"We have to be realistic. For us it's now almost impossible to catch Juventus," said Spalletti after a morale-crushing defeat that left Roma seven points adrift in second place, with Juventus also having a game in hand.
Belgium midfielder Mertens was given the nod ahead of striker Arkadiusz Milik despite the Poland star's recent return from a five-month injury lay-off.
Nainggolan helps Roma stun Inter 3-1
And coach Maurizio Sarri's intuition to keep deploying the Belgian midfielder as his main striker was proved right during an end-to-end thrill-fest that saw Napoli soak up long spells of pressure before seeing Mertens punish Roma's leaky defence.
Napoli took a 1-0 lead into half-time at the Stadio Olimpico after Mertens struck against the run of play to flick the ball over onrushing Wojciech Szczesny on 26 minutes.
Mertens completed his brace, taking his league tally for the season to 18 goals, five minutes into the second half with another cool finish following Lorenzo Insigne's inswinger towards the back post.
Nainggolan rescues Roma after Dzeko penalty woe
When Kevin Strootman reduced the arrears on 89 minutes it sparked a dramatic late fightback from Roma that saw Pepe Reina acrobatically palm Diego Perotti's deflected drive off the crossbar before clearing with his leg.
But Napoli, who saw Sarri sent to the stands for dissent midway through the second period, held on for a valuable win.
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