BIOLOGICAL BASIS OF BEHAVIOR
Psychology 321
Spring, 2005 HGH 225
Dr. John M. Morgan MWF, 8am to 9:00
INTRODUCTION
The drug lithium has been used for a variety of disorders such as
gout, diabetes, and epilepsy for over 100 years. It was not until
1949 when John Cade discovered that lithium had a calming effect
on guinea pigs that the possibilities of it being used for mania
were explored (Paykel, 1992). Since then, lithium has been
established as one of the primary treatments for manic depression
disorder. In the body of this paper we will explore the chemistry
of lithium, the synaptic transmitters involved, the parts of the
neuron affected, the inhibitory and excitatory potential changes,
the ion channels effected, the physiological changes, the primary
behavior changes, the side effect behavior changes and the effects
reported by users.
Joselyne Sulzner
CHEMISTRY
Lithium is a chemical element found in group IA of the periodic
table, along with sodium, rubidium, and cesium. Lithium has an
atomic number of 3, and an atomic weight of 6.94. In general,
lithium is more stable than hydrogen, and slightly less stable
than nitrogen, carbon, and oxygen. When looking at chemical ion
properties, it is useful to consider three main characteristics:
the size, or radius, of the ion, the charge, and the ion's
electron affinity. Lithium has a similar charge to radius ratio to
that of magnesium, which is in group IIA of the periodic table,
and so chemists say that the two elements are "chemically
similar." Lithium has low electron affinity in general, but it is
strong compared to other alkali metal cations and therefore is
highly polarizing (Williams, 1973). Lithium is the lightest known
solid element, and when dissolved in liquid ammonia it has the
lowest known density (Jefferson and Griest, 1977). In the body,
lithium ions can easily take the place of both sodium and
magnesium, although they appear to prefer magnesium receptors
because sodium is a slightly larger molecule than lithium and has
a less perfect fit (Williams, 1973).
When lithium is combined with other atoms, several useful
molecules can be created. For the purposes of this paper we will
consider the lithium salts, such as lithium carbonate, lithium
citrate, and lithium sulfate. These molecules, among others, are
used in psychiatry for the treatment of bipolar I disorder.
Lithium carbonate (Li2CO3) has an atomic weight of 73.89, and is
the most popular of the lithium salts in use today (Johnson,
1980). It is not clear why this is, as there does not appear to be
a significant difference between lithium carbonate and the other
lithium salts. For a complete listing of lithium salts currently
in use, see table 1. Lithium salts are preferred for medical use
because they are soluble in water, whereas natural lithium is
found in silicate form and is therefore not water soluble. Lithium
salts have a half life of approximately 1830 hours in the body,
depending on the weight of the subject (Williams, 1973).
ROUTE OF ACCESS
Lithium is usually taken orally in pill form, or injected directly
into the bloodstream. In pill form, there are normal and time
release doses available. Because the margin between a therapeutic
dose and a toxic dose (therapeutic index) is so small, the time
release form is more popular. In this way, the patient doesn't
experience rapid peaking of lithium in the bloodstream (Jefferson
and Griest, 1977). When taken orally the gastrointestinal tract
rapidly absorbs lithium, although specific locations along the
tract have not been identified. Lithium is widely distributed
throughout the body's water, both intracellular and extracellular,
though it is absorbed first by the kidneys, then the liver, the
bones, the muscles, and finally the brain (Williams, 1973).
Because the brain is so slow to absorb lithium, it can take up to
a week to normalize lithium concentrations within the body.
Lithium also leaves the brain very slowly, although not as slowly
as it leaves the bones. In one case, lithium was still detected at
high levels in a patient's bones even after he had been of lithium
for six months (Jefferson and Griest, 1977).
Lithium is not protein bound, and it is not metabolized into any
other compounds. Instead, it is excreted almost totally by the
kidneys. Because of this, lithium is contraindicated for those
with kidney or urinary disorders. Other bodily fluids such as
sweat, sperm, saliva and feces also excrete lithium, however this
makes up less than 5% of total lithium absorbed and is not
clinically significant (Jefferson and Griest, 1977). It is
important to monitor plasma levels of lithium to prevent toxicity.
As a point of interest, lithium used to be given as a salt
substitute to people with coronary heart failure! Needless to say
this is not longer practiced (Williams, 1973).
