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.

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. 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. Accessed April 18, 2018.

Post-Partum Depression Symptoms & Checklist: Psychiatric help in NYC

Dr. Saidi Post-partum Depression

In the first weeks to months after giving birth, many women experience feelings of sadness intermingled with the joy of having a new baby. Huge adjustments must be made quickly to adapt to the new life in your home and it is often a stressful period—especially for first time mothers. The effects of prolonged sleep deprivation do not help matters.

However, if symptoms of depression become apparent and linger after giving birth, something more serious might be occurring—you may be experiencing Post-Partum Depression (PPD). PPD occurs in about 13% of women, is a major cause of maternal and infant mortality, and can affect infant development. Many women who suffer from PPD frequently feel embarrassed or ashamed for not being able to leap into motherhood with all of the joy and enthusiasm that the rest of the world expects them to immediately have.

There are many reasons why PPD may occur, but the primary one appears to be a sudden d

rop in estrogen and progesterone hormone levels after childbirth. Also, a drop in thyroid hormones can deepen symptoms by causing fatigue, and, paired with changes in physical appearance brought on by pregnancy, feelings of depression can worsen. It is important to keep in mind that it can take weeks—sometimes even months—after the birth, for PPD to fully develop. In about 10% of cases PPD begins during pregnancy.

So how do you know if you are experiencing PPD, and not merely adjusting to yo

ur new baby? Here are some symptoms for you to look out for:

Post-Partum Depression Symptoms

  • Swinging between restlessness and extreme fatigue
  • Tearfulness, depressed feelings, and a sense of worthlessness
  • An increase in indecisiveness and an inability to retain focus
  • Increased anxiety caused by thoughts of harming one’s child (either accidentally or intentionally)
  • Insomnia
  • Changes in appetite
  • Extreme mood swings
  • A lack of motivation

If you are suffering from the above symptoms, it is important to remember that you are dealing with legitimate physical changes and issues that far surpass what are commonly referred to as “baby blues.”

Thanks to a variety ofcelebrities—including Courteney Cox, Gwyneth Paltrow and Marie Osmond—speaking publicly and openly about their own problems with PPD, there is now a wider understanding of the condition. Brooke Shields even wrote a book on the subject, Down Came the Rain: My Journey Through Postpartum Depression, which has proved helpful to thousands of women who felt they were alone in this condition.

So what should you do if you are experiencing PPD? The good news is that for many women the condition subsides within three months of giving birth. But any woman experiencing symptoms for longer than a two-week period should consult with a physician (e.g., psychiatry, primary care, obstetrics/gynecology, or pediatrics), who can help her decide if further treatment is needed. This may involve medications, psychotherapy, or both.

Symptoms can worsen over time if left untreated, so it is important to seek help as soon as you realize, or even suspect that, you are suffering from PPD. First and foremost, remember: you are not alone in experiencing this condition and asking for help is the first step on the road to healing.


Stowe ZN et al. The onset of postpartum depression: Implications for clinical screening in obstetrical and primary care. Am J Obstet Gynecol 2005 Feb; 192:522-6.

Dennis C-L et al. Effect of peer support on prevention of postnatal depression among high risk women: Multisite randomised controlled trial. BMJ 2009 Jan 15; 3


Guintivano J et al. Antenatal prediction of postpartum depression with blood DNA methylation biomarkers. Mol Psychiatry 2013 May 21; [e-pub ahead of print].

Insomnia and Depression: 7 ways to treat Insomnia

Dr. Saidi Depression, Insomnia

insomnia-depression-treatmentIt is well known that depression can result in sleep problems. But can sleep problems cause depression? Although most of us realize that poor sleep can result in daytime fatigue and irritability, scientific studies have provided evidence that insomnia can cause clinical depression. So there appears to be a bidirectional association between the two: each increases the risk for the other, even when controlling for factors such as lifestyle, demographics, and anxiety level. This is why it is important to screen for and treat insomnia in those that show signs of depression. Early treatment of sleep problems may prevent or mitigate a depressive episode.

How do we treat sleep? There is a wide assortment of drugs available for treating insomnia which I will discuss in a later blog, but for now I will mention some of the simple steps we can take to treat insomnia on our own without medications.

7 Tips to Treat Insomnia

  1. Go to sleep and rise at about the same time every day, including weekends. The mind and body rely on and adapt well to this consistent cycle.
  2. Minimize stimulation. Keep the bedroom as dark as possible and minimize ambient noise (use earplugs if needed, turn off the TV or music).
  3. Use the bed only for sleep or sex.
  4. If you wake up in the middle of the night and can’t fall back to sleep within five minutes, leave the bed and go to another room or seat to read until sleepy.
  5. Avoid meals at least three hours before sleep.
  6. Don’t use alcohol as a sleep aid. Alcohol may help you fall asleep initially, but it distorts your sleep architecture and ultimately robs you of the refreshing process your brain needs.
  7. Find a mantra to help you fall asleep. You’ve probably heard of “counting sheep.” However, a more functional and successful version is to think of non-stimulating topics that interest you, such as a song lyric or a movie plot. My favorite technique is based on mindfulness meditation: pay attention to the feeling, sound, and rhythm of your breathing and gently redirect your mind back to that each time it veers off to another thought.

Doing all of the above on a consistent and prolonged basis will significantly decrease the odds of having a sleep problem.


Sivertsen B et al. The bidirectional association between depression and insomnia: the HUNT study. Psychosom Med 2012 Sep; 74:758.