Confused about Lithium vs Depakote in Bipolar

[yanks26dmb]

My understanding is that both medications work better in acute mania than bipolar depression. However CANMAT seems to indicate good efficacy of both in bipolar depression. Though I've heard that VPA is better for mixed episodes. All things being equal how do you weigh starting Li vs VPA in a patient with no contraindications for either. Do you choose one over another based on presenting symptoms?

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[nexus73]

In general for male patients, I would choose Depakote all day every day as the first med. But if it was a woman of child bearing potential, I'd go Lithium first.

 

[deleted1100659]

At preventing mood episodes in general lithium has better data for efficacy. For depressive sx, lithium tends to work better in my opinion. For acute mania, I have better luck with VPA, because I can titrate it faster and load them up. I never use VPA in young women due to pregnacy risk, weight gain, PCOS, etc, etc.

If its a patient who never had full blown mania and its always been hypomania sometimes I will just use an SGA for mood stabilization.

Another thing to consider is your patient population. My patients often have multiple BPs meds such as Acei and ARBs, and have CKD. Obviously in that scenario lithium isnt a great choice.

For bipolar depression I tend to prefer vraylar or latuda. I have had some luck with symbyax but I reserve that for highly questionable bipolar depression, where it leans more towards BPD. The NICE guidelines favor it for bipolar depression though. Caplyta was recently approved for bipolar depression. I have a few on that and they seem to do well. I like that its stupidly easy to dose with no titration period, and can cause weight loss supposedly, rather than weight gain.

 

[calvnandhobbs68]

For bipolar depression I tend to prefer vraylar or latuda. I have had some luck with symbyax but I reserve that for highly questionable bipolar depression, where it leans more towards BPD. The NICE guidelines favor it for bipolar depression though. Caplyta was recently approved for bipolar depression. I have a few on that and they seem to do well. I like that its stupidly easy to dose with no titration period, and can cause weight loss supposedly, rather than weight gain.

Yeah but why Symbyax for questionable bipolar depression? Olanzapine has pretty solid data from what I've seen for bipolar depression but side effect profile is far and away the worst out of all of these. I tend towards olanzapine where I feel I'm pretty confident it's refractory bipolar depression and it's worth the side effect profile...otherwise it's hard to justify the r/b ratio. I'm almost certainly trying seroquel first anyway.

But yeah OP avoid valproic acid in young females. There's more recent thinking that lithium teratogenicity (despite what we all learn for Step 2/boards) is a bit overblown too, especially in comparison to neural tube defect risk from valproic acid.

 

[Stagg737]

Agree with most of the above. My preference for severe, acute mania is depakote d/t ability to give a loading dose immediately unless it's a woman <40yo. For bipolar I with minimal manic episodes and mostly depressive I prefer Lithium, especially if the depression is severe enough to warrant admission. For mixed episodes it would depend on their past history and I don't think I'd have a specific preference. I do think that Lithium is often underutilized and too many treating clinicians are too afraid to use it when it's indicated. SGAs can also be very useful and more than a few of our bipolar patients end up on an LAI (usually aripiprazole) d/t readmissions from poor compliance.

But yeah OP avoid valproic acid in young females. There's more recent thinking that lithium teratogenicity (despite what we all learn for Step 2/boards) is a bit overblown too, especially in comparison to neural tube defect risk from valproic acid.

Definitely overblown. Lithium was initially thought to increase the risk of Ebstein's anomaly 400x, but more current research shows the risk of Ebstein's in those exposed in utero to be 1:2000. I've spoken to several reproductive psychiatrists, and most of them actually didn't recommend discontinuation of lithium in women with bipolar disorder who become pregnant unless they've been really stable. There are plenty of things to monitor with lithium, but ebstein's is not something I worry about.

 

[Crayola227]

Yeah but why Symbyax for questionable bipolar depression? Olanzapine has pretty solid data from what I've seen for bipolar depression but side effect profile is far and away the worst out of all of these. I tend towards olanzapine where I feel I'm pretty confident it's refractory bipolar depression and it's worth the side effect profile...otherwise it's hard to justify the r/b ratio. I'm almost certainly trying seroquel first anyway.

But yeah OP avoid valproic acid in young females. There's more recent thinking that lithium teratogenicity (despite what we all learn for Step 2/boards) is a bit overblown too, especially in comparison to neural tube defect risk from valproic acid.

Eh, I'm not convinced they were wrong about lithium and Epstein's. I had a chance to talk to an MFM guy who saw it enough times that he wasn't a fan. If a patient is doing great on it, failed other drugs, sure.

