Suppressive effect of mirtazapine on the HPA system in acutely depressed women seems to be transient and not related to antidepressant action

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.

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“…Single substances, such as lithium in this study, may also 'break the rules' as has been reported for mirtazapine [38] .…”

Section: Discussionsupporting

confidence: 68%

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

et al. 2009

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“…74,75,82 Data from our group suggest, however, that while mirtazapine treatment has a significant attenuating effect on the cortisol response in the dex-CRH test, this effect is likely only transient, and a correlation of successful antidepressant treatment with mirtazapine and HPA-axis normalization can still be observed. 76,83 Below, we discuss the evidence that endocrine challenge tests not only correlate with antidepressant treatment response but might actually be used as predictors of treatment response. This evidence is summarized in Table 1.…”

Section: Endocrine Challenge Tests As Biomarkers For Depressionmentioning

confidence: 99%

Glucocorticoids as Predictors of Treatment Response in Depression

Horstmann

Binder

2011

Harvard Review of Psychiatry

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“…In contrast mirtazapine acutely inhibits HPA system activity [82], [83]. Lithium augmentation, as stated above, activates the HPA system, especially in responders [39], [42].…”

Section: Discussionmentioning

confidence: 91%

Lithium Monotherapy Increases ACTH and Cortisol Response in the Dex/CRH Test in Unipolar Depressed Subjects. A Study with 30 Treatment-Naive Patients

et al. 2011

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BackgroundDistorted activity of the hypothalamic-pituitary-adrenocortical (HPA) system is one of the most robustly documented biological abnormalities in major depression. Lithium is central to the treatment of affective disorders, but little is known about its effects on the HPA system of depressed subjects.ObjectiveTo assess the effects of lithium monotherapy on the HPA system of patients with major depression by means of the combined DEX/CRH test.MethodThirty drug-naive outpatients with major depression (single episode or unipolar recurrent; SCID I- and II-confirmed) were treated with lithium monotherapy for four weeks. The DEX/CRH test was conducted directly before intake of the first lithium tablet and four weeks thereafter. Weekly ratings with the HDRS21 were used to determine response (≥50% symptom reduction) and remission (HDRS ≤7).ResultsLithium levels within the therapeutic range were achieved rapidly. Tolerability was good; no patient terminated the treatment prematurely. Response and remission rates were 50% and 33% respectively. Compared to the DEX/CRH test before the start of the treatment, a considerable and significant increase in all CRH-stimulated ACTH and cortisol parameters could be detected in the second DEX/CRH test. When analysed with particular regard to responders and non-responders, that significant increase was only present in the responders.ConclusionsWe were able to demonstrate that lithium leads to a significant activation of the HPA system. This is possibly connected to stimulation of hypothalamic arginine vasoporessin (AVP), to direct intracellular effects of lithium on pituitary cells and to an induction of gene expression.Trial Registrationdrks-nue.uniklinik-freiburg.de DRKS00003185

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Suppressive effect of mirtazapine on the HPA system in acutely depressed women seems to be transient and not related to antidepressant action

Cited by 38 publications

References 71 publications

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

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

Glucocorticoids as Predictors of Treatment Response in Depression

Lithium Monotherapy Increases ACTH and Cortisol Response in the Dex/CRH Test in Unipolar Depressed Subjects. A Study with 30 Treatment-Naive Patients

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