Of course a busy schedule can disturb them in their energy balance in every game. These three certainly have a busy schedule because they have matches scheduled in the Champions League as well as several matches in local cup competitions. However, injuries often prevent a team from maintaining its best form, therefore we don't want to see their players injured this season. The fight for the title is more exciting if the team's strength is in perfect condition.
I think Napoli are still quite superior this season in defending the Scudetto trophy because they have a squad that has hardly changed drastically in this transfer window. So their mentality is still strong enough to provide a strong competition for their challenger team.
Indeed loss many important players, Napoli still strong team current last two matches in domestic league and keep in the winning trend, new manager Rudi Garcia still manage well with Napoli with consistent performance. I think when playing in Champion League group phase and Napoli have busy schedule matches its time to see how capacity from Rudi Garcia and Napoli will in the winning trend games or not. Last season with Spaletti, Napoli success winning Scudetto and Rudi Garcia must defend for becoming the winner in this season.
Champion League will start in few weeks later and Napoli has chance to be consistent in domestic league for few matches later, I think Napoli manager have to make their players keep fit and as possible they not get injured actually when group phase of Champion League will begin.