Valproic acid isn't great for the reasons you stated, but since it's coming up need to add that it is considered safe and compatible in breastfeeding with little monitoring.

Lithium on the other hand, sources will say you can, however a lot of docs (psych, ob/gyn, peds) seem a bit daunted at the prospect of monitoring after delivery. And then you also have to think about those wittle kidneys in addition.to other things. Might be enough to scare a lot of moms into quitting the med or the breastfeeding.

Seroquel basically doesn't get into the milk at all, but have to consider mom's sedation with a newborn baby.

Anyway, the issues with these meds and how they affect the 1 or 2nd trimester differently than the so-called 4th, might mean it would be good to consider these things and possible switching if it can be done safely.

 

[Crayola227]

Agree with most of the above. My preference for severe, acute mania is depakote d/t ability to give a loading dose immediately unless it's a woman <40yo. For bipolar I with minimal manic episodes and mostly depressive I prefer Lithium, especially if the depression is severe enough to warrant admission. For mixed episodes it would depend on their past history and I don't think I'd have a specific preference. I do think that Lithium is often underutilized and too many treating clinicians are too afraid to use it when it's indicated. SGAs can also be very useful and more than a few of our bipolar patients end up on an LAI (usually aripiprazole) d/t readmissions from poor compliance.


Definitely overblown. Lithium was initially thought to increase the risk of Ebstein's anomaly 400x, but more current research shows the risk of Ebstein's in those exposed in utero to be 1:2000. I've spoken to several reproductive psychiatrists, and most of them actually didn't recommend discontinuation of lithium in women with bipolar disorder who become pregnant unless they've been really stable. There are plenty of things to monitor with lithium, but ebstein's is not something I worry about.

Do want to point out that the approach with thinking about moving away from Li in pregnancy, would make sense to be different in preconception planning, vs unexpected pregnancy. I agree that in a patient already 6-8 weeks, and possibly more upon presentation to the psychiatrist, stopping Li because of concern about Epstein's may not make much sense.

But we should also consider how mom will do post pregnancy and her plans for feeding baby, in considering if once past embryonic stage if moving to a different med makes sense.

Obviously stability of mom comes first, just pointing out that if one can consider choices, to consider the above.

 

[deleted1100659]

Yeah but why Symbyax for questionable bipolar depression? Olanzapine has pretty solid data from what I've seen for bipolar depression but side effect profile is far and away the worst out of all of these. I tend towards olanzapine where I feel I'm pretty confident it's refractory bipolar depression and it's worth the side effect profile...otherwise it's hard to justify the r/b ratio. I'm almost certainly trying seroquel first anyway.

mainly i mean the people with significant medication histories and have not responded to most things, and I start to question the bipolar 2 diagnosis and think its more borderline. Zyprexa works good for some of my BPD patients, helps with mood regulation. Prozac has some evidence at reducing self harming behavior.

In prior settings, I would choose seroquel over zyprexa most of the time if i thought it was bipolar depression (not counting vraylar or latuda, i like meds that dont have significant weight gain).

In my current setting, seroquel is heavily abused here. Weve had numerous issues with people obtaining it illicitly, using more than prescribed, etc. Its not a good setting for medications like effexor and seroquel. A month ago, one guy made small holes in all his effexor capsules to empty them, and snorted them.

 

[deleted1100659]

Definitely overblown. Lithium was initially thought to increase the risk of Ebstein's anomaly 400x, but more current research shows the risk of Ebstein's in those exposed in utero to be 1:2000. I've spoken to several reproductive psychiatrists, and most of them actually didn't recommend discontinuation of lithium in women with bipolar disorder who become pregnant unless they've been really stable. There are plenty of things to monitor with lithium, but ebstein's is not something I worry about.

I agree on this I would have a hard time discontinuing lithium during pregnacy, especially if im the consult psychiatrist and dont know the patient too well. I would only do it if the patient and family adamantly wanted it, then maybe I would consider zyprexa or seroquel and hope that works well. Zyprexa has similar efficacy to preventing mood episodes per maudsley.

 

[surfguy84]

So what I've heard is that both lithium and depakote work better from the top down, meaning they're better at controlling acute mania rather than acute depression. In a bipolar depressive episode I feel the best evidence is for an SGA. If that alone doesn't do it, I would consider augmenting with lithium > vpa.

 

[whopper]

Depakote and Lithium are relatively high in side-effect burden. Doesn't rule it out but it does suggest it should only be used in tougher Bipolar Disorder cases.

