General synonyms:
* Weakening
* Debilitating
* Exhausting
* Draining
* Sap (verb)
* Depleting
* Lethargic (adjective, describing the effect)
* Prostrating
* Tire
More specific synonyms:
* Exhaustive: emphasizing the use of all energy and resources.
* Dispiriting: emphasizing the emotional effect, causing a loss of spirit.
* Crippling: emphasizing a severe debilitating effect.
* Devitalizing: emphasizing a loss of vitality and life force.
* Enervating: (this one emphasizes a loss of energy and strength, often due to heat or illness)
The best synonym to use will depend on the specific situation and the nuances of the desired meaning.