• Lithium prevents unipolar and bipolar depressions
• Increases hippocampal and cortical volume [it increases both the memory area the thinking area of the brain. Neuroscientists say this is good—-RDM]
• Reduces dementia diagnosis in old age [i.e., Alzheimer’s]
• 150mg/day slows progression over 1 year of Mild Cognitive Impairment (MCI). [MCI often converts to Alzheimer’s.  In one study, statistically fewer MCI patients converted to Alzheimer’s when on lithium -RDM ]. . 
• Has anti-suicide effects • (at clinical doses and at miniscule doses in water supply).
• Increases and normalizes length of telomeres. [As the terminals of DNA break off, aging inceases–RDM ]
• Reduces incidence of some neurological disorders and cancers.

Addenda from RDM:

#1: Areas of the world with high amounts of lithium in the drinking water [only ~0.3 mg per day] have significantly lower Alzheimer’s rates and lower suicide rates.   Even lithium orotate 5mg once a week [average of 0.7mg/day] should be reduce Alzheimer’s risk.  A daily dose of 5mg seems more reasonable, since it such a small dose.   [Dose for depression is ~150mg to ~750mg per day.   Dose for Manic Depression [Bipolar I Disorder] is ~900 to ~1500mg/day.  

• Lithium orotate 5mg, 10mg, 20mg, and 120mg can be obtained online and in some health food stores. The 120mg pill is high enough to help depression in some people, sometimes within 2 weeks, sometimes gradually over a year or two.
• Lithium orotate, lithium carbonate and lithium citrate [available in liquid] are different salts of lithium. They are equal in effect. When dissolved in blood, the lithium floats separately.
• Prescription lithium carbonate comes as: 150mg, 300mg, 450mg, and 600mg tablets or capsules.

#2:  A surprising number of patients have a surprising antidepressant benefit from lithium 150mg in < 2 weeks when added to stable regimen. [51 of my patients in 3+ years as of 5/24/2018].

#3:  Some patients have good benefit after 1 to 2 years.  This is hard to separate from multitude of other factors over such a long period. This case is particularly convincing:   Since her teens, a 62 y.o. professional experienced 10 minutes intense, barely bearable depression about twice per week. These episodes occurred even when essentially euthymic for long periods on antidepressants. Recently she was amazed to realize that she has not had a single episode in a year.  She cannot remember whether they were decreasing in frequency prior to that. She started on lithium 150 mg two years ago. She has also noticed that her “bottom is higher.”  If she slips below euthymia, it is now more like a 5% drop than a 10% drop.

• PLAN ON USING VERY LOW DOSE LITHIUM PROPHYLAXIS OF BOTH ALZHEIMER’S AND DEPRESSION:
• Add lithium  150mg  If the plan is to take 300 mg, take 150mg for a 1-2 weeks prior to increase to 300.  Lithium works much better at low doses – e.g., 150 mg to 750mg.   At high doses it is not an antidepressant. [For Manic Depression (Bipolar I Disorder) the usual dose of lithium is ~1200 to ~1500mg/day.
  • In the unlikely event that you have side effects on low dose lithium, don’t stop it. Skip lithium for a day or two until the side effects are gone. Then reduce to a much lower dose. If the side effects were on 150 mg, stir the powder of the lithium from a capsule into a glass of juice. If you drink about ¼ of the glass of juice every day, you will be on 37.5mg per day.
• Lithium prevents brain cells from dying. The word neurotrophic is often used for this.  It greatly increases Brain Derived Neurotrophic Factor (BDNF), which is the growth hormone of the brain, which also prevents cell death.
• It prevents Alzheimer’s; in areas of the United States where there is more lithium in the drinking water, there is significantly less suicide and Alzheimer’s compared to area that have less lithium in the water.
  • 1/3 of people with Bipolar I Disorder (manic depression) get Alzheimer’s. But if they are on lithium, only 1/20 get Alzheimer’s.
• If you get a stroke or other brain injury when on lithium, 50% more of your brain survives;
• lithium makes grey matter [the thinking matter] of the brain grow slowly over time. It is the only substance that makes the thinking part of the brain expand.   The neuroscientists say this is a good thing.  
• Lithium helps depression– even in small doses. Large doses do not help depression much.  For depression, it works much better at 300mg to 600mg than at 1200 or 1500mg/day.
• It is possible that low doses of lithium will gradually improve your mood disorder over time. If your chronic depression is vastly better 4 years from now, it could actually be secondary to the small dose of  lithium you were taking.  This is, of course, hard to study.
• Lithium specifically reduces suicide. I have seen people stop having suicidal ideation when lithium was added, even though the lithium did not help their depression.
• Lithium causes no sexual dysfunction, at least in low doses.

other benefits:  Lithium seems to help with herpes and with seborrheic keratosis.

It treats cluster headaches.

Sept 17, 2003 JAMA:  another study that indicates lithium specifically reduces suicide. 20,638 patients with at least one diagnosis of bipolar disorder were analyzed vis a vis suicide and their medication.  Patients on Depakote (divalproate) were 2.7 times more likely to commit suicide than patients on lithium.

