Optimal Dose of Selective Serotonin Reuptake Inhibitors, Venlafaxine, and Mirtazapine in Major Depression: A Systematic Review and Dose-Response Meta-Analysis

Furukawa, Toshi A.; Cipriani, Andrea; Cowen, Philip J.; Leucht, Stefan; Egger, Matthias; Salanti, Georgia

doi:10.1176/appi.focus.18204

Cited by 62 publications

(114 citation statements)

References 27 publications

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“…It therefore seems sensible to adjust antidepressant treatment recommendations for both dose and age to optimally meet the needs of individual age-groups. The present reanalysis therefore asked whether antidepressant dosing recommendations reported by Furukawa et al [1] would change in dependence on age.…”

Section: Introductionmentioning

confidence: 94%

“…The recent meta-analysis by Furukawa et al [1] reported optimal doses for the use of antidepressants in the acute-phase treatment of adult major depressive disorder (MDD). Results showed a moderate dose-dependent increase in efficacy (response rate) until 40 mg/day fluoxetine equivalents (mg/day FE ) associated with an exponential decrease in tolerability (dropouts due to adverse effects) up to 80 mg/day FE [2,3].…”

Section: Introductionmentioning

confidence: 99%

“…Results showed a moderate dose-dependent increase in efficacy (response rate) until 40 mg/day fluoxetine equivalents (mg/day FE ) associated with an exponential decrease in tolerability (dropouts due to adverse effects) up to 80 mg/day FE [2,3]. The current recommendation is therefore that the lower range (20À40 mg/day FE ) of the licensed dose (20À80 mg/day FE ) probably achieves an optimal balance between efficacy and tolerability for the majority of patients receiving antidepressants in MDD [1]. The meta-analysis by Furukawa et al [1] however did not adjust dosing for age, another important demographical covariate in antidepressant treatment [4À10].…”

Section: Introductionmentioning

confidence: 99%

“…The current recommendation is therefore that the lower range (20À40 mg/day FE ) of the licensed dose (20À80 mg/day FE ) probably achieves an optimal balance between efficacy and tolerability for the majority of patients receiving antidepressants in MDD [1]. The meta-analysis by Furukawa et al [1] however did not adjust dosing for age, another important demographical covariate in antidepressant treatment [4À10]. Antidepressant use in the elderly ( > 60 years) is associated with an increased risk of potentially clinical significant adverse events (AEs).…”

Section: Introductionmentioning

confidence: 99%

“…The present analysis made use of the same dataset assessed by Furukawa et al [1], the GRISELDA dataset provided by Cipriani et al [25]. which compares 21 antidepressants in adult MDD based on 522 randomized controlled trials (RCTs).…”

Section: Introductionmentioning

confidence: 99%

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Optimal doses of antidepressants in dependence on age: Combined covariate actions in Bayesian network meta-analysis

Holper

2020

eClinicalMedicine

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A B S T R A C TBackground: The meta-analysis by Furukawa et al. (The Lancet Psychiatry 2019, 6(7)) reported optimal doses for antidepressants in adult major depressive disorder (MDD). The present reanalysis aimed to adjust optimal doses in dependence on age. Methods: Analysis was based on the same dataset by Cipriani et al. (The Lancet 2018, 391(10128)) comparing 21 antidepressants in MDD. Random-effects Bayesian network meta-analysis was implemented to estimate the combined covariate action using restricted cubic splines (RCS). Balanced treatment recommendations were derived for the outcomes efficacy (response), acceptability (dropouts for any reason), and tolerability (dropouts due to adverse events). Findings: The combined covariate action of dose and age suggested agomelatine and escitalopram as the best-balanced antidepressants in terms of efficacy and tolerability that may be escalated until 40 and 60 mg/day fluoxetine equivalents (mg/day FE ), respectively, for ages 30À65 years. Desvenlafaxine, duloxetine, fluoxetine, milnacipran, and vortioxetine may be escalated until 20À40 mg/day FE , whereas bupropion, citalopram, mirtazapine, paroxetine, and venlafaxine may not be given in doses > 20 mg/day FE . Amitriptyline, clomipramine, fluvoxamine, levomilnacipran, reboxetine, sertraline, and trazodone revealed no relevant balanced benefits and may therefore not be recommended for antidepressant treatment. None of the antidepressants was observed to provide balanced benefits in patients >70 years because of adverse events exceeding efficacy. Interpretation: Findings suggest that the combined covariate action of dose and age provides a better basis for judging antidepressant clinical benefits than considering dose or age separately, and may thus inform decision makers to accurately guide antidepressant dosing recommendations in MDD. Funding: No funding.

