CHRIS AIKEN: I’ve an unhealthy worry of sure medicines. Tricyclics, MAOIs, and lithium. All of those have a popularity for hostile results that’s – maybe – unearned. In follow, I’m continuously stunned by how well-tolerated they grow to be. Within the case of lithium, that shock has been confirmed each in medical analysis and affected person surveys. In relation to the unwanted effects that matter most to sufferers – sedation,1 weight acquire,1 and cognition2,3 – lithium’s tolerability ranks proper behind lamotrigine if we take a look at the medical analysis. For instance, the risk of sedation is just one in 16 to 1 in 27 on lithium, in comparison with 1 in 5 for a lot of different temper stabilizers.
However let’s look past the medical analysis. A couple of years in the past a Google firm known as CureTogether posted an online survey asking folks with bipolar dysfunction what they discovered most useful of their restoration. Over 3000 responded, and solely 2 medicines made their prime 10 listing: Lamotrigine and lithium. The remainder of the highest 10 have been behavioral instruments.
KELLIE NEWSOME: Let’s learn all 10 of them:
1. Regimented sleep
2. Lowering alcohol
8. Self-tracking & journaling
9. Lowering caffeine
A lot of the lithium’s hostile results are manageable, and on this podcast we’ll present you learn how to do it. To begin with, titrate lithium slowly. Lithium’s fundamental advantages are in long-term prevention, so there’s normally no cause to hurry it (until you are attempting to assist a manic affected person keep out of the hospital). Begin with 300 mg at evening and lift it by 300 mg each 5-7 days. Reduce these numbers in half if the affected person is frail, aged, or is taking a drugs like a thiazide diuretic that may elevate lithium.
The primary cause folks cease lithium within the early part is nausea. A gradual launch model will cut back that danger, as will taking the lithium after a meal or with a glass of milk. Most different hostile results enhance with gradual launch as nicely – it cuts their general fee by about 50% – besides one: diarrhea. 4 Sufferers with diarrhea on lithium due higher with prompt launch lithium that will get out and in of their system quicker.8
Widespread treatments for nausea (eg, ondansetron, promethazine, ginger capsules) or diarrhea (eg, loperamide, milk of magnesia) are protected to take with lithium.
CHRIS AIKEN: One other means to enhance unwanted effects is to decrease the dose. For many sufferers, the optimum blood degree for long-term prevention is 0.6, or someplace within the vary of 0.4-0.8. The identical blood degree is right for treating melancholy – whether or not bipolar melancholy or unipolar. The one place the place you’ll want a excessive dose is in acute mania, the place serum ranges of 0.8-1.2 are normally essential.
Children want the identical blood ranges as adults, however the aged are completely different. Purpose for a serum degree that’s 30% beneath the same old in sufferers over age 60, after which additional personalize that dose based mostly on their response.6 The blood-brain barrier turns into extra permeable as we age, so extra lithium will get into the older mind at decrease serum ranges. Conservative dosing within the aged has one other profit: These sufferers are way more delicate to lithium’s unwanted effects, notably imbalance and tremor.
KELLIE NEWSOME: Tremor is among the most typical unwanted effects with lithium, and it is extremely delicate to the dose. Step one is to decrease caffeine and – if potential – different tremor-promoting medicines like bupropion (Wellbutrin) or atypical antipsychotics. Beta-blockers assist lithium tremor, and though propranolol is probably the most generally used, there may be analysis supporting different beta blockers like atenolol, metoprolol, and nadolol for lithium tremor.7 The typical dose of propranolol is round 120 mg/day. Often we begin with prompt launch propranolol after which change to the prolonged launch after determining how a lot they want.
Chances are you’ll learn that beta-blockers work together with lithium, and that is true, however the interplay is minor. They normally elevate its ranges by about 20%.
