# 21 - Management of treatment resistant depression # Management of treatment-resistant depression – other well- supported treatments Depression and anxiety disorders CHAPTER 3 Management of treatment-­resistant depression – other wellsupported treatments Less commonly used treatments for treatment-­resistant depression that are generally well supported by published literature are shown in Table 3.4. Table 3.4  Less commonly used treatments, well supported by published evidence (no preference implied by order). Treatment Advantages Disadvantages Add ketamine (0.5mg/kg IV over 40 minutes)1 Intranasal esketamine (licensed in most countries); dose is 28–84mg2 (see section on ketamine in this chapter) Oral ketamine (0.5–1.25mg/kg) effective but no licensed products3 ■ ■Very rapid response (within hours), including effects on suicidality4,5 ■ ■High remission rate6,7 ■ ■Some evidence of maintained response if repeated doses given8 ■ ■Usually well tolerated at this sub-­anaesthetic dose ■ ■IV needs to be administered in hospital ■ ■Cognitive effects (confusion, dissociation) and other psychiatric symptoms9 ■ ■Associated with transient increases in BP, tachycardia and arrhythmias. Pretreatment ECG required with IV form10 ■ ■Adverse effects may have been underestimated11 ■ ■Repeated treatment necessary to maintain effect Add lamotrigine (100mg, 200mg and 400mg a day have been used)12 ■ ■Reasonably well researched ■ ■Quite widely used ■ ■Probably the best tolerated augmentation strategy13 ■ ■Slow titration ■ ■Risk of rash ■ ■Optimal dosing unclear ECT14 ■ ■Well established ■ ■Effective ■ ■Well supported in the literature ■ ■Necessitates general anaesthetic ■ ■Needs specialist referral ■ ■Usually reserved for last-­line treatment or if rapid response needed ■ ■Usually combined with other treatments Add tri-­iodothyronine (20–50mcg/day) Higher doses have been safely used15–21 ■ ■Usually well tolerated ■ ■Good literature support22 ■ ■May be effective in bipolar depression ■ ■Clinical and biochemical TFT monitoring required ■ ■Needs specialist referral ■ ■Some negative studies ■ ■No advantage over antidepressant alone in non-­refractory illness23 TFT, thyroid function test.