What Is Your First Choice for Acute Bipolar Mania

[AD04]

Lots of the drugs for acute bipolar mania are very damaging. I'm trying to come up with a regimen that minimizes damages.

- antipsychotics can result in TD, which could be life-long even after stopping medications
- valproate can be hepatotoxic and could be fatal (pancreatitis) and also has a bunch of other side effects
- carbamazepine autoinduces and has interactions with lots of drugs and also has a bunch of other side effects
- lithium has narrow therapeutic index but it seems the least damaging overall and protects against suicidality

One of my attendings like lithium / lamotrigine combo which covers the acute, manic, and depressive phases of bipolar. That's what I'm leaning towards as well.

But in the community, I see antipsychotics being thrown around all the time as the first choice.

Assuming normal liver and renal function, what do you use and why?

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[hallowmann]

Now I'm just another resident, so I can only tell you what is commonly used in my program.

Lithium and lamotrigine are reasonable, but the degree of mania and how much time you have to control it/titrate up is also pretty important. I had a patient that was suffering from mania with psychotic features, big guy, frequently attacking people on the wards, regularly getting IM PRNs and spending time in seclusion. In that case, we started him on mood stabilizer as well as atypical antipsychotics and honestly built up to some heavy doses before bringing him down. Main recommendation if you go the antipsychotic route would be to start titrating those down as soon as you can. The plan is always to get them off of it as soon as possible if you can, and have them stabilized on the lowest possible dose of mood stabilizer.

 

[clausewitz2]

- antipsychotics can result in TD, which could be life-long even after stopping medications

Important point - tardive dyskinesia is a not an extrapyramidal symptom in the way acute dystonias are. If you withdraw antipsychotics in someone experiencing TD it generally gets much worse; whereas switching to a more potent D2 antagonist tends to reduce TD. Tardive dyskinesia is a problem of an excessively sensitive dopaminergic system, probably due to chronic up-regulation due to dopamine blockade. The things that seem to help TD either a) block dopamine receptors more aggressively or b) reduce dopamine uptake into synaptic vesicles and thus deplete available dopamine.

Just stopping someone's neuroleptic when they start developing TD is absolutely the wrong move.

 

[Liquid8]

It depends on the patient.

When I was training and working in an acute inpatient setting, we’d usually have involuntary patients so would use one of valproate, olanzapine or risperidone +/- benzodiapines, usually clonazepam or lorazepam. If that failed we’d go for the typicals like Zuclophenthixol which I don’t believe you have access to in the US. This kind of regime would quickly settle an acutely agitated patient, and aside from valproate all were available in IM forms to if noncompliance was an issue. As well as alleviating their distress, we also had to consider how to reduce but potential risks to ward staff and other patients, making a rapid onset of effect the main priority. While acute dystonias can be a potential concern in the short term, tardive dyskinesia is typically something seen with long term antipsychotic treatment and you would look at reducing these after the acute phase to minimise this occurring.

While lithium may be the superior mood stabiliser for mania, it’s also lethal in an overdose and often avoided if patients they had a history of non-compliance, ODing or a lack of social supports. Needing regular blood tests with dose increases was also seen as a potential barrier to compliance, and could also severely upset the involuntary patient. At the time lamotrigine cost too much for the department, but I’d still only use this for predominant bipolar depression. While Seroquel was also used, by some consultants it was frowned upon due to potential issues with drug diversion.

Now in my private setting, for an acute mania I’d go with lithium first line, with either an atypical or benzodiazepine PRN in the short term - usually seroquel, olanzapine or risperidone, but again depending on the patient. The demographic is completely different. Patients may have more social supports which can reduce some of the risks - Eg. someone at home to keep or help supervise medication. I probably get more females presenting who are generally less dysfunctional and can maintain some insight into their treatment even if elevated, so we can still have a discussion about side effects which usually leads to valproate being excluded they are thinking about having a family.

In the long term I will aim to have a patient on the lowest dose of medication possible, with the PRNs as a “break glass in case of emergency” mechanism if they start to display early warning signs (most commonly a reduction in sleep duration) to reduce the chances of a full relapse occurring. As my patients are usually working and can’t be heavily bombed out all the time, tapering off the more sedative agents usually happens fairly quickly.

