Bipolar Disorder Therapy, Sleep Comorbidities, and Weight Gain

In Part 1 of this podcast series, Psych Congress 2021 co-chair, Julie Carbray, PhD, FPMHNP-BC, PMHCNS-BC, APRN, Clinical Professor of Psychiatry and Nursing, University of Illinois at Chicago; Administrative Director, Pediatric Mood Disorder Clinic, Pediatric Brain Research and Intervention Center, Department of Psychiatry, Chicago, Illinois, moderates an audience question and answer session with Joseph F. Goldberg, MD, clinical professor of psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, from his session, “Personalized Medicine for Bipolar Depression: Combining Evidence and Clinical Wisdom to Improve Clinical Outcomes.”

Dr Golberg discusses L-methylfolate for the treatment of bipolar disorder, as well as how sleep comorbidities and weight gain phobia impact treatment options.

In the upcoming Part 2 and Part 3 of the podcast, Dr Golberg will address rapid cycling issues for women of child-bearing years, and bipolar disorder treatment options and how stimulants play a role.

Read the transcript:

Dr Julie Carbray: Hi, Joe. Hi, Dr Goldberg.

Joseph F. Goldberg, MD:  Hi, there. Can you hear me?

 Dr Carbray:  We can. Welcome, you have a full room and many questions.

Dr Goldberg:  I feel like Roy Orbison on tour.

Dr Carbray:  Absolutely. They're coming in very quickly, and interesting, here's the top 2 questions. The first is, "Is Deplin more effective than other L-methylfolates available?"

Dr Goldberg:  Probably not. I'm not aware of any head-to-head comparisons, but Deplin is a brand form of L-methylfolate, and L-methylfolate is what you want to use. L-methylfolate is L-methylfolate.

Dr Carbray:  How about comments on patients with highly difficult-to-treat sleep-onset issues and phobic about weight gain? That's almost like a double hitter there.

Dr Goldberg:  Sleep issues begs the question of why do they have sleep issues and back to deep phenotyping.

Is someone having insomnia or sleep disorders secondary to their mood disorder? In which case, focus on their mood disorder. Do they have comorbid simple insomnia, or do they have another sleep disorder altogether, of which there's a long differential diagnostic list. Periodic limb movement disorder, sleep apnea, etc.

I would try to make myself as confident as I can as to what the etiology is. Let's make sure they're not withdrawing from substances. Let's make sure they're not using a stimulant late in the day, or they have poor sleep hygiene, etc., etc. Make use of a sleep study if you have to, but at the end of the day, you're treating comorbid primary insomnia.

The question then is, "What are the most weight-sparing options to treat primary insomnia aside from CBT for insomnia and sleep hygiene?" and all those things that I know you're all doing anyhow, relative weight neutrality with either melatonin or Rozerem, the melatonin agonist.

The dual-orexin receptor antagonists such as suvorexant or lemborexant are another interesting way to shut down the wakefulness center, and don't have the antihistaminergic effects of all the other antihistaminergic things that we use. From some second-generation antipsychotics to trazodone, to Benadryl, etc.

If what you're saying is how can I avoid the antihistaminergic effects of soporific drugs, and if someone's not a good candidate for a Z-drug, then that's how I would think about it.

Dr Carbray:  Thank you. Could you make some comments on the patient who would be a good responder to the olanzapine and fluoxetine combination product, and what your thoughts are?

Dr Goldberg:  Sure. It does have its database both in treating resistant major depression and bipolar depression. As a starting point, those would be your logical candidates, and then from within that larger universe, in bipolar depression, we now have more options than we did a few years ago.

If the concerns are around metabolic safety and so on, that might steer you away from OFC. On the other hand, if someone has tried more metabolically-neutral options that have not been helpful, before resorting to more outright experimental approaches, you might say, at least in terms of shared decision-making with the patient, olanzapine/fluoxetine does work.

Now, as of -- what? -- this week, we have a brand-new way to give patients olanzapine that may at least diminish some of the potentials for weight gain in combination with samidorphan. I don't know if we'll see a resurgence of use of olanzapine/samidorphan proprietary with fluoxetine separately to create a more weight-neutral form of OFC.

It'll be interesting to see what clinicians do with this new product now that it's finally out and available. The metabolics have been the main disincentive for it, because the effect size is quite remarkable, and it's a drug that I certainly use quite a bit with patients.

Joseph F Goldberg, MD, is Clinical Professor of Psychiatry at the Icahn School of Medicine at Mount Sinai. He attended college at the University of Chicago, graduate school in neuroscience at the University of Illinois, and medical school at Northwestern University. He completed his residency and chief residency in psychiatry, and fellowship in psychopharmacology, at the Payne Whitney Clinic, New York Presbyterian Hospital, where he later served on the faculty and was site Principal Investigator at Weill-Cornell Medical Center for the NIMH STEP-BD program. He has published over 220 peer-reviewed papers on topics related mainly to the treatment and clinical features of bipolar disorder, as well as 4 books on bipolar disorder and psychopharmacology, most recently, "Practical Psychopharmacology: Translating Findings From Evidence-Based Trials Into Real-World Clinical Practice," with Stephen Stahl, MD, PhD, published in 2021 by Cambridge University Press. He serves on the Board of Directors for the American Society of Clinical Psychopharmacology and serves as a field editor for the Journal of Clinical Psychiatry and for CNS Spectrums. His research has been awarded funding from NARSAD, NIMH, the Stanley Foundation, and the American Foundation for Suicide Prevention. Dr Goldberg is a Distinguished Fellow of the American Psychiatric Association and has been listed for many years in Best Doctors in America and Castle Connolly's "America's Top Doctors."