Increase, Augment or Switch

Increasing / Optimizing the Antidepressant Dose

If the patient is not yet responding, and if the maximum is not yet reached, consider gradually increasing / optimizing the dose. If after 4 weeks of treatment there is no response consider switching rather than continuing to increase the dose according to 2023 CANMAT guidelines.

Note: Lower doses or less frequent dosage increase may be better for anxious or medically compromised patients.

Do not increase/maximize the antidepressant dose if:

• There are significant side effects or drug allergies
• Significant risk of drug interactions

Augmentation or Switching

Factors to consider in choosing between switching vs. augmenting:

According to 2016 CANMAT guidelines consider switching antidepressants when:

• it is the first antidepressant
• there are poorly tolerated side effects to the first antidepressant
• no response to (<25% improvement to the first antidepressant
• there is more time to wait for a response (less severe, less functional impairment)
• patient prefers to switch

CANMAT recommends considering adjunctive medication when:

• there have been 2 or more antidepressant trials
• the initial antidepressant is well tolerated
• there is a partial response (>25% improvement) to the initial antidepressant
• there are specific residual symptoms or side effects to the original antidepressant that can be targeted
• there is less time to wait for a response (more severe, more functional impairment)
• patient prefers to add on another medication

Augmentation

Consider an evidence-based psychotherapy as an augmentation strategy instead of medication.

• 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 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 with no risk factors for seizure  bupropion XL 150 mg po daily x 2 weeks. If less than 20% response and tolerating it, 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 starting at 1-2 mg p.o. daily. Titrate at more than 2 week intervals or longer in increments of 1-2 mg to a target dose range of 2-5 mg and a maximum dose of 10 mg

          OR

• for those sleeping poorly and who can tolerate weight gain quetiapine XR 50 mg po at supper x 1 week. If tolerated and not much improved increase by 50 mg per week to a target dose of 150 mg and a maximum dose of 300, as tolerated and as required. In more urgent situations the dose can be increased more quickly as follows:  50mg on Day 1, 100 mg on Day 2, 200mg on Day 3 and 300 mg on Day 4.
• 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
  • if remains on antipsychotic for more than one year check for tardive dyskinesia annually using the  Abnormal Involuntary Movement Scale AIMS.pdf

Switching

If considering switching CANMAT 2023 guidelines recommend switching to an antidepressant with evidence of superior efficacy (escitalopram, sertraline, paroxetine, vortioxetine, venlafaxine XR bupropion, or mirtazapine)

If you decide to switch from one medication to another please go to SwitchRx for assistance.

 For patients who do not respond to the above treatments please see the  Canadian Network for Mood and Anxiety Treatment (CANMAT) 2023 UPDATE for additional treatment strategies including other  augmentation options (e.g. with with ketamine) or using neuromodulation treatments (such as ECT or rTMS).

* 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