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.  

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. 

Immediate Release Vs Extended-Release Formulations in Psychiatry

Highlights From the Video

Immediate release the medication is released immediately and results is quick onset and a peak blood level. This type of formulation is generally less expensive and may be advantageous in some cases. For example, if you are using quetiapine at night in part for its sedating effects, I will use immediate release because I want a rapid effect. The same with methylphenidate or bupropion. 

The problem is this formulation requires twice a day or even three times per day dosing and results in more peaks and troughs. In general, for medications that are being used for maintenance you want consistent blood levels and not peaks and troughs.

With IR formulations, there can be more side effects and addictive potential. We believe it’s the rapid rise in blood levels of the medication that cause side effects and with medications like amphetamines for ADHD it’s the rapid rise in medication levels that can result in euphoria and thus addictive potential.

Extended release does not change the active ingredient in the medication, rather it provides a different delivery mechanism that slows the release of medication over an extended period of time. This has the opposite effect on blood levels when compared to IR. There will be less peaks and troughs and more sustained blood levels of medication. The advantage is once daily dosing and potentially fewer side effects for the pervious mentioned reasons. 

The downside is these medications tend to cost more money and some have argued when initiating these medications, a patient who has an adverse reaction will have symptoms longer with XR. Although clinically I’m not sure this is true and will generally use extended release if possible for maintenance medications.

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