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Lithium

Category: Medicines

Type

Involuntary

Introduction and description

Lithium compounds are used as a psychiatric medication. A number of salts of lithium are used as mood-stabilizing drugs, primarily in the treatment of manic depression [bipolar disorder], where they are used to treat mania, both acutely and in the long term. According to Wikipedia “lithium is more effective in preventing mania than depression”.  The main salts are

  • Lithium carbonate (Li2CO3), sold under several trade names, is the most commonly prescribed
  • Lithium citrate (Li3C6H5O7) is also used in conventional pharmacological treatments.
  • Lithium orotate (C5H3LiN2O4), has been ‘presented as an alternative’

Lithium bromide and lithium chloride have been used in the past, however they 'fell out of use in the 1940s when it was discovered they were toxic'. Many other lithium salts and compounds exist, such as lithium fluoride and lithium iodide, but ‘they are presumed to be toxic substances and have never been evaluated for pharmacological effects’.  Just as an added interest lithium disilicate is used in dental fillings.

Lithium treatment was previously considered to be unsuitable for children, “however, it is now being used in the treatment of early-onset bipolar disorder in children as young as eight. The required dosage (15–20 mg per kg of body weight) is slightly less than the toxic level, requiring blood levels of lithium to be monitored closely during treatment”.

I do not know what' early onset bipolar disorder' is.  Presumably it is children who are a little too enthusiastic as opposed to manic.  And who occasionally become a bit sad as opposed to depressed [sorry for the cynicism].

Upon ingestion, lithium becomes widely distributed in the central nervous system and interacts with a number of neurotransmitters and receptors.  The specific biochemical mechanism of lithium action in mania is unknown.

Background

Lithium was first used in the nineteenth century as a treatment for gout after scientists discovered that, at least in the laboratory, lithium could dissolve uric acid crystals isolated from the kidneys.

The levels of lithium needed to dissolve urate in the body, however, were toxic. Because of theories linking excess uric acid to a range of disorders, including depressive and manic disorders, Carl Lange in Denmark and William Alexander Hammond in New York used lithium to treat mania from the 1870s onwards. By the turn of the century, this use of lithium was largely abandoned, 'due to the reluctance of the pharmaceutical industry to invest in a drug that could not be patented'.

As accumulating knowledge indicated a role for excess sodium intake in hypertension and heart disease, lithium salts were prescribed to patients for use as a replacement for dietary table salt (sodium chloride). This practise was discontinued in 1949 when reports of side effects and deaths were published, leading to a ban of lithium sales.

The use of lithium salts to treat mania was promoted by the Australian psychiatrist John Cade in 1949. Cade was injecting rodents with urine extracts taken from schizophrenic patients, in an attempt to isolate a metabolic compound which might be causing mental symptoms. Since uric acid in gout was known to produce hallucinations, Cade needed soluble urate for a control. He used lithium urate, already known to be the most soluble urate compound, and observed that this caused the rodents to be tranquilized. Cade traced the effect to the lithium ion itself. Solely as a result of this effect, Cade proposed lithium salts as tranquilizers, and ‘soon succeeded in controlling mania in chronically hospitalized patients’.

The rest of the world was 'slow to adopt this treatment’, largely because of 'deaths which resulted from even relatively minor overdosing' [sic]. Largely through the efforts of Denmark's Mogens Schou and Poul Baastrup in Europe, and Samuel Gershon in the U.S., this resistance was ‘slowly overcome’. The application of lithium for manic illness was approved by the United States Food and Drug Administration in 1970.

In 2009, Japanese researchers at Oita University reported that low levels of naturally-occurring lithium in drinking water supplies reduced suicide rates.  This research was flawed.

We measured lithium levels in tap water in the 47 subdivisions of the East of England and correlated these with the respective suicide standardised mortality ratio in each subdivision. We found no association between lithium in drinking water and suicide rates across the East of England from 2006 to 2008.  PMID:  21525523

Neverthless, psychiatrist Peter Kramer raised the hypothetical possibility of adding lithium to drinking water.  Presumably the 99% of us that are not suicidal can go hang.   Be afraid - be very afraid.

Side effects

  • Dehydration and sodium imbalance  – as lithium interferes with the regulation of sodium and water levels in the body, lithium can cause dehydration. Dehydration, which is compounded by heat, can result in increasing lithium levels. The reason why water is lost is because Lithium inhibits the action of ADH (antidiuretic hormone)which enables the kidney to reabsorb water from urine. This causes an inability to concentrate urine leading to consequent loss of body water and thirst
  • Kidney disease – "In the long-term use, therapeutic concentrations of lithium have been thought to cause histological and functional changes in the kidney. The significance of such changes is not clear, but is of sufficient concern to discourage long-term use of lithium unless it is definitely indicated".
  • Diabetes - An important potential consequence of long-term lithium usage is the development of renal diabetes insipidus (inability to concentrate urine).