 

[clausewitz2]

I think the use of things like Seroquel and Zyprexa in acute mania are really using neuroleptics in the sense that led to them being called that in the first place - seizing the nerves. Induce a state of indifference in someone who is far too interested in everything. Quell excessive activity. And in an acute use I think this is very justifiable. At the same time I would be much happier about this if I saw more people in the community post discharge reducing/eliminating these medications, like, ever. They can say the words "medications for an acute episode may not be needed for prophylactic maintenance" but somehow this rarely translates in action. Sometimes that is patient-driven (most people who have any memory of what happened when they were manic really don't want to ever go through that again) but I suspect this is not usually the case.

The same really applies for acute psychotic episodes that don't have a chronically unremitting pattern, but that's another discussion.

 

[hamstergang]

Just stopping someone's neuroleptic when they start developing TD is absolutely the wrong move.

I don't know that this is fully correct. I believe TD can go away if you stop the offending agent. Sure, it will worsen initially but the dopamine receptors should reset back to normal if given time.

 

[clausewitz2]

I don't know that this is fully correct. I believe TD can go away if you stop the offending agent. Sure, it will worsen initially but the dopamine receptors should reset back to normal if given time.

https://www.sciencedirect.com/science/article/pii/S0022510X18300686?via=ihub

tl;dr evidence is not clear that remission actually happens in the long term with withdrawal but it is definitely the case that withdrawal dyskinesias can happen. Looking over the literature for specific numbers suggest that remission happens in less than 25% of cases where neuroleptics are stopped over long follow-up periods. I would generally advise against it, though of course some people may want to roll the dice.

further edit: So the literature seems to be moving at a good clip in this area. Current hypotheses of TD actually focus on abnormal plasticity and neuroleptic-induced structural changes (usually frontal) rather than receptor up-regulation, mostly because PET and post-mortem studies don't show an association between changes in D2 receptors and TD. And these people think the mechanism of TDs is actually overlapping with the mechanism of dyskinesias provoked by levodopa therapy in PD: Maladaptive Plasticity in Levodopa-Induced Dyskinesias and Tardive Dyskinesias: Old and New Insights on the Effects of Dopamine Receptor Pharmacology

 

[clozareal]

I like the discussion in this Lancet seminar by Iria Grande.

Several comprehensive systematic reviews of the management of mania have been published. With respect to efficacy, Cipriani and colleagues reported that, overall, antipsychotics were significantly more effective for treatment of mania than were mood stabilisers, with haloperidol, risperidone, and olanzapine ranked as the most potent. With respect to acceptability, defined as how many patients stayed on the allocated treatment, quetiapine, risperidone, and olanzapine showed the best results. In general, risperidone and olanzapine had the best efficacy and acceptability. By contrast, Yildiz and co-workers noted that discontinuation rates were lowest with aripiprazole, valproate, quetiapine, risperidone, and olanzapine, and no treatment was superior. In fact, sensitivity analysis by drug class indicated similar profiles for haloperidol, second-generation antipsychotics, and mood stabilisers. Nevertheless, in another study, Yildiz and colleagues showed larger or quicker responses for various antipsychotics compared with lithium, valproate, and carbamazepine, with no differences between lithium and valproate or between second-generation antipsychotics and haloperidol. Antipsychotics might have a more rapid onset of action; haloperidol in particular seems to have a faster antimanic action compared with second-generation antipsychotics. However, haloperidol has the substantive drawback of a greater risk of switching to depression and extrapyramidal side-effects. Apart from these results, combination treatment with an atypical agent and a mood stabiliser has a higher response rate in manic episodes than does monotherapy with either drug.

 

[Armadillos]

Personally if someone’s acutely manic needing involuntary admission I initially like to load some depakote+antipsychotic+benzo for a day or two to get patient to point they can decide what they prefer longer term. If patient is not involved in the choice and on board with the treatment choice after discharge we would just be wasting our time. Just don’t be that person discharging some risk taking, highly fertile 21yo F on depakote.

