Is nortriptyline (tricyclic antidepressant) a cause of orthostatic hypotension?

Nortriptyline and Orthostatic Hypotension

Yes, nortriptyline is a known cause of orthostatic hypotension, particularly in older adults and those with pre-existing cardiovascular conditions.

Mechanism and Risk

Nortriptyline, a tricyclic antidepressant (TCA), can cause orthostatic hypotension through its alpha-1 adrenergic receptor blocking properties. This leads to peripheral vasodilation and impaired compensatory vasoconstriction when changing positions.

• Multiple guidelines specifically list TCAs including nortriptyline as medications that can cause orthostatic hypotension 1
• The European Society of Cardiology specifically mentions tricyclic antidepressants as medications that can cause orthostatic hypotension and other autonomic symptoms 1
• The European Heart Journal guidelines on syncope identify drug-induced autonomic failure as a frequent cause of orthostatic hypotension, with diuretics and vasodilators being the most important agents 1

Risk Factors for Nortriptyline-Induced Orthostatic Hypotension

The risk of orthostatic hypotension with nortriptyline is higher in:

1. Older adults: Elderly patients are more susceptible to orthostatic effects 1
2. Patients with pre-existing cardiovascular disease 2
3. Patients taking other medications that can cause hypotension (diuretics, vasodilators, other antihypertensives) 1
4. Higher doses: Risk increases with higher doses 3, 4

Clinical Evidence

Research studies have demonstrated this association:

• A systematic review found orthostatic hypotension was significantly higher in nortriptyline users than in comparator groups (relative risk 2.8; 95% CI 1.4,5.3) 2
• In a study of elderly depressed outpatients, plasma levels of nortriptyline metabolites were associated with dizziness and symptoms of orthostatic hypotension 5
• In cardiac patients treated with nortriptyline, the drug reduced standing systolic blood pressure by a mean of 14 mm Hg (p < 0.05), with drug discontinuation required in some patients due to symptomatic orthostatic hypotension 4

Management Considerations

When prescribing nortriptyline:

1. Screen for risk factors for orthostatic hypotension before initiating therapy
2. Start with lower doses in at-risk patients, particularly the elderly
3. Monitor blood pressure in both supine and standing positions
4. Educate patients about symptoms of orthostatic hypotension and precautions when changing positions
5. Consider alternative medications in patients at high risk or with pre-existing orthostatic hypotension

Interesting Clinical Paradox

Interestingly, one study found that pretreatment orthostatic hypotension in elderly depressed patients actually predicted a better response to nortriptyline therapy 6. However, this finding should not override safety concerns, as orthostatic hypotension remains a significant risk factor for falls and cardiovascular events in the elderly.

Alternative Medications

For patients at high risk of orthostatic hypotension who require treatment for neuropathic pain or depression, consider:

• Pregabalin or gabapentin for neuropathic pain 1
• Duloxetine (SNRI) for both neuropathic pain and depression 1
• SSRIs for depression (less likely to cause orthostatic hypotension)

In conclusion, clinicians should be vigilant about the risk of orthostatic hypotension when prescribing nortriptyline, particularly in vulnerable populations, and should implement appropriate monitoring and preventive strategies.