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For locking, I prioritize ones that give a buff without a dependency. +speed, +accuracy are the best. If you have Color of Madness Luminous is great, and Hippocratic on a healer. I also like Steady (-10% stress) and Tough (+HP).
In terms of locking quirks, I never honestly bother unless (a) I'm stinking rich and/or into the end-game, or (b) when you activate the sanitarium-related town event to make quirk management free for a week. That's pretty much the only reason I level up the Sanitarium at all, because having 3 cells + free week = three heroes with a locked positive + removed negative at no gold cost. Outside of that, you rarely -- if ever -- need three cells available at one time.
In terms of removing negatives, there are only a few I really bother with -- such as Kleptomania, Curious, and Antsy (which causes idle heroes to generate stress at the Hamlet). I may also consider some very specific forced curio-interaction quirks.
Forced-interaction quirks will often cause your heroes to automatically screw your profits, hurt themselves, acquire more stress, slap themselves with dots, debuffs, diseases, wreck your +buff potential, ruin quirk-removing curios (like coral or scrolls), and various other nuisances that you just don't want. There's really only three I worry about, and the rest I try to remove over time via quirk-removing curios, free sanitarium events, or allowing other negative quirks to overwrite another.
The only exception is removing specific interaction quirks from my dedicated Crimson Court team, because there's nothing more annoying than going for a one-shot clear, but your idiot hero decides to smash the bottles you wanted to turn into campfires.
By comparison, it's very easy to render combat into guaranteed victory conditions just by hero/skill levels and trinkets, even when some of your heroes are sporting annoying combat-related quirks, so I don't usually bother with them as much.
Luminous is probably best one: +2 SPD +5 DODGE. All SPD quirks are insanely good: worst case you strap a Legendary Bracer on a raw damage character and you still have +1 SPD and +20% DMG
Any +ACC modifier affects both Ranged and Melee skills. Then there's specific ones for Ranged and Melee. I.e: an Arbalest is perfecly fine with +5 Ranged ACC,
Hippocratic is instant lock for Vestal, Crusader and Occultist.
+DMG are also worth lock for characters than have strong damage skills
+CRIT may be worth locking in certain cases: cleaves like Hound Quarry, Grappling Shot and Impale benefit greatly form increased CRIT since every target rolls the CRIT dice.
Instant removals are: Kleptomaniac, Curious, Compulsive, Hylomania. They all can make you lose money in one or two interactions.
The 1st three can activate with any curio with Kleptomania stealing the loot.
Hylomania only activates with any curio that screams money on sight: lockets, chests, bags. Problem is: lockets and many chests give a ton of money if open with a key/shovel, which your character will not use resulting in no loot. With this quirk you can avoid Cove and Ruins if you don't want it screwing your loot: that's too much asking from me so I remove it.
Imposter Syndrome: 4% chance to skip an action, no need to say it.
Other to consider are opposites from good locks: that means -SPD, -ACC. If they are conditional I usually ponder over the condition for them to activate.
As RopeDrink said: "Gather Medicines" quest sometime appears in Weald which if succeded triggers "Caregivers Convention" town event which is basically free sanitarium for a week. Sanitarium can be used to remove one negative and lock/remove one positive quirk in one use, don't forget. Major money saver: absolutely recommended to upgrade sanitarium cells and chase the event.
Also Cove and Warrens have curios with 100% one negative quirk removed. But it's random, so pay heed to use them on characters that have negatives that doesn't bother: a meaningless negative is there preventing another meaningful negative to use the slot, that's a plus you don't want to remove.
"Eerie Coral" when using "Medicinal Herbs"
"Pile of Scrolls" when usins "Torch"
I prefer unlocking the sanitarium asap - I use JES/CRU/HM for stress relief, not the abbey - and de-redding my entire roster. You can and I do remove every negative quirk. Unless I run out, my sanitarium is always full.
Well, almost asap; I could go faster by converting heirlooms, but that's too expensive.
I will lock the heck out of +spd on plague doctors and hippocratic on vestals and occultists. Blinding gas with +spd is pure hax, and the trinkets VES/OCC can use, if they can afford to drop a +heal trinket, are insanely good.
Hard Skin (+10% PROT)
Tough (+10% HP)
all great on someone that guards like your Man at Arms.
https://darkestdungeon.fandom.com/wiki/Quirk
Steady and Photomania. Precisely because MAA can guard others he's an extremely stress sensitive hero: he may eat a CRIT targeted at someone else, he may eat an stress attack aimed at his protegee.
Then he also gets his fair share as a party member.
If he's tanking he doesn't stress heal by landing critical hits and killing enemies like other heroes.
I have never feared a tank MAA getting a death blow in battle: his guard gives him more than enough PROT and it's easy to heal HP. On another hand I have seen dozens of times MAA going nuts in combats way sooner than others if he doesn't has a stress heal around.
Exactly. Money is easier saved when you know how to bust combat, keep heroes stress-free without gold, etc, and quirks are just the proverbial cherry on top of the specialization cake, so to speak. If you're winning, you can afford to manage more quirks and win some more. If you can't, chances are that quirks are the least of your concerns. Either way, they're an aid rather than a requirement (and shouldn't be your main focus).
My new saves generally go something like this:
~ Endure until week 5.
~ Builds comps and synergies (Guild) and start generating desired trinkets.
~ Start stomping through the game -- keeping an eye out for quirk-removing curios and the convention to help winners win more along the way.
If stinking rich, I will consider using the sanitarium to specialize heroes I know for an absolute fact I will want to use later on, such as my dedicated Crimson Court team for one-shot curse-wipes. Those are the type of heroes I will consider manually nuking interaction-quirks on, because I know I will want to loot specific curios to turn into campfires or extra stress-relief, and having a hero randomly interact with them will ruin it.
The only other consideration I really give quirks is when picking heroes from the Coach. I won't let their quirks outright dictate the process -- such as "I won't recruit X hero unless they have pristine quirks", as that's silly. But yes, if you want X hero, and there are multiple of X on offer, and one of them has worse quirks than another, then you're obviously going to take the one that hasn't got as many problematic quirks. Other than that, I don't think about it much.
The only non-interaction quirk I give any kind of attention to is Antsy. Basically, if a hero is Antsy, they will gain stress when left idle at the Hamlet -- which is not very pleasant.
But yeah antsy+five weeks = instant affliction if you take them on a quest. It's bad if you're likely to be low on cash for the abbey or lose track of the issue.
Idling often goes underappreciated, and Antsy takes that passive stress-relief and turns it into a negative.
Lots of heroes have downtime in my saves (as a serial dabbler and comp-experimentor), so I'd rather their stress went down for free instead of up for free during my escapades -- and also prefer not being influenced into taking a comp I may not have initially wanted to take (purely so that I can serenade an Antsy hero back to normality), even if that is slightly less annoying than having to do the same for a free disease cure.
Please!