 

[clausewitz2]

Personally if someone’s acutely manic needing involuntary admission I initially like to load some depakote+antipsychotic+benzo for a day or two to get patient to point they can decide what they prefer longer term. If patient is not involved in the choice and on board with the treatment choice after discharge we would just be wasting our time. Just don’t be that person discharging some risk taking, highly fertile 21yo F on depakote.

I have seen it argued that for involuntary hospitalization kind of mania we ought to be depakote loading like the neurologists do for seizures and titrating lithium to a therapeutic level in the mean time. The idea would be that the depakote would come off when the acute episode is subsiding and lithium is becoming therapeutic; after all, depakote's long-term data are pretty terrible. In principle it sounds like an interesting approach but I have never seen someone gutsy enough to do it.

 

[Crayola227]

I would second @clausewitz2 point about antipsychotics and "seizing" the nerves

Seems to me one reason some lean towards antipsychotics vs lithium right away, I was told, is that that class of drugs' sedating effects promoting sleep is somewhat independent of their effect cooling mania. It's doing double-duty. I've heard some joke that getting your manic patients to sleep isn't just alleviating their condition or improving a symptom, it's its own cure.

I know there's some data that shows that sleep disturbance isn't just a side effect of mania, it's causative.

Lithium is great because it is anti-manic and isn't sedating. Antipsychotics have their place partly for being both.

The suicide risk of lithium is always mentioned, I always just wonder about lamotrigine. The talks I've seen psychiatrists give about the lethality of lithium toxicity (um, usually not in so many words, actually) vs the severe warnings you have to give people about SJS, I always wonder why you don't see more patients in after taking a whole bottle of lamotrigine. Of course, I have seen OD but apparently it was an accident. In any case, the patient who seems keen to take a whole bottle of something and hope to die worries me with that but I don't know how much a concern it is.

 

[thoffen]

The answer depends upon the clinical scenario. Risks and benefits are different for every patient, and it's flatly wrong to think that TD is a compelling risk to avoid in acute mania. I am certainly aware that these things have a tendency to stick after resolution of an episode, but really it's not the dilemma you are faced for managing mania. I'm much more concerned with acute EPS/NMS/catatonia, metabolic concerns, anticholinergic symptoms in that setting.

Overall I don't use lamotrigine much for anything.

 

[clausewitz2]

I would second @clausewitz2 point about antipsychotics and "seizing" the nerves

Seems to me one reason some lean towards antipsychotics vs lithium right away, I was told, is that that class of drugs' sedating effects promoting sleep is somewhat independent of their effect cooling mania. It's doing double-duty. I've heard some joke that getting your manic patients to sleep isn't just alleviating their condition or improving a symptom, it's its own cure.

I know there's some data that shows that sleep disturbance isn't just a side effect of mania, it's causative.

Lithium is great because it is anti-manic and isn't sedating. Antipsychotics have their place partly for being both.

The suicide risk of lithium is always mentioned, I always just wonder about lamotrigine. The talks I've seen psychiatrists give about the lethality of lithium toxicity (um, usually not in so many words, actually) vs the severe warnings you have to give people about SJS, I always wonder why you don't see more patients in after taking a whole bottle of lamotrigine. Of course, I have seen OD but apparently it was an accident. In any case, the patient who seems keen to take a whole bottle of something and hope to die worries me with that but I don't know how much a concern it is.

I think the basic reason why lamotrigine causes less concern about suicide is the SJS reaction is relatively rare and requires your immune system to be configured in a certain way, whereas there is a dose of lithium that is easy to stockpile that will kill or hospitalize just about anyone. On a population level you are preventing suicides by writing got more lithium but that doesn't change the facts for an individual.

 

[calvnandhobbs68]

I've been taught to start out with antipsychotics and add on a mood stabilizer towards the tail end/after the acute agitation from mania is improved. Hopefully then come down on the antipsychotic a bit, if not totally, eventually.

