During the trying period of the rehearsals for Dom Sébastien new and grave signs of Donizetti's physical deterioration became apparent. For a long time he had worked at a strenuous pace, but all through 1843 he labored practically without respite, against time one cannot help but feel. His inexorable disease was passing out of its relatively latent phase. Sometimes he would have lapses of memory and would become acutely embarrassed when they were called to his attention. Sometimes in mid-sentence he would lose track of his thought and stare in a queer, fixed manner. His temper would explode in sudden bursts of fury that would leave him shaken and confused. The Parisian music-publisher Léon Escudier recounts an episode during the rehearsals of Dom Sébastien when Stolz objected to standing around with nothing to do during Camoëns's offstage barcarolle of Act 5 and the management ordered the number to be cut in half, whereupon Donizetti's furious protests brought on some sort of seizure and he had to be helped home, barely able to stand. At first he seemed to recover from these alarming symptoms, but each new recurrence gravely troubled his friends.

He arrived in Vienna from Paris on 30 December 1843. Now he was taking digitalis on a doctor's prescription. His Viennese doctors prescribed baths and applications of boiling mustard to his neck. Although he tried to carry on his career, it was becoming increasingly apparent that his ability to concentrate was impaired.