CHRIS AIKEN: Another choice with dual-benefits for lithium tremor is nimodipine. This calcium-channel blocker has good analysis for important tremor, and is used third-line for mania and mania and speedy biking.7 It’s nicely tolerated, and a typical goal dose is 120mg a day. In case your affected person doesn’t wish to add one other treatment in and prefers pure treatments, there’s high-dose vitamin B6. In doses from 900-1200 mg/day vitamin B6 improved lithium-related tremor, and it might cut back hostile results on antipsychotics as nicely. B6 has open-label knowledge for akathisia and tardive dyskinesia.7 Though pure, high-dose B6 just isn’t danger free and may hardly ever trigger neuropathy which normally resolves with discontinuation of the vitamin. It’s onerous to seek out B6 in a dose that top, so I hold an inventory of merchandise on my website (moodtreatmentcenter.com/merchandise).
KELLIE NEWSOME: Weight acquire is a facet impact on most affected person’s minds when contemplating lithium, however the danger of great weight acquire is far decrease than most sufferers count on. I begin with some reassuring knowledge: In a big meta-analysis, sufferers really misplaced weight on lithium in the course of the acute part of remedy.20 Over the long-term, nonetheless, weight acquire is feasible. About 1 in 3 sufferers will acquire 4-10 lbs on lithium, and most of that weight acquire happens within the first few years of remedy.9
However an important a part of this training is to let your affected person know that there’s something they’ll do about it. Lithium will make them thirsty, so in the event that they follow water and keep away from caloric drinks they’ll decrease that danger – and that features avoiding weight loss plan delicate drinks which really trigger weight acquire via oblique metabolic results despite the fact that they don’t have any energy of their very own.
One other strategy to cut back weight acquire is to optimize thyroid operate on lithium. Past that, any affordable approaches for weight reduction can be utilized, similar to weight loss plan, train, or medicines like topiramate 50-100 mg/day.
Like most psychiatric medicines, lithium may cause sexual dysfunction. We all know of 1 evidence-based treatment for this: Aspirin, not less than for males. In a randomized, double-blind trial of males with sexual dysfunction on lithium aspirin 240 mg/day improved the issue.10
Phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil) may also be used.
CHRIS AIKEN: Now we get to probably the most critical danger with lithium: Renal insufficiency. Here’s what I inform sufferers. As you age, the kidneys are inclined to decelerate, and lithium could make them decelerate much more in some sufferers who take it long run. We’ll monitor the kidneys and should have to decrease or cease it if we see this taking place, as a result of if we don’t catch it it might – very hardly ever – go on to kidney failure.
There are not less than 3 methods to guard in opposition to renal issues on lithium.
First, give all the dose at evening. This technique improved renal operate in a couple of long run comparability research.4,8
Subsequent, keep away from poisonous ranges. Excessive ranges of lithium can kill kidney cells, and that could be why one giant research discovered a direct correlation between variety of poisonous episodes on lithium and renal issues. It additionally seemed just like the kidneys have been spared in that research if the lithium ranges have been saved at or beneath 0.8.
Be careful for excessive polyuria and polydipsia. These are indicators of nephrogenic diabetes insipidus, which is each an hostile impact on lithium and a danger issue for renal insufficiency. A laboratory take a look at will reveal elevated sodium within the blood and really dilute urine; test for urine osmolality, urine sodium, primary metabolic panel. Nephrogenic diabetes insipidus is a danger issue for future renal insufficiency, and there may be some proof that treating the syndrome can cut back that danger by stopping fibrotic adjustments within the kidneys, similar to with amiloride.11
If the serum creatinine begins to rise, decrease the lithium to the bottom efficient dose and test it extra typically. Seek the advice of a nephrologist if the serum creatinine rises to 1.5 mg/dl.8
One other medical danger with lithium is hypothyroidism. That is normally treatable with a thyroid complement, and also you don’t have to cease lithium as a result of the thyroid operate goes down. For those who do come off lithium, the hypothyroidism normally resolves – however not at all times – so you possibly can gingerly attempt to come off the thyroid treatment whereas checking ranges.