 

[sloop]

If people are likely to tolerate it, my answer is almost always lithium. It seems to work the best and as long as people don’t have jacked up kidneys it seems to be tolerated better. The main alternative that I consider sort of in the same league for treatment of true Bipolar I is Depakote, but in the patient population at my hospital (really sick, comorbid substance use, hep C, etc) it tends to mess up people’s livers too much. Also, I’ve seen a fair number of cases where people have to stop it due to blood dyscrasias, etc. Not to mention, I worry about it with reproductive age women (which is a lot of people).

I feel like lamictal is weak sauce for Bipolar I. Anecdotally I’ve found it to work better for depressive episodes than mania. It’s also a massive pain to titrate and Bipolar I patients aren’t known for their ability to stick to a medication without lapses. By the time you get to therapeutic lamictal doses you can be left wondering whether the mania ended because it reached the end of its natural course. I don’t like being stuck perpetually titrating and prefer stuff that I can get to something therapeutic quickly.

In acute mania I’ve almost always used an antipsychotic in conjunction with the mood stabilizer.

A lot of this is probably a product of my training, though. We use a ton of lithium at my program and it seems to be by far the preferred agent.

 

[tr]

Important point - tardive dyskinesia is a not an extrapyramidal symptom in the way acute dystonias are. If you withdraw antipsychotics in someone experiencing TD it generally gets much worse; whereas switching to a more potent D2 antagonist tends to reduce TD. Tardive dyskinesia is a problem of an excessively sensitive dopaminergic system, probably due to chronic up-regulation due to dopamine blockade. The things that seem to help TD either a) block dopamine receptors more aggressively or b) reduce dopamine uptake into synaptic vesicles and thus deplete available dopamine.

Just stopping someone's neuroleptic when they start developing TD is absolutely the wrong move.

Argh no!! Don't *up* the blockade!
That feeds the cycle!

TD results when the body responds to chronic dopamine blockade by upregulating dopamine receptors. Increasing dopamine blockade in response of course will temporarily reduce the TD, but it's an arms race you can't win, because you precipitate further receptor upregulation. Removing the offending agent results in temporary worsening of TD because now the increased dopamine sensitivity is unopposed, but in the long run the body at least has a chance to readjust dopamine receptor complements back to normal.

You can't 'treat' TD by adding *more* DA blockade. That's how you get permanent intractable dyskinesia. Withdrawing the agent doesn't always work but increasing it is bound to make things worse.

Anyone here had success with valbenazine? I've tried it on one patient so far. She said it made her oral dyskinesias worse and quit it after 3 months.

 

[Animal Mother]

I didn’t know this was a major subject of debate. Practice guidelines will probably list first-line treatment as an antipsychotic + lithium or valproate and usually consider tapering off the antipsychotic when stabilized. For less ill patients, mono therapy with a mood stabilizer may be fine but might take longer. Antipsychotics are significantly more effective than mood stabilizers for manic stuff. Which approach and meds you choose depend on a lot of factors. I still use lamictal quite a bit over lithium and depakote due to tolerability. Also have some bipolar pts on LAIs and a couple on clozapine.

 

[Animal Mother]

Anyone here had success with valbenazine? I've tried it on one patient so far. She said it made her oral dyskinesias worse and quit it after 3 months.

I have a handful of patients on it. It actually really works well. The problem is it’s incredibly expensive (~$7000 per month), and my severely ill patients are costing taxpayers tons of money now getting treatment indefinitely for symptoms that half of them don’t even realize they have. I’ve scaled back prescribing it to new patients just because of the cost. I usually exhaust other options first and save Ingrezza for those higher functioning pts experiencing distress from their symptoms.

 

[clausewitz2]

Argh no!! Don't *up* the blockade!
That feeds the cycle!

TD results when the body responds to chronic dopamine blockade by upregulating dopamine receptors. Increasing dopamine blockade in response of course will temporarily reduce the TD, but it's an arms race you can't win, because you precipitate further receptor upregulation. Removing the offending agent results in temporary worsening of TD because now the increased dopamine sensitivity is unopposed, but in the long run the body at least has a chance to readjust dopamine receptor complements back to normal.

You can't 'treat' TD by adding *more* DA blockade. That's how you get permanent intractable dyskinesia. Withdrawing the agent doesn't always work but increasing it is bound to make things worse.

