# 23 - Treatment resistant depression  other reporte

# Treatment-resistant depression – other reported treatments

Depression and anxiety disorders
CHAPTER 3
Treatment-­resistant depression – other reported treatments
A very wide range of treatments have been investigated as potential therapy for 
treatment-­resistant depression. Table 3.5 briefly describes strategies that have limited 
support for their use but may be worth trying in exceptional circumstances. Prescribers 
should familiarise themselves with the primary literature before using these strategies.
Table 3.5  Other reported treatments (alphabetical order – no preference implied).
Treatment*
Comments
Ayahuasca1
Effective but specialist use only
Buprenorphine2
0.8–2mg/day?
Reasonable evidence but obvious contraindications
Dexamethasone3,4
3–4 mg/day
Limited data
Dextromethorphan + quinidine5–7 
45/10mg twice a day
Promising novel treatment. NMDA antagonist. Quinidine is needed 
as CYP2D6 inhibitor to prolong action of dextromethorphan8
Folate/methyl folate9
Possible benefit
Hyoscine10,11
(scopolomine) (4mcg/kg IV)
Growing evidence base of prompt and sizeable effect
MAOI and TCA12–14
e.g. trimipramine and phenelzine
Formerly very widely used, but great care needed
Minocycline
200mg/day
Several positive meta-­analyses in both animals15 and humans.16,17 
Recent failed RCTs.18,19
Modafinil20
100–400mg/day
See section on stimulants in depression (this chapter)
Naltrexone21,22
100mg/day
No studies in non-­opiate misusers
Nitrous oxide23–25
Short-­lived effect
Nortriptyline ± lithium26–29
Re-­emergent treatment option
Oestrogens30
(various regimens)
Limited data
Omega–3-­triglycerides EPA31–33
Many failed trials. Therapeutic dose not defined.
Pindolol34–39
5mg three times a day or 7.5mg once daily
Well tolerated, can be initiated in primary care. Data mainly relate 
to acceleration of response. Refractory data somewhat 
contradictory.
Pramipexole40
0.125–5mg/day
Probably effective
Psilocybin41
10/25mg 1 week apart
Effective but specialist use only
Risperidone42
0.5–3mg/day to antidepressant
Good RCT support as add-­on treatment
S-­adenosyl-­l-­methionine43–45
400mg/day IM; 1600mg/day oral
Limited data in treatment-­resistant depression.
Use weakly supported by a Cochrane review.46
(Continued)