artorious22

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Hi,
I was wondering do certain lithium levels correspond with how well they will work in certain instances? Like a level of 0.5-0.7 for helping with suicidality of a level of 1.0 or so for mood stabilization?

Please advise on this.

Thanks
 

milesed

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With the adolescents I see, they often respond to lower than accepted therapeutic levels, but they often need a lot more mg/day to get there (better functioning kidneys?). I tell them this up front and leave the level sub-therapeutic as long as symptoms are doing well. I know of no studies supporting this or linking a specific level to a specific response.
 

hamstergang

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With the adolescents I see, they often respond to lower than accepted therapeutic levels, but they often need a lot more mg/day to get there (better functioning kidneys?).
On average, compared to adults, kids have an increased kidney : body size ratio and also and increased body water : body fat ratio. So despite the smaller overall size, the volume of distribution and clearance are not proportionately smaller (if even smaller at all? I don't know the real numbers).
 
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artorious22

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Is it ok to give lithium to a pregnant woman who is very manic and at say 3rd trimester? if nothing else is working?

Also, if someone has CKD, with Cr of like 5-6, would you guys do it?

I know in textbooks, of course not, but if the benefits outweigh the risks, do you guys do it in real life?
 

splik

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why wouldn't you give lithium in the trimester? the fetus has developed at that point. I certainly have and would - pretty safe and we have the most data about it in pregnancy out of the psychotropics
 

splik

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as for lithium in CKD - no I wouldn't start someone on it but if it had been proven to effective or lifesaving for them, the patient wanted to be on it, and nephrology was on board then yes I have and would use it. I don't think you will find much sympathy from a nephrologist for initiating lithium in someone whose kidneys were packed in though and I can't say I'd blame them
 

tr

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OK to give Li in pregnancy, certainly 3rd tri is relatively low risk for congenital anomalies (biggest concern is for cardiac/Ebstein's anomaly which is in 1st tri).
Make sure to stop Li 24-48 h before delivery because large fluid shifts during delivery can cause wild swings in serum levels and raise risk for toxicity. Restart after baby is out and mom stabilized.

I rec avoid breastfeeding on lithium because it passes into breastmilk in quantity and there have been several case reports of nursing infants with thyroid or other toxicity (usually premature, newborn, or dehydrated infants). MGH has a monitoring protocol for nursing infants on lithium but it requires regular blood draws from the baby which are not trivial and really not worth the pain or the risk IMO. Better to stick with bottle feeding.

Agree with splik on the CKD. Would avoid at all costs unless previously shown to be the only effective medication for that patient and nephrologist agreed and you had developed an appropriate monitoring plan in consultation with renal.
 
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Crayola227

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Aside from ZERO medication, what would be your ideal regimen in a pregnant woman for maintanence in bipolar? Say this is your bipolar daughter planning a pregnancy and you have a pretty free hand in what you can do

Or more than one regimen depending on drug and when you can start/stop it during the pregnancy?

I hope my question is clear
 

hamstergang

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Aside from ZERO medication, what would be your ideal regimen in a pregnant woman for maintanence in bipolar? Say this is your bipolar daughter planning a pregnancy and you have a pretty free hand in what you can do
Haldol is what I'd go for, but I don't know how great it really is. Although we don't have any controlled data in human pregnancy, it's been used long enough in the SMI population that we have something backing the lack of known problems.

I did this once during residency but, due to the nature of residency, I didn't get enough follow up to see how it went.
 
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clausewitz2

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Aside from ZERO medication, what would be your ideal regimen in a pregnant woman for maintanence in bipolar? Say this is your bipolar daughter planning a pregnancy and you have a pretty free hand in what you can do

Or more than one regimen depending on drug and when you can start/stop it during the pregnancy?

I hope my question is clear
In our corner of the world, lamotrigine + a neuroleptic seems like a popular choice. Lamotrigine is tricksy if they were on it before pregnancy, because the levels can drop precipitously (like to 10℅ of normal concentration) and so the dose will have to go up. This is also one of the few scenarios in which drawing lamictal levels makes sense.

There are more specific guidelines for managing lamotrigine in pregnancy in the neurological literature. There is maybe a risk of cleft palate, but it isn't clear from Danish registry studies if this is real and the risk of serious congenital abnormalities is certainly much lower than other mood stabilizers.
 

PistolPete

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In our corner of the world, lamotrigine + a neuroleptic seems like a popular choice. Lamotrigine is tricksy if they were on it before pregnancy, because the levels can drop precipitously (like to 10℅ of normal concentration) and so the dose will have to go up. This is also one of the few scenarios in which drawing lamictal levels makes sense.

