Evidence Why Paroxetine Dose Escalation is Not Effective in Major Depressive Disorder: A Randomized Controlled Trial With Assessment of Serotonin Transporter Occupancy
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CONCLUSION:
Previous studies had failed to demonstrate a clinical benefit of dose escalation by SSRIs, but had methodological limitations (Ruhe et al, 2006; Adli et al, 2005; Baker et al, 2003). Addressing those limitations, our trial replicates that dose escalation of paroxetine above the 20 mg per day standard dose has no additional clinical benefit. As a novel extension, we revealed the underlying neurobiological mechanism for this inefficacy: maximum SERT occupancy was already reached with the standard dose. Similarly, high SERT occupancies reported with low doses of other SSRIs suggest that our conclusion may be applicable to the entire drug class. However, this does not exclude that dose escalation has clinical benefits for antidepressants with additional molecular targets, eg the norepinephrine transporter, such as venlafaxine. This drug has shown dose dependency of the clinical response in fixed dose studies (Thase et al, 2006; Rudolph et al, 1998).
If dose escalation is not promising for paroxetine and presumably other SSRIs, two clinical options remain for the treatment of nonresponders to standard doses. These are either continuation of treatment until 10 weeks while waiting for a potential delayed response, or a change to a different and potentially more effective treatment strategy.
Both strategies will further improve response rates, but studies directly comparing these strategies have not yet been performed.
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