We report the case of a patient who developed severe hypernatraemic dehydration following a head injury. Ten years previously he had been diagnosed to have lithium-induced nephrogenic diabetes insipidus, and lithium therapy had been discontinued. He remained thirsty and polyuric despite cessation of lithium and investigations on admission showed him to have normal osmoregulated thirst and vasopressin secretion, with clear evidence of nephrogenic diabetes insipidus. Lithium induced nephrogenic diabetes insipidus is considered to be reversible on cessation of therapy but polyuria persisted in this patient for ten years after lithium was stopped. PMID:9226773

  • Thyroid disease - Lithium “reduces the activity of thyroid hormone resulting in hypothyroidism”.
  • Encephalopathy - haloperidol, fluphenazine, or flupenthixol "may be hazardous when used with lithium; irreversible toxic encephalopathy has been reported". 
  • Poisoning - Concurrent use of diuretics that inhibit the uptake of sodium by the distal tubule (e.g. thiazides) is also hazardous  - "plasma concentrations in excess of 2.5 mmol Li+/L are usually associated with serious toxicity requiring emergency treatment. When toxic concentrations are reached, there may be a delay of 1 or 2 days before maximum toxicity occurs".  For example,

We report a case of a 75-year-old male patient who presented to the emergency room with arterial hypotension and impaired vigilance. The patient was on lithium therapy due to mood disorder. One month earlier medication with a betablocker, a loop-diuretic and an ACE-inhibitor had been started due to heart failure. Findings at admission included renal insufficiency, pneumonia and a slightly increased serum level of lithium. Three days later his Glasgow Coma Scale Score was 7, ..Diagnosis of chronic intoxication with lithium was made PMID: 19551652

  • Physical nervous system disease The most common side effects are an overall dazed feeling and a fine hand tremor. These side effects are generally present during the length of the treatment, but can sometimes disappear in certain patients.  "Li+ is similar enough to Na+ that under experimental conditions, Li+ can replace Na+ for production of a single action potential in neurons".
  • Headache
  • Mineral imbalance - Lithium unbalances electrolytes; to counteract this the medical people suggest ‘increased water intake is suggested’.
  • Brain damage – “The average developmental score for the lithium-exposed group of children was 7–8 points lower than the control group (siblings), but well within the normal range of 100±15” [sic].  And for adults “Lithium toxicity may occur in persons taking excessive amounts accidentally and in patients who accumulate high levels during ongoing chronic therapy. As the control of dose is difficult to estimate overdose is a high risk. The manifestations include asthenia [dizziness, weakness, fatigue], ataxia [dysfunction of the nervous system], muscle twitching, confusion, lethargy, seizures, convulsions and coma. Persons who survive a poisoning episode may develop persistent neurotoxicity
  • Memory impairment - if it does not cause permanent brain damage it may cause memory impairment.   "Lithium treatment has been found to inhibit the enzyme inositol monophosphatase, leading to higher levels of inositol triphosphate. This effect was enhanced further with an inositol triphosphate reuptake inhibitor. Inositol disruptions have been linked to memory impairment and depression".
  • Obesity - Lithium is known to be responsible for significant amounts of weight gain.  
  • Depression – lithium “may cause more depression than before with suicidal thoughts and actions
  • Nystagmus - Lithium is “a well known cause of downbeat nystagmus The nystagmus may be permanent or require several months of abstinence for improvement".
  • Damage to unborn babies - Lithium is "a teratogen causing birth defects in a number of new born babies. If taken during a woman's pregnancy can cause her child to develop Ebstein's anomaly, a heart defect".
  • Death -  Overdosage, usually with plasma concentrations over 1.5 mmol Li+/L, may be fatal, and toxic effects include tremor, ataxia, dysarthria, nystagmus, renal impairment, confusion, and convulsions.

