A Comparison of Lithium and T 3 Augmentation Following Two Failed Medication Treatments for Depression: A STAR*D Report

Department of Psychiatry, Columbia University, New York, New York, United States
American Journal of Psychiatry (Impact Factor: 12.3). 09/2006; 163(9):1519-30; quiz 1665. DOI: 10.1176/appi.ajp.163.9.1519
Source: PubMed


More than 40% of patients with major depressive disorder do not achieve remission even after two optimally delivered trials of antidepressant medications. This study compared the effectiveness of lithium versus triiodothyronine (T(3)) augmentation as a third-step treatment for patients with major depressive disorder.
A total of 142 adult outpatients with nonpsychotic major depressive disorder who had not achieved remission or who were intolerant to an initial prospective treatment with citalopram and a second switch or augmentation trial were randomly assigned to augmentation with lithium (up to 900 mg/day; N=69) or with T(3) (up to 50 mug/day; N=73) for up to 14 weeks. The primary outcome measure was whether participants achieved remission, which was defined as a score < or =7 on the 17-item Hamilton Depression Rating Scale.
After a mean of 9.6 weeks (SD=5.2) of treatment, remission rates were 15.9% with lithium augmentation and 24.7% with T(3) augmentation, although the difference between treatments was not statistically significant. Lithium was more frequently associated with side effects (p=0.045), and more participants in the lithium group left treatment because of side effects (23.2% versus 9.6%; p=0.027).
Remission rates with lithium and T(3) augmentation for participants who experienced unsatisfactory results with two prior medication treatments were modest and did not differ significantly. The lower side effect burden and ease of use of T(3) augmentation suggest that it has slight advantages over lithium augmentation for depressed patients who have experienced several failed medication trials.

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    • "The results from the meta-regression demonstrate that the difference in effect sizes according to the degree of treatment resistance is statistically significant (Z = 0.121257, p = 0.050). In the STAR*D report, as participants required more and more treatment steps, the response and remission rates became lower (Nierenberg et al., 2006; Rush et al., 2006). These studies showed that multiple treatment failures (in Figure 2. "
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    ABSTRACT: Atypical antipsychotic augmentation was demonstrated to be efficacious in treatment resistant depression (TRD) in previous meta-analyses. We investigate whether there are differences in the effect size of atypical antipsychotic augmentation in major depressive disorder according to the degree of treatment resistance. A comprehensive search of four databases identified eleven randomized controlled trials. The eleven trials, which included 3,341 participants, were pooled using a random-effects meta-analysis. Atypical antipsychotic augmentation of antidepressant therapy showed superior efficacy compared to antidepressant monotherapy in TRD in terms of both response and remission rates (response, risk ratio (RR) = 1.38 (95% CI= 1.25 to 1.53); remission, RR = 1.62 (95% CI= 1.42 to 1.85)). In addition, regarding response rates in the TRD trials, atypical antipsychotic augmentation exhibited significantly different effect sizes according to the degree of treatment resistance (TRD 1: RR= 1.24; TRD 2: RR=1.37; TRD 2-4: RR=1.58). In non-TRD trials, atypical antipsychotic augmentation failed to show superior efficacy over antidepressant monotherapy in terms of remission rates (RR = 0.89 (95% CI= 0.69 to 1.14)). Atypical antipsychotic augmentation of antidepressant therapy exhibits greater effect size in patients with a higher degree of treatment resistance. This finding strengthens the rationale for considering atypical antipsychotic augmentation among depressed patients with multiple previous treatment failures in clinical practice. The efficacy of atypical antipsychotic augmentation for non-TRD seems to be different from that for TRD, and, thus, further studies of non-TRD populations are needed. © The Author 2014. Published by Oxford University Press on behalf of CINP.
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    • "Interestingly, T3 is widely used to improve the therapeutic outcome of AD drugs in patients who exhibit poor response to treatment (Aronson et al., 1996; Nierenberg et al., 2006), particularly in those treated with TCAs. Successful treatment with T3 alone has also been reported in some older studies (Feldmesser- Reiss, 1958; Flach et al., 1958; Wilson et al., 1974). "
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    ABSTRACT: Depression is one of the most frequent and severe mental disorder. Since the discovery of antidepressant (AD) properties of the imipramine and then after of other tricyclic compounds, several classes of psychotropic drugs have shown be effective in treating major depressive disorder (MDD). However, there is a wide range of variability in response to ADs that might lead to non response or partial response or in increased rate of relapse or recurrence. The mechanisms of response to AD therapy are poorly understood, and few biomarkers are available than can predict response to pharmacotherapy. Here, we will first review markers that can be used to predict response to pharmacotherapy, such as markers of drug metabolism or blood-brain barrier (BBB) function, the activity of specific brain areas or neurotransmitter systems, hormonal dysregulations or plasticity, and related molecular targets. We will describe both clinical and preclinical studies and describe factors that might affect the expression of these markers, including environmental or genetic factors and comorbidities. This information will permit us to suggest practical recommendations and innovative treatment strategies to improve therapeutic outcomes.
    Full-text · Article · Nov 2013 · Frontiers in Pharmacology
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    • "Response, remission and drop-out rates after HF-rTMS for major depression 233 remission rates after lithium carbonate or triiodothyronine augmentation of a second unsuccessful antidepressant course were 20.4% (Nierenberg et al. 2006). More specifically, HF-rTMS in the current meta-analysis was associated with remission rates of 18.6% in depressed individuals who had often not responded to at least two antidepressant trials in the current episode. "
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    ABSTRACT: Background: Meta-analyses have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) has antidepressant properties when compared with sham rTMS. However, its overall response and remission rates in major depression (MD) remain unclear. Thus, we have systematically and quantitatively assessed the efficacy of HF-rTMS for MD based on randomized, double-blind and sham-controlled trials (RCTs). Method: We searched the literature from 1995 through to July 2012 using MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, SCOPUS, and ProQuest Dissertations & Theses. We used a random-effects model, odds ratios (ORs) and the number needed to treat (NNT). Results: Data from 29 RCTs were included, totaling 1371 subjects with MD. Following approximately 13 sessions, 29.3% and 18.6% of subjects receiving HF-rTMS were classified as responders and remitters, respectively (compared with 10.4% and 5% of those receiving sham rTMS). The pooled OR was 3.3 (p < 0.0001) for both response and remission rates (with associated NNTs of 6 and 8, respectively). Furthermore, we found HF-rTMS to be equally effective as an augmentation strategy or as a monotherapy for MD, and when used in samples with primary unipolar MD or in mixed samples with unipolar and bipolar MD. Also, alternative stimulation parameters were not associated with differential efficacy estimates. Moreover, baseline depression severity and drop-out rates at study end were comparable between the HF-rTMS and sham rTMS groups. Finally, heterogeneity between the included RCTs was not statistically significant. Conclusions: HF-rTMS seems to be associated with clinically relevant antidepressant effects and with a benign tolerability profile.
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