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Title: Mood Stabilizers
Author: Anthony Kane, MD
Website: http://addadhdadvances.com
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Mood Stabilizers
by Anthony Kane, MD
Introduction
Mood stabilizers are the treatment of choice for bipolar
disorder, a condition that often accompanies ADHD. However,
these drugs have other clinical uses.
Currently, mood stabilizers are being used to treat patients who
display symptoms of violent aggression, impulsivity or agitation.
These symptoms are quite common in ADHD, especially in those
children who suffer from a number of other co-morbid disorders.
Aggression and Impulsivity
Most people have violent thoughts out of frustration, but they
will not act on these impulses unless they lose control. People
with trouble controlling impulsive behavior frequently act out
in an aggressive manner. Aggressive behavior is common in
variety of conditions such as:
-ADHD
-Conduct disorder
-Psychotic disorders
-Mood disorders
-Intermittent explosive disorder
-Adjustment disorder
-Personality disorders (mainly paranoid, antisocial, borderline)
-Mental retardation
-Delirium
-Dementia
Many of these disorders are co-morbid with ADHD and ODD. Mood
stabilizers can be used to treat these conditions.
Agitation
Agitation is a form of severe anxiety associated with motor
restlessness. It may lead to inappropriate verbal, vocal, or
motor activity. It is associated with strong emotion, anxiety,
tension, urgency, and fear, and it may lead to aimless
wandering, pacing, cursing, or arguing.
Agitation may accompany:
-Psychosis
-Mood disorders
-Anxiety disorder
-Insomnia
-Dementia
Excessive agitation may occur in a number of disorders that are
co-morbid with ADHD and ODD. Mood stabilizers can be used to
treat these conditions.
Classification of Mood Stabilizers
There is no agreed-upon definition of the term mood stabilizer.
We all use the term, but it is nowhere officially defined.
There are about 4 major classes of drugs that are being used as
mood stabilizers.
These are:
-Lithium
-Anti-epileptics
-Antidepressants
-Neuroleptics (Anti-psychotics)
We shall now discuss some of these drugs in depth.
Lithium
Lithium has been used for the treatment of acute bipolar mania
for over 50 years. It is an alkali metal similar to sodium and
comes as one of two salt preparations, lithium carbonate or
lithium citrate.
In the US, lithium is considered the drug of choice for adults
and children with bipolar disorder. However, European
psychiatrists do not use lithium in children, and in Israel the
largest child psychiatric hospital does not even have lithium on
the hospital formulary.
Lithium has multiple complex neurochemical effects, with impact
on ion channels, serotonin, dopamine, and norepinephrine
neurotransmitter systems, as well as on second messenger systems.
So how does it work? Nobody really knows.
Side effects:
Up to 75% of patients treated with lithium experience some side
effects. Most of these are minor and can be reduced or
eliminated by lowering the lithium dose or changing the dosage
schedule.
Endocrine: Lithium has been associated with thyroid
abnormalities. Hypothyroidism occurs in up to 35% of patients
treated with lithium.
Renal: Lithium inhibits reabsorption of water leading to
excessive urination and thirst. There have been some reports
of structural kidney damage with long-term lithium use.
Cardiovascular: Lithium disrupts the cardiac conduction system
and can cause arrhythmias. These changes are usually not
significant.
Dermatological: Lithium can induce or exacerbate acne, which
is a problem for adolescent patients. It is also associated
with hair loss.
Neurological: Lithium may produce a variety of neurological
effects, including muscle weakness, tremor, lethargy, cognitive
blunting, and headaches. In children, lithium has been reported
to alter EEG patterns and to decrease performance on cognitive
testing.
Toxicity
Even though lithium has a very long list of side effects, that
is not what concerns most physicians. The real concern is the
toxicity. The blood levels in which, lithium becomes toxic are
not much higher than the levels that are necessary for
treatment. This combined with the fact that patients who
require lithium treatment usually are not particularly reliable
or compliant, makes treatment with lithium somewhat precarious.
Toxic effects of lithium include marked tremor, nausea and
diarrhea, blurred vision, vertigo, confusion, and increased
deep tendon reflexes. With higher levels, patients may
experience more severe neurological complications and
eventually experience seizures, coma, cardiac arrhythmia,
permanent neurological damage, and death.
Hemodialysis is the only reliable treatment for lithium
overdose.
Conclusion
You are probably wondering by now after reading this list, why
would anyone want to go near this stuff. The bottom line is
this. Lithium works, and it probably works better than anything
else that we have. This is very important. These conditions,
bipolar disorder, aggressive personality disorders, conduct
disorder, psychotic disorders, etc., are serious psychiatric
conditions. Left untreated, they have serious life long and
sometimes life terminating consequences.
Anticonvulsants
Valproic acid (Depakene, Valprotate)
Valproic acid is a simple bracket chain carboxylic acid
currently available in two preparations; valproic acid, and
divalproex sodium a combination of valproic acid and valproate.