SYNAPTIC TRANSMITTERS INVOLVED
I should first state that causes for the therapeutic effect of
lithium are unknown (Jefferson and Griest, 1977). The brain is
such a complex structure that it is almost impossible at this
stage to make statements regarding the correlation and causation
of a drug and a process. That being said, there have been hundreds
of studies using rats, dogs, cats, mice, monkeys and various other
nonhuman animals to try and find out the exact changes lithium
makes to the brain. Human studies are less numerous and more
anecdotal, as it is hard to conduct statistically significant
research on human subjects. For one thing, many studies would
require the death of the subjects. Aside from ethical concerns, it
would simply be hard to find volunteers! It is also hard to find
enough subjects to make any worthwhile comparisons. Mental health
hospitals have patients with such varying symptoms that it is hard
to find a group of people similar enough to compare. As a result,
most of the major studies about lithium involve clinical trials.
Even though the research is limited at best, it still contributes
to our knowledge of how this drug works.
Lithium is thought to have an effect on several neurotransmitters,
especially catecholamines and indoleamines (Davis, Janowsky and El
Yousef, 1973). Because lithium can act by ion substitution (more
on this later) it is probable that this is how lithium alters
these processes. Lithium has also been connected with changes in
glutamate and gamma aminobutyric acid (GABA), and possibly even
acetylcholine (Williams, 1973).
When rats are treated with lithium, there is a marked acceleration
of the disappearance of norepinephrine, and a lower amount of
norepinephrine in the brain overall (Schildkraut, 1974). When
norepinephrine is metabolized, it turns into tritiated deaminated
catechol metabolites. There are higher levels of these metabolites
found in rats that are treated with lithium (Schildkraut, 1974).
So, lithium increases the intraneuronal inactivation of
norepinephrine (by deamination), thereby decreasing the amount of
norepinephrine available to interact with andrenergic receptors
(Schildkraut, 1974). Lithium also increases the reuptake of
norepinephrine in nerve ending cells (synaptosomes). Because the
studies with rats were so promising, researchers were disappointed
to find that human subjects had less apparent changes on the
norepinephrine system (Haskovec and Rysanek, 1969, as cited in
Gershon and Shopsin, 1973). There were some initial problems
duplicating the rat studies, but overall the human subjects
studies confirmed the idea that lithium decreases the amount of
norepinephrine in the brain. What this tells us about lithium's
mood stabilizing effects is as yet unclear.
There are similar studies conducted for serotonin, although the
results are less obvious. A summary of the findings is presented
below: Corrodi and his associates (1967)(as cited in Gershon and
Shopsin, 1973) reported that, in rats, acutely administered
lithium did not affect the metabolism (turnover) of serotonin.
Schildkraut (1974) reported an increase of brain serotonin in rats
after acute administration of lithium (decrease in serotonin
turnover). Later, Corrodi and his associates (as cited in Gershon
and Shopsin, 1973) again looked at lithium dosing in rats, this
time looking at chronic administration. This time the authors
concluded that a prolonged exposure to lithium could lead to
decreased activity in serotonergic neurons. A study by Ho et. al.
(1970)(as cited in Gershon and Shopsin, 1973), looked at the same
thing and found a decrease in the rate of serotonin turnover, and
yet another study by Bliss and Ailion (1970)(as cited in Gershon
and Shopsin, 1973), reported no changes. Overall it is perhaps
possible to say that if there is any effect on serotonin, lithium
appears to decrease the turnover rates and increased brain levels
of serotonin.
Several studies have also looked at the effects of lithium on
glutamate and GABA in monkeys. Although more information is
needed, the consensus is that after lithium treatment there is a
decrease in brain glutamate (Delgado, 1969, as cited in Gershon
and Shopsin, 1973), an increase in glutamate in the hypothalamus
and amygdala (Gottesfeld 1971, as cited in Gershon and Shopsin,
1973), and an increase in GABA in the hypothalamus (Gottesfeld,
1971, as cited in Gershon and Shopsin, 1973).
Studies about the effects of lithium on Acetylcholine and dopamine
show mixed results (Schildkraut, 1974) and need further testing.
PART OF THE NEURON AFFECTED
Studies show that lithium acts on the postsynaptic receptor of the
nerve cell. Although a lithium specific receptor has not been
identified, studies have shown that lithium interacts with the
adenyl cyclase cyclic AMP system (Gershon and Shopsin, 1973).
Regarding the turnover of norepinephrine, lithium has been shown
to affect cranial nerve terminals (Schildkraut, 1974). In
crayfish, Obara and Grundfest (As cited in Gershon and Shopsin,
1973) discovered that lithium acts differently on different parts
of the nerve cell. This study showed that lithium created a
stronger depolarization in the soma, or cell body, membrane of the
nerve than in the axonal membrane. Therefore, during an exposure
to lithium, the cell fired for a period of time and then declined.