Anyone here had success with valbenazine? I've tried it on one patient so far. She said it made her oral dyskinesias worse and quit it after 3 months.

Look upthread to the AAN guidelines and the paper I posted. There are very low remission rates following neuroleptic withdrawal and very good reason to think that upregulation in dopamine receptors are not actually the cause of TD. I don't doubt valbenazine works, but if we tool the receptor story to be true, please explain why reducing dopamine availablity in the synaptic cleft and thus achieving less frequent binding of dopamine to it's receptor is going to have a different effect on dopamine receptors than something else binding to them and leading to less frequent binding of dopamine to receptors.

On the other hand, if receptor changes are not actually the cause of tardive dyskinesia, that is a different story. It also makes sense of the fact that SGAs, even those with less affinity for D2, actually do seem quite capable of causing TDs and it is not clear they do so at a lower rate when chronically given at the megadoses that used to be associated with haldol and co.

Obviously the real moral is lowest effective dose always and everywhere. I am just trying to say knee-jerk stopping the neuroleptic is often not going to work but is going to have consequences of its own.

 

[Mass Effect]

I usually go for mood stabilizier + antipsychotic in the acute phase. Once the mania is under control, I generally taper the antipsychotic, but not always. Examples where I may not taper the antipsychotic: patient who prefers the antipsychotic to the mood stabilizer and has the capacity to understand the risks and benefits of both treatments (I had a guy with Bipolar I since the age of 18. I got him at age ~40ish. He'd been through just about all the meds and really preferred Abilify, which also kept him stable. I kept him on that and had no problem with doing so after making sure he understood the other options. I also keep patients on LAI if they're non-compliant or too chronically disorganized to take meds every day. If Haldol dec is the only thing that keeps someone stable due to non-compliance, that's going to be what I recommend.

With regard to lithium -- I use it all the time. Keep in mind that patients can OD on most meds at any time with dire consequences. It's not just psychiatric meds and it's not just lithium. I would never second-guess using what I know is proven to work in the literature because of what the patient could do with it unless they actually have the idea of using it in that way or have previously OD'd on it with poor insight into their current condition. I've also seen chronically suicidal patients on a low dose (600 mg TDD) to protect against suicidality while other meds treat the psychiatric illness, though I've never prescribed it for this reason. When I start someone on lithium, I tell them the risks, including long-term use and the effect on kidneys (I had a 34-year-old patient on dialysis due to chronic lithium use). I also tell them why it's important to get levels and what could happen as a result of lithium toxicity, including neurologic insults and permanent deficits.

I use lamictal for bipolar depression, though I know many who don't believe it does much. I tell patients about SJS and I tell them why it's very important to up-titrate slowly and to take it every day (had a patient who took a dose of 200 as needed when I got her).

During the acute manic phase, I usually do the antipsychotic, mood stabilizer, and prn benzos if needed. Are you guys using benzos scheduled?

 

[Armadillos]

During the acute manic phase, I usually do the antipsychotic, mood stabilizer, and prn benzos if needed. Are you guys using benzos scheduled?

My personal preference for mania is if someone is agitated about being hospitalized and acting out on the unit then schedule TID Ativan +prn. If they are in relatively good behavioral control, but not sleeping then schedule qhs klonopin. (In addition to whatever your using as far as antipsychotic/mood stabilizer).

 

[tr]

Look upthread to the AAN guidelines and the paper I posted. There are very low remission rates following neuroleptic withdrawal and very good reason to think that upregulation in dopamine receptors are not actually the cause of TD. I don't doubt valbenazine works, but if we tool the receptor story to be true, please explain why reducing dopamine availablity in the synaptic cleft and thus achieving less frequent binding of dopamine to it's receptor is going to have a different effect on dopamine receptors than something else binding to them and leading to less frequent binding of dopamine to receptors.

On the other hand, if receptor changes are not actually the cause of tardive dyskinesia, that is a different story. It also makes sense of the fact that SGAs, even those with less affinity for D2, actually do seem quite capable of causing TDs and it is not clear they do so at a lower rate when chronically given at the megadoses that used to be associated with haldol and co.

