Mr O'Brien was speaking after the UN Security Council held an urgent meeting to discuss the crisis in the rebel-held town near Damascus.
Earlier, an aid convoy brought food to 40,000 town residents who have been under government siege for months.
The UN says it has received credible reports of people dying of starvation.
Monday's aid delivery was the first allowed into Madaya since mid-October, when the UN's World Food Programme took a month's supply of food rations for 20,000 people.
Simultaneously, aid lorries entered two towns besieged by rebel forces in the northern province of Idlib under a deal between the warring parties.
The situation in Foah and Kefraya is also said to be dire, with an estimated 20,000 people trapped there since March.
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