The 33-year-old was diagnosed with a rare brain tumour last year, which threatened his eyesight, before immediately undergoing surgery and radiotherapy.
However, despite overcoming a life threatening health issue, it was a knee injury in 2013 whilst at Liverpool which he believes "was the worst time" of his life.
He left Anfield in 2016 and was forced to retire a year later with a recurring knee problem when spending one season at Real Zaragoza in his homeland.
"Even after this [tumour] I say that the time after the injury was the worst of my life," Enrique told The Times, who spent four years on Tyneside.
"Before the injury, I was at a good level. I still played some games after that (in September 2013) but my knee never felt right. We couldn't work out what was wrong.
"One day I would be training well with my team-mates, the next day, I couldn't train at all. It was so frustrating and I couldn't accept it.
"I couldn't handle the injury or the fact that, physically, I couldn't play at the same level any more."
Enrique, after starring for Newcastle in the club's 2009/10 Championship winning campaign and later featuring in standouts results over Sunderland and Arsenal, left United in 2011 for £6million.
Unfortunately for the Spaniard, he was unable to rediscover his form from St James's Park with a career on Merseyside blighted by injuries, all of which led to serious mental health issues.
He added: "Mentally, I was really bad. I had anxiety and panic attacks. You're thinking too much and worrying too much and it overwhelms you and you can't breathe.
"For a time, nobody knew except Amy. I didn't want to say anything because, as a man, you sometimes feel you can't. In the end I went to a psychiatrist.
"I took medication which helped, but this was a really difficult time. Physically, I was still in good shape but I felt really down, really weak, no energy.
"People don't realise how many players go through difficulties like this. Not just the names you know but a lot of other players who haven't said anything yet."
Enrique is currently living back in Valencia with his English wife Amy as he continues his recovery.