Some physicians feel that overall this drug is just as
effective as lithium and has less serious side effects.
Valproate may have a quicker onset of action than lithium.
Side effects:
-Weight gain
-Tremor
-Dizziness
-Sedation
-Headache
-Nausea
-Indigestion
-Bruising
-Hair loss
Rarely, valproic acid has been associated with fatal hepatic
toxicity, hemorrhagic pancreatitis, and agranulocytosis.
Valproic acid may increase testosterone levels in teenage girls
and produce polycystic ovary syndrome in women who began taking
the medication before age 20.
Carbamazepine (Tegretol)
Carbamazepine is an anticonvulsant drug, chemically related to
the tricyclic antidepressants.
Carbamazepine is effective in controlling impulsive and
aggressive behavior. As a mood stabilizer, it is generally felt
to be inferior to both lithium and valproic acid and it has a
much worse side effect profile than valproic acid.
Up to 50% of patients receiving carbamazepine experience side
effects, and the drug is associated with potentially serious
adverse reactions
Side effects
-Aplastic anemia
-Hepatic toxicity
-Impaired learning and memory
-Emotional affects such as irritability and agitation
-Insomnia
-Changes in vision
-Fatigue
-Nausea
-Water retention
-Weight gain
-Dermatitis
-Pancreatitis
The most commonly seen side effects with this agent in children
are drowsiness, loss of coordination, and vertigo. Overdose of
Carbamazepine can be fatal.
Oxcarbazepine (Trileptal)
Oxcarbazepine is a chemical analogue of carbamazepine. The
chemical difference translates to a more favorable adverse-
effect profile when compared with carbamazepine.
Side effects
-Dizziness
-Nausea
-Headache
-Diarrhea
-Vomiting
-Upper respiratory tract infection
-Constipation
-Dyspepsia
-Ataxia
-Nervousness
Each of these side effects occurred in at least 5% of patients.
Another significant side effect occurring in 2.5% of patients is
low sodium blood levels.
Even though oxcarbazepine seems to be a better alternative to
carbamazepine, its usefulness in the treatment of agitation,
aggression and impulsivity has not been scientifically verified.
Lamotrigine (Lamictal)
Although the FDA has approved lamotrigine for use in "mood
episodes," studies show that it is only effective in preventing
depression. In mania, it seems less effective than other drugs.
Serious rash is it’s only major side effect, and it occurs more
frequently in children than in adults. There are no data on
lamotrigine’s efficacy as mood stabilizers in children or
adolescents.
Gabapentin (Neurontin)
The major advantage of gabapentin is its relative safety and
lack of interactions with other drugs. Its major drawback is
that it doesn’t work. Parke-Davis sponsored a study in
preparation to an FDA application for use as a mood stabilizer
and found it was no better than placebo. In combination with
other medications,gabapentin seems to be helpful in managing
anxiety and aggression.
Topiramate (Topamax)
Topiramate is yet another anticonvulsant with mood stabilizing
effects for some patients. It seems to help with anxiety and a
number of eating disorders. It is being used clinically to
counteract the weight gain caused by valproic acid.
The most common adverse events were sweating, blurred vision,
difficulty sleeping, tremors, and paresthesia.
Levetiracetam (Keppra)
Levetiracetam is an anticonvulsant approved in the US in late
1999. There are now anecdotal reports of its action as a mood
stabilizer.
Antidepressants
There are seven distinct classes of antidepressants. The
tricyclic antidepressants and monoamine oxidase inhibitors have
been around the longest. The serotonin selective reuptake
inhibitors are the most popular antidepressants used today.
Three other classes also affect the serotonin system, but have
additional affects on other systems. These are the dual
serotonin and norepinephrine reuptake inhibitors, the
serotonin-2 antagonism/reuptake inhibitors, and alpha2
antagonism plus serotonin-2 and -3 antagonizers. The final
category is the norepinephrine reuptake inhibitors.
Antidepressants tend to work slowly. It usually takes several
weeks before they begin to work and it may take as much as three
months before their full benefit is realized. Most
antidepressants cause a weight gain of about ten pounds within
the first six months. Many cause sexual dysfunction. They
also tend to interact negatively with many other drugs. These
drugs must be used carefully in bipolar depression, because they
have a tendency to push the patient into a manic episode.
Monoamine Oxidase (MAO) Inhibiters
The MAO inhibitors were discovered in the 1950’s and were the
first antidepressant drugs. These drugs cause dangerous
hypertension reactions in patients who take these drugs and who
ate certain common foods (cheese) or used certain medications.
These drugs are still used in patients who fail on safer drugs.
They are helpful in controlling depression and anxiety.
Common drugs:
-Phenelzine (Nardil)
-Isocarboxazid (Marplan )
-Tranylcypromine (Parnate )
Tricyclic Antidepressants (TCAs)
As mood stabilizers, the newer antidepressants have eclipsed
the tricyclic antidepressants. However, in the treatment of
ADHD, these drugs are very effective. They help 70% of
children who fail on stimulants.
