Switching Selective Serotonin Reuptake Inhibitors in Adolescents with Selective Serotonin Reuptake Inhibitor-Resistant Major Depressive Disorder: Balancing Tolerability and Efficacy

Jeffrey R. Strawn, Jeffrey A. Mills, Paul E Croarkin

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

To guide clinicians in selecting the "next line" selective serotonin reuptake inhibitor (SSRI) for adolescents with treatment-resistant major depressive disorder, we sought to compare response rates among SSRIs in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study and to jointly model tolerability and efficacy for the specific SSRI comparisons. Methods: Efficacy and tolerability data for paroxetine, citalopram, and fluoxetine were extracted from the TORDIA study. Using a joint bivariate normal likelihood for response and tolerability (based on the maximum implied variance from the 95% credible intervals previously reported for the three SSRIs), a Monte Carlo pseudorandom sample (100,000 draws) was obtained, from which credible intervals, means, posterior tail probabilities, etc. were determined. Joint null hypotheses of no difference in efficacy and tolerability were then evaluated with regard to superiority of each SSRI over the others. Results: No significant differences in response were observed for citalopram compared with fluoxetine (p = 0.247) or for fluoxetine compared with paroxetine (p = 0.110), although citalopram trended toward being superior to paroxetine (mean difference: 0.2, p = 0.055). For efficacy-tolerability models, citalopram and fluoxetine were superior to paroxetine (p = 0.029 and p = 0.022, respectively) but did not differ between each other (p = 0.146). Conclusions: Joint efficacy-tolerability models suggest that citalopram and fluoxetine were statistically significantly superior to paroxetine while citalopram trended toward superiority over paroxetine in the efficacy model. These findings provide a more granular and practical evidence base for clinicians faced with treatment sequencing decisions in adolescents with SSRI-resistant depression.

Original languageEnglish (US)
Pages (from-to)250-255
Number of pages6
JournalJournal of Child and Adolescent Psychopharmacology
Volume29
Issue number4
DOIs
StatePublished - May 1 2019

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Paroxetine
Citalopram
Major Depressive Disorder
Serotonin Uptake Inhibitors
Fluoxetine
Treatment-Resistant Depressive Disorder
Joints
Depression
Therapeutics

Keywords

  • depression
  • fluoxetine
  • major depressive disorder
  • paroxetine
  • sertraline

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

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title = "Switching Selective Serotonin Reuptake Inhibitors in Adolescents with Selective Serotonin Reuptake Inhibitor-Resistant Major Depressive Disorder: Balancing Tolerability and Efficacy",
abstract = "To guide clinicians in selecting the {"}next line{"} selective serotonin reuptake inhibitor (SSRI) for adolescents with treatment-resistant major depressive disorder, we sought to compare response rates among SSRIs in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study and to jointly model tolerability and efficacy for the specific SSRI comparisons. Methods: Efficacy and tolerability data for paroxetine, citalopram, and fluoxetine were extracted from the TORDIA study. Using a joint bivariate normal likelihood for response and tolerability (based on the maximum implied variance from the 95{\%} credible intervals previously reported for the three SSRIs), a Monte Carlo pseudorandom sample (100,000 draws) was obtained, from which credible intervals, means, posterior tail probabilities, etc. were determined. Joint null hypotheses of no difference in efficacy and tolerability were then evaluated with regard to superiority of each SSRI over the others. Results: No significant differences in response were observed for citalopram compared with fluoxetine (p = 0.247) or for fluoxetine compared with paroxetine (p = 0.110), although citalopram trended toward being superior to paroxetine (mean difference: 0.2, p = 0.055). For efficacy-tolerability models, citalopram and fluoxetine were superior to paroxetine (p = 0.029 and p = 0.022, respectively) but did not differ between each other (p = 0.146). Conclusions: Joint efficacy-tolerability models suggest that citalopram and fluoxetine were statistically significantly superior to paroxetine while citalopram trended toward superiority over paroxetine in the efficacy model. These findings provide a more granular and practical evidence base for clinicians faced with treatment sequencing decisions in adolescents with SSRI-resistant depression.",
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author = "Strawn, {Jeffrey R.} and Mills, {Jeffrey A.} and Croarkin, {Paul E}",
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T1 - Switching Selective Serotonin Reuptake Inhibitors in Adolescents with Selective Serotonin Reuptake Inhibitor-Resistant Major Depressive Disorder

T2 - Balancing Tolerability and Efficacy

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AU - Mills, Jeffrey A.

AU - Croarkin, Paul E

PY - 2019/5/1

Y1 - 2019/5/1

N2 - To guide clinicians in selecting the "next line" selective serotonin reuptake inhibitor (SSRI) for adolescents with treatment-resistant major depressive disorder, we sought to compare response rates among SSRIs in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study and to jointly model tolerability and efficacy for the specific SSRI comparisons. Methods: Efficacy and tolerability data for paroxetine, citalopram, and fluoxetine were extracted from the TORDIA study. Using a joint bivariate normal likelihood for response and tolerability (based on the maximum implied variance from the 95% credible intervals previously reported for the three SSRIs), a Monte Carlo pseudorandom sample (100,000 draws) was obtained, from which credible intervals, means, posterior tail probabilities, etc. were determined. Joint null hypotheses of no difference in efficacy and tolerability were then evaluated with regard to superiority of each SSRI over the others. Results: No significant differences in response were observed for citalopram compared with fluoxetine (p = 0.247) or for fluoxetine compared with paroxetine (p = 0.110), although citalopram trended toward being superior to paroxetine (mean difference: 0.2, p = 0.055). For efficacy-tolerability models, citalopram and fluoxetine were superior to paroxetine (p = 0.029 and p = 0.022, respectively) but did not differ between each other (p = 0.146). Conclusions: Joint efficacy-tolerability models suggest that citalopram and fluoxetine were statistically significantly superior to paroxetine while citalopram trended toward superiority over paroxetine in the efficacy model. These findings provide a more granular and practical evidence base for clinicians faced with treatment sequencing decisions in adolescents with SSRI-resistant depression.

AB - To guide clinicians in selecting the "next line" selective serotonin reuptake inhibitor (SSRI) for adolescents with treatment-resistant major depressive disorder, we sought to compare response rates among SSRIs in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study and to jointly model tolerability and efficacy for the specific SSRI comparisons. Methods: Efficacy and tolerability data for paroxetine, citalopram, and fluoxetine were extracted from the TORDIA study. Using a joint bivariate normal likelihood for response and tolerability (based on the maximum implied variance from the 95% credible intervals previously reported for the three SSRIs), a Monte Carlo pseudorandom sample (100,000 draws) was obtained, from which credible intervals, means, posterior tail probabilities, etc. were determined. Joint null hypotheses of no difference in efficacy and tolerability were then evaluated with regard to superiority of each SSRI over the others. Results: No significant differences in response were observed for citalopram compared with fluoxetine (p = 0.247) or for fluoxetine compared with paroxetine (p = 0.110), although citalopram trended toward being superior to paroxetine (mean difference: 0.2, p = 0.055). For efficacy-tolerability models, citalopram and fluoxetine were superior to paroxetine (p = 0.029 and p = 0.022, respectively) but did not differ between each other (p = 0.146). Conclusions: Joint efficacy-tolerability models suggest that citalopram and fluoxetine were statistically significantly superior to paroxetine while citalopram trended toward superiority over paroxetine in the efficacy model. These findings provide a more granular and practical evidence base for clinicians faced with treatment sequencing decisions in adolescents with SSRI-resistant depression.

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