How does one begin to approach Synecdoche, New York, first-time director Charlie Kaufman’s tortured and often brilliant tale of an artist paralyzed by his insecurities and haunted by opportunities missed?

It’s not so much that his film defies description as that none could adequately prepare you for the experience of watching it, which is at once agonizing, infuriating and profoundly baffling. Kaufman’s existential musings on life, death and the pursuit of love are sometimes messy and maddeningly self-indulgent, stuffed into a sprawling, surreal narrative that unfolds like a dream, but they are also heartfelt, painfully honest and wickedly funny.

If that makes Synecdoche sound like a contradiction of sorts, you’re starting to get the picture. The story of Caden Cotard (Philip Seymour Hoffman, at his most achingly melancholy) is a work of abstract expressionism that erases the line between life and art, plunging its ineffectual hero into an increasingly epic dramatization of his own unhappy existence. Caden is a frustrated theater director trapped in a loveless marriage to Adele, a painter so precise in her artistic vision that her miniscule portraits must be viewed through a jeweler’s loupe.

Catherine Keener, so often cast as a hard-hearted emasculator, plays Adele, whose icy dismissal of Caden seems cruel but inevitable. She is an urban socialite marooned in downscale Schenectady, N.Y., starved for passion and adventure. Caden is hopelessly mired in depression, convinced of his impending death and lost in his art. His latest production, an avant-garde take on “Death of a Salesman,” is met with rave reviews, but Caden wants to do something bigger, broader and decidedly imprecise, a play about “death, birth, life…everything.”

Adele takes their 4-year-old daughter, Olive (Sadie Goldstein), and heads to Berlin for the art exhibit that will make her an overnight sensation. She never returns, leaving Caden to make good on his casual flirtations with Hazel (Samantha Morton), the vivacious ticket taker at the community theater where he works. Hazel, with her wild red curls and sweetly seductive smile, is the perfect cure for Caden’s loneliness, but for the fact that he’s impotent to act on her advances. She moves on.

Caden wins a MacArthur “genius” grant, moves to New York and begins work on the production that will consume the rest of his days, an all-encompassing recreation of his own universe that, if properly rendered, will reflect every last nuance of the human comedy. It’s a massive endeavor, as Caden casts, recasts and casts again all the key players in his real-life drama – Adele, Hazel and a second wife (Michelle Williams), who tolerates his navel-gazing far longer than any woman should – until art and reality become hopelessly intertwined.

Caden shares a series of unrewarding romances with the actresses he hires to play Hazel, always chasing the one who got away. But as whole decades slip away, with his production drifting into self-parody and his ever-expanding cast rehearsing for an opening night that will never come, he begins to see a certain hopelessness in the struggle to make sense of it all. He wants to understand love and loss, to invest his art with the wisdom of life experience, but how can he? He’s spent so much time living in an elaborate fantasy world that the real one seems a distant memory.

There is a bleak undercurrent to Synecdoche (pronounced “si-nek-duh-kee”), as we follow Caden from the dissolution of his first marriage to his dying breath and realize that there’s no end to the pain, the confusion and the constant longing for things we can’t have. Kaufman seems to suggest that Caden’s journey is no different from anyone else’s, that nobody is special in the end. Maybe so, but what a mournful world it would be if everyone’s struggles were as self-consuming as Caden’s.

Kaufman, who previously wrote Being John Malkovich, Adaptation and Eternal Sunshine of the Spotless Mind, is capable of being hilariously funny, and though Synecdoche is sometimes too joyless for its own good – the downside to contemplating human futility, I suppose – it is also filled with moments of surprising humor. That Kaufman can explore the gloomy absurdities of Caden’s Job-like quest for fulfillment and relieve the sadness with laughter is one of the film’s real strengths.

At just over two hours, Synecdoche is dense and burdened with more ideas than it can possibly accommodate, as if Kaufman gave in to every creative whim in his desire to hit all the notes in his register. Still, it’s hard to argue with the result. His directorial debut may be flawed, but it remains a startlingly original, tirelessly ambitious contemplation of life, with all its bitter defeats and frustrated hopes.