Question

What would you do next?

Discontinue the bupropion-XL as it has been dose maximized and is not being tolerated, and change to a more classic antidepressant in another class such as a TCA or an MAOI

Change to another novel antidepressant in another class such as trazodone (Desyrel/Oleptro) or nefazodone (Serzone), vilazodone (Viibryd), vortioxetine (Brintellix)

Lower the bupropion-XL to a dose where diaphoresis is alleviated and augment with an antiepileptic or mood stabilizer such as lamotrigine (Lamictal) or gabapentin (Neurontin)

Augment with an atypical antipsychotic such as aripiprazole (Abilify), quetiapine-XR (Seroquel-XR), lurasidone (Latuda)

Augment with lithium or thyroid hormone

Attending physician’s mental notes: interim follow-up visits through seven months

Patient has now failed SSRI, SNRI, NaSSA, NDRI antidepressant trials and CBT

His prognosis for full depressive remission seems poorer

Discussions around changing the class of medication to an MAOI, or augmenting with an atypical antipsychotic, or use of ECT are held

Case outcome: interim follow-up visits through 24 months

MAOI is selected by the patient based on balance of efficacy and tolerability

• – Prefers less risk of movement disorder and metabolic syndrome

• – Feels he can be safe with diet and drug interactions

Titrated on the selegiline transdermal patch (Emsam 6 mg/d initially and then to 9 mg/d), to which there is a 30% improvement at best

• – Unfortunately develops an allergic glue reaction (contact dermatitis) to the patch and it is discontinued, and the MAOI washed out over two weeks

Changing to a new MAOI would require a two-week washout, and use of another MAOI might limit future augmentation strategies

Other available MAOIs appear to have greater side-effect burden with regard to sedation, orthostasis, weight gain, and sexual dysfunction

• – Next choice is an atypical antipsychotic augmentation as he is afraid of the washout period again needed for a new MAOI

He also requires a new approved antidepressant monotherapy

• – He is titrated onto venlafaxine-XR (Effexor-XR) SNRI therapy and also onto quetiapine (Seroquel) atypical antipsychotic as an augmentation therapy in a CIT strategy

  • Doses reach 300 mg/d and 400 mg/d, respectively

  • He tolerates these well without issue and finally gains a 50% response in his symptoms, which is his best to date

• – Able to lower alprazolam anxiolytic dose as he is calmer and sleeping better

• – He is still not in remission

Next, there is failure to remit with

• – L-methylfolate (Deplin) augmentation

• – Modafinil (Provigil) augmentation

• – Intolerability to d-amphetamine (Dexedrine) augmentation

Begins couples counseling and chooses to officially retire early, which lowers social stress

• – For the latter, he does not have to confront his performance anxiety and these symptoms are mitigated

• – He begins working out at a gym routinely, which restores some self-esteem

• – He is about 60% improved in MDD symptoms

• – His generalized anxiety-type symptoms resolve

Case debrief

Two-thirds of patients have TRD

Treatment resistance in this case appeared to be low initially as the patient had a clear stressor induce his first, and only, MDE

However, his anxiety and fear of failure and performance seemed to increase his pharmacological treatment resistance, where he failed to respond to SSRI, SNRI, NDRI, NaSSA, and MAOI treatments, as well as several augmentations

He was also resistant to a trial of CBT and marital therapy

He finally achieved a sustained response, but not remission, on an SNRI plus an atypical antipsychotic and a BZ

Dynamically, he lowered his stress by finally deciding to take a financial loss, by retiring early, which also contributed to symptom reduction

This way, much of his anxiety about the future and guilt about his past was no longer relevant