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Dr. Joseph Goldberg on the Role of Family History in Bipolar Disorder Treatment Choices

November 11, 2020

(Part 5 of 5)

In this video, Joseph F. Goldberg, MD, explains the role of family history in bipolar disorder treatment choices.

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


Read the transcript:

Let's spend a moment talking about family history as it pertains to treatment response.

There's a couple of issues here. One is to what extent do the symptoms that a first‑degree relative with, say, bipolar disorder has that resemble the profile that you have.

If my father had bipolar disorder that involved psychosis or rage and aggression or a prominent sleep disorder or anxiety comorbidity, we can certainly ask and want to know is the phenotype that occurs in me reminiscent of what happens in my relative.

It's not a one‑to‑one correspondence. In fact, my relative could have mainly recurrent depression, and I have mania. My relative could have schizoaffective disorder, and I may have bipolar depression. My relative could have a suicide attempt, and I have bipolar mania.

Family history is not always black and white, but it is useful to know what kinds of target symptoms have occurred because we at least want to be alert to them. Psychosis, for example, might want to inform our thinking. You have genetic vulnerability to psychosis when your mood symptoms are present—so, take that into account—or anxiety symptoms.

Let's call that the phenotype aspect. What kinds of symptoms might have some heritability that might inform our thinking about the kinds of medicines to use?

The second way, which is not as extensively studied, is does drug response in my relative inform about the chance that I too will share the same response. The reason I say this is not as well‑studied is we don't know how much drug responsivity, which has many factors that go into it, is governed or influenced by genetics.

So many things go into drug response—the clinical profile, the factors around symptoms and severity and chronicity and comorbidity and so on, compliance, nonadherence, side effects. A lot of things affect drug response.

How much genetics plays a role, or familiality, better to describe...If my father likes lasagna, does that mean that I'm going to like lasagna? If my father went to medical school, does that mean I'll go to medical school? How much does it run in families? We don't know, with just a handful of exceptions.

Lithium is probably the best example of the exception. There is some nice research looking at bipolar pedigrees, showing that in a first‑degree relative, parent, sibling, offspring—not your third cousin twice removed—first‑degree relative, lithium response has about a two‑thirds concordance.

If a first‑degree relative did well with lithium, that's a point in favor of giving you lithium. If they didn't do well, it doesn't negate the possibility. For that matter, you could have multiple relatives, but lithium may have some familiality.

In the world of depression more broadly, there's been a little bit of research with some SSRIs, fluvoxamine in particular, some research in Italy saying, similarly, if a first‑degree relative with depression had a good response to this SSRI, it may inform the likelihood that you too will have the same kind of response. That's in the unipolar world. It hasn't been looked at in the bipolar world.

To my knowledge, we don't have data to tell us if your first‑degree relative got better with a certain second‑generation antipsychotic or a mood stabilizer other than lithium or some other medicine, does that inform our response to you.

We often ask the question. We often say, as we're asking our questions, "So and so in your family has a mood disorder. Are you aware of what their treatment was?" "Yes. My cousin Sally got better with mirtazapine."

Clinicians will sometimes say, "Well, then let's give you mirtazapine." If there's a psychological halo effect to that, that's fine, but we don't really have any genetic or familial data aside from the lithium and the SSRI data that I mentioned to, in a more scientific way, say, "This runs in families. Let's give it to you."

It doesn't negate the possibility. Listen, if my friend got better with such‑and‑such a drug and I have a very positive valence in my mind, and association, never mind the genetics, that alone can certainly capitalize on some of the nonpharmacodynamic factors that go into drug response.

In short, anything that we can look for that will enhance our sense of optimism on the patient's part, counts. If family history falls in that category, that's fine, but lithium and some SSRIs are the most evidence‑based for familiality.


More with Dr. Goldberg:
Guidelines for Using Lithium as a Treatment for Bipolar Disorder
Using Antidepressants in Patients With Bipolar Disorder
Optimizing Response to Bipolar Disorder Treatment
Clinical Characteristics Affecting Response to Bipolar Disorder Treatment


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