During this decline, the action potentials first ceased in the
soma, but they persisted in the axon. In addition, when sodium is
replaced by lithium in the cervical ganglia, the nerve impulses
produced are smaller in direct proportion to the percentage of
sodium that has been replaced (Small and Small, 1973). More on the
effects of lithium on ion channels will be discussed later in this
paper.
REFERENCES
Davis, J.M., Janowsky, D.S., and El Yousef, Khaled. 1973.
Pharmacology: The Biology of Lithium. In Gershon, S. and Baron
Shopsin (Eds.), Lithium: its Role in Psychiatric Research and
Treatment. (pp. 167). New York: Plenum.
Enna, S.J., Malick, J.B., Elliott, R. 1980. Antidepressants:
neurochemical, behavioral, and clinical perspectives. New York:
New York University Press.
Gershon, S., and Shopsin, B. (Eds.) 1973. Lithium: its role in
psychiatric research and treatment. New York: Plenum Press.
Jefferson, J., Griest, John. 1977. Primer of lithium therapy.
Baltimore: Williams and Wilkins.
Johnson, F.N. 1980. Handbook of lithium therapy. Baltimore:
University Park Press, c1980.
Lithium. Encyclopedia Britannica. Retrieved February 27, 2005,
from Encyclopedia Britannica Premium Service.
http://www.britannica.com/eb/article?tocId=9048517
Schildkraut, J.J. 1974. The Effects of Lithium on Norepinephrine
Turnover and Metabolism: Basic and Clinical Studies. Journal of
Nervous Mental Disorders, 8:146.
Shou, Mogens. 1973. Preparations, Dosage and Control. In Gershon,
S. and Baron Shopsin (Eds.), Lithium: its Role in Psychiatric
Research and Treatment. (pp.189). New York: Plenum.
Small, J, and Small, I. 1973. Pharmacology: Neurophysiology of
Lithium. In Gershon, S. and Baron Shopsin (Eds.), Lithium: its
Role in Psychiatric Research and Treatment. (pp.83). New York:
Plenum.
Williams, R.J.P. 1973. The Chemistry and Biochemistry of Lithium.
In Gershon, S. and Baron Shopsin (Eds.), Lithium: its Role in
Psychiatric Research and Treatment. (pp. 15). New York: Plenum.
Jessica O'Donnell
INHIBITORY OR EXCITATORY POTENTIAL CHANGES
Graded potentials can be either hyperpolarizations (inhibitory) or
depolarizations (excitatory). Inhibitory postsynaptic potential,
also referred to as IPSP, is the temporary hyperpolarization of a
membrane. An inhibitory postsynaptic potential occurs when
synaptic input selectively opens the gates for potassium ions to
exit the cell (carrying a positive charge with them) or for the
chloride ions to enter the cell (carrying a negative charge with
them). Inhibition is not just the absence of excitation, it is an
active brake that is able to suppress the excitatory responses
from occurring (Kalat, 2004).
Excitatory postsynaptic potential, also known as EPSP, is a graded
depolarization. As a result of sodium ions enter the cell,
excitatory postsynaptic potential occurs. As a result of the
synaptic activation, the sodium gates open, allowing an increase
in the flow of sodium ions crossing the membrane. Excitatory
postsynaptic potential is a subthreshold event that decays over
space and time, meaning its magnitude decreases as it travels
along the membrane (Kalat, 2004).
Lithium has both inhibitory and excitatory features. Evidence has
shown that lithium alters sodium transportation
(http://www.mentalhealth.com). In the extracelluar fluid lithium
may replace sodium. During the process of depolarization lithium
has an extremely rapid intracellular influx. Although, it is not
effectively removed by the sodium-potassium pump. According to
Kalat (2004) the sodium-potassium pump, "[is] a protein complex
that repeatedly transports three sodium ions out of the cell while
drawing two potassium ions into the cell" (p. 41). As a result,
it prevents the cellular reentry of potassium. This interferes
with the electrolyte distribution across the neuronal membrane,
resulting in a decrease in the membrane potential, changes in
conduction and neuronal excitability. As measured by cortical
evoked potential, for humans lithium alters the excitability of
the central nervous system (http://www.mentalhealth.com).
