Lithium in Primary Care

How lithium improves outcomes in primary care

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? 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, unlike antidepressants, it has also been shown to be directly “anti-suicidal.”Baldessarini In a recent review, only lithium, not antidepressants, clearly reduced risk for suicide.Ernst On this basis German reviewers suggested lithium prescription rates should be 10 times higher than at present.Muller-Oerlinghausen

Full-dose 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 low-dose, adjunctive lithium  (150-450, maybe 600; blood levels <0.7) is almost a different drug.  Even with NSAIDS or antihypertensives you’re unlikely to get in trouble (though always check creatinine first; must be less than 1.0 for this strategy).  Check TSH at 6 weeks and 3 months and don’t let it go up. And no psoriasis; lithium can cause or exacerbate even at low doses.

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. Or jump to Tips.

Data 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):

Lithiu1 (1)

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 55 or so. 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 10 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, so we have to do a few blood tests early on.

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:

(Paste into Patient Instructions)

  1. Start with 150 mg capsules at night (take with food or a glass of milk if any nausea). If no better in a week, but no side effects, increase to 300 mg nightly. After another week, if still no better, and still no side effects, increase to 450 mg nightly.
  2. Lower the dose one step if any side effects bother you.
  3. Get your blood tested, in the morning, not fasting, in a month.
  • For tremor or nausea, switch to slow release (generic is fine) and/or suggest bid dosing.
  • For diarrhea on slow-release, switch back to immediate release

Note to doctor: The 150 mg does not come as an ER formulation, but the 300 mg (Lithobid) and 450 mg (Eskalith) do. The ER formulation has fewer side effects so it may be best to write for a supply of “Lithium carbonate 150mg” and “Lithobid 300mg” to allow the patient to switch up to the ER when they raise the dose).

If the blood level on 450 mg is less than 0.6 mmol/L, you can consider one more step up to 600 mg. Get another level 5-7 days after the increase. Remind the patient to lower the dose again if bothersome side effects.


  • With lithium level,  check TSH (you have a baseline, don’t you? of course) at 6 weeks and 3 months, repeating until clearly no upward trend; if must supplement with T4, target a TSH around 1.0-1.5, not just “normal range”.
  • Repeat TSH, lithium level, and creatinine at 6 months and 1 year if you’re still going.
  • When you stop lithium, taper it; decrease by one pill per month (two unipolar patients in Bauer’s continuation study relapsed with manic episodes when tapered over 1 week to placebo).

(updated 11/2020)