Treatment-Resistant Depression: A Closer Look at Four Augmentative Treatments
In the realm of mental health, finding effective treatments for those who suffer from treatment-resistant depression (TRD) is a priority. A recent systematic review and network meta-analysis published in the journal Journal of Affective Disorders by Itsuki Terao and colleagues has shed light on the comparative efficacy, tolerability, and acceptability of four very effective augmentative treatments for TRD: intravenous racemic ketamine, intranasal esketamine, aripiprazole, and lithium. This blog delves into the findings of this study, offering insights into how these treatments stack up against each other, their dosing, timing of use, potential side effects, and interactions with other medications.
Intravenous Racemic Ketamine
Efficacy and Acceptability: Intravenous racemic ketamine stands out for its significant effectiveness and acceptability compared to intranasal esketamine and aripiprazole. Its rapid onset of action and substantial antidepressant effects make it a promising option for TRD patients.
Dosing and Timing: Treatment typically involves six infusions over 12 days, although the exact regimen can vary based on individual response.
Side Effects and Interactions: While generally well-tolerated, potential side effects include dissociation and elevated blood pressure. Its interaction with other psychiatric medications is an area of ongoing research[4].
Intranasal Esketamine
Efficacy: Approved for TRD treatment, esketamine has shown benefits in both acute onset and ongoing treatment. However, it is less effective than racemic ketamine[2].
Dosing and Timing: Administered on a weekly or biweekly basis after an initial phase of twice-weekly administration.
Side Effects and Interactions: Common side effects include dissociative symptoms, nausea, and increased blood pressure. Its convenience as an intranasal spray does not mitigate these concerns[5].
Aripiprazole
Efficacy and Tolerability: As an augmentative treatment, aripiprazole has shown effectiveness in TRD. However, it is less tolerable than placebo, with side effects impacting its overall acceptability[1].
Dosing and Timing: The dosing regimen often starts low and is adjusted based on therapeutic response and tolerability.
Side Effects and Interactions: Side effects can include akathisia and weight gain. Aripiprazole can interact with other medications metabolized by the CYP2D6 and CYP3A4 pathways.
Lithium
Efficacy, Tolerability, and Acceptability: Lithium's efficacy, tolerability, and acceptability do not significantly differ from intravenous racemic ketamine, making it a viable option for some patients with TRD[1].
Dosing and Timing: Requires careful monitoring of blood levels to ensure therapeutic efficacy while minimizing toxicity.
Side Effects and Interactions: Potential side effects include tremor, cognitive effects, and thyroid dysfunction. Lithium can interact with NSAIDs, diuretics, and ACE inhibitors.
In conclusion, this research provides valuable insights into the comparative benefits and drawbacks of four augmentative treatments for TRD. For Dr. Danish and his team at Philadelphia Integrative Psychiatry, these findings support the importance of a personalized approach to treatment, considering the unique needs and circumstances of each patient. By staying informed on the latest research, practitioners can make educated and balanced decisions, optimizing care for those struggling with TRD.
For further reading on the efficacy and safety of ketamine and esketamine in unipolar and bipolar depression, please visit: https://pubmed.ncbi.nlm.nih.gov/37949235/
Citations:
[1] https://pubmed.ncbi.nlm.nih.gov/37949235/
[2] https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370%2823%2900304-8/fulltext
[3] https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1283733/full
[4] https://www.cambridgebiotherapies.com/research/ketamine-research/
