GURPS Magic has some hostile spells that can really mess you up long-term - Flesh to Stone,
The curse spell is just a mechanical way of inflicting a penalty until a sufficiently good roll is turned into a failure. It's a nice spell, but what if you want to inflict some specific harm on the victim in a way that isn't just a penalty?
In my post about revisiting the Charm Trio, I postulated the idea of a lasting version of Loyalty and Charm at x2.5 cost. Pay 2.5x and the spell, if it is successful and the victim fails to resist, lasts until removed by Remove Curse or other, appropriate magical reversal.
Here are some spells I think would be appropriate for this approach.
Strike Numb (and other Strike spells)
. . . and more.
Any spell that has a hostile effect of some kind, especially if it's not just a stat reduction, should warrant a look to see if it makes a good "curse."
Optionally, allow for a curse that cannot be removed with Remove Curse, but only by satisfying a condition specified by the caster. The caster must specify an "escape clause." If he or she does not, the spell is removable with a simple Remove Curse. The clause can be as reasonable or unreasonable as the GM allows. Fulfilling the letter of the clause ends the spell, even if it wasn't the intended way out.
FAQ: I know one of my players will ask this, so let's address it now:
Can you pay the extra cost after you put the spell on a victim? No. You must pay the "lasting" cost when you first cast it. You cannot "upgrade" an exisiting spell on a victim except by casting it again at the full cost.
Can this work on beneficial spells? No. It's too cheap for a "lasting" buff, so no, it can't. I don't think you can fairly price buffs that last until magically removed and don't count as a spell "on."
Note that some spells already have a "permanent" or "lasting" version (or effect). Use those as written instead - you can't make a lasting Forgetfullness, for example - just cast Permanent Forgetfullness, instead.