Long-Term Outcome after Lithium Augmentation in Unipolar Depression: Focus on HPA System Activity

Abstract

Background: Lithium augmentation is a first-line strategy for depressed patients resistant to antidepressive therapy, but little is known about patients’ subsequent long-term course or outcome predictors. We investigated long-term outcomes of unipolar depressed patients who had participated in a study on the effects of lithium augmentation on the hypothalamic-pituitary-adrenocortical system using the combined dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test. Methods: Twelve to 28 months (mean 18.6 ± 4.6 months) after lithium augmentation, 23 patients were assessed with a standardized interview, of which 18 patients had complete DEX/CRH test results. Relapse was diagnosed by DSM-IV criteria (Structured Clinical Interview for DSM-IV; SCID I). Results: Only 11 patients (48%) had a favorable follow-up, defined as absence of major depressive episodes during the observation period. Patients with a favorable and an unfavorable course did not differ in clinical or sociodemographic parameters, endocrinological results or continuation of lithium. However, fewer previous depressive episodes tended to correlate (p = 0.09) with a favorable course. Conclusion: Results from studies using the DEX/CRH test to predict relapse in depressed patients treated with antidepressants were not replicated for lithium augmentation. Our finding could reflect the elevation of DEX/CRH results by lithium, independent of clinical course. Limitations of the study are its small sample size, the heterogeneous clinical baseline conditions and the lack of lithium serum levels. The fact that lithium continuation did not predict the course might be related to the difference between the efficacy of lithium in controlled studies and its effectiveness in naturalistic settings.

Lithium or an atypical antipsychotic drug in the management of treatment-resistant depression: a systematic review and economic evaluation

“…One assumption that contradicts available evidence is the assumption that relapse rates following augmentation or combination therapy would be the same as following first-line treatment. 96 However, this assumption can be regarded as conservative as any bias would be directed against escitalopram. The source of effectiveness data was clearly described for patients at all 54 stages of the model pathways.…”

A placebo-controlled study of sertraline’s effect on cortisol response to the dexamethasone/corticotropin-releasing hormone test in healthy adults

“…A number of investigations in depressed patients have highlighted a pattern of diminished Dex/CRH test cortisol response over time as a correlate or predictor of clinical improvement during antidepressant therapy (Sagud et al 2002; Schule et al 2006), with persisting patterns of elevated cortisol response to the test despite clinical remission predicting enhanced risk for future relapse. Very few have found increased cortisol reactivity in depressed patients associated with chronic pharmacotherapy, though two studies reported increased cortisol reactivity following lithium augmentation of antidepressants (Adli et al 2009; Bschor et al 2002). …”