Primary Care Providers' Resource Center

Primary Care Lithium Primer 
(revised 8/2011)

For treatment of depression, primary care providers using the Texas Medical Algorithm (TMAP) got better results than those providing "treatment as usual".Trivedi  What's in that algorithm that you aren't already doing?  For most of the PCP's I've talked with, here's a big one:  lithium. 

Can primary care providers really use lithium?  The TMAP says yes:  lithium augmentation is step 1A in that approach!  

Why be hesitant?  Some of your colleagues have said "hey, you can kill people with lithium, and it's hard to do that with an SSRI."  However, although lithium is more directly potentially lethal, it has also been shown to be "anti-suicidal" in many studies; e.g. see the excellent analysis by Baldessarini et al.   In a recent review, only lithium, not antidepressants, clearly reduced risk for suicideErnst  On this basis German reviewers suggested lithium prescription rates should be 10 times higher than at present.Muller-Oerlinghausen

Certainly lithium is a "high-maintenance drug".  One must monitor lithium levels, thyroid and renal function, and weight.  Simple dehydration can raise lithium levels (though, interestingly, not via intense exercise, as sweating loses lithium 4 times faster than sodiumJefferson), and a mere viral infection can cause a dramatic rise in lithium level.e.g. Abraham

But you already use numerous drugs with narrow therapeutic indices, such as coumadin and gentamicin.  So it can't be just therapeutic drug monitoring that's holding you back.  Whatever it is, here are some data that may sway you, followed by some tips on using lithium.

Lithium Augmentation in Major Depression

Here are randomized trial data, presented courtesy of Dr. Michael Bauer, whose 2004 review with colleagues points out  that "...lithium augmentation is the best-documented approach in the treatment of refractory depression":  

(ellipse sizes indicate sample size in each trial, scale at lower right):    

Although it might take a moment to figure out the format of this picture, you can see that the response rates to lithium augmentation are generally around 45%, much higher than the placebo rates (if they were the same, they would lie on the diagonal line).  

In these 9 randomized trials of lithium augmentation in treatment-resistant depression, 4 were negative studies, probably because the sample size was too small to see a difference; because in a meta-analysis of those 9 trials,  Drs. Bauer and Doepfmer found this result:

Per their data, you'll need to treat about 4 patients with lithium to see one clear response in a patient who was otherwise "treatment resistant". 

Tips on Using Lithium as Augmentation in Major Depression

Don't try this for the first few times on anybody over 50.  Save those folks for later, as lithium gets trickier with age in most folks. 

Check a creatinine and TSH before you start.  (Some say get an ECG as well if the patient is over 45).  

If TSH is greater than 3.0, consider augmentation with levothyroxine instead of lithium. Baseline TSH was inverse, in one study, to post-treatment depression scores.Gitlin One small open trial found this useful even when TSH was in the normal range.Lojko  

If creatinine is greater than 0.8; or if the patient is on an antihypertensive or daily NSAID's; be more cautious than below but you can still consider this approach, especially if the patient is less than 40 years old. 

Tell the patient: 

"Lots of people think lithium is scary but low-dose lithium is like a different drug, much safer, and it can really help with depression. About 1 person in 15 or so will just hate it: it makes them "flat", dull, blah. That side effect does not go away so if this happens to you, just stop it. 

"Otherwise, we're shooting for no side effects at all. Some people get a little nausea when they first start. That should go away. You'll read about "kidney failure" on lithium but that is extremely rare, very much like weird rare reactions most medications have, like aspirin. There is a slow decrease in kidney function if you take a high dose over a decade, but we will use a low dose temporarily, so this is not really an issue. Women with a family history of thyroid problems are quite likely to become hypothyroid (explain what that is) while taking lithium; whereas for a man with no such history this is uncommon. Either way we'll keep an eye on your thyroid, as we have to do a few blood tests early on to make sure we know what your lithium level is. 

"If you get the flu or something like it, don't take any lithium until you're better, drinking and not losing fluids with vomiting or diarrhea."

How to start: 

If the blood level on 600 mg is less than 0.7 mmol/L, you can consider one more step up to 900 mg. Get another level 5-7 days after the increase. Remind the patient to lower the does to 600 mg again if bothersome side effects.