There are more specific guidelines for managing lamotrigine in pregnancy in the neurological literature. There is maybe a risk of cleft palate, but it isn't clear from Danish registry studies if this is real and the risk of serious congenital abnormalities is certainly much lower than other mood stabilizers.
Why not just manage her with one atypical antipsychotic, rather than also with lamotrigine, in order to reduce cumulative effects on the fetus? Or use haldol alone?
 

clausewitz2

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Why not just manage her with one atypical antipsychotic, rather than also with lamotrigine, in order to reduce cumulative effects on the fetus? Or use haldol alone?
My guess is that the culture around here has a lot of people ending up on lamotrigine for maintenance against bipolar depression, and pregnant ladies end up coming to the attention of the reproductive psychiatry-minded folks around here when their usual med regimen stops working. Hence the combo.
 

Crayola227

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thanks for the responses guys. learning a lot here.

say they went into pregnancy with nothing on board or maybe just lamotrigine, and were OK but needed something added down the road to maintain control, what would you add and why?

(like add ___ for mania, or ____ for depression, ____ for mixed episode)
 

splik

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thanks for the responses guys. learning a lot here.

say they went into pregnancy with nothing on board or maybe just lamotrigine, and were OK but needed something added down the road to maintain control, what would you add and why?

(like add ___ for mania, or ____ for depression, ____ for mixed episode)
cookie cutter approaches are of least use in these sorts of situations. personally I try and avoid or minimize medications as much as possible (though I am in the minority of psychiatrists who believe that most patients with bipolar disorder do not need long-term medication). I would prioritize exercise, behavior activation, and psychotherapy for the depressive phase of bipolar disorder, and for the more severe cases offer ECT as a non-medication alternative. I would avoid haldol in non-psychotic bipolar patients given its propensity to cause depression, though it is probably the most effective acute treatment for mania. I would use benzodiazepines judiciously from the second trimester onwards (there is a small risk of cleft lip/palate in 1st trimester) though with great caution late in pregnancy (risk of floppy baby syndrome and neonatal withdrawal syndrome). Second generation neuroleptics such as olanzapine have a role in mania and possibly depression. however if we have a woman with gestational diabetes or who is african american/latina and at higher risk I would use a neuroleptic with a lower metabolic burden. lithium has been around long enough and there are a number of good registries that it is definitely my go-to for bipolar disorder.

It's a difficult call - there evidence is fairly overwhelming that being depressed/manic during pregnancy is bad for the baby, and there is an increased risk of complications. In some cases there may be quite clear risk to the fetus and the benefits of meds outweight the risks. What meds don't appear to do is reduce the psychiatric sequalae of mom being acutely depressed/manic during pregnancy, but of course separating out genetic/epigenetic/environmental/drug exposure risks is tricky. At the same time, if there are complications, even if they are not caused by the drugs (and of course it can be hard to tease out the effects of mentally ill mom from the drugs), the mother will likely blame herself for taking medications or blame you etc. As such, where possible, extensive counseling and collaboration with the patient and partner/family is important presenting all of the available options, making your own recommendation but allowing the patient to make her own decisions as far as possible.

Of all the inequalities that exist in mental health care, they are no more striking than in perinatal psychiatry. The world of difference between the care that affluent women receive and the poor receive is staggering and shameful. There is a reason the US has such high maternal mortality rates (largely explained by African American women). Seriously mentally ill women often do not receive obstetric care, let alone mental health care during pregnancy until they end up hospitalized. One the other end of the spectrum are mildly depressed pregnant women paying cash for TMS.
 

Armadillos

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Haldol is what I'd go for, but I don't know how great it really is. Although we don't have any controlled data in human pregnancy, it's been used long enough in the SMI population that we have something backing the lack of known problems.

I did this once during residency but, due to the nature of residency, I didn't get enough follow up to see how it went.
If using for maintenance why haldol over lurasidone or some other atypical monotherapy?
 

thoffen

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Regardless of what treatment you choose for whatever reason, the biggest mistake made is an inappropriate benefit-risk assessment. The benefit to both mother and child's development / attachment must be considered to the risk of both mother and fetus AND also the risk to both mother and fetus of inadequately treated bipolar disorder both pre and post-natal.
 
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hamstergang

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If using for maintenance why haldol over lurasidone or some other atypical monotherapy?
Haldol's been around longer so we can be more sure of its relative safety. We basically say these meds are ok to use based on an absence of evidence of teratogenicity so a longer time period for this absence of evidence means something.
 

Merovinge

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Haldol's been around longer so we can be more sure of its relative safety. We basically say these meds are ok to use based on an absence of evidence of teratogenicity so a longer time period for this absence of evidence means something.
Second generation drugs have been around for quite awhile by this point. I was initially very skeptical about Seroquel as a drug for anything but its well evidenced for Bipolar Disorder and appears to be pretty safe. You do have Spilk's concerns about metabolic effects, which are patently true, so they are not ideal for every patient, although even then I think most folks can withstand a trial of Abilify or Latuda metabolically.

