Exploring Options: Augmentation Strategies for Difficult-to-Treat Depression

If you’ve been taking an antidepressant for a while but still struggle with significant symptoms, you’re not alone. A recent large-scale analysis looked at what happens when people don’t improve enough on their current medication: Is it better to switch to a whole new antidepressant, or add a second medication instead? The findings suggest that adding (or “augmenting”) another medication can be a valuable option—often leading to better outcomes than swapping antidepressants outright.

Which Medications Were Studied?

Researchers focused on drugs commonly used as add-ons to standard antidepressants. The ones that showed clear benefits included certain antipsychotics (like aripiprazole and quetiapine), stimulants (such as lisdexamfetamine), and other agents like lithium, modafinil, and thyroid hormone (T3). These add-ons helped more people achieve meaningful relief compared to placebo. Interestingly, some medications widely believed to help, such as bupropion or buspirone, didn’t stand out as clearly in this particular analysis—though they remain viable options for many individuals.

Weighing Risks and Benefits

No single medication was dramatically superior, and all medications come with potential downsides. For example, some antipsychotics can cause sedation, weight changes, or restlessness, while stimulants may raise blood pressure or disrupt sleep. Lithium has unique benefits for mood stability but requires regular blood checks. Even with these concerns, the overall message is that augmentation can pay off when carefully chosen based on your personal situation.

Beyond Medication

This study looked only at pharmacological (medication-based) strategies, but there are many other ways to enhance treatment. Talk therapy, especially cognitive behavioral therapy or other evidence-based modalities, can be powerful in moving treatment-resistant depression forward. Lifestyle approaches—like consistent exercise, good sleep hygiene, or even nutritional supplements—may also help. And for some people, procedural interventions, such as transcranial magnetic stimulation or ECT, can offer additional relief.

Next Steps

If you’ve been on an antidepressant without feeling the improvement you’d hoped for, don’t lose heart. An “augmentation” approach could provide a new path toward better mood and functioning. In the end, no single strategy works for everyone. Work with your mental health provider to weigh benefits, side effects, and individual preferences. With thoughtful planning, you can find the right blend of treatments to help you move forward.