Lithium enhances the uptake of norepinephrine and serotonin into
the synaptosomes, thus reducing their action. Lithium also
reduces the release of norepinephrine from synaptic vesicles and
inhibits production of cAMP. "Lithium inhibits the synthesis of
cAMP by the adenylyl cyclase in many brain regions, including the
cerebral cortex, caudate, and hippocampus, but not the brain stem
or cerebellum"
(Feldman, Meyer & Quenzer, 1997).
"The inhibitory action of lithium on NE-sensitive adenylyl cyclase
is a consistent finding, but lithium clearly has distinctive
effects on the adenylyl cyclase that is coupled with receptors
other than NE. For example, instead of inhibition, lithium seems
to have a stimulatory effect on DA-sensitive adenylyl cyclase or
no effect at all in ex vivo studies" (Feldman, Meyer & Quenzer,
1997). Since the adenylyl cyclase activation occurs at a point
beyond the neurotransmitter receptor, the inhibition of their
actions by lithium suggests an action beyond the receptor
stage(Feldman, Meyer & Quenzer, 1997).
Lithium might possibly have several inhibitory sites. Competing
for Mg² acutely and an inhibitory action on GTP activation.
Another significant action lithium has on the PI cycle is the
inhibition of the phosphatase that converts inositol monophosphate
into inositol. "Lithium's effects on the PI cycle have generated
a good deal of excitement: because the phospholipid second
messenger is coupled to both excitatory and inhibitory
neurotransmitter receptors, lithium can have an antimanic and/or
an antidepressant effect" (Feldman, Meyer & Quenzer, 1997).
"Inhibition of inositol monophosphatases is the only one of the
potential sites proposed for lithium action on the second
messenger" (Feldman, Meyer & Quenzer,1997).
"The dampening of phosphoinositide-mediated signal transduction in
both inhibitory and excitatory neurons may explain the antimanic
as well as antidepressant effects of lithium" (Feldman, Meyer &
Quenzer, 1997).
ION CHANNELS EFFECTED
The known neurotransmitter receptor produces two different general
classes of effects, one of which is they can directly control or
gate the opening of an ion channel (Hyman, Arana & Rosenbaum,
1995). "Ion channels are highly specific filters, allowing only
desired ions through the cell membrane"
(http://www.omedon.co.uk/shadow). Evidence has suggested that
lithium interferes with ion exchange mechanisms and nerve
conduction. Within two to four hours after lithium has been
administered, lithium ions are rapidly absorbed from the
gastrointestinal tract and plasma (http://www.mentalhealth.com).
Since lithium is in the same group of elements as potassium and
sodium and has a monovalent charge when ionized, it has been
suggested that lithium may produce a therapeutic effect by
modifying neuronal ionic mechanisms. Lithium also has an ionic
radius very similar to those of calcium and magnesium, indicating
its action may be related to interaction with these divalent
cations (Feldman, Meyer & Quenzer,
1997).
Many investigators have found that in red blood cells the ration
of intracellular to extracellular lithium ion is higher for
bipolar patients in comparison to normal controls when both groups
have administered lithium. "The best evidence for an ionic
mechanism of action for Li involves Ca²" (Feldman, Meyer &
Quenzer, 1997).
Along with acting on neuronal ionic mechanisms, lithium has a wide
range of biological effects on many different systems (Feldman,
Meyer & Quenzer, 1997).
PHYSIOLOGICAL CHANGES
"For the majority of patients with bipolar disorder, lithium
carbonate (Carbolith, Lithane)is the most effective medication and
is the usual drug of choice" (Feldman, Meyer & Quenzer, 1997).
The primary purpose of administering lithium carbonate is to treat
the manic stage of bipolar disorder (manic-depressive illness).
Bipolar patients experience severe mood changes, ranging from an
excited or manic state (for example, anger or irritability) to
depression or sadness(http://www.medlineplus.gov). Lithium is
used in order to reduce the frequency and severity of manic
states. Evidence has suggested that lithium is less effective in
preventing the recurrence of depression compared to mania
(Feldman, Meyer & Quenzer, 1997). Symptoms of mania involve
aggressiveness, flight of ideas, grandiosity, hypersomnia, motor
hyperactivity, and poor judgement.
