo 3

Clinical Application for Pain

• Start with 10-25 mg nightly and increase every 3-5 days to 50-150 mg nightly 2
• Desipramine is better tolerated than tertiary amine tricyclics (amitriptyline, imipramine) with fewer anticholinergic effects like sedation, dry mouth, and urinary hesitancy 2
• Use as a coanalgesic in combination with opioids for the neuropathic component of pain 2
• The National Comprehensive Cancer Network specifically recommends desipramine for cancer-related neuropathic pain 2

Evidence Quality Caveat

• While widely used and guideline-recommended, the Cochrane review found only very low quality evidence from small, methodologically flawed studies for neuropathic pain 4
• Despite limited high-quality evidence, clinical guidelines consistently recommend desipramine based on clinical experience and mechanistic rationale 2

Other Clinical Uses

Chronic Depression

• Desipramine is effective for chronic depression and maintaining recovery during long-term treatment 5
• Effective in elderly patients over 75 years, though response rates may be lower than in younger populations 6

ADHD (Augmentation Strategy)

• Used in combination with methylphenidate for ADHD, particularly when comorbid mood disorders are present 2
• Dosing studied at 2.4-6.1 mg/kg per day with plasma levels of 121-291 ng/mL 2
• The combination was generally safe with no unique serious side effects beyond those of desipramine alone 2

Alzheimer's Disease-Related Symptoms

• Recommended for depression in Alzheimer's patients at 10-25 mg in the morning, increasing to maximum 150 mg 2
• Tends to be activating (reduces apathy) with lower risk for cardiotoxic, hypotensive, and anticholinergic effects compared to other tricyclics 2

Critical Safety Considerations

Absolute Contraindications

• Never combine with MAOIs—risk of serotonin syndrome 1, 7
• Contraindicated with other serotonergic drugs including SSRIs, SNRIs, other tricyclics, fentanyl, tramadol, and triptans due to serotonin syndrome risk 1
• Requires 2-week washout when switching to/from MAOIs (5 weeks for fluoxetine) 7

High-Risk Populations Requiring Extreme Caution

• Cardiovascular disease—risk of conduction defects, arrhythmias, tachycardia, stroke, and myocardial infarction 1
• Family history of sudden death or cardiac dysrhythmias 1
• Urinary retention or glaucoma due to anticholinergic properties 1
• Angle-closure glaucoma risk from pupillary dilation 1

Monitoring Requirements

• Screen for bipolar disorder before initiating—may precipitate manic episodes 1
• Monitor closely for suicidality, especially in patients under 25 years during initial months and dose changes 1
• Prescribe smallest quantity consistent with good management to reduce overdose risk 1