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Guidelines for Using Lithium as a Treatment for Bipolar Disorder

October 20, 2020

(Part 4 of 5)

In this video, Joseph F. Goldberg, MD, explains the conditions under which lithium may be an effective treatment for patients with bipolar disorder.

Dr. Goldberg, Clinical Professor of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, spoke at at Psych Congress 2020 on "Tailoring Individualized Pharmacotherapy for Bipolar Disorder: How to Translate Findings from Clinical Trials to a Single Patient."

Read the transcript:

In talking about mood stabilizers, lithium, often called the “gold standard” of mood stabilizers, when should it be used nowadays? We have decades of experience with this molecule. That research experience has given us a very nice treasure trove of information about knowing not whether it should be used but when it should be used, that is when is it advantageous.

We can make a profile of a good lithium‑responsive patient. Here's what that profile looks like. Pure euphoric manias, not so much mixed features or dysphoric manias. There's research saying that even low‑grade depression during mania makes for a less robust response to lithium than does a euphoric, expansive, grandiose kind of mania.

Lithium seems to work better in the first few episodes, as compared to certain other medicines, like divalproex, which may work just as well on your seventh manic episode as your first or second. If lithium has bang for its buck, it's especially going to be prominent before many episodes have gone by in time.

Some people think that has to do with the notion of kindling, which is the idea that more episodes just beget more episodes. They come with increasing frequency or facility over time, like the system gets primed. Your best shot may be early on rather than later on.

Lithium intends to work better when the illness is more mania‑prone than depression‑prone. That means manias precede depressions, not the other way around with depressions preceding manias.

If you were to go through someone's longitudinal course and count out their episodes over their recent years and you find there's just more activity on the high side than on the low side, lithium might be a better choice than is the case when depressions more predominate.

Unfortunately, most people with bipolar disorder have more depression phases of illness or periods of illness than they do high periods, which is one reason that's been proposed why lithium doesn't always work as well as we wish. In a pure euphoria, mania‑prone, polarity‑proneness in the first three episodes, lithium has particular value.

Lithium is one of the rare drugs that seems to have some familiality to it. If a first‑degree relative with bipolar disorder improved with lithium, there's about a two‑thirds chance that that will be the same result in the patient in front of you. We can't say that about all medicines, but it has been shown with lithium, so familiality.

Lithium seems to have an anti‑impulsivity effect. That's been implicated in its anti‑suicide property. You may be familiar with the notion that lithium can reduce the chance of suicidal behaviors.

It hasn't so much been shown to reduce suicidal thoughts so much as behaviors. Maybe that comes from putting a break on the impulse to act on a suicide thought or the ability to tolerate the distress and the negative affect states that can often be associated with suicidal thoughts. You may be less inclined to see a suicide attempt or a gesture when lithium is in the picture.

Lithium is a drug that requires end‑organ monitoring for thyroid and kidney function. In particular if someone has abnormalities in kidney function, that makes them less ideal a candidate for lithium. If someone is already on lithium but they start to have some decline in their renal function, it doesn't automatically mean they've lost their candidacy for lithium.

In fact, quite the opposite. It means the risk‑benefit analysis really comes into focus. If someone is doing particularly well with lithium, it may mean trying to minimize the potential negative impact on the kidney, such as lowering the dose, assuring only once‑daily dosing, consultation with a nephrologist, ruling out any other possible causes for renal insufficiency in a patient such as that.

If a patient develops thyroid disease, that's not rare. Maybe 1 in 20 people who takes lithium will start to experience a rise in their thyroid‑stimulating hormone levels. Then we check and see if they make antibodies to their thyroid and to see if lithium revealed an autoimmune thyroiditis. If that is the case, we treat it with thyroid hormone. That's a manageable side effect.

If a woman gets pregnant on lithium and she's an excellent responder to lithium, we do not automatically say, "Take away the lithium." Back to risk‑benefit. We say, "Look, you are an excellent responder. We know how this drug works for you. We have to weigh that against the potential impact of cardiac valve malformations."

There's about a 1‑in‑1000 to 1‑in‑2000 risk and some potential for obstetrical complications, low birth weight, polyhydramnios. It's a dialogue to have. It's not a black‑and‑white, "Take this away. We're leaving the picture." It's a discussion about “Is this drug right for you?”

It's been said that lithium is an excellent treatment in about 10 percent of people with bipolar disorder. If you fit that profile and you're in that 10 percent, you want to hold onto that quite strongly. It may bear you well through your life. You may never have a future episode.

If you're in the more middle ground, where it's partially helpful or it's an augmentation, things become a little less black and white. If it's not helpful, then we have other options to consider.

As with so many things, it comes down to profiling someone's candidacy for being a likely responder and whether they have a robust response.

More with Dr. Goldberg:

Clinical Characteristics Affecting Response to Bipolar Disorder Treatment
Optimizing Response to Bipolar Disorder Treatment
Using Antidepressants in Patients With Bipolar Disorder

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