Conference Coverage

Choosing pharmacotherapy for bipolar disorder requires a risk-benefit analysis


 

FROM PSYCHOPHARMACOLOGY UPDATE

Bipolar disorder with anxiety

An association exists between comorbid anxiety disorders in patients with bipolar disorder and having a younger age of onset, in people who are less likely to recover from an initial mood episode, in people with poorer quality of life and role functioning, and in people who are less euthymic and more likely to attempt suicide, Dr. Goldberg said.

In addition, some patients may demonstrate symptoms of anxiety that aren’t part of the DSM-5 criteria for an anxiety disorder. Dr. Goldberg said he asks his patients to specify what they mean when they say they feel anxious.

“I always ask patients to tell me in very basic terms what [they] mean by anxiety. If they say, ‘I just I can’t sit still; I’m very fidgety,’ maybe that’s akathisia,” he said. “Or maybe if they say they’re very anxious, what they mean is they have so much energy they can’t contain it. This is mania or hypomania that they’re misconstruing as anxiety. We have to be very diligent and vigilant in clarifying the language here.”

To treat comorbid anxiety in patients with bipolar disorder, consider adjunctive olanzapine or lamotrigine, as both have evidence of anxiolytic efficacy. “Olanzapine does count as an antianxiety agent. Would you use it just as an antianxiety agent? Probably not in and of itself, but there’s other compelling reasons to use it,” he said. Before assuming you need to add another medication to address anxiety in a patient, “step back and think perhaps their anxiety symptoms will in themselves remit with olanzapine,” he said. Olanzapine can also be potentially used in cases where a patient has mania and anxiety to treat both conditions, he added.

Divalproex is another option for patients that has anxiolytic efficacy. “In the context of bipolar depression, divalproex does have antianxiety properties,” Dr. Goldberg said. Other anxiolytic options include lurasidone, cariprazine, quetiapine, and combination olanzapine–fluoxetine.

Bipolar disorder and ADHD

Among patients with bipolar disorder and comorbid adult ADHD, cognitive dysfunction inherent to bipolar disorder may be difficult to distinguish from signs of ADHD, Dr. Goldberg explained, with about 20% of people with bipolar I disorder and about 30% of people with bipolar II disorder have deficits of attentional processing, verbal memory, and executive functioning.

“Some researchers are very intrigued by the notion that cognitive problems and attentional problems aren’t necessarily a sign of [ADHD] comorbidities. They might be, but they may just be part of the endophenotype or the non-overt, genetically driven phenomenology that makes bipolar disorder so heterogeneous,” he said.

Patients with bipolar disorder and comorbid ADHD are more likely to have mania than depression, the condition is more common in men, and these patients are more likely to have substance use problems, increased risk of suicide attempts, problems in school, lower socioeconomic status, greater unemployment history, higher divorce rates, and low family history of bipolar disorder. Clinicians should check a patient’s history if they suspect comorbid adult ADHD in their patients with bipolar disorder, as there is a good chance evidence of ADHD will be present around the time of adolescence.

“You don’t wake up with [ADHD] at age 40, at least that’s not the prevailing perspective,” Dr. Goldberg said.

Focus on the ADHD symptoms that do not overlap with bipolar disorder, such as nondiscrete, chronic symptoms; lack of psychosis and suicidality; no evidence of grandiose beliefs; lack of hypersexuality; and depression that is not prominent. “You really need to go back in time and get some clarity as to the longitudinal course. If this was present earlier on and it persists into adulthood and it’s not better accounted for by either what we think of as the cognitive pervasive problems that emerge in bipolar disorder, or in relatives as a collaborator for attentional problems and bipolar disorder, we can then contemplate [whether] there’s a plausible basis for using a stimulant or [other ADHD] treatment,” he said.

In patients who are found to have adult comorbid ADHD and are nonmanic and nonpsychotic, stimulants do have an effect. Studies suggest that amphetamines such as adjunctive lisdexamfetamine added to a mood stabilizer show an improvement in ADHD symptoms after 4 weeks (Hum Psychopharmacol. 2013; 28[5]:421-7).

Adjunctive methylphenidate added to a mood stabilizer has also shown evidence of not causing treatment-emergent mania. “If you’re going to use methylphenidate, make sure it’s in the context of an antimanic mood stabilizer,” Dr. Goldberg said. In one study, methylphenidate without a mood stabilizer caused an increase in manic episodes within 3 months (Am J Psychiatry. 2017 Apr 1;174:341-8).

“All may pose safe and effective evidence-based, albeit provisional, but evidence-based options to consider in targeting the attentional symptoms in patients with bipolar disorder,” Dr. Goldberg said.

He reported that he has been a consultant for BioXcel Therapeutics, Medscape/WebMD, Otsuka, and Sage Therapeutics. In addition, Dr. Goldberg is on the speakers bureau for Allergan, Neurocrine, Otsuka, and Sunovion; and receives royalties from American Psychiatric Publishing. Global Academy and this news organization are owned by the same parent company.

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