At what point during a drought does the despair of deprivation set in? I’d peg it at about seven years — or roughly how long it’s been since filmmaker Charlie Kaufman’s last intoxicating eat-me, drink-me exploration of existential ennui.

Synecdoche, New York, Kaufman’s combative, but indispensable, directorial debut from 2008, gained neither awards nor much in the way of box office. Thus began a frustrating period of funding that fell through on several fertile ideas (including a musical-comedy called Frank or Francis).

For Kaufman’s latest film, Anomalisa — a title of similarly playful semantics as Synecdoche — he and co-director Duke Johnson turned to Kickstarter backers. (An end-credits list includes Raphael Bob-Waksberg, creator of Netflix’s BoJack Horseman.) Theirs were most charitable donations, indeed.

Anomalisa is a stop-motion animation tale about a socially harried, unhappily married and prescription-medicated customer-service guru named Michael Stone (voiced by David Thewlis). Michael meets a woman named Lisa (Jennifer Jason Leigh) while on a business trip at a Cincinnati hotel. As they start to fall for each other, it’s clear Lisa will either deliver Michael from his world of insistent and persistent loneliness … or forever resign him to it.

This might sound like at worst a work of novelty animation or, at best, a novella of an idea for Kaufman to mark time until something meatier. Perhaps his spin on Up in the Air or Lost in Translation or, given Michael’s paranoia that society is conspiring to tear apart this presumably true love, The Adjustment Bureau.

To reveal too much more about Anomalisa would sour the delight of discovering its simultaneous beauties and horrors. But Kaufman and Johnson assuredly transcend surface quirks of mondegreens and mediums to deliver a film rife with rich, rewarding revelations about emotional insecurity, delusional envy and the myopia of loneliness — namely that it is only as pervasive as we persuade ourselves it is.

And as with most Kaufman films, revisiting Anomalisa deepens it in the most sophisticated ways — coloring in context and suggesting alternative interpretations while leaving some mysteries blissfully unexplained. (Other than verisimilitude, I remain baffled by the stop-motion version of the film My Man Godfrey Michael watches in his hotel.)

Take the opening scene, in which we track a plane through the clouds until it simply disappears behind one of them. Maybe it descended normally behind the cloud. Maybe the plane is plummeting toward a crash. Maybe it means nothing at all. Regardless, that’s not the plane Michael is on, as he begins his own normal descent into haughty impatience and social anxiety.

Michael makes a living delivering seminars based on his book, How May I Help You Help Them? — a book that seems to have universal success at raising customer satisfaction by 90%. In reality, he’s a prickly loner whose occupation seems to tab him as the ultimate fraud — a man peddling interaction while preferring isolation. Sorting through the best possible reintroductions to a once-close companion after 11 years of silence, Michael chooses a greeting so impersonal it sounds like a telemarketer with first-day jitters. Kaufman and Johnson go all in on his selfish, self-centered traits, but they also uncover the tragedy behind his emotional impotency: He is powerless to change his flaws, no matter how slowly and silently they may be killing him.

“Sometimes there’s no lesson, and that’s the lesson in and of itself,” Michael says late in the film, perhaps realizing his encounter with Lisa will only reinforce a horrible history he’s destined to repeat. Through his clipped British accent, Thewlis perfectly evokes Michael’s exasperation and desperation.

Despite her own lack of self-esteem, Lisa is comparatively effervescent — a customer-service representative in the food industry with a love of languages and Cyndi Lauper songs. Leigh’s vocal work here stands in delightful contrast to the diabolical criminal she portrays in The Hateful Eight. But we still question how much she’s truly revealing to Michael about herself rather than keying in on that in which he expresses even the slightest interest. It’s a deeply nuanced turn from Leigh, sounding both giddy and guarded in Lisa’s responses to Michael’s romantic guile, which is seductive to her while feeling a little bit sad to us. Note how the camera cuts to Michael’s face on a certain line of the song as Lisa sings “Girls Just Wanna Have Fun” for him; Kaufman finds a believably downbeat lament in an otherwise upbeat pop opus.

Kudos also to Tom Noonan, who, with just slight shifts in inflection and tone, transforms how you feel about a pivotal supporting character that occasionally turns up. He also warbles the film’s original song, “None of Them Are You,” a They Might Be Giants-ish tune that complements Carter Burwell’s melancholy score.

You might wonder what Anomalisa gains from stop-motion over live-action. There simply may be no better way to capture the sensation that Michael and Lisa are somehow outside of themselves — them, but not quite them — when acting on their most nervous impulses. They are both in this moment and removed from it, wonder and woe working against, and alongside, each other in the time they spend together.

And what a marvel of realistic imperfections their puppets are, with not only persuasive expressiveness, texture and color tone but believable paunches, scars and, uh, modestly scaled packages. For all the imaginative enormity that Laika films (Coraline, The Boxtrolls) bring to their stop-motion work, Johnson and Kaufman counter with almost-nightmarish claustrophobia to match the constricted emotions.

Anomalisa makes Michael and Lisa’s hotel feel like an inescapable labyrinth. The sound design is ominous and omniscient, with an oppressively loud din from fellow travelers and ceaseless rattles from the AC and ice machine as if they’re demanding souls. But it’s also a space in which to indulge Kaufman’s wicked sense of humor about the banalities and bothers of regular travel.

The inability to master an unfamiliar shower without first scalding your genitals then shocking them with cold water. The absurdity of confusing hotel-phone icons. The way a cabbie insists Michael follow his itinerary during downtime (specifically the chili and the “zoo-sized” zoo). Just like Michael, the service-industry folks serving him assert control, albeit in a way befitting comic relief. (My favorite: When a room-service rep reads back Michael’s order of “salmon and a salad” using the overly floral adjectives Michael purposefully skipped.)

Anomalisa works either as actuality or allegory, the latter much like a fairy tale without the moralizing; I will spoil nothing regarding that read other than to suggest paying attention to a certain voice in the third act and to Lisa’s phrasing when mentioning her favorite languages.

No matter how you interpret it, Kaufman’s latest exploration of the grace in our failings is a dizzying, disarming and dazzling movie about love and loneliness. Acridly funny, achingly resonant and meticulously constructed, it’s yet another a vital, complex masterwork from Kaufman and one of 2015’s very best films.