Dependent on the patient's sensitivity to lithium and the dosage
prescribed, adverse reactions may vary. Adverse reactions may
occur at serum lithium concentrations below 1 mmol/L. The most
frequently reported adverse effects are due to the rapid rise in
serum lithium concentrations are the initial postabsorptive
symptoms. Symptoms at this level can include, but are not limited
to, a dazed feeling, gastrointestinal discomfort, muscle weakness,
nausea and vertigo. After the stabilization of therapy these
symptoms may vanish. Though the more common and persistent
adverse reactions are fatigue, fine hand tremors, nephrogenic
diabetes insipidus (kidney), polyuria (excessive urination) and
thirst. It is important to note that having any of these
reactions does not necessarily mean that a reduction of dosage is
need.
Mild to moderate adverse reactions generally occurs at serum
lithium concentrations ranging from 1.5 to 2 mmol/L. Moderate to
severe adverse reactions may occur at serum lithium concentrations
greater than or equal to 2 mmol/L (http://www.mentalhealth.com).
In the midrange serum concentration levels of lithium, 1.5 to 2
mmol/L, might cause diarrhea, drowsiness, lack of coordination,
muscular weakness, and vomiting. Under the higher serum
concentration levels of lithium, 2 mmol/L or more, there is even a
greater inability to coordinate voluntary muscular movements.
Their vision may be blurred. A ringing noise may persist in the
patient's ear. Giddy behavior has been noted by some patients.
The patient may also experience a polyuria, excessive urination,
producing a large output of dilute urine.
As the serum concentration levels increase to over 3 mmol/L,
complex problems involving multiple organs and organ systems may
occur. Hence the reason serum concentration levels of lithium are
recommended not to exceed 2 mmol/L. Remember individual responses
will vary to the different lithium serum concentration levels.
Out of all the side effects that have resulted from taking
lithium, the majority of the side effects are experienced in the
nervous system. Within the central nervous system (CNS) there
have been many adverse effects that have been reported.
Anesthesia of the skin (a general loss of the senses of feeling,
such as pain, temperature, or touch) may occur. Experiencing
blurred vision can take place. A patient might experience
blackout spells, headaches, and possibly seizures. Their speech
might become slurred. Tongue movements and deep tendon reflexes
have also been noted. There may be muscle hyperirritability, this
can range between slight twitching to movement of whole limbs.
The patient might also become very restless. These adverse side
effects, along with others, have been related to the lithium serum
concentration levels affecting the central nervous system. In the
autonomic nervous system the side effects that have been noted are
blurred vision, dry mouth, and also impotence.
In the cardiovascular system many adverse side effects can occur.
This can include cardiac arrhythmia (a disturbance in the rhythm
of the heartbeat) and abnormally low blood pressure. Bradycardia,
relatively slow heart action, can lead to a loss of consciousness
due to insufficient blood flow to the brain.
Gastrointestinal complications can occur from taking lithium. The
adverse side effects include diarrhea, nausea, and vomiting would
fall under this category. Anorexia nervosa has been associated
with lithium. Patients can suffer from abdominal pain, flatulence
(having an accumulation of gas in the intestinal tract), and
indigestion. A patient's salivary glands might swell or excrete
an excessive amount of salvia. Gastritis, inflammation of the
mucus membrane of the stomach has been reported.
Dermatological effects may occur as a result from lithium therapy.
Breakouts of acne, itching, and psoriasis (scaly patches) may
occur. It is also possible for a patient to lose skin sensation.
Dryness or thinning of the hair is a potential side effect. A
patient could possibly develop leg ulcers due to lithium.
Genitourinary functions adverse reactions are very significant
since lithium is excreted almost completely by the kidneys.
Albuminuria, is the presence of albumin in the urine can occur.
Along with glycosuria, which is the excretion of glucose in the
urine. As well as oliguria. Even though polyuria can take place,
so can a reduction of urine.
Usually transient gastrointestinal symptoms (e.g., abdominal pain,
diarrhea, thirst, vomiting, etc.) the first side effects to occur.
Throughout the therapy a mild degree of fine hand tremors may
persist. In early intoxication, thirst and polyuria may be
followed by blurred vision, drowsiness, along with other side
effects. As the intoxication progresses a patient may experience
confusion, diarrhea, seizures, and possibly either coma or death
(http://www.mentalhealth.com).
REFERENCES
Feldman, Robert S., Meyer, Jerrold S., & Quenzer, Linda F. (1997).
Principles of Neuropsychopharmacology. Massachusetts: Sinauer
Associates Inc., Publishers.
Hyman, Steven E., Arana, George W., & Rosenbaum, Jerrold F.
(1995). Handbook of Psychiatric Drug Therapy. New York: Little,
Brown Company.
Kalat, James W. (2004). Biological Psychology 8th Edition.
