What are the chances of relapse after discontinuing lithium augmentation of nortriptyline (Pamelor) in a patient with a history of major depressive episodes, initially managed with electroconvulsive therapy (ECT)?

Risk of Relapse After Discontinuing Lithium Augmentation of Nortriptyline Following ECT for Major Depression

The risk of relapse is extremely high (approximately 84%) within 6 months after discontinuing lithium augmentation of nortriptyline in patients who received ECT for major depression. 1

Evidence on Relapse Rates

• Without active treatment, virtually all patients (84%) who achieved remission with ECT relapse within 6 months of stopping ECT 1
• Nortriptyline monotherapy has limited efficacy with a 60% relapse rate over 24 weeks 1
• The combination of nortriptyline and lithium significantly reduces relapse rates to approximately 39% over 24 weeks 1
• Most relapses with nortriptyline-lithium occur within the first 5 weeks after ECT discontinuation 1

Factors Affecting Relapse Risk

• Medication resistance prior to ECT is associated with more rapid relapse (HR 4.48) 2
• Female patients have shown more rapid relapse in some studies 1
• Older age is associated with a significantly lower risk of relapse (p=0.039) 3
• Patients with psychotic features have a significantly decreased risk of relapse (HR 0.33) 2, 3
• Higher depression severity before ECT is associated with lower relapse risk (HR 0.88) 2
• Greater number of previous depressive episodes increases relapse risk (p=0.028) 3
• Bipolar II diagnosis (but not bipolar I) is associated with worse long-term outcomes (p=0.030) 3

Importance of Continuation Treatment

• ECT is effective only in resolving acute illness and will not prevent relapse without continuation treatment 4
• After successful ECT treatment, patients should be placed on an appropriate therapeutic regimen designed to maintain treatment response 4
• In a double-blind trial, patients receiving placebo after ECT spent an average of 7.8 weeks with depressive episodes during the following year, compared to only 1.7 weeks for those on lithium (p<0.02) 5

Lithium's Role in Preventing Relapse

• Lithium significantly reduces post-ECT morbidity compared to placebo 5
• Lithium augmentation is particularly effective in unipolar depression following ECT (p=0.027) 3
• The combination of nortriptyline and lithium is more effective than nortriptyline alone, though relapse rates remain high, particularly during the first month 1

Alternative Continuation Strategies

• Venlafaxine combined with lithium appears equally effective as nortriptyline with lithium for continuation therapy after ECT 6
• Starting an antidepressant during ECT (versus after completion) does not significantly affect relapse rates 6
• Treatment regimens should be tailored to the presenting disorder and may include an antidepressant in unipolar depression, a mood stabilizer in bipolar illness, or judicious use of combined pharmacotherapies 4

Clinical Implications

• Discontinuing lithium augmentation of nortriptyline after ECT places patients at very high risk for relapse 1, 5
• The highest risk period for relapse is within the first 5 weeks after ECT discontinuation 1
• Relapse rates remain substantial (39-50%) despite intensive continuation pharmacotherapy 1, 6
• Careful monitoring for mood changes and suicidal ideation is essential for several weeks after ECT 4

Common Pitfalls to Avoid

• Discontinuing continuation pharmacotherapy too early after ECT 1, 5
• Failing to recognize that ECT without continuation therapy is not a satisfactory treatment for depressive illness 5
• Underestimating the high risk of relapse in the first month after ECT, particularly in medication-resistant patients 1
• Not considering patient-specific risk factors for relapse when planning continuation treatment 2, 3