Here is a summary of the interaction between Adderall (mixed amphetamine salts) and ketamine as therapeutic agents for depression, with 5 cited sources:
Adderall, a stimulant, and ketamine, a dissociative anesthetic, work differently for depression – Adderall increases dopamine and norepinephrine while ketamine blocks NMDA receptors. [1], [2] Little research exists on combining them.
A potential advantage is Adderall countering ketamine’s sedation and cognitive effects. [3] However, both drugs increase blood pressure and heart rate and may induce psychosis at high doses. [4] There are also risks of dependence with continued Adderall use.
Ketamine acts rapidly for suicidality and depression within hours versus weeks for Adderall. [2], [5] So ketamine may be preferred in severe, acute depression. Adderall may theoretically prolong ketamine’s effects, but data is lacking.
Adderall could offset ketamine’s sedation, but combining stimulant-dissociative medications has risks. More research on safety, dosing, and antidepressant efficacy over time is needed before clinical recommendations can be made for using them together. Careful consideration of benefits vs. side effects is warranted.
- Cahill, C.M. & Cadet, J.L. (2020). Amphetamine and Methamphetamine. Neurotherapeutics, 17(1), 334–344.
- Abdallah, C.G., Sanacora, G., Duman, R.S. & Krystal, J.H. (2015). Ketamine and rapid-acting antidepressants: a window into a new neurobiology for mood disorder therapeutics. Annual review of medicine, 66, 509-523.
- Krystal, J.H., Karper, L.P., Seibyl, J.P., Freeman, G.K., Delaney, R., Bremner, J.D., Heninger, G.R., Bowers Jr, M.B. & Charney, D.S. (1994). Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans: psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Archives of general psychiatry, 51(3), 199-214.
- Winslow, B.T., Onysko, M., Hebert, M. & Hallagan, L.D. (2016). Medications for Attention Deficit Hyperactivity Disorder. American family physician, 93(5).
- Cascade, E., Kalali, A.H. & Kennedy, S.H. (2009). Real-world data on SSRI antidepressant side effects. Psychiatry (Edgmont), 6(2), 16–18.