Canada: Thomson Learning, Inc., Wadsworth.
http://www.medlineplus.gov
http://www.mentalhealth.com
http://www.omedon.co.uk/shadow
Aileen "Liz" Johnson
PRIMARY BEHAVIOR CHANGES
Though the drug lithium is used for a number of disorders ranging
from acute depression to eating and personality disorders (Paykel,
1992), it's primary use is for bipolar disorder, also known as
manic depression. Patients with bipolar disorder "between two
poles: depression and its opposite, mania" (Kalat,2004), often
with periods of normal behavior in between (Jamison,1993). In
addition, the patient is also prone to "mixed episodes" in which
symptoms of both mania and depression are present. Intensity of
these episodes can range from mild to dangerous, as in the case of
a manic depressive mother who severed the arms of her 10 month old
daughter (Associated Press, 2005). Despite its genetic origin
(Kalat. 2004; Jamison, 1993; DBSA, 2005), the onset of symptoms
and behavior is rather late, averaging 18 years of age (Jamison,
1993).
There are two types of manic episodes: manic and hypomanic. The
DSM describes a manic episode as "a distinct period of abnormally
and persistently elevated, expansive, or irritable mood,"
(Jamison, 1993). Symptoms include inflated self esteem, a reduced
need for sleep, increased talkativeness and sociability, flight of
ideas, distractibility, an increase in goal directed activities
(such as work, school or sex), and an excessive involvement in
pleasurable activities (PsychologyNet, 2003). The occurrence of
these symptoms must not be able be confused with a mixed state
(see description below), must impair the individual's ability to
function normally, and cannot be explained by the effects of a
substance (i.e. alcohol, hallucinogenics) or a medical condition
(i.e. hyperthyroidism) in order for the episode to be considered
"manic."
Hypomanic episodes are similar but shorter and often less intense.
Behaviors include "increased productivity, often with unusual and
self imposed working hours," "uninhibited people seeking,"
"hypersexuality," "inappropriate laughing, joking, punning," and
"excessive involvement in pleasurable activities with lack of
concern for painful consequences," (Jamison, 1993). Hypomanic
individuals also have increased creativity, inflated self esteem,
decreased need for sleep and an excess of energy (Jamison, 1993).
As one patient describes it, "At first when I'm high, it's
tremendous… ideas are fast… like shooting stars you follow until
brighter ones appear… all shyness disappears, the right words and
gestures are suddenly there… uninteresting people things, become
intensely interesting. Sensuality is pervasive, the desire to
seduce and be seduced is irresistible. Your marrow is infused
with unbelieveable feelings of ease, power, well being,
omnipotence, euphoria… you can do anything… but, somewhere this
changes," (Bipolar Disorder Manic Depression Support Group Chat,
2005).
Depressed periods often follow manic and hypomanic episodes.
Symptoms such as prolonged sadness, changes in eating and sleeping
patterns, irritability, anger, worry, agitation, anxiety, apathy,
feelings of guilt/worthlessness, social withdrawal, inability to
concentrate, indecisiveness, suicidal or morbid thoughts (DBSA,
2005), among others over a period of at least two weeks are the
makings of major depression.
The third type of episode characteristic of bipolar disorder is a
"mixed state." Mixed states are periods of time when the patient
experiences symptoms of both mania and depression. French
composer Hector Berlioz described it as a state of mind which was,
"mocking, active, passionate, malignant," (Jamison, 1993). They
last at least one week in length (PsychologyNet, 2003). Of the
three types of episodes, the mixed state can be the most dangerous
as they "are closely associated with the damaging and killing
sides of manic depression: alcoholism, drug abuse, and suicide,"
(Jamison, 1993).
Bipolar disorder can be divided into two main categories: bipolar
I and bipolar II. Bipolar I is your classic case of bipolar
disorder, incorporating at least one manic/mixed state and one
depressed state (DBSA, 2005). Bipolar II is similar, except that
the subject rarely experiences full blown episodes of mania,
experiencing hypomania instead (Kalat, 2004).
Lithium has been found most effective in patients with bipolar I
disorder. The drug works to "stabilize the mood of a bipolar
patient, preventing a relapse into either mania or depression,"
(Kalat, 2004). Lithium (particularly Lithobid, a time released
version of it) works to treat the following symptoms of mania:
"pressure of speech, motor hyperactivity, reduced need for sleep,
flight of ideas, grandiosity, elation, poor judgment,
aggressiveness, and possible hostility," (Solvay, 2002).
