The Value of Low-Dose Lithium

A reader asked if I would comment on whether low doses of lithium, well below the high-risk levels that can swing up into "lithium toxicity", might still have benefit -- particularly in Bipolar II depression.

The answer is clearly yes. Indeed, lithium has shown value at low doses as an add-on treatment for "unipolar" depression. In other words, lithium has value even if there is no obvious bipolar component to one's depression. And, it has value at low doses: when added to other medications that are not working well enough, it can boost their effects.

(On the other hand, we could wonder whether there might perhaps have been an "bipolar component" in the person's depression, and that is why the antidepressant was not working well enough -- and why lithium helped. In other words, does lithium helping mean that there might have been some degree of bipolarity in the depression? For the moment, until we have a better way of knowing when bipolar disorder is present, in any degree, we should assume that the answer to this question is no. That is, we should assume lithium can treat depression of any kind, not just bipolar depression.)

Recent data suggest that lithium's benefit in bipolar disorder is stronger against preventing manic recurrences, than against preventing depression recurrences. Nevertheless, many of us use it for a very different purpose, namely adding some antidepressant "oomph" when other treatments have not effectively treated depression. In this role, sometimes tiny doses of lithium are sufficient. One of my patients even responded to 150 mg, half of the usual smallest dose. Her response was unequivocal, and has been sustained for over three years now.

What about blood levels? At these low doses, the level of lithium can be far below the "therapeutic range". On the laboratory data sheet, such a result is often marked with an L, indicating an abnormal value, in this case too low. This can worry people who don't really understand what we are doing here. When lithium is used at a low dose, as an add-on medication, we are usually targeting a particular symptom that is already present -- usually depression (as opposed to targeting the prevention of recurrence when a patient is well. That requires knowing that the lithium level is sufficient to award that benefit. We know from research and experience that this requires requires being in the "therapeutic range". Indeed, that range is defined by a lower limit below which the preventive benefit is unlikely to occur; and an upper limit beyond which dangerous side effects become common).

In the low- dose approach, one simply turns the dose up until the target symptom is responding, or until a side effect appears, or until the patient reaches 600-900 mg, at which point we get our first blood test to make sure that she/he is not approaching the upper end of the therapeutic range.

If a good response occurs at a very low dose, e.g. 300-600 mg, the blood level is likely to be low -- so it is important to be prepared for that low number, prepared to disregard it. The main reason for the test is simply to establish that the level is not near the upper end of the therapeutic range, which even at low doses can occur sometimes. It is safe to be at that upper level, but then one has to be more careful about anything that can raise lithium levels spontaneously (for example: dehydration, adding a blood pressure medication, using ibuprofen, getting the flu). One has to be careful about such factors in any case, but when the lithium level is known to be high, then any such changes may warrant repeating the lithium level to be sure it has not gone too high. Knowing that the level is "low" allows for a little more breathing room in this respect.

In summary: low-dose lithium is a great medication. It is inexpensive, and under these circumstances can often be taken with no side effects at all. The risk to one's thyroid production is still there, and long-term monitoring of kidney safety is still warranted (although that risk is likely to be much lower with the lower dose).

I tell my patients: lithium is like two different medications. Low- dose lithium is a "low-maintenance" medication, whereas high- dose lithium warrants careful attention to levels and other variables. Unfortunately, when most people think of lithium, they think of the high-dose approach and may therefore overlook a really excellent medication option.

Thanks to anonymous for the question.
Dr. Phelps