How to Approach Poor Response to Antidepressants  

What defines Treatment Resistant Depression (TRD)

Stage 1: more than one adequate trial of 1 major class of antidepressants 

Stage 2: Failure of more than 2 adequate trials of two different classes of antidepressants 

Stage 3: stage 2 + TCA 

Stage 4: Stage 3 + MAOI 

Stage 5: Stage 4 + bilateral ECT 

With every medication or neuromodulation procedure used that doesn’t work, the more treatment resistant the depression becomes. 

Antidepressant Response Rates 

Frist Medication Trial: 50% respond and 37% have remission 

Second Medication Trial: Another 29% respond and 31% have remission 

Third Medication Trial: 17% respond and 14% have remission

Fourth Medication Trial: 16% respond and 13% have remission 

The overall cumulative remission rates are 67%, keeping in mind that people who progressed through more treatment stages had higher relapse rates and more residual symptoms including anhedonia, emotional blunting, and lack of motivation.

If someone is having a poor response to medication, what do you do?

We know that bipolar disorder is missed in a significant number of patients who present with depression about one in five will be misdiagnosed. We also know that antidepressants can be mood destabilizing in bipolar illness resulting in mixed features and rapid cycling. Other things that can interfere with response include substance use disorder, personality traits, and PTSD. 

Medical Comorbidities that can interfere with antidepressant response include hypothyroidism, Cushing disease, Parkinson’s disease, cancer, vitamin/nutritional deficiencies, and viral infections 

Psychosocial factors that contribute to treatment resistance 

-Female sex 

-Older Age 

-Single Unmarried (happiness studies indicate that good relationships are very important) 

-Unemployment 

Symptoms that make TRD more Likely 

-Recurrent episodes usually 3 or more 

-Severe depression and inpatient admission 

-Anxiety, Insomnia, or Migraine 

When Your First Choice Fails

There are several approaches

-Switch antidepressant classes 

-Combine antidepressants 

-Add a dopamine blocking medication

-Add L-methylfolate 

-Add Psychotherapy 

-Start Neuromodulation 

What’s the most effective strategy

Hands down the most effective thing to do if a patient has a poor response to the initial antidepressant treatment is to add a dopamine blocking medication. Response and remission rates are much higher, but it comes at the price of increased side effect potential. 

What are the most used Dopamine Blockers in Antidepressant Augmentation

-Quetiapine 

-Olanzapine

-Risperidone 

-Aripiprazole 

-Ziprasidone 

Older patients 65 years and older respond better to aripiprazole augmentation than switch to bupropion, or combination with bupropion. 

Brexpiprazole: 1-3 mg/day Adjunctive for Depression 

Most Common Concerns patients have about being on dopamine Blocking Medication 

-Weight gain 60% of people report this concern 

-Metabolic side effects 

-EPS

-Sedation 

-Akathisia 

-Prolactin-related Effects 

Anti-Inflammatory Medications 

For those with elevated inflammatory biomarkers specifically c-reactive protein there is some emerging evidence that these treatments work. 

-Medications like Celecoxib, Omega-3 fatty acids, statin drugs and minocycline 

-Weight loss 

-Effect Size: 0.55 

-Higher response and remission rates 

-May only work in those with high inflammatory biomarkers 

Glutamate Modulators 

-Ketamine Infusions and Esketamine: both work and a reasonable option if TRD 

-There are several medications in development 

Psychotherapy in TRD

Unfortunately, what we find with TRD is psychotherapy does not prevent TRD, it doesn’t mean there is no benefit it just means future episodes will not be prevented by psychotherapy. On its own, psychotherapy may not be as helpful as we would like in TRD but when combined with medication it does help. That tells us about the importance of evaluating severity of depressive episode.

