Considering it's once weekly, tolerance would decrease significantly back towards baseline - ketamine is 99% eliminated in 21 hours (7 half-lives). iirc the mechanism is BDNF expression and reverting neuron energy metabolism conditions - one could potentially speak of the antidepressant effect of exercise also increasing in tolerance via that mechanism, but what I know about what we know so far makes it seem like it is worth the decrease in anhedonic/depressive symptoms.
The other options are pretty much worse, although more common:
- a daily SSRI (thus increases tolerance much faster), and has a larger range of significant side effects, such as anorgasmia, increased depression or emergence of suicidal tendencies, weight gain, "electric zaps"/spontaneous muscle spasm/discontinuation syndrome for months after cessation, dulled affect, increased proclivity towards serotonin syndrome
The other options are pretty much worse, although more common:
- a daily SSRI (thus increases tolerance much faster), and has a larger range of significant side effects, such as anorgasmia, increased depression or emergence of suicidal tendencies, weight gain, "electric zaps"/spontaneous muscle spasm/discontinuation syndrome for months after cessation, dulled affect, increased proclivity towards serotonin syndrome
- leaving depression untreated