How to choose a mood stabilizer in older adults.
KELLIE NEWSOME: Side effects are different in the young and old. Today, we’ll show you how to choose a mood stabilizer in older adults.
CHRIS AIKEN: Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003. I’m Chris Aiken, the editor in chief of the Carlat Report. And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue.
KELLIE NEWSOME: We’ve broken the paywall for the 15 most read articles from the past year. They are now free online, and today’s podcast is based on #5: Mood Stabilizers for Bipolar Disorder in Older Adults by Rehan Aziz, MD. Like all our podcasts, this one is eligible for a touch of CME. Here’s a preview of the quiz, which you can find on the Carlat website or through the link in the show notes
1. Which side effect of valproate (Depakote) is more common in the elderly
C. Weight gain
D. Elevated ammonia
CHRIS AIKEN: Lithium is often called the gold standard in bipolar disorder, and it works particularly well in patients with classic bipolar symptoms – euphoric manias or hypomanias that are followed by depressions, with full recovery between episodes, as if following the law of what comes up must come down. Lithium also has anti-suicide effects, not a trivial matter in older adults. White men aged 85 and older have the highest suicide rate of any population. If you use lithium in older adults, you are in good company. A recent paper surveyed geropsychiatrists and found that 100% endorsed lithium in older adults. Dr. Aziz found further support in a 2017 study that compared lithium to valproic acid (Depakote) in 224 older adults with a manic, hypomanic, or mixed episode. Both mood stabilizers were equally well tolerated, but lithium reduced manic symptoms more than valproic acid (Young RC et al, Am J Psychiatry 2017;174(11):1086–1093).
KELLIE NEWSOME: Lithium is very effective, it’s the gold standard, and it has one more benefit for the elderly: preliminary studies suggest it prevents dementia, even in low doses. Learn more about that in our Sept 2022 issue online by Dr. Jim Phelps.
CHRIS AIKEN: When dosing lithium in the elderly, aim for slightly lower levels. The brain absorbs more lithium in the elderly. For maintenance treatment and depression, the target levels are 0.6-0.8 for most adults, 0.4-0.8 for ages 60-79, and 0.4 – 0.7 over age 80. That’s quite a spread, which means you really need to invidualize this based on the patient’s response. If they are having active mania, you may need to aim a little higher. Just as with younger adults, we follow thyroid and renal function on lithium, though we check labs more often in the elderly, especiallyy if drug interactions are involved. Another difference is the cardiac risks. An EKG is in order after age 50, and you’ll probably want to avoid lithium if they have sick sinus syndrome, a slowing of the heart where lithium is a relative contraindication. Start slow with lithium in the elderly, such as 150 mg or 300 mg at night and raise by 150-300mg every week. Once at 600 mg QHS for five to seven days, check the lithium level and response. Dosing all at night helps protect the kidneys.
KELLIE NEWSOME: Next is valproic acid, Depakote. This is one of the most commonly used mood stabilizers in late-life mania, but Dr. Aziz’s article suggests that practice might need to shift because lithium has a slight efficacy advantage. However there is one area where valproate tends to work better: Rapid cycling, which means they’ve had at least 4 episodes of mania or depression in a year.
CHRIS AIKEN: Those of you who are bipolar die-hards may have heard that Depakote is also better than lithium in mixed states. That little pearl has since been discredited by a large trial. We’ll cover that more in an upcoming interview with Dr. Gitlin, for now it looks like most mood stabilizers don’t work as well in mixed states – and this problem is not limited to lithium.
KELLIE NEWSOME: And if you’re a podcast die hard, you’ll recall from our last episode that mixed states are more common in older patients with mania. Valproate’s most common side effects are nausea, sedation, and weight gain. Less common are hair thinning or hair loss, thrombocytopenia – that’s decreased platelet count, Parkinsonism, ataxia, hepatotoxicity, and pancreatitis. Those last two – hepatotoxicity and pancreatitis – are actually less likely in older age. One that you see more commonly in the elderly though is elevated ammonia, NH4, which can be quite insidious, causing sedation, muscle twitching, and confusion, known as hyperammonemic encephalopathy. If their ammonia is high, you may need to stop valproate but you can also treat with L-carnitine supplementation and lactulose. Here’s how to dose valproate in older adults. You need to go slow because a little increase will jump the levels up more than it will for younger folk. The reason is that older patients have less protein around to bind to the drug, so valproate circulates more freely. Valproate comes in many formulations, but the ER formulation is the one to remember – it is the best tolerated. For outpatients, start with 250 mg daily and raise to 500 mg daily after one week. That’s right – we said daily – the ER formulation actually peaks 12–15 hours after taking it, so morning dosing can IMPROVE sedation. Morning dosing also lets you get a more accurate serum level, because you can measure the trough right before they take it. Otherwise they’d have to go to the lab in the evening with the way the ER form is released. Aim for a level of 65–90 for active mania. If you need to get a more granular dose, use some depakote DR which comes in smaller increments like 125 mg. The dosing we gave – raising little by little each week – is for oupatients – you may need to go faster if they are in the hospital or having severe symptoms.