Jonah Hill’s Netflix Doc: ‘Stutz” 

Recently Jonah Hill celebrated the gift of therapy with his Netflix documentary ‘Stutz’ which chronicles his journey through therapy and his friendship with Phil Stutz co-author of The Tools. This film was intended to highlight the benefits of psychotherapy and celebrate the teachings of Dr. Stutz. Personally, I think the documentary was low on practical advice for the average person, but it did highlight one very important factor that affects therapy outcomes. That will be the topic of today’s video, can we have a therapist who is also our friend?

Therapeutic Alliance and Why It’s so Important 

This documentary raises many questions for someone who has been in both roles as therapist and patient. Time and time again we see that the most important factor in psychotherapy outcomes is the strength of the therapeutic alliance. The therapeutic alliance is a working relationship between the patient and their therapist that allows them to work together on established goals of therapy. 

To me this comes down to how much do you like, trust, and feel comfortable opening up to the therapist. When we like someone and feel-good talking to them, we feel better regardless of what type of therapeutic techniques they use. Research has suggested that the quality of this relationship is a reliable predictor of positive clinical outcomes independent of the psychotherapy approach used. I remember in training hearing many of my psychotherapy preceptors make similar statements. Jonah Hill did a wonderful job of demonstrating the power of this alliance throughout the film. For me this was the big takeaway, considering Stutz is not a traditional psychotherapist.

Having a Therapist as Your Friend

I do not believe it’s ever a good idea to become friends with a patient. There are reasons we do not accepts gifts from patients, hangout with them outside of the assigned appointment times, or have romantic relationships. These to me are boundary crossings which will interfere with the work. Yes, in the case of this film it all worked out fine, at least that’s what they want you to believe. It did not appear that Hill had fully come to terms with his past, or unstable self image. He still seemed vulnerable and is possibly worse off as he’s come to depend on the relationship with Stutz for relief.

The goal of any good therapist should to teach our patients to become their own therapist. To use and apply the skills learned in the work of therapy, not to come for some friendly advice or a chat like old college buddies. The therapist is there to help guide the work in a warm empathetic way that allows the patient to take control of their life.

What Makes Stutz a Good Therapist?

It’s very difficult to make a blanket statement about how good Stutz is as a therapist. For Hill, he helped him process some very difficult work including making peace with his brother’s untimely death and working on self-esteem and body image. Stutz is honest, warm, and empathetic during his encounters. He knows how to push sensitive buttons in a playful manner and can establish a strong therapeutic alliance. These are things any aspiring psychotherapist can and should learn to use.

Some Things That Are Not So Good

When you start psychotherapy with any patient you must establish a therapeutic framework where the work of psychotherapy will be carried out. While I believe there is a loose framework established in the film it doesn’t appear to be well developed. This opens the door for boundary crossing which you as the therapist might not be aware is occurring because the frame is so weak. He also relies on self-developed Tools that aren’t validated by scientific evidence and appears at times as an authority figure giving out life advice. Advice can be useful in supportive psychotherapy, but most patients will not follow advice alone. Is this entirely bad? No, but it might not work for most patients unless you share the same feelings for the therapist as Hill does. 

Therapist Reputation and Outcomes 

Sometimes a therapist will develop a reputation as being “good.” Clearly, in celebrity circles Stutz has that reputation. When a new patient comes there is a belief that this therapist has access to special knowledge or skills that cannot be had any other way is already established. I do not think the tools as presented in the book/film are groundbreaking or things people have not heard before. In the film Stutz words are seen as absolute truth and there is full buy in from Hill which is probably why he felt better. While his tools are developed from his clinical practice, they are not validated scientifically. In place of science, we have a charismatic therapist asking for full faith in a program with no scientific validity. For some this approach clearly works, but it’s not because the tools are any better than other techniques used in psychotherapy. 

Final Thoughts

I really Like Stutz and I do believe there are people that would benefit from his approach to therapy. However, the main benefit would not come from the tools he teaches because they are largely similar to other techniques and not scientifically validated. What you would benefit from in this brand of therapy is a warm, emphatic, and charismatic listener with some good advice if you’re willing to take it. After all, maybe that is really where the magic of therapy comes from anyway.

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