The most common drugs in this category are imipramine
(Tofranil), nortriptyline, and desipramine (Norpramin). In
practice, we have more clinical experience with imipramine, but
there is mounting evidence that desipramine may be the better
choice.
Imipramine and desipramine have played an important role in
research. Thesedrugs have been used as the control drugs when
testing the newer antidepressants. In general, all the newer
drugs have been better mood stabilizers than the tricyclic
antidepressants. However, the TCAs are still considered a better
choice in ADHD children, and in ADHD children with other
psychiatric disorders such as depression or anxiety disorder
they may work better than the stimulants.
Serotonin Selective Reuptake Inhibitors (SSRIs)
These are the most popular antidepressants used today. In
general, they work better than the older tricyclic
antidepressants and have fewer side effects.
Long-term use of these drugs is associated with significant
weight gain and sexual dysfunction.
Common drugs:
-Fluoxetine (Prozac)
-Paroxetine (Paxil)
-Citalopram (Celexa, Cipramil)
-Sertraline (Zoloft)
Serotonin and Norepinephrine Re-uptake Inhibitors (SNRIs)
Venlafaxine is the paradigm drug in this category. It tends
to work better than the SSRIs, but is associated with the
increase of aggressive behavior when used together with
clonidine.
Other Classes of Serotonin Uptake Inhibiters
Nefazodone (Serzone)
Nefazodone inhibits serotonin and norepinephrine reuptake. It
has an advantage over the SSRI’s in that it causes fewer
gastrointestinal side effects and does not cause weight gain or
sexual dysfunction.
Mirtazapine (Remeron)
Mirtazapine has a weaker antidepressant effect than other drugs,
but it seems to be more effective against anxiety disorders.
Mirtazapine is associated with significant weight gain early in
therapy.
Norepinephrine Reuptake Inhibitors
Bupropion ( Amfebutamone, Wellbutrin, Zyban )
Bupropion is a selective norepinephrine and dopamine reuptake
inhibitor. It is as effective an antidepressant as the SSRI’s
and has fewer side effects. Bupropion does not cause sexual
dysfunction and is less likely than other antidepressants to
induce mania in bipolar patients.
Reboxetine (Edronax)
Reboxetine is a selective norepinephrine reuptake inhibitor
similar to Strattera. Reboxetine itself typically doesn't have
the disruptive effects on cognitive function or psychomotor
performance common to older antidepressants. I have seen this
drug used successfully in the management of ADHD patients who
did not do well with stimulants or other antidepressants. I
have also seen this drug induce Raynaud’s syndrome in one child,
which is not a reported side effect of the drug.
This drug is licensed in over 50 countries. However, the FDA
declined Pharmacia's license application for the North American
market. This was a surprising event, considering the FDA
approved a similar drug, Strattera, a short time later. The FDA
has not revealed the grounds for the decision, but I have
my $uspicion$.
Anti-Psychotic Drugs (Neuroleptics)
These are not really mood stabilizers, but in practice they
are used short term and in low doses to control some of the
symptoms that accompany mood disorders. These drugs have
significant long-term side effects and risks so they are not
commonly used as a maintenance drug in mood disorders.
Risperidone (Risperdal)
There are a lot of ADHD children with bipolar disorder on this
drug. It has received FDA approval for the short-term treatment
of manic episodes.
The most common side effects are restlessness, tremors, muscle
stiffness, sleepiness, nausea, abnormal vision, increased
saliva, abdominal pain, and urinary incontinence.
Olanzapine (Zyprexa)
Olanzapine is an anti-psychotic drug that has received FDA
approval for the treatment of acute mania, although it has on
occasion induced mania. On the whole olanzapine is a very
effect mood stabilizer and it appears that it might be a good
maintenance drug.
Olanzapine has side effects similar to other anti-psychotic
drugs, though like other newer anti-psychotics, these side
effects are less severe than with older drugs.
Clozapine (Clozaril)
Clozapine is effective both in unresponsive mood disorders.
Conclusion
There are numerous drugs being used as mood stabilizers and
there are going to be a lot more. The current trend is toward
using these drugs more often to manage short-term and long-term
behavior and mood disorders.
Although these drugs all have serious long-term side effects,
they are usually fairly safe short-term if the patient is managed
closely.
Anthony Kane, MD
ADD ADHD Advances
http://addadhdadvances.com
================================================================
Anthony Kane, MD is a physician and international lecturer.
He is the author of a book, numerous articles, and a number of
online programs dealing with ADHD treatment
(http://addadhdadvances.com/childyoulove.html), child behavior
issues (http://addadhdadvances.com/child-behavior.html), ODD, and
education. Visit his site at http://addadhdadvances.com.
To sign up for the free ADD ADHD Advances online journal send
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