5 Stage Method for Treatment Resistant Depression (TRD)

I get a lot of questions that go something like this, I’ve been on X, Y, Z medications and nothing seems to help. It seems that what most are asking about is what is the algorithm for treating depression and when does it become treatment resistant. This video will provide a look at what treatment resistant depression is and provides a 5-stage strategy to medication selection.  

Psychotropics: Acamprosate For Alcohol Use Disorder

I received a question asking me to discuss acamprosate as a medication and specifically to address any evidence to support its use to reduce urges to self-harm. I did the research, and this is what I found. 

The Only Medication Proven to Reduce Suicide

As a psychiatry trainee you will never forget that the two medications that reduce suicide are lithium and clozapine. In the case of clozapine, it has been shown in RCTs to reduce suicidal thoughts but not necessarily completed suicides. Lithium on the other hand has RCT data that indicates it reduces suicidal thoughts as well as completed suicide.

Lithium has anti-suicidal effects even at low doses. Lithium’s anti-suicidal effects are beneficial for both unipolar and bipolar depression. Unlike standard antidepressants that can increase the risk of suicide specifically in younger patients under the age 24, lithium has a prophylactic effect to prevent suicide. 

While lithium overdoses can be fatal, this outcome is less likely given the anti-suicidal properties of this medication. We should not avoid prescribing it for this reason. 

Psychiatrists Are More Than Just Prescribers

Introduction:

I get a lot of comments that go something like this “All psychiatrists do is prescribe medications.” Naturally, people are shocked when I talk about nutritional psychiatry, lifestyle modification, or the value of psychotherapy. I cover a lot of medication information on social media because there is significant confusion, misinformation, and a general benefit for patients to know more about the medications they routinely use. 

While medication management is a substantial portion of the work most psychiatrists do it’s not the only things we do. 

Psychotherapy

Most psychiatrists are well trained in at least one type of psychotherapy. The most common ones include cognitive behavioral therapy, interpersonal therapy, and motivational interviewing. Some are trained extensively in psychoanalysis which usually requires a 5-year commitment and engagement in psychoanalysis as a patient.

Procedures

Many psychiatrists offer procedure-based interventions such as electroconvulsive therapy (ECT), and trans cranial magnetic stimulation (TMS). We may also consult on cases of vagus nerve stimulation or deep brain stimulation used to treat severe depression. 

Neurological Disorders

As a psychiatrist you are trained to handle some of the common neurological disorders (e.g. migraine). One third of our board examination is focused on neurological disease. In rural parts of the United States sometimes there is no one else to treat these disorders and the responsibility falls to psychiatry. 

Medical Disorders

Most psychiatrists can treat things like hypertension or hypothyroidism. Many make the choice not to if the patient has a primary care physician. Like the treatment of neurological disorders sometimes there is no choice, and a psychiatrist will need to treat the medical condition. 

Social Work

Not everyone is lucky enough to have designated social workers so they can focus exclusively on the treatment of patients. We all know how important social determinates of mental health are, and sometimes altering these circumstances is the responsibility of the psychiatrist. 

New medication Monday: Combination Dextromethorphan and Bupropion AXS-05

The result of research to develop a nonaddictive cough suppressant produced dextromethorphan. It was FDA approved in 1954 but the pharmacology of this cough suppressant is complex. It functions as an uncompetitive NMDA-glutamate blocker (thin ketamine), sigma-1 stimulator, and serotonin reuptake inhibitor. It should start to become clear why there is renewed interest in this medication. 

Bupropion functions as a selective norepinephrine/dopmaine reuptake inhibitor. It’s currently used to treat depression, seasonal affective disorder, and nicotine dependence. Recent research suggests it acts as a potent inhibitor of cytochrome P450 2D6 (CYP2D6). Understanding the cytochrome P450 system is not a primary concern here but this enzyme metabolizes dextromethorphan. 

The combination of these two drugs dextromethorphan 45 mg and bupropion 105 mg two times per day is AXS-05. The proposed mechanism is prolongation of dextromethorphan activity by CYP2D6 inhibition with the added benefit of norepinephrine/dopamine reuptake inhibition. 

A phase-3 RCT of AXS-05 in patients with MDD outperformed placebo and improved depression scores over 6 weeks. 

Schizoaffective Disorder: A Confusing Diagnosis

Introduction: 

  • Schizoaffective disorder has features of both schizophrenia and mood disorders (bipolar and depression). 
  • Two sub types: depressed type and bipolar type 
  • The diagnosis can get complicated because primary mood disorders can have psychotic features (MMD with psychotic features or bipolar disorder with psychotic features), patients with schizophrenia can have mood symptom most commonly depression. 