Stabilization generally occurs within 1 to 3 weeks and when taken
regularly the drug should also bring down the intensity of future
highs (Solvay, 2002).
The efficacy of lithium when it comes to the depression side of
the disorder seems to be debated as it is heralded as effective in
some texts (Paykel,1992; Kalat, 2004) and ineffective or passed
over in others (Solvay, 2002; Centerwatch, 2004). Often lithium
is relied on primarily for the treatment of mania, paired with an
antidepressant (i.e. Prozac, etc.) to curb depression (J blue,
2004; stfelony, 2004). However, many studies have found lithium
to be effective in reducing suicidality (Paykel, 1992; Jamison,
1996).
SIDE EFFECTS
In exchange for response rates as high as 90% (Centerwatch, 2004),
the use of lithium can bring with it many side effects. Side
effects generally come in two waves: initial postabsorptive
symptoms and more common, persistent adverse reactions (Long,
2005; Solvay, 2002).
"[A]t first, I experienced mild nausea, drank litres and litres of
water, and had a mild headache, but on the whole, felt fine. [A]
bit dull, but that was sort of the point. I started sleeping
again, and by the end of the week was surprisingly functional in
school," (stfelony, 2004)
The initial symptoms are "believed to be associated with a rapid
rise in serum lithium concentrations," (Long, 2005).
"[G]astrointestinal discomfort, nausea, vertigo, muscle weakness
and a dazed feeling" (Long, 2005) are common initial symptoms.
Generally, they disappear within a few weeks or as soon as the
drug therapy has been stabilized (the dosage of lithium is often
varied initially to gauge the correct level of lithium needed for
treating the patient). Signs of an incorrect dosage can include
anoerexia, metallic taste, weight gain or loss, general muscle
weakness, slurred speech, blurring of vision, blackout spells,
headaches, seizures, dryness and thinning of hair, skin rash,
anemia, and many others (Long, 2005).
The more persistent symptoms include fine hand tremors, fatigue,
thirst, polyuria (frequent urination), and nephrogenic diabetes
insipidus (Long, 2005). In addition, diarrhea and muscle weakness
have been observed (Paykel, 1992). These symptoms typically stay
throughout treatment and are unwavering to dosage change.
More serious side effects, such as hyperthyroidism and kidney
troubles, have also been observed (Paykel 1992; Long 2005). Some
evidence has also shown that long term usage may cause medical
complications such as hypercalcemia (Bilanakis, 2004).
Due to the proximity of therapeutic and toxic levels of lithium,
the blood levels of patients must be monitored closely (Long,
2005; Paykel, 1992). Unfortunately, the signs of lithium
intoxication can often overlap or simply be more intense versions
of the existing side effects. "Confusion, increasing
disorientation, muscle twitchings, hyperreflexia, nystagmus,
seizures, diarrhea, vomiting, and eventually coma and death"
(Long, 2005), are among the signs of toxicity. Reduction or
withdrawal of treatment can remedy the toxicity if caught early
enough.
EFFECTS REPORTED BY USERS
Lithium, though effective in some individuals, has a wide range of
effects:
"[I] was feeling slowed down…. [m]y overabundance of racing
thoughts was still in my head; it just felt as though [I] had to
work harder to reach out and grab one…. [I] still felt pressed to
talk incessantly in social situations, only instead of feeling
exceptionally witty and brilliant, [I] felt as though [I] was
constantly tripping all over myself or watching myself from afar,"
stfelony, The Icarus Project (stfelony, 2004)
"[M]y focus, my intellect, my memory, all of it has been
negatively affected by the Lithium…. I can't even read,"
britneyspearsherself, The Icarus Project (J blue, 2004)
The majority of personal accounts of the effects of lithium focus
on the difficulties of the side effects associated with the drug.
Most, however, also go on to say that without lithium, their life
would be even more difficult:
"Lithium robs me of life itself. I become the walking dead. A
big do nothing. Everything is sooo hard to do. To do 3 simple
things in a row, like fill up with gas, go to the bank, go to the
grocery store… is so hard, as to almost be impossible…. I had only
2 hours functional a day on Lithium…. I was extremely good at
staring off into space and not minding doing so…. [However,]
lithium did make it easier for me to fight and stay alive. It
also nearly prevented migraines in me and untangled mixed states
for me," room42, The Icarus Project (J blue, 2004)
With the right dosage (the finding of which appears to be a
precise art form), the side effects can be minimized and
functionality maximized. Psychiatrist Kay Redfield Jamison (who
is manic depressive, herself) talks about her experience in her
memoir "An Unquiet Mind":
"Lowering my lithium level had allowed not only a clarity of
thinking, but also a vividness and intensity of experience, back
into my life…. Gradually, as I began to look around me, I realized
that this was the kind of evenness and predictability most people
had…."
