Lithium and Triiodothyronine Augmentation of Antidepressants

Sokolov, Stephen T.H.; Levitt, Anthony J.

doi:10.1177/070674370605101209

Cited by 30 publications

(17 citation statements)

References 7 publications

(2 reference statements)

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“…There are several open-label trials supporting the efficacy of T 3 augmentation of SSRI for TRD, as reviewed by Cooper-Kazaz and Lerer [64]. However, a single RCT did not show differences between T 3 , lithium and T 3 plus lithium as augmenting agents for TRD [65]. As discussed previously, the STAR*D trial compared T 3 with lithium augmentation for TRD and found no significant differences in remission rates, although T 3 was better tolerated [60].…”

Section: Resultsmentioning

confidence: 99%

The Integrative Management of Treatment-Resistant Depression: A Comprehensive Review and Perspectives

Carvalho

Berk

Hyphantis

et al. 2014

Psychother Psychosom

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Background: Major depressive disorder is a prevalent and disabling illness. Notwithstanding numerous advances in the pharmacological treatment of depression, approximately 70% of patients do not remit after first-line antidepressant treatment. Methods: The MEDLINE/PubMed, EMBASE and ClinicalTrials.gov electronic databases were searched from inception to October 1, 2013, for randomized controlled trials (RCT), relevant open-label trials, meta-analyses and ongoing trials of pharmacological and psychotherapeutic approaches to treatment-resistant depression (TRD). Results: Switching to a different antidepressant is a useful option following nonresponse to a first-line agent. Although widely used in clinical practice, there is limited evidence to support antidepressant combination for TRD. Notwithstanding evidence for lithium or T₃ augmentation to be successful in TRD, most studies were carried out when participants were treated with tricyclic antidepressants (TCA). Of the available strategies to augment the response to new-generation antidepressants, the use of some atypical antipsychotics is best supported by evidence. Several novel therapeutic options are currently discussed. Evidence suggests that cognitive therapy (CT) is an effective strategy for TRD. Conclusions: The success of switching to a different antidepressant following a first-line agent is supported by evidence, but there is limited evidence for effective combination strategies. Lithium and T₃ augmentation of TCA have the strongest evidence base for successful treatment of TRD. The use of augmentation of newer-generation antidepressants with atypical antipsychotics is supported by a growing evidence base. Current evidence supports CT as an effective strategy for TRD. There is a need for additional large-scale RCT of TRD. The development of new antidepressants targeting novel pathways opens a promising perspective for the management of TRD.

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Section: Resultsmentioning

confidence: 99%

The Integrative Management of Treatment-Resistant Depression: A Comprehensive Review and Perspectives

Carvalho

Berk

Hyphantis

et al. 2014

Psychother Psychosom

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“…Five studies were identified that included a randomization component (Appelhof et al, 2004;CooperKazaz et al, 2007;Joffe et al, 2006;Nierenberg et al, 2006;Posternak et al, 2007). These are summarized in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…These are summarized in Table 1. Three were enhancement studies in which T3 and a SSRI were administered concurrently from the inception of treatment (Appelhof et al, 2004;CooperKazaz et al, 2007;Posternak et al, 2007) and two were augmentation studies in which T3 was added to the ongoing treatment of patients who had not responded (Joffe et al, 2006;Nierenberg et al, 2006). No open enhancement studies were identified and no specifically designed acceleration studies.…”

Section: Resultsmentioning

confidence: 99%

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Efficacy and safety of triiodothyronine supplementation in patients with major depressive disorder treated with specific serotonin reuptake inhibitors

Cooper‐Kazaz

Lerer

2007

Int. J. Neuropsychopharm.

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The thyroid hormone, triiodothyronine (T3), is used as a supplement to antidepressant treatment of major depression, to accelerate and enhance response and as an augmenter in patients who have not responded. While there is support from controlled trials and meta-analyses for the use of T3 in conjunction with tricyclic antidepressants, the evidence base for supplementation of specific serotonin reuptake inhibitors (SSRIs) with T3 is more limited. We reviewed the available literature on T3 supplementation of SSRIs including open-label studies and randomized controlled trials (RCTs). Five RCTs were identified. Three were enhancement studies in which T3 was administered concurrently with the antidepressant from the start of treatment and two were augmentation studies in which T3 was added to the antidepressant treatment of patients who had not responded. Three open augmentation studies were identified. The RCTs were too disparate in methodology to allow a meta-analysis to be performed. The enhancement studies are inconclusive in that one showed strongly positive effects of T3, one showed no effect and one showed a trend. The open augmentation studies supported an effect of T3 in SSRI non-responsive patients with some support from a large RCT; a smaller, underpowered RCT did not show efficacy. T3 was well tolerated in most of the studies and adverse effects do not seem to be an impediment to clinical use. Some of the studies identified clinical and thyroid function correlates of response that require further investigation. Further research is needed before it can be definitively established whether T3 is an effective supplement to SSRIs in patients with MDD. The appropriate timing of T3 supplementation needs to be explored and also the dose and length of treatment.

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“…These studies also mixed non-resistant with varying percentages (8–38%) of TRD patients. There are several open-label studies showing benefits for thyroid augmentation in TRD patients using SSRIs as a primary treatment,46–48 and one controlled study showing no difference between augmentation with T3, lithium, and T3 plus lithium in TRD patients 49. The STAR*D study compared T3 and lithium augmentation and found no significant difference in remission rates between the two, but did find T3 was better tolerated 50…”

Section: Pharmacotherapy For Trdmentioning

confidence: 99%

Pharmacologic approaches to treatment resistant depression: a re-examination for the modern era

Philip

Carpenter

Tyrka

et al. 2010

Expert Opinion on Pharmacotherapy

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Importance of the field Treatment-resistant depression (TRD) is common and debilitating. Initial treatment is often insufficient to achieve full remission in a given depressive episode, resulting in more frequent episodes, worsened severity, and major disability. Areas covered in this review This review surveys literature on the diagnosis and pharmacological management of TRD in light of recent developments. Evidence regarding commonly used treatment options is critically examined and key recommendations are offered. The review ends by considering drugs acting on the melatonin, acetylcholine, and glutamate systems that hold promise as future options for TRD. What the reader will gain Recent trends and research findings have impacted how the evidence supporting different approaches to TRD should be evaluated. For example, many earlier TRD studies employed tricyclics (TCAs) as the primary antidepressant, but TCAs have now been superseded by selective serotonin reuptake inhibitors (SSRIs) in routine clinical practice. This deficiency has been addressed by the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, the largest effectiveness study of TRD ever conducted. However, design characteristics of the STAR*D study preclude simple comparisons with earlier studies. Take home message A shortcoming of most treatment recommendations for TRD is their reliance on older studies that do not reflect the current preeminence of SSRIs in clinical practice. This has distorted the prioritization of pharmacological strategies for TRD. Efforts to correct this distortion with effectiveness research, designed to better reflect current practice trends, require critical consideration of the strengths and limitations of this approach.

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Lithium and Triiodothyronine Augmentation of Antidepressants

Abstract: There may be no advantage to a combination of these augmenting agents, although we failed to show separation between active treatments and placebo.

Cited by 30 publications

References 7 publications

The Integrative Management of Treatment-Resistant Depression: A Comprehensive Review and Perspectives

The Integrative Management of Treatment-Resistant Depression: A Comprehensive Review and Perspectives

Efficacy and safety of triiodothyronine supplementation in patients with major depressive disorder treated with specific serotonin reuptake inhibitors

Pharmacologic approaches to treatment resistant depression: a re-examination for the modern era

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