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Clinical Characteristics Affecting Response to Bipolar Disorder Treatment

September 10, 2020

(Part 1 of 5)

In this video, Joseph F. Goldberg, MD, explains which clinical characteristics of a patient could affect their response to a treatment for bipolar disorder. Dr. Goldberg, Clinical Professor of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, gave a presentation at the virtual Psych Congress 2020 titled "Tailoring Individualized Pharmacotherapy for Bipolar Disorder: How to Translate Findings from Clinical Trials to a Single Patient."

Read the transcript:

When we think about treatment response in bipolar disorder, it's worth asking, "Are there particular characteristics of any given patient that might inform or influence the likelihood of a certain outcome?" We now know, over decades of research, there's a few things that are worth noting.

Let's talk about mania. We'll talk about depression for starters. In mania, episodes can involve pure euphoric mania or mixed features that involve signs of both high and low. Manias can involve psychosis. Manias can involve suicidality. Manias can involve high impulsivity. Manias can involve substance use comorbidity.

Manias can involve cognitive disorganization. Manias can involve delirium, where there's frank breakdown in orientation and alertness. Manias can involve medical comorbidities. There's a lot of features that come into play.

Here's one way to think about it. Characteristics such as pure euphoric mania tend to respond better to lithium than to certain anticonvulsants like divalproex or carbamazepine.

Dysphoric manias, or mixed‑feature manias, tend to be the opposite. They tend to do a little better with divalproex, say, than lithium. Patients who have frequent episodes per year, so‑called rapid cycling, tend to do not as well with monotherapies as combination therapies.

The best of studies would say this manic patient with rapid cycling is more likely to respond to a combination of mood stabilizers than a single agent, lithium and divalproex being the best studied. Second‑generation antipsychotics also have value in rapid cycling. Eliminating antidepressants has value in treating rapid cycling as well as treating mixed states.

Those are some of the characteristics. Things like psychosis really demand consideration of an antipsychotic drug in the mix, although among mood stabilizers there are data showing that divalproex when it's orally loaded at 20 to 30 mg/kg actually can treat psychotic mania even all by itself. Psychosis as a factor plays a role in determining what's the best treatment.

Substance use comorbidities, which are common in people with bipolar disorder, differ in their responsiveness to particular medicines. Lithium tends not to work as well when alcohol or substance use is in the picture. By contrast, there's a bit more data with divalproex in the setting of bipolar disorder with substance use, in particular alcohol use disorders.

In the setting of bipolar depression, there's much controversy about should antidepressants be used or not. We could now say there are certain patient characteristics that profile the likelihood of response to antidepressants.

Pure depressed phases, no mixed features, no recent mania, no rapid cycling, no substance abuse, the history of a very good response to an antidepressant, a particularly robust initial effect, not a mediocre effect, the presence of bipolar II versus bipolar I disorder would be some of the examples of things that would lean one to say an antidepressant may be more useful in this setting than another.

The absence of those features, bipolar I depressed, maybe with mixed features, maybe with rapid cycling, the FDA‑approved treatments remain the gold standard. That is lurasidone, olanzapine‑fluoxetine combination, cariprazine, and quetiapine. All are very evidence‑based.

Again, this is a quick summary of some of the kinds of clinical characteristics that one would want to think about in choosing from among otherwise appropriate agents in different phases of the illness.

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