Pharmacological Treatment Algorithm for Treatment-Refractory Depression

These recommendations are based on the Maudsley Prescribing Guidelines 2018, according to which, depression is treatment refractory when it does not respond to sequential trials of three different antidepressants as recommended in their algorithms. 

In the first three steps below, we have enlisted the recommended pharmacological treatment options for an episode of depression. subsequently, we list the options for treatment-refractory depression. Maudsley Prescribing Guidelines focus on the pharmacological treatment options and algorithms, never nevertheless, they acknowledge the important role of non-pharmacological interventions in its treatment and recommend considering one of the appropriate options like cognitive behaviour therapy and/or behavioural activation and other factors identified as being responsible for resistance.

Step 1:

Recommend an SSRI or mirtazapine. monitor for signs and effects for 3- to 4 weeks. 

Step 2:

if no effects are appreciated, increase the dose, if appropriate (eg for escitalopram, sertraline etc) else, switch to another antidepressant (eg if the patient is on fluoxetine, where dose escalation does not produce any beneficial effects).  

Step 3:

Consider vortioxetine, agomelatine, or mirtazapine, if not already tried.

1. Vortioxetine
2. Agomelatine
3. Mirtazapine

Fourth line 

Augment with either lithium or low-dose quetiapine/aripiprazole, OR Combine mirtazapine (with SSRI or venlafaxine), bupropion (with SSRI), olanzapine (with fluoxetine)

(or first line for refractory depression):

Mnemonic: AV BLOQ

● Aripiprazole augmentation
● Venlafaxine (in combination with mirtazapine)
● Bupropion (+SSRI)
● Lithium augmentation
● Olanzapine and fluoxetine
● Quetiapine augmentation

Next

• Augment with anyone of an antipsychotic (risperidone), T3, buspirone, lamotrigine, OR
• Give Ketamine IV or intranasal esketamine, OR
• Start ECT, OR
• Give high-dose venlafaxine (above 200mg)