Pramipexole in Treatment-Resistant Depression – Mechanism of Action and Prescribing Strategies

Posted on:February 17, 2020
Last Updated: November 24, 2023
Time to read: 9 minutes

The National Institute of Mental Health-sponsored Sequenced Treatment Alternatives to Relieve Depression (STAR*D) showed that approximately 30% of MDD patients exhibit a failed response to antidepressants or psychotherapy. [Rush et al. 2006]

  • The STAR*D trial is the largest real-world psychiatric clinical trial ever conducted and was designed to analyse the acute and long-term effect of sequential antidepressant treatment.
  • The response rate to standard antidepressant treatments is very poor, with only 10% of community-based patients exhibiting a 1-year response. [Dunner et al 2006]
  • TRD is the failure of 2 adequate dose-duration antidepressants from different classes and psychotherapeutic treatments either in combination or succession in the current episode. [Conway et al. 2017]

Although primary care physicians tend to follow antidepressant treatment guidelines, TRD is frequently undetected in the community with some patients undergoing up to eight antidepressant trials. In the STAR*D trial, it was shown that acute remission rates decreased from 37% to 31% to 14% with each adequate dose duration treatment. [Rush et al. 2006]

Learn More: RANZCP Guidelines for Depression

Primary care providers also find it difficult to distinguish unipolar depression from bipolar depression. [Hirschfield et al. 2005; Olfson et al. 2005]

The prevalence of bipolar disorder is relatively high in primary care settings and most patients are not engaged in specialist mental health care despite the clinical complexity and risk of self-harm. [Wang et al. 2005]

  • Accurate recognition of BD takes on average of 6–8 years between onset and diagnosis. [Wang et al. 2005]
  • The most common misdiagnosis is unipolar depression, with the real risk of antidepressant treatment worsening the disorder.  [Hirschfeld et al 2003]
  • Practice guidelines state that antidepressant monotherapy increases the risk of inducing a manic episode. [Pacchiarotti et al. 2013]


Learn More: Is it Unipolar or Bipolar Disorder?

Based on the time during which patients are symptomatic of depression, bipolar disorder is often conceptualised as a predominantly depressive disorder. As such, it is critically important to re-evaluate TRD patients for a history of manic or hypomanic episodes to determine whether there is a bipolar diathesis.