When More is Not Better
Understanding Augmentation vs. Switching
After a patient has failed to respond to a first-line antidepressant, the clinician faces a critical crossroads: should we switch to a new medication, or should we augment by adding a second one? This decision is one of the most consequential in psychiatric practice, and it’s based on a careful evaluation of the patient’s response so far.
Switching is the strategy used when the first medication has failed due to either intolerable side effects or a complete lack of efficacy. If a patient takes sertraline for 8 weeks, has no improvement in mood, and feels nauseated constantly, there is no reason to keep them on that drug. The doctor will typically “wash out” the medication (taper off) and start a new one from a different class or with a different mechanism of action. For example, they might switch from an SSRI to an SNRI or to bupropion. The goal of switching is to find a “clean” alternative that the patient can tolerate and respond to.
Augmentation is a different strategy. It is used when a patient has a partial response to a medication. Let’s say a patient is on escitalopram. They report that their mood has improved 30-40%. Their energy is better, and they’re not crying every day, but they still struggle with anhedonia (inability to feel pleasure) and obsessive rumination. In this case, the patient is tolerating the medication well and is getting some benefit. The doctor will likely not want to discard that partial benefit. Instead, they will “augment” by adding a second medication to boost the effects of the first.
Common augmentation strategies include:
Adding an atypical antipsychotic: Medications like aripiprazole (Abilify), brexpiprazole (Rexulti), or quetiapine (Seroquel) are FDA-approved for augmentation in treatment-resistant depression. At low doses, they modulate dopamine and serotonin in a way that can “supercharge” the antidepressant effect.
Adding lithium: Low-dose lithium (not the high doses used for bipolar disorder) is a powerful augmenting agent for unipolar depression. It has been shown to enhance the effects of antidepressants and reduce suicidal ideation.
Adding buspirone or bupropion: These are often added to an SSRI to either boost the anti-anxiety effect (buspirone) or to counter sexual side effects and fatigue (bupropion).
The choice between switching and augmenting is a nuanced one. Augmentation is often preferred when the patient is reluctant to give up a drug that has provided some relief, or when they have failed multiple other medications in the past (indicating they may be hard to treat). Switching is often preferred when side effects are intolerable or when the patient’s lack of response is total.
There is no universally correct path. Studies show both strategies are effective. The decision ultimately hinges on the patient’s history, the severity of the side effects, and the collaborative conversation between the doctor and the patient about their goals and preferences.