Depression is one the most complex mental health conditions with equally complex treatment. Psychotherapy and medications are the clinical treatments for depression, yet in approximately 10-30 percent of cases, traditional psychotherapy and/or antidepressants do not yield satisfactory improvement. The result? The conundrum of Treatment Resistant Depression (TRD). In these cases, psychiatrists may turn to an approach known as augmentation.
WHAT IS AUGMENTATION?
Essentially, augmentation refers to the practice of prescribing two or more medications to treat one single condition (also known as Combination Therapy). When single antidepressant medication proves ineffective in reducing symptoms, research supports the use of augmentation as a viable option. The Sequenced Treatment Alternatives to Relieve Depression study (STAR*D), enrolled more than 4,000 participants ages 18-75. The results showed that approximately one-third of patients who had not previously responded to treatment with the SSRI citalopram (Celexa) achieved remission of depressive symptoms after augmentation with bupropion (Wellbutrin) or buspirone (BuSpar)
The STAR*D study uncovered several more viable augmentation options. Lithium is a medication typically used to treat Bipolar disorder. It’s also frequently utilized in combination with antidepressants to combat TRD. In STAR*D, adding lithium or thyroid hormone to a current antidepressant helped a minority of patients (about 16–25% reached remission). A class of medications known as Atypical Antipsychotics is another evidence-based augmentation option. Four have been FDA approved as an adjunctive treatment for major depression: aripiprazole, quetiapine extended-release, brexpiprazole (2015) and cariprazine (2022). Lithium requires regular blood-level monitoring.
WHAT ARE THE RISKS OF MEDICATION AUGMENTATION?
Naturally, an important precaution when introducing more medications is the consideration of potential side-effects. Zhou and colleagues conducted a meta-analysis to assess which medications are most helpful and which produce unwanted side-effects.
The meta-analysis included data on nearly a dozen different augmentation options. Results showed that: Quetiapine, Aripiprazole, Thyroid Hormone, and Lithium were significantly better than placebo as augmenting treatments for depression. This study noted that quetiapine and aripiprazole were somewhat more effective than thyroid hormone and lithium.
SUPPLEMENTS
Another viable route for augmentation is in the form of natural supplements. Several supplement options have positive results in research studies for reducing depressive symptoms. Omega-3 fatty acids may help mood for some people. A 2012 study found that combining omega-3s with Citalopram, produced favorable results. Other supplements including creatine, SAMe, and l-methylfolate have shown benefit in some studies when added to an antidepressant. Supplements can interact with antidepressants (SAMe, for example, may add to serotonin effects, and high-dose fish oil can increase bleeding risk with blood thinners), so check with your clinician before starting, especially if you take psychiatric medication, are pregnant or breastfeeding.
Psychotherapy is also an important part of the treatment of treatment resistant depression. In addition there are a variety of non-medication and non-supplement treatments that can help with addressing depression symptoms, for example healthy nutrition, exercise, light therapy, mindfulness and a variety of mind-body approaches.
SHOULD I SEEK AUGMENTATION?
If your depression is severe and has not responded to traditional approaches, augmentation may be a good option. You will need to work with a skilled psychiatrist to manage this more complex medication regimen. Consider working with a practitioner who is experienced with integrative psychiatry as this can allow you to develop a comprehensive approach to addressing your health.