Obviously the real moral is lowest effective dose always and everywhere. I am just trying to say knee-jerk stopping the neuroleptic is often not going to work but is going to have consequences of its own.

That review cites several different lines of evidence that are consistent with the receptor upregulation hypothesis, and then one study that does not support it. That study looked at differences in DA receptor density between individuals with and without TD, and found no differences. That could argue against the receptor upregulation hypothesis, sure. But it's important to keep in mind that different individuals probably have very different sensitivity thresholds depending on inherent receptor complements and degree of exposure to DA blocking drugs. What you would really want to see is imaging of the same individual's DA receptor complement before and after treatment/development of TD. I don't find this one study particularly strongly convincing against the multiple other lines of animal and human evidence cited by the review.

Regarding the possibility that reducing DA availability could worsen TD in the long term, I think that's a really good point and frankly we do not have very long-term data. It looks like there are a number of observational studies of Ingrezza going out to a year, but TD can take years to manifest in the first place. Hopefully someone more expert than I has already thought about this.

 

[NickNaylor]

Antipsychotics are generally my go-to unless someone is willing to take lithium and there are no medical concerns that would prevent the use of lithium. I generally avoid VPA if possible. BZDs are also helpful though obviously the goal is eliminate those as soon as possible.

Why would you use lamotrigine in the setting of acute mania? What's the rationale? That seems like an odd choice.

 

[Animal Mother]

Why would you use lamotrigine in the setting of acute mania? What's the rationale? That seems like an odd choice.

It’s not for treating mania. Antipsychotics usually work just fine on their own for that. It would be for the maintenance phase when you eventually taper them off of the antipsychotic. Not everyone is agreeable to taking meds long-term that mess up your kidney/thyroid, cause gain weight, and make your hair fall out.

 

[NickNaylor]

It’s not for treating mania. Antipsychotics usually work just fine on their own for that. It would be for the maintenance phase when you eventually taper them off of the antipsychotic. Not everyone is agreeable to taking meds long-term that mess up your kidney/thyroid, cause gain weight, and make your hair fall out.

Yes, I know it’s not for treating acute mania. Seems like an odd choice to automatically start for most people IMO, but yes, you’re right that lamotrigine is beneficial from a side effect perspective.

 

[AD04]

Yes, I know it’s not for treating acute mania. Seems like an odd choice to automatically start for most people IMO, but yes, you’re right that lamotrigine is beneficial from a side effect perspective.

My biggest worry in this case is about patients after they leave the hospital. The outpatient psychiatrists that I've seen tend to keep patients on the same discharge medications instead of titrating down / switching to a something more benign and appropriate (e.g. titrating down valproate after acute mania subsides). Some even increase antipsychotics or keep valproate without a second thought. I was wondering if there is something I could do to guide the follow up psychiatrist to a more benign regimen. Maybe I'm overthinking things and should care less about happen afterwards.

 

[tr]

My biggest worry in this case is about patients after they leave the hospital. The outpatient psychiatrists that I've seen tend to keep patients on the same discharge medications instead of titrating down / switching to a something more benign and appropriate (e.g. titrating down valproate after acute mania subsides). Some even increase antipsychotics or keep valproate without a second thought. I was wondering if there is something I could do to guide the follow up psychiatrist to a more benign regimen. Maybe I'm overthinking things and should care less about happen afterwards.

No I think you are completely right about this, it's a huge problem and it's true that many community psychiatrists are way too hesitant to titrate down off meds that were instituted for acute mania or psychosis but really not required for maintenance. I think a couple of things you can do are to explicitly put your suggestions for discontinuation in the discharge summary, and then also *inform the patient* which med(s) are intended for maintenance and which should be reduced or discontinued eventually.

 

[whopper]

It depends on the patient.

Yep.

Acute mania is a big range. If the guy's punching holes in the wall, running through the streets naked, in short on a YMRS he's scoring close to the maximum you give him way way way more potent meds. Some of the more potent meds are Haloperidol, Olanzapine, Risperidone, Lithium (but you're going to need labs first)

Mania could also be a guy who can still go to work and is safe but showing mania for more than 7 days.