Anecdotally and empirically non-treatment during pregnancy is a huge issue given the increased rate of mood episodes. After seeing a lady who had her first manic episode with her first child impale her mother to death driving 80 mph in a 25 mph zone and then seeing her psychiatrist D/C her mood stabilizer during her second pregnancy because they "don't feel comfortable" treating pregnant patients... well lets just say the janitors in OB triage were not going to have a great day after she defecated all over the floor while singing/dancing.
 
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michaelrack

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Also, if someone has CKD, with Cr of like 5-6, would you guys do it?
?
If someone has a Cr in that range, they would likely be on dialysis. So I would dose lithium post-dialysis http://www.ncbi.nlm.nih.gov/pubmed/16628141

Lithium can be used in CKD http://www.ncbi.nlm.nih.gov/pubmed/26535805. My main concern in these patients, say with a Cr in the 1.4-2 range, is toxic lithium levels. If u are going to use Li in CKD, start low and go slow and carefully monitor levels. also, make sure the patient has seen a nephrologist
 
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hamstergang

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Second generation drugs have been around for quite awhile by this point. I was initially very skeptical about Seroquel as a drug for anything but its well evidenced for Bipolar Disorder and appears to be pretty safe. You do have Spilk's concerns about metabolic effects, which are patently true, so they are not ideal for every patient, although even then I think most folks can withstand a trial of Abilify or Latuda metabolically.
Seroquel was FDA approved 19 years ago, Abilify 14 years ago, and Haldol 49 years ago. Since we can't have a clear, controlled trial, I find it comforting to be able to tell the patient that the medication I'd recommend has been in use since before either of us were born. I wouldn't fault the use of the atypicals, though, and would still consider them.
 
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tr

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Haldol's been around longer so we can be more sure of its relative safety. We basically say these meds are ok to use based on an absence of evidence of teratogenicity so a longer time period for this absence of evidence means something.
Whoa you guys. There have now been a sufficiently large number of controlled observational studies of psychotropics in pregnancy that we do not need to rely on accumulated years of clinical use in the absence of controlled studies. None of the potential negative effects from these drugs are common or obvious enough that a single clinician would be likely to notice them without a rigorously chosen comparison group, hence 'years of clinical use' really does not mean very much.

Haldol has actually not been as well studied in pregnant women as the older SGAs, although it was the go-to for pregnant women in past decades based pretty much solely on this 'clinical-use' thing. FGAs as a class have been clearly associated with preterm birth and reduced birth weights however. (Newham et al. BJP 192:333, Reis et al. J Clin Psychopharm 28:279, Habermann et al. J Clin Psychopharm 33(4):453, Lin et al., Schizophrenia Res 2010; 116: 55–60 )

We do have quite a bit of info on the older SGAs (olanzapine, risperidone, quetiapine) in this population and although most of the available studies are underpowered to rule out small increases in MCM rates, most recently, a study of 1.3 million pregnant women on Medicaid with 9K on antipsychotics confirmed the suggestion of older, smaller studies that congenital malformations are not increased with either FGA or SGA, although a possible small increase with risperidone was flagged for the first time. (Huybrechts et al., JAMA Psychiatry Aug 2017)

All other things being equal my go-to mood stabilizers in pregnant women are lamotrigine (good evidence going out to 6 years of absolutely normal cognitive development in babies exposed antenatally to lamotrigine: Meador et al. New England Journal of Medicine, 360(16), 1597-1605 and The Lancet Neurology 12, no. 3 (2013): 244-252)
and Seroquel (because of evidence of lower rates of placental passage with this than with other atypicals and Haldol (Newport et al. AJP 164:8, 2007)).

But all other things are rarely equal and in general one should privilege whatever medication has been shown to be helpful for the particular individual. No point in putting someone on lamotrigine if it's going to be insufficient to control their rampant mania resulting in multiple undesirable pregnancy outcomes. Polypharmacy should be avoided insofar as possible as adverse outcomes when they occur are almost always linked to women using multiple psychotropics at once (Sadowski et al., BMJ Open 2013;3:e003062).


If using for maintenance why haldol over lurasidone or some other atypical monotherapy?
There has never been a single study of lurasidone (or the other newer SGAs like asenapine, iloperidone) in pregnant women and I therefore never use them in this population. Absence of evidence of harm is not evidence of absence of harm.


Overall I would like to point out that the perinatal psychiatry literature is extremely complex to interpret because RCTs are not a possibility. A close reading of the methods is essential to understand whether any given study yields important information or just bunk, and it's often very difficult to interpret the literature without a good grasp of what has been published in the past and how new work fits into that framework. It's hard to attain or maintain this level of familiarity without at least some formal training in this area.

For general psychiatrists, unless you have had explicit training in perinatal psychiatry I would strongly recommend getting a consultation from someone who specializes in this if you need to treat a pregnant patient.