Clinical Switching Strategies of Various Antidepressants to Vortioxetine in the PREDDICT Trial

Int J Neuropsychopharmacol. 2021 Apr 21;24(4):314-321. doi: 10.1093/ijnp/pyaa092.


Background: Partial response to antidepressant medication as well as relapse and treatment resistance are common in major depressive disorder (MDD). Therefore, for most patients with MDD, there will be a need to consider changing antidepressant medication at some stage during the course of the illness. The PREDDICT study investigates the efficacy of augmenting vortioxetine with celecoxib.

Methods: We describe the method used in the PREDDICT study to change participants, who were already taking antidepressant medication at the time of the screening visit, to vortioxetine. We used a cross-titration to change study participants to vortioxetine.

Results: Of a total of 122 study participants who were randomized to receive vortioxetine plus celecoxib or vortioxetine plus placebo at the study baseline visit, 82 were taking antidepressant medication (other than vortioxetine) prior to randomization. These medications were selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, tricyclic antidepressants, mirtazapine, or agomelatine. Eighty of these 82 participants completed the changeover to vortioxetine as well as the study baseline visit. We found side effects were generally mild during this changeover period. In addition, there was a reduction in mean total Montgomery-Åsberg Depression Rating Scale score of 2.5 (SD 6.0) from study baseline to week 2 and a further reduction in mean total Montgomery-Åsberg Depression Rating Scale of 2.5 (SD 5.9) from week 2 to week 4.

Conclusion: Changing other antidepressants to vortioxetine can be done safely and was generally well-tolerated. However, there are some antidepressant classes, in particular monoamine oxidase inhibitors that require a washout period, which were not represented in this study.

Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR); ID number 12617000527369p;

Keywords: Major depressive disorder; cross-titration; side-effects; switching; vortioxetine.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / pharmacology*
  • Depressive Disorder, Major
  • Drug Substitution*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Vortioxetine / administration & dosage
  • Vortioxetine / adverse effects
  • Vortioxetine / pharmacology*
  • Young Adult


  • Antidepressive Agents
  • Vortioxetine