Increasing / Optimizing the Antidepressant Dose

If the patient is not yet responding, and if the maximum is not yet reached, consider increasing / optimizing the dosage, up to the recommended maximum dosage.

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


Consider an evidence-based psychotherapy (CBT, IPT or PST) as an augmentation strategy instead of medication.

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

Step 1. Choose either:
  • Mirtazapine 30 mg po qhs x 2 weeks. If less than 20% response, consider increasing to 45 mg po qhs, or
  • 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
  • Aripiprazole 2 mg po daily x 2 weeks. If less than 20% response increase to 5 mg po daily, or
  • Quetiapine XR 50 mg po at supper x 1 week, then increase to 100 mg x 1 week and if tolerated then increase it to150 mg po q supper. If less than 20% response after 2 weeks then increase to 300 mg po q supper


If a trial of a medication is not working, then consider switching from the current antidepressant class to a different antidepressant class. (Note however, evidence for this strategy is limited.)

If you decide to switch from one medication to another, this switching guide from may be helpful.