Understand the impulse to relate to people who have created great work while in private pain, but I think it is absolutely critical not to frame this in such shapeless modern terminology as "life is meaningless." https://twitter.com/bradleybirzer/status/1308162001064124416
Insofar as we dare to guess about his internal life, I would say his despair was a combination of alienation from and grief. There are indeed things much more painful and horrible than meaninglessness. It is watching everything you love perish, possibly without redemption.
He was a boy without a home, whose earliest life was marked by death, turmoil, and family rejection. Despite this he learned to love what he had been given, to study it with a clear mind. Then the war came and blew what fragile peace he had created to hell.
In later life he saw writing on the wall regarding Oxford and thus all education and thus reality itself; he saw the destruction by the car and Saruman's armies regarding the landscape he loved, which was from God; he saw what seemed the mauling of the language of faith.
He was a man marked by loneliness who couldn't rebuild his friendship with Lewis; able to create otherworldly beauty, he went his last decades through this world motivated mainly by duty and love of his family members, to chaperone them in a way he had not known.
It is difficult for me not to see that inner pain represented best by the resolution after the temptation of Galadriel: "I will diminish and go into the West." He was leaving a world where children would be punished for the sins of the Mordor their forebears built.
Yes, I think he was gravely bummed out sometimes and had to be hospitalized. Not because his life was meaningless, but because his very best work could not stop what was coming. A crisis of faith over suffering, not meaning.
If the crisis and the tension hadn't happened the work wouldn't have half the importance it does. It hurts to see good things destroyed. It breaks the heart to see lights go out. We summon all our faith just to read Beren's farewell song:
"Though all to ruin fell the world
and were dissolved and backward hurled
unmade into the old abyss,
yet were its making good, for this-
the dusk, the dawn, the earth, the sea-
that Lúthien for a time should be."

If Tolkien's heart wasn't breaking we wouldn't believe him.
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