NEGATIVES: it increases psoriasis and acne

LARGE DOSES OF LITHIUM  [e.g., ≥ 900mg/DAY] are used to stop mood cycling–not for depression–largely in manic depression (Bipolar II Disorder):

SIDE EFFECTS:      Tell your doctor about any side effects.

Shaking hads

Frequent urinating

Mild thirst—(because of urinating so much)

• Rare/Severe Side Effects: Stop lithium and call me and seek immediate medical attention if any of these side effects happen to you. 

Diarrhea

Vomiting

Drowsiness

Muscle weakness

Loss of ability to move easily

Feeling giddy

Ringing in the ears

Blurred vision

Passing large amounts of urine

• Common signs of LITHIUM TOXICITY are: severe tremor [i.e., more than your usual lithium tremor], diarrhea, confusion, dysarthria [slurring of speech], ataxia [unsteadiness walking], anorexia [severe lack of appetite], nausea, vomiting, and diarrhea

If these occur, stop lithium, drink plenty of fluids with a lot of salt, call me [and/or seek other immediate medical attention].

• The toxic level of lithium is only a little higher than the therapeutic level when treating Manic Depression (Bipolar I Disorder), especially when treating acute mania.  Extra care is necessary when using lithium.  Frequent monitoring of lithium level is necessary when the dose is relatively high.   
  • When lithium is used for depression, the dose is much smaller. Careful, frequent monitoring is not as important.
• After 6-10 manic episodes, lithium stops working. Efficacy approaches that of placebo.  This can be deadly.

AVOID THE SUBSTANCES BELOW:  they cause the body to retain lithium and thus raise lithium levels:

1. Avoid significant reductions in your salt intake. If you take in much less salt than usual, then your kidneys will work hard at keeping salt in the body –not urinating  it out.   But where salt goes, lithium goes.  So the kidneys will also be keeping more lithium in the body and this could build up to toxic levels.   On the other hand, i and side effects making f you were to increase your salt intake—e.g., by eating vastly more potato chips than usual or drinking liquids with salt [such as in hot summers].   When kidneys excrete extra salt, then will also excrete more lithium.   Your lithium level could decrease to a level where it is no longer of benefit.
2. Avoid NSAID’s [non-steroidal anti-inflammatory drugs]  like aspirin and ibuprofen [Advil, Motrin], Celebrex and naproxyn with lithium , as they add to the toxicity on the kidney.  Tylenol/ acetaminophen is OK.
3. Avoid diuretics. [Blood pressure medications that work by causing an increase in urine outflow.]   (These medication can be used with lithium, but downward dosing of the lithium may be necessary as well as more careful monitoring of level.)
4. Avoid ACE inhibitors, [and a few reports of angiotensin II antagonists (e.g., candasartan, losartan, valsartan)], the most important type of blood pressure medication. (These medication can be used with lithium, but downward dosing of the lithium may be necessary as well as more careful monitoring of level.)

Lithium is a very valuable medication, and we should not waste this resource by underusing it or over using it.  If you use too small a dose [or none], it won’t work.   If we use a larger dose than necessary, then we run the risk of excessive side effects, including renal toxicity [kidney damage].  This is a complicated issue.  For example, a patient might have an excellent response to lithium for 30 years at an average level of ~0.9, but then have to stop or drastically reduce lithium because of renal toxicity.  If the same patient were maintained at an average level of ~0.6 or less, he/she might be able to stay on lithium indefinitely.

#1:   If side effects make you reluctant to stay on it, don’t stop it.  Lower it to tolerable dose and talk with your physician. It can have enormous benefit at low doses—if not now, then over time.

#2: After 6-10 affective episodes, the efficacy of lithium approaches that of placebo—i.e., it stops working. So we should avoid major affective episodes—by both prophylaxis and rapid Rx.

#3:  if you are on a substantial dose of lithium (≥ 750mg/day) avoid NSAID’s  like aspirin and ibuprofen [Advil, Motrin] and naproxyn with lithium , as they add to the toxicity on the kidney.  Tylenol/ acetaminophen is OK.

BIRTH DEFECTS: Lithium increases risk to the fetus by 10 to 20 times for Ebstein’s cardiac anomaly.  The incidence when not on lithium is 1/20,000.  The risk 1/1000 and 1/2000 if the mother is on lithium.   1/1000-1/2000  (0.1% to 0.2%)  risk is enormous when you consider that the rate of birth defects is 1-2% in mothers on no medication.  The risk from any medication can be avoided if it is avoided for the first trimester.   Using a lower dose of lithium would also probably help.

The risk of birth defects higher with  Tegretol / carbamazepine  and Depakote  / divalproate –both antiseizure medications that are also used in mood disorders.

NOTE:   A combination lithium and Lamictal/lamotrigine is often an ideal and effective antidepressant.  Both are in low doses.  They work best  for atypical depressions [some history when depressed of oversleeping, over eating, and rejection sensitivity] and/or for anyone in the bipolar spectrum.  When the depression is still severe, more aggressive treatment may also be necessary.