Since I've done private practice I hardly prescriber either. Why? Cause most of my Bipolar Disorder patients aren't severe enough to go to inpatient often. I've also noticed some of the newer atypicals are controlling their Bipolar Disorder better and with less side effects than the older generation SGAs. E.g. when I was a resident the only atypicals were Clozapine, Risperidone and Olanzapine-all high risk. Aripiprazole and Ziprasidone came out my PGY-IV year but they don't work as well. The last few, however, Vraylar, Latuda, Caplyta, Fanapt, not only have decent efficacy, and less side effect burden, most of them work too for Bipolar Depression.

If I still did inpatient or PACT Teams I'm sure I'd still be prescribing much more Valproic Acid and Lithium, but likely not on an order I was before these newer SGAs came out.

 

[Sikrouf]

Are we talking about maintenance or acute treatment here?
Are we taking about severe or mid-spectrum bipolar disorder ? There are several moderating factors

As an inpatent psychiatrist about every single bipolar patient has a trial of lithium, albeit being on VA for acute episodes i only resort to VA for maintenance after LI and other monotherapy has been doomed ineffective because of the metabolic issues with VA when you re stuck with high plasma levels

 

[Celexa]

Although both are on the high end for side effect burden, my experience has been that lithium is better tolerated and I tend to prefer it in otherwise young and healthy pts.

I see way too many reproductive age women placed on Depakote without even a discussion of its risks. In one howler of a case the pt had been put on it by one psychiatrist with no discussion of risks. Went to a second and was told about the metabolic and pcos risks but not the teratogenicity. Finally got to my clinic and was shocked to hear its not recommended for repro age women. It makes me angry. I myself would never do it in a patient capable of pregnancy except as a last resort in treatment resistant mania.

I would also never take a truly good lithium responder (someone with a history of true manic episodes, stable and euthymic on lithium) off of the med even in preconception counseling. Risk of relapase is too high. I am comfortable with patients being on it for pregnancy.

In the geri population I start leaning to Depakote given that it overall plays better in the sandbox with all the other meds they're likely to be on (ace inhibitors, etc).

Regardless, treatment algorithms are useful suggestions, not gospel. Treat the individual patient in front of you.

 

[Stagg737]

Do want to point out that the approach with thinking about moving away from Li in pregnancy, would make sense to be different in preconception planning, vs unexpected pregnancy. I agree that in a patient already 6-8 weeks, and possibly more upon presentation to the psychiatrist, stopping Li because of concern about Epstein's may not make much sense.

But we should also consider how mom will do post pregnancy and her plans for feeding baby, in considering if once past embryonic stage if moving to a different med makes sense.

Obviously stability of mom comes first, just pointing out that if one can consider choices, to consider the above.

To clarify my previous post a bit, I was speaking in terms of the inpatient setting and looking specifically at Lithium vs VPA. My points regarding younger women were in regards to women already pregnant or attempting to get pregnant. There are too many factors involved, even if neither are directly contraindicated, to give a straight neigh or yay to either med.

On the outpatient side, I prefer lithium over VPA in patients with true bipolar I d/t efficacy for prevention of mania and depressive states. I also commonly used lamotrigine or some SGAs (usually olanzapine or Abilify, Latuda if we had samples or insurance covered it which was very hit or miss). I also initiated a couple of patients on carbamazepine, but that is certainly further down my list.

For pregnant women, Trileptal is also a potential option as it's been shown to be safer in pregnancy than most other meds and Maudsley stated that it's "likely effective for mania", though data is lacking. I inherited a couple of patients at the VA with true bipolar who had been stable on Trileptal for years and had one patient in our academic center who I transitioned from Lithium to oxcarb after she delivered her child. Ended up transferring her to our reproductive psych clinic as she was struggling with ongoing depression, but she didn't become manic for the first 3-4 months post-partum. So it can be considered in some cases, but not something I'd typically use.

Regardless, treatment algorithms are useful suggestions, not gospel. Treat the individual patient in front of you.

This was the advice we were given by one of our clinical lecturers in med school. It has always stuck with me as the best advice I've gotten as a physician and has had a huge impact on how I practice and work with patients.

 

[mistafab]

I would use Li if suicidailty is high

 

[Merovinge]

The last few, however, Vraylar, Latuda, Caplyta, Fanapt, not only have decent efficacy, and less side effect burden, most of them work too for Bipolar Depression.

We definitely need more research here but it looks like Latuda and Caplyta should lead the way before Vraylar. Hoping to use some Caplyta in practice soon. I am not familiar with using Fanapt in bipolar disorder, is there good research behind this?