Clinical Insights Regarding the Management of Bipolar Disorder


Gus Alva, MD, DFAPA, discusses key takeaways for the management of bipolar disorder.

Gus Alva, MD, DFAPA: The key takeaways from the roundtable discussion we had that stood out to me after hearing from colleagues is that there is still a fair amount of use of the older medicines out there like lithium. Part of the problem is, however, when we take a look at agents with a low therapeutic index. There is the possibility of no benefit depending on too low a level, or the possibility of serious life-threatening issues with too high a dose; thus the need for monitoring. There is also a need to consider issues based on thyroid function and renal function aside from the litany of thins, including dermatological and central nervous system issues associated with this basic elemental solve.

The use of anticonvulsants also came up. In individuals that may be “self-medicating” with alcohol, some agents like depakote might be more useful in individuals with underlying hostility or explosiveness aimed at potentially harming others. Agents like carbamazepine or divalproex might be useful agents. There was discussion about lamotrigine, but that is a medicine that is also FDA approved for bipolar depressive maintenance. There are several studies where it did not show solid efficacy; additionally, you have to titrate up very gradually to avert the likelihood of Stevens-Johnson syndrome. The possibility of these additional factors might become problematic for individuals, keeping it mind that it certainly could be something useful.

The utilization of atypical antipsychotics has now garnered a bit more attention; certainly, the advent of Seroquel XR (quetiapine) helped lead a charge of taking a look at the malleability associated with atypical antipsychotics prior to that olanzapine combined with fluoxetine would certainly be a consideration. Trying to keep things as simple as possible can be a challenge when mixing in additional medicine. That is where single agents may be worthwhile. With Seroquel XR, unfortunately, 1 out of 2 people feel very sleepy, 1 out of 3 have severe dry mouth. Sometimes, finding the right dose can be difficult. That is where the dosing becomes a little bit trickier. It is a medicine given with food and can give a severe hungover feeling in individuals later on; that is where clinicians may feel reticent.

Latuda (lurasidone) has a decent track record. Unlike Seroquel XR, it should be given with food for it to work well. Otherwise, you only get half the benefit. And then the question is: what does will you need. And sometimes people may experience nausea and sedation associated with the use of the medicine, thereby limiting sometimes the possible full use of the agent. Vraylar (cariprazine) is a newer medicine that does not have the same track record a Latuda based on how long it has been available, but it certainly is one of the few medicines that has a broader spectrum of utilization, not just in the depressive episode but also the manic mixed episode state. That, to a degree, also brings a sense of comfort for clinicians, because Latuda is only approved for bipolar depression. Sometimes clinicians may feel gun-shy: might this medicine activate individuals and flip them over into a manic episode, and, if so, do we really have a sufficient amount of data associated with its use? Vraylar can be given once-daily it is not sedating, not activating, and it has a very long half-life, which means that sometimes people forget to take their medicine, that is ok. The flip side to that, though, side effects might linger for a week. It is a drug that has been well studied in doses even up to 3 times its highest dose. It is currently FDA recommended as not really compromise when it comes to cardiac status and has a placebo like effect on metabolics. It looks quite attractive for individuals where you don’t want gaining weight or having specific issues that might compromise metabolics. The other nice use of that particular medicine is that when patients show up with predominantly depressive symptoms, they will start out at the lowest dose and for the most part stay there. We certainly note that 1.5 mg but up to 3 mg will work there. If patients are having more mixed symptoms that is where the 3 mg dose might be better. If they are having more manic symptoms, that is where 4.5 mg or 6 mg might be a better fit.

Latest entrant in this game is Caplyta (lumateperone). It has a fixed dose of 42 mg and is only indicated for bipolar depression, but it is indicated for bipolar type 1 and type 2, which is interesting because only Seroquel XR and Caplyta have been studied in bipolar 2 patients and you see benefit there. You also note a very clean metabolic profile associated with the medicine. Part of the discussion with the colleagues was taking a look at all of the different options we have, keeping in mind that lithium is the only medication we have that averts suicidality in bipolar disorder. Sometimes patients don’t just respond to one medicine. That is where additional data with other agents are useful.

The important thing is that when we take into consideration bipolar depression, this is a topic that on the surface looks simple but, in reality, can be complex but at the same time training individuals even in the primary care setting to take into consideration these options can help someone so that they are not necessarily lingering in a state in which they are experiencing different difficulties because of financial or interpersonal problem or even the likelihood of suicidality.

Wrapping it all up, there is a current sentiment that we have evolved to the point at which that although some individuals may be treatment refractory and require things including ECT or otherwise. Other modalities like repetitive transcranial magnetic stimulation, intranasal esketamine are not FDA approved in bipolar disorder. It resolves some discussion that ECT-intravenous ketamine might sometimes be useful for some individuals. But the important point is that we have additional tools in our psych-armamentarium and that readily help many individuals in the past that have been mired in suffering and might have experienced additional problems.

Causes like this represent to us the fact that moderate depressive symptoms are not always what they seem. We need to instruct our colleagues and counterparts about the differential associated with depressive symptomatology to take into consideration prior history, family history, and the comorbidity that the induvial experiences, also keeping in mind the aspirational note of what were trying to accomplish: above all, do no harm, and when presenting someone with options, make sure out option list is comprehensive and readily understood.

I appreciate the opportunity of taking part in this didactic experience and the fact that we continue to move down a path in which additional tools are set before us as clinicians. Thank you.

Transcript Edited for Clarity

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