Section - Quick Takes

04. Is Pramipexole Effective for Treatment-Resistant Depression?

Published on January 1, 2026 Certification expiration date: January 1, 2029

Paul Zarkowski, M.D.

Clinical Associate Professor - University of Washington

Key Points

Pramipexole (0.375mg daily) showed superior efficacy over amantadine and quetiapine for treatment-resistant depression, achieving 50% remission rate. However, unclear baseline HAM-D criteria limit interpretation.
In the PAX-D study, pramipexole (2.3mg mean dose) achieved 44% response versus 16% placebo at 12 weeks. Benefits persisted through 48 weeks but 20% discontinued due to side effects versus 5% on placebo.
Screen for bipolar disorder, psychosis, and impulse control history before initiating pramipexole. Monitor for emerging dopaminergic side effects.

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Novel Mechanisms for Treatment-Resistant Depression

The key to the effective management of treatment-resistant depression is to trial medications with different mechanisms of action. But after three or four or five trials with inadequate response, the options with a different mechanism of action become limited. Thus, randomized clinical trials of medications with novel mechanisms of action are of particular interest.

Today, I’d like to discuss two recent studies exploring novel mechanisms for managing treatment-resistant depression (TRD). As clinicians, we know that finding effective treatments for TRD can be challenging, especially after multiple failed medication trials.

The first study, published in the Journal of Affective Disorders, compared pramipexole, amantadine, and quetiapine ER as augmentation strategies. The second, known as PAX-D, focused solely on pramipexole versus placebo.

JAD Study: Pramipexole vs. Amantadine vs. Quetiapine

The authors assessed the efficacy of pramipexole and amantadine. Pramipexole is a full dopamine agonist with much greater affinity

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05. Are Generic Drugs Truly Interchangeable With Originals?

Learning Objectives:
After completing this activity, the learner will be able to:

Apply plateau cross-titration strategies when switching between oral antipsychotics to minimize rebound phenomena and maintain therapeutic efficacy.
Identify older adults at risk for prolonged antipsychotic use after delirium.
Recognize the clinical presentation of xylazine intoxication.
Evaluate the evidence for pramipexole augmentation in treatment-resistant depression.
Differentiate between bioequivalence and clinical equivalence when switching CNS medications.

Original Release Date: January 01, 2026
Expiration Date: January 01, 2029

Experts: Oliver Freudenreich, M.D., Scott R. Beach, M.D., Paul Zarkowski, M.D. & David A. Gorelick, M.D., Ph.D., D.L.F.A.P.A., F.A.S.A.M. & Derick Vergne, M.D.
Medical Editors: Flavio Guzmán, M.D. & Sebastián Malleza M.D.

Relevant Financial Disclosures:
Oliver Freudenreich declares the following interests:
– Karuna: Research grant to institution, advisory board
– Vida: Consultant
– American Psychiatric Association: Consultant
– Medscape: Speaker
– Wolters-Kluwer: Royalties, editor
– National Council for Wellbeing: Consultant

All the relevant financial relationships listed above have been mitigated by Medical Academy and the Psychopharmacology Institute.

None of the other faculty, planners, and reviewers for this educational activity has relevant financial relationships to disclose during the last 24 months with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

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Complete the Post-Activity Evaluation to provide the necessary feedback for continuing accreditation purposes and for the development of future activities. NOTE: Completing the Post Activity Evaluation after the quiz is required to receive the earned credit.
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This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education through the joint providership of Medical Academy LLC and the Psychopharmacology Institute. Medical Academy is accredited by the ACCME to provide continuing medical education for physicians.

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Medical Academy designates this enduring activity for a maximum of 0.5 AMA PRA Category 1 credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.