Areas › Low mood and hard feelings › When everything feels flat
If the usual antidepressants have not reached you, there are treatments that work on an entirely different system in the brain. They are worth asking about.
Esketamine, given as a nasal spray in a clinic, acts on glutamate rather than on serotonin or noradrenaline, and the change it brings can arrive in hours rather than weeks. It is for depression that has not responded to proper trials of the usual options, and it is given under supervision. The wider point holds even if this route is not for you: failing to respond to one family of treatments does not mean nothing will reach you.
Qur’an and Sunnah
Do not despair of God's mercy (Quran 39:53). It is addressed to people who believe they have ruined their own case, which is close to how a long run of failed treatments can feel.
۞قُلۡ يَٰعِبَادِيَ ٱلَّذِينَ أَسۡرَفُواْ عَلَىٰٓ أَنفُسِهِمۡ لَا تَقۡنَطُواْ مِن رَّحۡمَةِ ٱللَّهِۚ إِنَّ ٱللَّهَ يَغۡفِرُ ٱلذُّنُوبَ جَمِيعًاۚ إِنَّهُۥ هُوَ ٱلۡغَفُورُ ٱلرَّحِيمُ
Say, ‘[God says], My servants who have harmed yourselves by your own excess, do not despair of God’s mercy. God forgives all sins: He is truly the Most Forgiving, the Most Merciful
Qur’an 39:53read it in the library
Translation: M.A.S. Abdel Haleem, The Qur'an, Oxford University Press, 2004.
What the research says
A route that looks nothing like the standard one can still do the work. Across randomised trials, behavioural activation, which is the systematic return to meaningful activity, outperformed control conditions for depression and was as effective as full cognitive behavioural therapy. Unlike does not mean lesser.
Ekers, D.; Webster, L.; Van Straten, A.; Cuijpers, P.; Richards, D.; Gilbody, S. (2014). Behavioural Activation for Depression; An Update of Meta-Analysis of Effectiveness and Sub Group Analysis. PLoS ONE doi
BA comparable to full CBT protocols.
Strength of evidence: one line of research. A single study, or a theoretical account.
Why it works
A treatment working through a different system is not bound by what the first one could not do.
When not to
This is a supervised treatment for depression that has not responded to adequate trials of the usual options, not a next step to arrange for yourself.
This one is still a draft. It is waiting on a scholar and a clinician to read it before it is published.
Near this one
Ask why the tablets take weeks. That one question sorts the honest accounts of how they work from the tidy story about a chemical being low.
Stopping suddenly can bring lethargy, nausea, irritability and headache within a few days. That is discontinuation, not the illness coming back.
If you know something about a person's history that the prescriber may not, say it. A past eating disorder or a single seizure can change what is safe to prescribe.