Antidepressants often don't work well enough. In fact, only about a third of people taking any given medication for depression will get complete relief.
When the first drug a doctor tries fails to completely relieve symptoms, there are three options:
- Switch to a new medication
- Add a second drug that acts in a different way
- Add psychotherapy to drug treatment
The second and third options are called "augmentation" strategies. They are especially good to try if you've only gotten partial relief from an antidepressant drug.
No two depressions are alike, so it is impossible to make one recommendation that is best for everyone. Therefore, it makes sense for you and your doctor to keep trying treatments.
If you are taking an antidepressant, but haven't yet tried talk therapy, consider adding this option. A large study called the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) found that both psychotherapy and drugs are about equally effective as augmentation strategies.
About one-third of patients who had not previously responded to treatment with an antidepressant medication were as likely to improve with cognitive behavioral therapy (CBT) as they were with the addition of a second medication.
CBT is the most studied psychotherapy, but it is not the only type to consider. Your primary care doctor may be able to help you with a referral to a good therapist in your area. Psychotherapy takes more time and effort, but there is some evidence that the positive effects are longer lasting.
Add a Second Drug
Augmenting an antidepressant with a second drug involves finding one with a different mechanism of action than the first. The reason is to target different brain pathways at the same time in the hope of providing symptom relief.
Bupropion – This drug affects uptake of the neurotransmitters norepinephrine and dopamine. It's often used to augment drugs such as selective serotonin reuptake inhibitors (SSRI) that act primarily on serotonin. Bupropion is also sometimes prescribed to counter sexual side effects of SSRIs. One possible drawback: Bupropion may cause tremor when combined with an SSRI or serotonin norepinephrine reuptake inhibitors (SNRI).
Buspirone – Among other actions, this anti-anxiety drug is a partial trigger of serotonin receptors, so it affects serotonin pathways differently from SSRIs. Randomized controlled trials have produced mixed results about this drug's efficacy at augmenting antidepressants.
Mirtazapine – Mirtazapine (Remeron), which increases the release of the neurotransmitter norepinephrine, tends to counter SSRI-related side effects such as anxiety and sexual dysfunction. A disadvantage of mirtazapine augmentation is that this drug may cause weight gain and sedation.
Antipsychotics – A number of medications in this class have been used for augmentation: aripiprazole (Abilify), extended-release quetiapine (Seroquel), olanzapine (Zyprexa), risperidone (Risperdal) and ziprasidone (Geodon). It is not clear how these drugs work to complement antidepressant medications. But because they affect neurotransmitter systems in a variety of ways, they may help the anxiety and agitation that are often part of depression. The side effects can be significant. They include weight gain, metabolic syndrome (a combination of risk factors that affect heart health), and extrapyramidal symptoms (such as muscle spasms and restlessness).
T3 thyroid hormone – This hormone is essential to proper regulation of mood. Over all, T3 thyroid hormone has a good side effect profile compared with other augmenting agents. However, with long-term use, this hormone may worsen cardiac arrhythmias or cause bone loss.
Lithium – The mechanism of action of this mood stabilizer is still not well known. It appears to interact with several neurotransmitter systems and modulates the functioning of nerve cells in helpful ways. A disadvantage to lithium augmentation is that it requires frequent blood tests to monitor lithium levels. That's because there is a small difference between a therapeutic dose and a dangerous dose that could damage vital organs.