Treatment-Resistant Depression (TRD)

Dr. Saidi Depression, Treatment-Resistant Depression

Overview: What is Treatment-Resistant Depression?

Treatment-Resistant Depression

About one-third of people with major depression will respond to the first prescription antidepressant. In the remainder of cases, depressive symptoms may continue despite treatment, and is referred to as treatment-resistant depression (TRD). A person is labeled to have TRD when the symptoms fail to respond to at least two trials with separate classes of antidepressants.

How is TRD treated?

The flip side with TRD is that it can be misdiagnosed when instead there was simply a problem with either medication compliance or appropriate dosing. (1)

The initial steps are, therefore, to confirm or rule out TRD are:

1. Assess compliance with medication

You and your doctor should review the manner in which you are taking the medicine. Are you taking it every day (if so prescribed)? Should you be taking it with meals? Are you taking any other medications, supplements, or substances (e.g. alcohol) that can significantly interact with the absorption and metabolism of your medication?

2. Maximize the current antidepressant dose

Another factor that may lead to a false TRD label is that your doctor may not have tried the antidepressants at their maximum recommended doses and/or for the maximum duration. Hence, the next step will be to check and increase the dose of the antidepressant if required.

3. Check for any other illness

There is also a possibility that you have some other unaddressed medical or psychiatric illness that may be making the depression more resistant to treatment.

Next Steps for TRD

After confirming that you have TRD, your doctor may have to do a few trials to find the therapy that best works for you.

Your doctor may:

4. Switch your current medication to a different antidepressant

Your doctor may switch within the same antidepressant class such as switching from one SSRI (selective serotonin reuptake inhibitor) to another, or switch between classes (e.g., change from an SSRI to a non-SSRI antidepressant like mirtazapine, bupropion or venlafaxine.

The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study showed that switching the current antidepressant citalopram, an SSRI, to other antidepressants resulted in remission (disappearance) of symptoms in about one-fourth of the depressed individuals. (2)

5. Add a non-SSRI antidepressant to the current medication

If you’re on an SSRI currently, your doctor may use an antidepressant from a different class as an add-on treatment. Studies show that combination therapies may be more effective against TRD symptoms than the switching approach. (3, 4)

When combined, some non-SSRIs may work better than others such as:

  • bupropion (which is a norepinephrine dopamine reuptake inhibitor) may be effective against TRD symptoms and is frequently used to counter some SSRI-associated side effects such as decreased libido or erectile problems. (5)
  • combining mirtazapine (a non-SSRI antidepressant) with an SSRI or another non-SSRI antidepressant may also benefit TRD (4, 6)

6. Add other forms of treatment to the current medication(s), such as psychotherapy

Combining the antidepressant switch approach with psychotherapy, in particular, cognitive-behavioral therapy (CBT) provides greater benefit against TRD when compared to switching medications alone. (7)

7. Add an antipsychotic to the current medication(s)

Your doctor will weigh the risks and benefits of adding an antipsychotic as an augmenting agent. Studies show that using an antipsychotic like aripiprazole (Abilify) as an add-on treatment may help achieve a recovery from TRD faster. (8, 9)

8. Add medicines not approved by the FDA for TRD

A non–FDA-approved formulation of ketamine named esketamine, when sprayed into the nose, shows a rapid and sustained response in TRD. It also seems to address possible suicidal thoughts during a severe depressive episode. (10) This club-drug derivative is superior to the conventional antidepressant pills that take longer to show their effects and fail to cease the suicidal thoughts in the immediate depressive crisis.

9. ECT (Electroconvulsive Therapy), VNS (vagal nerve stimulation), and rTMS (repetitive transcranial magnetic stimulation)

These neurostimulative modalities are being employed more readily as data regarding their efficacy build. Nonetheless, they are typically used when medication treatment, as described above, fail to achieve a significant response.

For more information about Treatment-Resistant Depression, please contact Dr. Sina Saidi, MD.

References
1. Al-Harbi KS. Treatment-resistant depression: therapeutic trends, challenges, and future directions.
Patient preference and adherence. 2012;6:369-388. doi:10.2147/PPA.S29716.
2. Rush AJ, Trivedi MH, Wisniewski SR et al. Bupropion-SR, sertraline, or venlafaxine-XR after failure of
SSRIs for depression. New England Journal of Medicine. 2006 23;354(12):1231-42.
3. Lam RW, Hossie H, Solomons K, Yatham LN. Citalopram and bupropion-SR: combining versus
switching in patients with treatment-resistant depression. J Clin Psychiatry. 2004;65(3):337-40.
4. Blier P, Gobbi G, Turcotte JE et al. Mirtazapine and paroxetine in major depression: a comparison of monotherapy versus their combination from treatment initiation. European Neuropsychopharmacology. 2009;19(7):457-65.
5. Ionescu DF, Rosenbaum JF, Alpert JE. Pharmacological approaches to the challenge of treatment-resistant depression. Dialogues in Clinical Neuroscience. 2015;17(2):111-126.
6. Rush AJ. Combining antidepressant medications: a good idea? The American Journal of Psychiatry. 2010;167(3):241-3.
7. Zhou X, Michael KD, Liu Y, et al. Systematic review of management for treatment-resistant depression in adolescents. BMC Psychiatry. 2014;14:340. doi:10.1186/s12888-014-0340-6.
8. Fava M. Lessons Learned From the VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) Study. JAMA. 2017;318(2):126–128. doi:10.1001/jama.2017.8030.
9. Mohamed S, Johnson GR, Vertrees JE et al. The VA augmentation and switching treatments for improving depression outcomes (VAST-D) study: Rationale and design considerations. Psychiatry Research. 2015;229(3):760-70.
10. clinicaltrials.gov A Double-Blind Study to Assess the Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicide Ideation, in Participants Who Are Assessed to Be at Imminent Risk For Suicide. NCT02133001. https://clinicaltrials.gov/ct2/show/NCT02133001. Accessed April 18, 2018.