Augmentation

Click here for psychotherapy resources (best evidence for CBT in augmentation)
Other non-medication augmentation options (second-line as per CANMAT 2023 guidelines) for moderate severity MDE include:
- exercise pdf
- light therapy pdf (note: indicated for nonseasonal MDE)
- adjunctive sleep hygiene and CBT-i
- adjunctive healthy diet including Mediterranean diet (third line recommendation)

If using a medication for augmentation, consider this two step process:

Step 1*

Choose:

for those with insomnia and who can tolerate weight gain consider mirtazapine 30 mg po qhs x 2 weeks. If less than 20% response and tolerating it, consider increasing to 45 mg po qhs, OR
for those without risk factors for seizures and who are lacking energy consider bupropion XL 150 mg po daily x 2 weeks. If less than 20% response, consider increase to 300 mg po daily**
If on either bupropion or mirtazapine as an initial agent, consider augmenting with an SSRI or SNRI

If Step 1 interventions are ineffective or not tolerated, then proceed to Step 2…

Step 2

Choose:

Aripiprazole 2 mg po daily x 2 weeks. If less than 20% response increase to 5 mg po daily, OR
for those sleeping poorly and who can tolerate weight gain quetiapine XR 50 mg po at supper x 1 week. If tolerated then increase it to 150 mg po q supper. If less than 20% response after 2 weeks and if tolerated then consider increase to 300 mg po q supperB
Brexpiprazole is also approved for augmentation and can be started at 0.5 mg po daily (or at night) and increased in increased in increments of 0.5 mg every 2 weeks, based on response an tolerance, to a maximum dose of 2.0 mg as required
Note:
- While on antipsychotics need to check lipids, fasting glucose or HbA1c and weight at baseline, at 3 months, and periodically thereafter
- If no response to antipsychotic augmentation we suggest tapering and removing the antipsychotic over several weeks to avoid unnecessary side effects
- If there is a good response to antipsychotic augmentation try to taper and remove the antipsychotic gradually after 6-9 months to avoid unnecessary side effects

* Note: CANMAT recommends antipsychotics as first line augmentation options but due to side effect profile we have recommended them as second line options.

** If adding bupropion to vortioxetine may need to decrease dose of vortioxetine