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Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Optimal doses of antidepressants in dependence on age: Combined covariate actions in Bayesian network meta-analysis

Holper

2020

eClinicalMedicine

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Neglected but not negligible aspects of antidepressants and their availability in bipolar depression

Terao

2021

Brain and Behavior

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Objectives: Although many antidepressants are available, they are not always used appropriately. For appropriate use of antidepressants, the old concept of a linear doseresponse relationship, in which the dose is linearly increased to achieve a sufficient antidepressant effect, should be reconsidered. Furthermore, there is ongoing debate on the safe and appropriate use of antidepressants in patients with bipolar depression.Antidepressants may be used under certain conditions in patients with bipolar depression. These neglected-but not negligible-aspects of antidepressants have been discussed herein. Methods: A narrative qualitative reviewResults: Dose-response relationships of antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are not linear. They may be bell-shaped, with efficacy initially increasing with an increase in dose but decreasing when the dose is increased beyond a certain point. Despite using international diagnostic criteria, uncertainty remains on whether operationally diagnosed depression is latent bipolar I depression, latent bipolar II depression, or true depression. Furthermore, operationally diagnosed bipolar II depression may be latent bipolar I depression, true bipolar II depression, or depression with false hypomanic episodes. Manic/hypomanic switches are most likely to occur in patients receiving tricyclic antidepressants, followed by those receiving serotonin and noradrenaline reuptake inhibitors and SSRIs, in that order. Also, these switches are most likely to occur in patients with bipolar I depression, followed by those with bipolar II depression and true depression, in that order. Conclusions:Considering the diagnostic subtype of bipolar depression and antidepressant properties may help to determine the optimal treatment strategy. K E Y W O R D S5-HT 1A autoreceptor, antidepressants, bipolar depression, dose-response relationship, selective serotonin reuptake inhibitorsThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Comparing outcomes in chronic depression following inpatient psychotherapy for patients continuing versus discontinuing antidepressant medication

Høstmælingen

Ulvenes

Nissen‐Lie

et al. 2021

Clin Psychology and Psychoth

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Research indicates that combination of psychotherapy and antidepressant medication (ADM) provides cumulative effects and thus outperforms monotherapy in treating chronic depression. In this quasi‐experimental study, we explored symptom change for patients with chronic depression treated with ADM when presenting for a 12‐week psychotherapeutic inpatient treatment programme. We compared outcomes through treatment and follow‐up of patients who continued medication with those who discontinued. We also tested possible moderator effects of initial depression severity on change between the groups. Based on prior research, we hypothesized that combination treatment would yield better results (i.e., more reduction in depression). Patients (N = 112) were referred from general practitioners or local secondary health care. Outcome was measured by Beck Depression Inventory‐II (BDI‐II), and comparisons were carried out using multilevel modelling. Although 35 patients discontinued ADM during treatment, 77 continued. Both continuers and discontinuers had a significant treatment effect that was maintained at 1‐year follow‐up. There was no difference in outcome between continuers and discontinuers of ADM. Patients with severe depression had significantly more symptom improvement than patients with moderate depression, but depression severity did not affect outcomes across continuers and discontinuers of ADM differently. The results could indicate that patients had developed resistance and/or tolerance to the prophylactic effects of medication and that ADM did not contribute to the reduction of depressive symptoms. The findings may also indicate that psychotherapy alone in some instances can be a viable alternative to continued combined treatment. Clinicians should carefully assess benefits of patients' ongoing use of antidepressant medication when entering psychotherapy.

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Optimal Dose of Selective Serotonin Reuptake Inhibitors, Venlafaxine, and Mirtazapine in Major Depression: A Systematic Review and Dose-Response Meta-Analysis

Cited by 62 publications

References 27 publications

Optimal doses of antidepressants in dependence on age: Combined covariate actions in Bayesian network meta-analysis

Optimal doses of antidepressants in dependence on age: Combined covariate actions in Bayesian network meta-analysis

Neglected but not negligible aspects of antidepressants and their availability in bipolar depression

Comparing outcomes in chronic depression following inpatient psychotherapy for patients continuing versus discontinuing antidepressant medication

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