Charlie Kaufman’s Anomalisa — somber, heartbreaking, darkly funny, deeply weird — may do a number on you. The screenwriter of Eternal Sunshine of the Spotless Mind and Adaptation hasn’t directed a movie since 2008’s Synechdoche, New York, and some of us have missed his cinematic examinations of massive self-involvement. His newest, a stop-motion animated feature co-directed by Duke Johnson, is all about depression, loss and the struggle to find human connection.

In outline, it sounds deceptively simple. Michael Stone, a middle-aged motivational speaker and best-selling British author on the subject of customer service (voiced perfectly by David Thewlis), checks into a Midwest hotel, the Al Fregoli, where he is set to deliver a keynote conference address. He’s so tired, bored and disconnected that everyone he meets appears to have the same voice, the same face. (A nice touch, that hotel name. Those who suffer from the Fregoli delusion believe that different people are, in fact, the same person in disguise.)

Unsatisfied with his marriage and life, he calls an old lover and, on an excruciatingly awkward reunion date at the hotel bar, says things aloud like, “There is something wrong with me.“ Losing it by the second, Michael blunders into a new relationship with conference attendee, a slightly disfigured, insecure and not especially bright groupie (Jennifer Jason Leigh, just great) who is pretty much thrilled just to be breathing the same air as he does. For a night, Michael feels almost alive again and babbles about leaving his wife and young son and, while he’s saying it aloud, he even seems to believe it. Lisa certainly thinks he means it — at least, to a point.

You might want to hate Michael, but his wishes to be bigger, to feel more, to find transcendence are too sad, too universal. His ache is palpable; his actions — toilet habits, sexual technique, a visit to an all-night sex toy store — are joyless and repetitive. The pace of the movie feels like a despondent slog, as if everything were happening underwater. And things get alarmingly surreal and nightmarish as the characters’ essential isolation becomes stunningly obvious.

Very few movies exert the emotional tug and pain of Anomalisa. It’s almost a relief that the whole thing is done with puppets. Otherwise, it might be unbearable.