Hypothyroidism could also be value addressing on lithium even when it’s subclinical. A managed research from the Mayo Clinic discovered that sufferers prescribed lithium have been much less more likely to relapse into melancholy if their TSH was near 2.4 microIU/ml.12
KELLIE NEWSOME: Lithium has a number of dermatologic dangers. It might trigger pimples and psoriasis, and a few sufferers report thinner, brittle hair on it though overt hair loss is uncommon.
Any customary therapies for pimples can be utilized with lithium,10 however one to contemplate is minocycline. This antibiotic has neuroprotective and antiinflammatory results, and it might deal with melancholy, in response to a handful of small-to-medium dimension managed trials in bipolar and unipolar melancholy (the dose of minocycline for melancholy is 200 mg/day;13 decrease doses are used for pimples, eg, 1 mg/kg/day).14
I counsel sufferers to take a probiotics together with their antibiotic to keep away from issues within the intestine microbiome. Probiotics even have a rising proof base in melancholy, nervousness, and bipolar, and there’s some proof that probiotics assist pimples. Psoriasis – these scaly, dry patches of pores and skin that worsen within the winter and have a tendency to indicate up on the elbows, knees, palms, face, or again – is a relative contraindication with lithium. For this I’ll discuss with a dermatologist, however I’ll counsel 2 CAM therapies that may assist bipolar and psoriasis. In a couple of small trials, psoriasis improved with inositol (6 g/day)8 and excessive dose omega-3 fatty acids (4-6 g/day)15 – each of that are pretty danger free and have small research in bipolar melancholy.
Though lithium is a first-line remedy that ranks excessive on the listing of affected person’s favorites, it has fallen out of normal use, notably in the USA.16,17 When medicine meet that destiny, they’re typically reserved for probably the most refractory sufferers, similar to sufferers with extreme mania who require excessive doses, which doesn’t assist lithium’s popularity. Opposed results mustn’t stand in the best way of its utilization – when they’re managed rigorously and I’ve discovered that surprisingly tolerable.
However nonetheless, about 1 in 10 sufferers don’t tolerate it and should cease the treatment.
About 1 in 3 sufferers with bipolar dysfunction reply very nicely to lithium – and these are usually the sufferers with traditional, “textbook case” bipolar – with euphoric manias which might be cleanly separated from depressions, and low charges of speedy biking, combined states, and main psychiatric comorbidities. These needn’t be sufferers with bipolar I although – sufferers with bipolar II can have traditional hypomanias, and in a single research lithium labored higher for bipolar II than bipolar I.
When lithium works nicely, its advantages are inclined to final. It’s among the many prime medicines that forestall hospitalization.19 Its preventative results have outshined different temper stabilizers, like valproate, in head-to-head trials, and it has added advantages which might be related to bipolar dysfunction. Lithium prevents suicide, dementia, and a few new proof suggests it might decrease the stroke danger and help cardiac reworking after a coronary heart assault – that’s excellent news if it holds up, as a result of stroke is the #1 reason behind demise in bipolar dysfunction, and heart problems tends to start out 20 years earlier in sufferers with bipolar dysfunction than it does within the normal inhabitants.17-18
KELLIE NEWSOME: I hope you’ll be part of us once more for extra sensible updates on PsychPearls, and you may as well catch us each Monday on the Carlat Psychiatry Podcast.
Chris Aiken, MD, is the Temper Issues Part Editor for Psychiatric OccasionsTM, the Editor in Chief of The Carlat Psychiatry Report,and the Director of the Mood Treatment Center. He has written a number of books on temper issues, most just lately The Depression and Bipolar Workbook. He may be heard within the weekly Carlat Psychiatry Podcast along with his cohost Kellie Newsome, PMH-NP. The writer doesn’t settle for honoraria from pharmaceutical firms however receives royalties from PESI for The Depression and Bipolar Workbookand from W.W. Norton & Co. for Bipolar, Not So Much.
Kellie L. Newsome, PMH-NP, is the cohost of the Carlat Psychiatry Podcast and can be a practising Psychiatric Psychological Well being Nurse Practitioner in Winston Salem, NC, on the Temper Remedy Middle. Raised in Tasmania, Australia, Kellie moved to the USA in 1998.
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