Epidemiology:

  • The lifetime prevalence is less than 1%, the most recent data indicates 0.3% but I would say there is a range between 0.5-0.8%
  • More women have the depressed type greater than 2:1 ratio 
  • Equal number of men and women have the bipolar type 
  • The cause of schizoaffective disorder is unknown. It may be a type of schizophrenia, a type of mood disorder, but most likely it’s a spectrum that combines all these things.
  • Schizoaffective disorder has a better prognosis than schizophrenia but a worse prognosis than primary mood disorders. 
  • Patients are said to have a nondeteriorating course and respond better to lithium than patients with schizophrenia. 

Diagnosis:

  • Schizoaffective disorder combines the features of both schizophrenia and affective mood disorders. 
  • If the mood is primarily manic, it’s called schizoaffective disorder bipolar type 
  • If the mood is primarily depressed it’s called depressed type 
  • The mood component should be present for the majority > 50% of the total illness 
  • You must have a two-week period where psychotic symptoms and are present in the absence of mood symptoms

Treatment:

  • Treatment will depend on the predominant symptoms. If the patient has more mania than a mood stabilizer will be used (e.g., lithium) 
  • For psychotic symptoms, dopamine blocking medications will be used (e.g., risperidone) 
  • For depressive symptoms serotonin reuptake inhibitors will be used (e.g., sertraline)

Why Psychiatrists do not Wear White Coats

I trained in a location where white coats were never worn by psychiatrists. I only wore mine during the professional photos on the first day of residency. From that point forward it remained in my closet. 

The choice to discard the white coat always made sense to me, because I believe one of the most healing aspects of psychiatry is the physician patient relationship. One way to enhance that relationship is to make my patients feel as comfortable as possible. There is a concept in primary care called “white coat hypertension” where some patients have increased blood pressure only when coming to see their doctor. In psychiatry you can imagine a similar scenario. Some patients experience severe anxiety prior to the initial encounter. Others have had previous bad experiences with psychiatrists making them more prone to this “white coat syndrome.”

My goal is to have a meaningful conversation with my patients, and some of the material we discuss is very sensitive. There is no reason to make that conversation any more intimidating than it already is. Everything from my style of interviewing, to dress is meant to be casual to help establish trust. Trust is an important foundation for any relationship and is critical for any physician patient relationship. 

I detached myself long ago from white coats as a symbol of knowledge or prestige. I trust in my skills as a physician and allow those skills to speak for themselves. 

Grounding Technique For Anxiety

Anxiety is something most of us have experienced. This five-step exercise can be helpful during periods of anxiety by helping to ground you in the present moment. 

Start the exercise by drawing attention to your breathing. Slow, deep, breaths can help you induce a feeling of relaxation. Once you feel relaxed, go through the following steps to ground yourself: 

One: Note ONE thing you can taste

Examples may include: gum, sugar free candy, coffee, sparkling water (anything you can taste in the moment). 

Two: Note TWO things you can smell 

Examples may include: fresh air, scented candle, flowers, food cooking (anything around you that you can smell)

Three: Note THREE things you can hear 

Examples may Include: people talking, cars driving, wind blowing, rain falling (anything in the environment you can hear) 

Four: Note FOUR things you can touch 

Examples may Include: desk, chair, pen, phone (anything around you that you can touch) 

Five: Note FIVE things you can see 

Examples may include: door, computer screen, car, tree, house (anything you see around you)

Intramuscular Medication (IM) in Psychiatry: Is it Better?

Intramuscular medication as the name implies is a long-acting injectable form of medication that is usually administered into the gluteal muscle or deltoid muscle and it’s designed to take the place of PO or oral formulations.

The medications available in IM formulations

  • Aripiprazole (Abilify Maintena) 
  • Aripiprazole lauroxil (Aristada) 
  • Fluphenazine (prolixin)
  • Haloperidol (Haldol)
  • Olanzapine pamoate (Zyprexa Relprevv) 
  • Paliperidone (Invega Sustenna, Invega Trinza) 
  • Risperidone (Risperdal Consta) 

Most last between 2-4 weeks but medications like Invega trinza lasts up to 3 months 

This solves one of the major issues when prescribing medication, which is adherence with treatment. 

Notice that all these medications are first- or second-generation dopamine blockers. These medications are commonly used to treat disorder like Bipolar and Schizophrenia (serious mental illness). These populations often have difficulty with medication adherence. 

Clinically most psychiatrists will tell you IM medication improves patient outcomes. However, they may not outperform PO medication taken daily and consistently. Where these medication formulations have the biggest impact is for people who had improvement on oral medication but often forget to take medication or do not want to take medication daily. Many patients with serious mental illness stop taking medication when symptoms resolve making relapse likely. 

Side effects will be similar to the oral medication with the added logistical issue of coming to the office for the injection, and pain at the injection site. Normally we assess tolerability and risk of side effects with oral medication before giving IM medication. This avoids the potential for long lasting side effects. 

Olanzapine (Zyprexa) Without the Weight Gain

While Olanzapine is an effective medication, it’s side effect profile can be nasty. Things like weight gain, changes in blood lipids, and changes in blood glucose are common. ALKS 3831 attempts to fix this problem by adding Samidorphan to olanzapine to reduce weight gain.

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