The actor checked out of rehab early against doctors' advice and his wife, Rose Murphy Stahl, and family are worried about him.
"He's been missing for four days," Rose told E! News on Monday. "But I don't want to comment any further."
Nick, 32, was last seen in downtown Los Angeles last week after checking out of rehab.
"Now he's disappeared. We can't find him anywhere. He has not made contact with anyone. We are all just desperately looking for him," a source told E!.
"Everyone just wants him to come home. It's a terrible situation. We are searching, but we've had no solid leads."
The first time Nick went missing, Rose feared the worst saying, "He could have overdosed, that's one thought. And I'm wondering if there will be a body recovered."
The couple, married since 2009, have a two-year-old daughter. Rose had recently requested the court bar Nick from seeing the little girl without first taking a blood test to prove he was drug-free.
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