Loss of response to antidepressants and subsequent refractoriness: diagnostic issues in a retrospective case series

Background: The loss of response to antidepressant drugs is not an uncommon phenomenon. While some patients respond to changes in the drug regimen, others develop resistance to various treatment modalities. Method: I describe 15 cases who had a loss of response to repeated trials of antidepressants before developing a chronic and severe, refractory depression. Results: These patients had failed to respond to various treatment strategies including substitution with other antidepressant drugs, augmentation with agents such as T3 and lithium; and finally electroconvulsive therapy (ECT). Following discontinuation of antidepressants and treatment with mood stabilizers, there was a sustained improvement. Notably some of the patients who had earlier failed to respond to mood stabilizers in combination with unimodal antidepressants improved upon discontinuation of antidepressants and continued treatment with mood stabilizers. Limitations: Open trial, retrospective design and small sample size. Conclusion: These clinical findings suggest that some refractory depressives represent cryptic bipolar disorders. Prospective validation is necessary to support this conclusion.