The use of lithium carbonate in the treatment of mood disorders - William T. Brown, m.d., ph.d., Vancouver, B.C.
During the initial weeks of lithium therapy some patients may experience  gastrointestinal irritation nausea, abdominal pain and loose stools. There may also be muscular weakness, a dazed feeling, polyuria, thirst and fine tremor of the hands. ....The fine hand tremor, polyuria and thirst may persist for long periods, even when the patient is on an extremely low dose of lithium. The tremor does not respond to antiparkinsonian drugs. These reactions are reversible and will disappear when lithium therapy is withdrawn. …Toxic manifestations as they affect organ systems are:

  • Gastrointestinal: anorexia, nausea, vomiting, diarrhea, thirst, weight loss, dry mouth
  • Neuromuscular: weakness, ataxia, tremor, muscle hyperirritability, increased deep tendon reflexes, choreoathetotic movements Central nervous system: incontinence, slurred speech, blurred vision, dizziness, vertigo, epileptiform seizures
  • Mental status: somnolence, confusion, stupor, coma
  • Cardiovascular: pulse irregularities, hypotension, hypertension, electrocardiographic changes (T-wave flattening or inversion), peripheral circulatory failure
  • Miscellaneous: polyuria, glycosuria, dehydration, headache, anemia, leukopenia, dryness and thinning of hair, skin rash, leg ulcers.

Enough said.

How it works

People on lithium get hallucinations, visions, out of body experiences and occasionally near death experiences.  Why?

We could simply say well they are being poisoned and leave it at that, I think the side effects alone are enough to convince anyone that poisoning is the principle cause for any spiritual experiences, but I think it also helps to look at why Lithium theoretically 'sedates' a manic depressive person.

Remembering that manic depression is caused by brain damage, it cannot correct or even compensate for the brain damage, all it can do is help to dampen down the overactivity when a flip to one side occurs.

You need to have the Model of the Mind open and have read How spiritual experience works.

Any substance that enters our bodies is assessed for whether it is a help or a threat.  When any substance enters via whatever route – by mouth, by wounds, by injection, by inhalation, by smoking or snuffing or smearing on our skin as an ointment and thus absorption via the skin, the body’s defence mechanism checks to see what it is and whether it is friend or foe.

At too high a level, at levels where cell destruction can take place and the body itself is at risk, the cells send out a message to the Will via the nervous system which says HELP HELP HELP THREAT THREAT THREAT we are being attacked we are dying DO SOMETHING.

The Will responds by mobilising its defence systems – immune system, the system of the kidneys and liver which act as filters, the stomach with the acid, the blood filtering system and so on.  But at overdose levels the defence systems may be overwhelmed and the messages keep on coming in.

HELP, HELP, HELP, THREAT, THREAT, THREAT, we are being attacked, we are dying DO SOMETHING.

The Will can do no more from a defensive point of view, but what it may do is tell the autonomic system to sedate the person whilst it tries to muster the defences of the body to counteract  the threat. And the Will starts to shut down functions we no longer have need of because the energy is better targeted to survival. 

At this point we might start to get hallucinations as the non essential functions of Memory and Learning are gradually shut down.

But if the overdose is severe and the messages continue HELP, HELP, HELP, THREAT, THREAT, THREAT, we are being attacked, we are dying DO SOMETHING. the Will takes some very drastic action and mobilises all its energy and defenses into the autonomic system.

Now comes some serious activity when we can go out of body, because the Reasoning system Memory and Learning system have all been shut down and we are in effect on automatic pilot – we have gone AWOL.

Unless the autonomic systems can handle the threat, from this point on we are dying.

At the stage where death is inevitable what is going on is a form of controlled shut down of practically all the functions of the mind. 

The function of the ‘will’ continues to manage the autonomic systems, but consciousness may be transferred from the Personality to the Higher spirit.  The person is actually perceiving as the spirit from that point on.  And at this point the person gets a near death experience.

Observations

The eHealthme web site has the number of hallucinations caused by lithium and its salts but sadly does not distinguish between near death, out of body, vision or hallucinations, so the figures below are a sort of total of all experiences as of 2010.

Pharmaceutical

No of hallucinations

Lithium carbonate

187

Eskalith

12

Eskalith chromium

2

Lithonate

53

The observations provide some more current figures.

Since the figures were collected in 2010, the use of Lithonate has dropped to almost nothing and now there are no hallucinations recorded.  Side effects are being recorded, however, and these are from eHealthme:

Most common Lithonate side effects

  • Weight increased - (8 reports)
  • Vision blurred - (7 reports)
  • Fall - (7 reports)
  • Suicide attempt - (6 reports)
  • Drug dependence - (6 reports)
  • Alcohol poisoning - (5 reports)
  • Diabetes - (5 reports)
  • Clavicle fracture - (5 reports)
  • Hepatic fibrosis - (5 reports)
  • Hepatic encephalopathy - (5 reports)

Related observations