CHRIS AIKEN: Carbamazepine is 2nd line after lithium and valproate, because we don’t have as much data on this meds efficacy – particularly over the long term – and there are a lot of drug interactions to worry about in the elderly. Carbamazepine can also cause neurotoxic effects in the elderly like blurred vision, double vision, nystagmus, confusion, and agitation. In terms of labs, we monitor for changes in blood counts (agranulocytosis, aplastic anemia); these are very rare but are seen more often in older adults. OK, I’ve just listed 7 problems that are more common in older patients on carbamazepine, but I’m not done. Hyponatremia, severe allergic rashes, bradycardia and atrioventricular conduction delays, and urinary retention also show up more here. This is a long list, and if you’re exercising or doing chores while you listen to this podcast you might have missed it. That’s OK – just remember this pearl. Carbamazepine has a tricyclics structure. That’s right, as in tricyclics antidepressant. It’s a wonder the thing doesn’t cause mania – but as far as we know it doesn’t. The brain is full of wonders – clearly carbamazepine doesn’t act like a tricyclic antidepressant when it comes to its mood effects, but it does resemble a tricyclic in some of its side effects – cardiac delays, urinary retention, anticholinergic stuff. Dosing of carbamazepine is complicated because this medication induces its own metabolism, requiring a raise in the dose after 4-6 weeks. Check Dr. Raziz’s online article for full details.KELLIE NEWSOME: Our final mood stabilizer is lamotrigine, which is different from the others in that it does not treat active mania. Lamotrigine prevents mania a little, but not enough that you’d want to rely on it as monotherapy in bipolar I. For bipolar II, lamotrigine is a great monotherapy choice because its main actions are against the depressive pole. Lamotrigine is one of the best tolerated mood stabilizers for young and old alike. The main risk is a severe Stevens Johnson rash in the first few months on it, and we can lower that risk by raising the dose slowly – sometimes extra slow if they are on meds like valproate that raise lamotrigine levels. Lamotrigine tends to cause vivid dreams so we dose it in the morning. There are also XR and orally disintegrating versions which are generic and useful if your patient has nausea or difficult swallowing the drug. One side effect we see more often in the elderly is word finding problems. Lamotrigine is an odd one – there’s evidence that it can improve cognition, but cognition is also a side effect, and whether it helps or harms seems to depend on the dose. With younger adults, we rarely see cognitive problems in the typical levels used for mood – 100 to 200mg daily. In older adults, we often have to lower the dose into the 50-150mg range if they have any cognitive slipping.
CHRIS AIKEN: Dr. Aziz’s article has a table with all the dosing details on these drugs. His article focused on the traditional mood stabilizers – and you’ll notice that the antipsychotics are left out. Most experts don’t classify them as mood stabilizers because they don’t have well validated preventative properties. They are better for short term use of acute manic or depressive symptoms, particularly in the elderly where the risk of tardive dyskinesias is double on them, not to mention falls, constipation, Parkinsonism, and temperature imbalance – all of which older patients are more at risk for. It’s hard to say which antipsychotic is best. All of them have liabilities. For the elderly, I’ll usually start with cariprazine (Vraylar). Why? This one has evidence in both mania and depression – the only other that can claim to work on both ends is quetiapine, but quetiapine has more side effects particularly orthostasis and falls. Cariprazine is pretty middle of the road with its side effects – in one meta analysis it was the best tolerated of the antipsychotics in bipolar disorder. But if I’m not as worried about depression I might use aripiprazole, which is one of the better tolerated atypicals and has a lot of studies in the elderly. I may even use risperidone if other meds don’t work. Risperidone rises to the top for efficacy in acute mania, but it also has a high risk of Parkinsonism and elevated prolactin. This podcast is based on an article by Rehan Aziz from the Jan 2023 Carlat Geropsychiatry Report. Dr. Aziz is an associate professor of psychiaitry and neurology at Rutgers Robert Wood Johnson Medical School and he has nothing to disclose.
KELLIE NEWSOME: To read all 15 of the most popular articles, check the link in the show notes or Google “Top 15 Carlat Psychiatry Articles of 2023.” They are all free, and if you want to subscribe take $30 off with the promo code PODCAST. We’ll be back with more greatest hits. Next time: Auvelity, a fast-acting antidepressant. Meanwhile, get daily research updates on Dr. Aiken’s social media feeds – search for ChrisAikenMD on twitter, linkedin, facebook, and that new one – Threads.