 

[Crayola227]

As far as initiating lamotrigine ASAP, I can kind of understand a certain rationale.

I've heard it said that it seems like most people seem to go directly from mania into depression, like even with appropriate treatment of mania with a drug known to have antidepressant benefit, such as lithium or seroquel, a lot of meds that cool off the mania don't necessarily drop you right off into euthymia without a stop at depression for a while.

So I've heard it said a really important aspect of managing bipolar illness after the manic phase is watching for what seems to be almost inevitable depression for a good number of folks. Not everyone, obviously, but as I understand it, a lot of folks, and it's even to be worth a thought.

So I know some providers that start planning for dealing with the depressive phase in an individual pretty much right away. Which makes sense given how quickly you can get a manic phase under control, it hardly seems like jumping the gun as far as timeline, to consider a plan for depression which is likely to occur.

So especially for someone who has a significant history of bipolar depression, particularly following manic episodes, lamotrigine might be worth thinking about and initiating early. I don't know that would mean starting the med inpt or before discharge or before depression actually manifests, but since it's mostly indicated for prevention of depression as opposed to treatment, it might be a reasonable step if you think that is where things may go.

The tendency to go from mania to depression, I've also heard cited for why someone might also use seroquel during the acute manic phase and going into d/c, basically continuing for some time past mania. Another reason why lithium is favoured as well. Lots of drugs will cool mania, not many of them keep patients out of the dumps.

Given how long it takes to get lamotrigine to therapeutic, if the whole clinical picture in your manic patient seems to suggest that it would be a good plan for them moving forward, it might make sense initiating ASAP.

 

[whopper]

In addition to above, while I generally don't like the idea of more than 1 med at a time (cause if the patient gets better or worse you don't know which med did what), I generally don't see this as a problem with Lamotrigine.

If I started 2 meds at the same time and one of them is Lamotrigine, I've almost never seen anyone get any effect good or bad from the starting dosage of 25 mg daily and as most of you know you have to keep the person on it for 2 weeks before you raise the dosage.

 

[Crayola227]

Look upthread to the AAN guidelines and the paper I posted. There are very low remission rates following neuroleptic withdrawal and very good reason to think that upregulation in dopamine receptors are not actually the cause of TD. I don't doubt valbenazine works, but if we tool the receptor story to be true, please explain why reducing dopamine availablity in the synaptic cleft and thus achieving less frequent binding of dopamine to it's receptor is going to have a different effect on dopamine receptors than something else binding to them and leading to less frequent binding of dopamine to receptors.

On the other hand, if receptor changes are not actually the cause of tardive dyskinesia, that is a different story. It also makes sense of the fact that SGAs, even those with less affinity for D2, actually do seem quite capable of causing TDs and it is not clear they do so at a lower rate when chronically given at the megadoses that used to be associated with haldol and co.

Obviously the real moral is lowest effective dose always and everywhere. I am just trying to say knee-jerk stopping the neuroleptic is often not going to work but is going to have consequences of its own.

I worked with a neurologist at a movement disorders clinic for some time.

Even if the remission rate isn't zero, any improvement in TD is worth considering stopping the antipsychotic. TD is hugely upsetting to many patients, and can cause significant challenges to quality of life both in terms of actual symptoms being limiting as well as the distress.

That said, you have to consider if the patient can be successfully managed off the drug, but if they can, common wisdom is to get them off the med, and I am siding with common widsom here for a reason. Every neurologist I've talked to has been really upset that appropriate steps to dc were not attempted. Because some patients will get better, and some will get worse if the med is continued. Barring the patient having an unacceptable course without the med, it should be dc'd. It can take years to see what may be the full improvement possible from TD, but it happens.

I would honestly try to get my patient in to see a neurologist that is good with movement disorders/TD, to get some input on the best way to handle it from that perspective. Just as they are not the experts on managing someone's bipolar illness, nor are the rest of us as good with handling TD. Many of the approaches to sx management in TD have psychiatric implications as well. I've seen the collaboration between psychiatrist and neurologist be quite useful in the setting of mental illness, medication management, and TD.