REFERENCES
Associated Press (2005, February 15). Mom accused of severing
baby's arms incompetent for trial. CNN.com. Retrieved February
28, 2005 from the World Wide Web:
http://www.cnn.com/2005/LAW/02/15/severed.arms.ap/index.html
Bipolar Disorder Manic Depression Support Group Chat (2005).
Bipolar disorder, manic depression symptoms. Support 4 Hope.
Retrieved March 2, 2005 from the World Wide Web:
http://support4hope.com/bipolar_disorder/manic_depression_symptoms
.htm
Bilankis, N. & M. Gibiriti. (2003). Lithium intoxication,
hypercalcemia and "accidentally" induced food and water aversion:
a case report. Progress in Neuro-Psychopharmacology & Biological
Psychiatry 28, 201-203.
Centerwatch Newly Approved Drug Therapies Listing. (2004, June
29). Drugs approved by the FDA: Drug name: Lithobid (lithium
carbonate). Thomson Centerwatch. Retrieved March 2, 2005 from the
World Wide Web:
http://www.centerwatch.com/patient/drugs/dru50.html
DBSA (2005, February 22). Bipolar disorder. Depression and Bipolar
Support Alliance. Retrieved February 28, 2005 from the World Wide
Web: http://www.dbsalliance.org/info/bipolar.html
PsychologyNet (2003). Diagnostic criteria. PsychologyNet.org.
Retrieved March 4, 2005 from the World Wide Web:
http://www.psychologynet.org/bipolar1.html
Gorman, J., MD (2002, September). Lithium. NAMI. Retrieved
February 28, 2005 from the World Wide Web:
http://www.nami.org/Template.cfm?Section-
About_Medications&Template=/TaggedPage/TaggedPageDisplay.cfm&TPLID
=51&ContentID=20820
Jamison, K.R., PhD (1993). Touched with fire: Manic depressive
illness and the artistic temperament. New York: Free Press.
Jamison, K.R., PhD (1995). An unquiet mind: A memoir of moods and
madness. New York: Vintage Books.
J blue (2004, November 5). is it lithium or is it me? The Icarus
Project. Retrieved February 28, 2005 from the World Wide Web:
http://theicarusproject.net/community/viewtopic.php?t=1197
Kalat, J.W. (2004). Biological psychology (8th ed.). Belmont, CA:
Wadsworth/Thomson Learning.
Long, P.W., MD (2005). Lithium carbonate. Internet Mental Health.
Retrieved February 28, 2005 from the World Wide Web:
http://www.mentalhealth.com/drug/p30-102.html
Solvay Pharmaceuticals (2002). Lithobid. Solvay Pharmaceuticals,
Inc. Retrieved March 5, 2005 from the World Wide Web:
http://www.fda.gov/cder/foi/label/2002/187027s40s46s49s49lbl.pdf
Paykel, E.S. (1992). Handbook of affective disorders (2nd ed.). New
York: The Guilford Press.
Rennert, N.J., MD. (2004, April 19). Medical encyclopedia:
hypercalcemia. Medline Plus. Retrieved March 2, 2005 from the
World Wide Web:
http://www.nlm.nih.gov/medlineplus/ency/article/000365.htm
stfelony (2004, November 7). lithium questions, or "what is wrong
with me?!" The Icarus Project. Retrieved February 28, 2005 from
the World Wide Web:
http://theicarusproject.net/community/viewtopic.php?t=1187
CONCLUSION
Lithium, or, more commonly, Lithium Salt, is an element used to
treat bipolar disorder in humans. Bipolar disorder consists of
severe highs and lows of mood, ranging from deep depression to
extreme mania. The cycling of the disorder depends on the person,
but it can vary from many shifts within one day (rapid cycling) to
extended periods of each. Lithium is indicated primarily for
patients who are not rapid cycling. Like many other medications,
the exact effects of Lithium are unknown. Psychiatrists and
Chemists have isolated many of the physiological and behavioral
changes that occur after the administration of Lithium, and yet
the exact cause of its therapeutic effect is not fully understood.
Go back to the beginning
Copyright © 2005, Dr. John M. Morgan, All rights
reserved -
This page last edited 1-3, 2005
If you have any feedback for the author, E-mail me
