IN HIS SCREENPLAYS for Being John Malkovich, Eternal Sunshine of the Spotless Mind, and Adaptation, Charlie Kaufman demonstrated two things: that he's fond of exploring themes of identity, memory, romantic love, and self-loathing; and that his own un-spotless mind is a fevered, neurotic wonderland.

Kaufman's latest, Anomalisa, isn't a departure from any of that. Its most obvious distinction—that it was filmed with lifelike puppets and stop-motion animation instead of live actors—is an ingenious and necessary component of the story, not an oddball aesthetic choice (or not just an oddball aesthetic choice, anyway). After the tragically under-seen Synecdoche, New York, this is only the second film that Kaufman has directed himself, and it has a similar heartrending poignance that resonates far longer than its comedic elements.

This is the story of Michael Stone (voiced by David Thewlis), a depressed businessman who's in Cincinnati for one night to give a presentation about customer service. (He's an expert on the subject, having authored such books as How May I Help You Help Them?) As he endures mundane, banal conversations with the taxi driver, the hotel clerk, the bellhop, we realize that all of their voices are the same (provided by Tom Noonan). When he calls his wife to have a conversation that should be more meaningful than the ones he has with strangers, we notice the same thing.

This is why the film had to be animated: From Michael's point of view, everyone besides him has the same voice. It holds true even for old movies he watches on TV. This is what life is like for him, an endless series of pointless interactions with people who all blend together and might as well be one person.

That is, until he meets Lisa. Her voice is different. (To be specific, it's the voice of Jennifer Jason Leigh.) She and her friend Emily are attending Michael's conference and are a bit star-struck to meet him in the hotel. Emily flirts with Michael, but timid, reluctant Lisa is the one he wants. Emily is just another Tom Noonan in a world full of Tom Noonans. Lisa is special.

Kaufman (who co-directed with animator Duke Johnson) uses the central metaphor to great effect, showing how the giddy excitement of infatuation can make a person's flaws vanish. Lisa is vulnerable and usually overlooked by men ("Most people like Emily," she says simply), but that doesn't matter to Michael. Not right now, anyway. But an encounter with an ex-girlfriend shows how oblivious he can be to other people's feelings, so wrapped up is he in his own melancholia.

There are sporadic bursts of caustic and surreal humor, often from out of nowhere, as if Kaufman can't help being funny even when he's trying to be serious. These light moments are welcome and occasionally sublime, but it's the heavier stuff that matters. As always, Kaufman isn't afraid to showcase a protagonist who's a total wreck of a human being, one whose breakdown we can watch with pity from a safe distance. The painstaking work of stop-motion animation is admirable (the sheer number of different facial expressions is staggering), but it's the story itself—hopeful, mournful, and sadly relatable—that will pierce your soul.