Universidad del Desarrollo

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Efficacy and Tolerability of Combination Treatments for Major Depression: Antidepressants plus Second-Generation Antipsychotics vs. Esketamine vs. Lithium
(2021)
Gustavo H. Vázquez
;
Anees Bahji
;
UNDURRAGA FOURCADE, JUAN PABLO
;
Leonardo Tondo
;
Ross J. Baldessarini
<jats:sec><jats:title>Background:</jats:title><jats:p> Successful treatment of major depressive disorder (MDD) can be challenging, and failures ("treatment-resistant depression" [TRD]) are frequent. Steps to address TRD include increasing antidepressant dose, combining antidepressants, adding adjunctive agents, or using nonpharmacological treatments. Their relative efficacy and tolerability remain inadequately tested. In particular, the value and safety of increasingly employed second-generation antipsychotics (SGAs) and new esketamine, compared to lithium as antidepressant adjuncts remain unclear. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> We reviewed randomized, placebo-controlled trials and used random-effects meta-analysis to compare odds ratio (OR) versus placebo, as well as numbers-needed-to-treat (NNT) and to-harm (NNH), for adding SGAs, esketamine, or lithium to antidepressants for major depressive episodes. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Analyses involved 49 drug-placebo pairs. By NNT, SGAs were more effective than placebo (NNT = 11 [CI: 9–15]); esketamine (7 [5–10]) and lithium (5 [4–10]) were even more effective. Individually, aripiprazole, olanzapine+fluoxetine, risperidone, and ziprasidone all were more effective (all NNT < 10) than quetiapine (NNT = 13), brexpiprazole (16), or cariprazine (16), with overlapping NNT CIs. Risk of adverse effects, as NNH for most-frequently reported effects, among SGAs versus placebo was 5 [4–6] overall, and highest with quetiapine (NNH = 3), lowest with brexpiprazole (19), 5 (4–6) for esketamine, and 9 (5–106) with lithium. The risk/benefit ratio (NNH/NNT) was 1.80 (1.25–10.60) for lithium and much less favorable for esketamine (0.71 [0.60–0.80]) or SGAs (0.45 [0.17–0.77]). </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> Several modern antipsychotics and esketamine appeared to be useful adjuncts to antidepressants for acute major depressive episodes, but lithium was somewhat more effective and better tolerated. </jats:p></jats:sec><jats:sec><jats:title>Limitations:</jats:title><jats:p> Most trials of adding lithium involved older, mainly tricyclic, antidepressants, and the dosing of adjunctive treatments were not optimized. </jats:p></jats:sec>
30Scopus© Citations 66
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Antidepressant responses in direct comparisons of melancholic and non-melancholic depression
(2020)
Juan Undurraga
;
Gustavo H Vázquez
;
Leonardo Tondo
;
Ross J Baldessarini
<jats:sec><jats:title>Background:</jats:title><jats:p> Efforts to develop less heterogeneous, more clinically useful diagnostic categories for depressive disorders include renewed interest in the concept of melancholia (Mel). However, clinical or biological differentiation of Mel from other (nonMel) episodes of depression has been questioned, and it remains unclear whether pharmacological responses proposed to be characteristic of Mel are supported by available research. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> We carried out a systematic review seeking treatment trials reports comparing Mel and nonMel depressed subjects for meta-analyses of their differences in responses (a) to antidepressants overall, (b) to tricyclic (TCAs) or serotonin-enhancing agents (serotonin reuptake inhibitors/serotonin–norepinephrine reuptake inhibitors) and (c) with placebo treatment. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> We identified 25 trials in 16 reports comparing 2597 Mel with 5016 nonMel subjects. Overall, responses to antidepressant treatment did not differ between Mel (39.4%) and nonMel (42.2%) subjects. However, all subjects responded better to TCAs (50.6%) than SRIs (30.0%; p<0.0001). Mel subjects also responded less well with placebo, but also were significantly more severely depressed at intake. </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> Antidepressant responses were similar in Mel and nonMel depressed patients. Mel subjects responded 25% less with placebo but were more severely depressed initially, and there was preferential response to TCAs in both Mel and nonMel subjects. The findings provide little support for proposed differences in responses to particular treatments among Mel versus nonMel depressed patients, and underscore the need to match for illness severity in making such comparisons. </jats:p></jats:sec>
6Scopus© Citations 12
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Lithium treatment for unipolar major depressive disorder: Systematic review
(2019)
Juan Undurraga
;
Kang Sim
;
Leonardo Tondo
;
Ariel Gorodischer
;
Emilio Azua
<jats:sec><jats:title>Background:</jats:title><jats:p> The potential value of lithium treatment in particular aspects of unipolar major depressive disorder remains uncertain. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> With reports of controlled trials identified by systematic searching of Medline, Cochrane Library, and PsycINFO literature databases, we summarized responses with lithium and controls followed by selective random-effects meta-analyses. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> We identified 36 reports with 39 randomized controlled trials: six for monotherapy and 12 for adding lithium to antidepressants for acute major depression, and 21 for long-term treatment. Data for monotherapy of acute depression were few and inconclusive. As an adjunct to antidepressants, lithium was much more effective than placebo ( p<0.0001). For long-term maintenance treatment, lithium was more effective than placebo in monotherapy ( p=0.011) and to supplement antidepressants ( p=0.038), and indistinguishable from antidepressant monotherapy. </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> The findings indicate efficacy of lithium as a treatment for some aspects of major depressive disorder, especially as an add-on to antidepressants and for long-term prophylaxis. It remains uncertain whether some benefits of lithium treatment occur with many major depressive disorder patients, or if efficacy is particular to a subgroup with bipolar disorder-like characteristics or mixed-features. </jats:p></jats:sec>
Scopus© Citations 64 8

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