Tachyphylaxis is the continued or repeated exposure to a drug that may lead to a weakened pharmacological response. This thought to be due to diminished receptor sensitivity in response to the persistent stimulation by an agonist drug, which produces a diminished pharmacological response.

The pathophysiology of tachyphylaxis is distinct from tolerance. The desensitization process from tachyphylaxis can be due to a decrease in the number of receptors or an attenuation of the response because the drug has promoted neurotransmitter release in excess of presynaptic production. The presence of certain enzymes can limit cyclic AMP-based signalling, disrupt second messenger systems, and diminish the availability of receptors at the cell membrane.

Antidepressant tachyphylaxis (also known as antidepressant tolerance, “poop-out,” or “breakthrough depression“) describes a condition in which a depressed patient loses a previously effective antidepressant treatment response despite staying on the same drug and dosage for maintenance treatment.[1][2]