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What Is an Antipsychotic?
What are they used for?
Antipsychotic medications were invented to treat psychosis. Psychosis
means “out of touch with reality” and typically includes
hallucinations, delusions, and severe often bizarre or very paranoid
thinking disorders. Generally people experiencing psychosis have
schizophrenia, psychotic depression, or bipolar disorder (manic
depression), but may have drug or medicine toxicity or withdrawal, may be
reacting to a catastrophe (brief reactive psychosis) or may have a brain
injury or disorder like dementia or delirium, or have certain other severe
health conditions. Antipsychotics were discovered in the 1950’s and were
first used to treat forms of schizophrenia, psychotic depression, and
bipolar disorder. They are often very helpful.
Over the last 40 to 50 years we have learned antipsychotics, like other
medicines, may help some other conditions as well. Used alone or in
combination with other treatments, antipsychotics are effective for nausea
and vomiting (e.g. Compazine), are good sedatives, help sleep, calm
agitation and irritability, help impulsive aggression, anger, rage, and
temper, treat Tourette’s syndrome, suppress tics, help the behavioral
problems associated with head injuries, and may help autism and related
conditions, etc. Antipsychotics are sometimes used as boosters to make
other medicines more effective in obsessive compulsive disorder, some
depressions, and other conditions where thinking, compulsive behavior, or
impulsive behaviors are problems. Atypicals are often very helpful
medicines in treating behavioral and neuro-psychiatric complications of
Alzheimer’s disease and other dementias. At least Zyprexa and Risperdal
of the newer “atypical” antipsychotics also work as mood stabilizers
and may treat or help treat even non psychotic Major Depressions.
The “atypicals” are Clozaril (clozapine), Risperdal (risperidone),
Zyprexa (olanzapine), Seroquel (quetiapine), Geodon (Ziprasidone), and
Abilify (ariprazole). Clozaril is used least despite excellent
benefits because it has some quite troublesome side effects. Abilify, the
newest, is actually a “third generation” antipsychotic known as a
“dopamine system stabilizer” which means it focuses its dopamine
blocking more loosely and primarily on the targeted thought disorder sites
in the brain and not on the movement sites thereby lessening those side
effects.
There are two main groups of antipsychotics - typical and atypical.
Atypical means not typical. All antipsychotics decrease action of the
neurotransmitter dopamine in the brain. Atypical antipsychotics (called
“atypicals” for short) also partly decrease the action of serotonin.
This double, or dual, action gives atypicals their broader benefit and
changes their side effect patterns, generally for the better.
My medicine chart on
Antipsychotics, page 1, gives useful information about the typical
antipsychotic group including names, doses, common side effects, pros, and
cautions. Some common and useful typicals include Haldol, Thorazine, Moban
(the least likely to increase weight), Orap (pimozide - often the best for
tics and Tourette’s) and several others.
The updated medicine
chart Antipsychotics, page 2 provides the same categories of
important information about the atypical antipsychotic group. Atypicals
are newer, still under patent, and are much more expensive than the
typicals, but are usually preferred due to their broader benefits and
substantially reduced rate of short and long term “extrapyramidal”
side effects. Another advantage of the atypicals, unlike typicals, is they
help not only the obvious schizophrenia symptoms of hallucinations,
delusions, and severe thought disorder but also better reduce so called
“negative” symptoms of apathy, poor motivation, and alienation from
society and also help mood. Unfortunately, some atypicals (Zyprexa,
Risperdal, and sometimes Seroquel) may cause weight gain, increase the
risk of diabetes, may raise cholesterol and triglyceride levels, and may
sedate patients.
The two main advantages of the atypicals over the typicals is the
broader range of diagnoses and symptoms they treat and their greatly
reduced, though not zero, risk of causing extrapyramidal symptom (EPS)
side effects. Short term reversible EPS include parkinsonian symptoms
(looks like but isn’t Parkinson’s disease), akathisia (internal
restlessness), acute dystonic reactions (scary intense muscle tightness
but often easily treated), and related effects. These short term
reversible EPS side effects can be reduced or cured by changing the
antipsychotic medicine dose, changing the antipsychotic medicine, stopping
the antipsychotic, adding a medicine like Cogentin (benztropine), Artane,
benadryl, amantadine or a beta blocker to counteract the EPS.
Tardive Dyskinesia (TD) is a possibly ireversible EPS movement disorder
long term side effect. The primary risk is from long term (usually years,
rarely , if ever, less than six months), high dose treatment with the
older typical antipsychotics which are also known as neuroleptics. The
risk of TD is essentially zero for low dose short term (weeks to months)
use. The risk of TD with the old typical group is about 5% per year (this
means about 5 of every 100 persons who takes an average dose of one of
these medicines for a year will show some TD at the end of that year).
Risk increases with age (especially in women), dose, duration, and being
nonwhite. The newer atypical antipsychotics have a much lower risk,
estimated at roughly 0.1% to 0.5% per year (1 to 5 in 1000 will show TD
after a year). Risperdal and Geodon are probably close to the 0.5% risk
while Seroquel, Zyprexa, and Abilify are at the 0.1% level. Clozaril may
even treat or reverse TD. Antidepressants, anti-anxiety meds, sleeping
meds, mood stabilizers, and stimulants do not carry any TD risk at all. TD
is a group of abnormal movements that typically start mildly with subtle
involuntary snake like (choreo-athetoid) and/or chewing-like frequent
movements of the tongue and mouth and may progress, especially with
continued use of the medicine, to affect the arms, legs, and other parts
of the body in severe cases. TD may be very mild to severe and disabling
with the degree usually related to the dose and duration of antipsychotic
medicine exposure. TD symptoms are not always caused by medication.
Abnormal movements indistinguishable from TD occur in some people with
other neurologic conditions, some people with schizophrenia, and even in
some elderly persons, even without any treatment ever with an
antipsychotic medicine. About 1/3 of TD cases believed to be caused by
antipsychotic medication recover completely without any special treatment.
Another 1/3 improve with time and treatment but not fully. The final 1/3
do not improve or recover and may progress. The best treatment for TD is
using Clozaril or high dose vitamin E; other options exist but are less
consistently helpful or are experimental. Prevention of TD is the best
treatment. My patients who take the antipsychotics become very used to
the modified AIMS testing I do at a number of the follow-up visits. They
are most aware of the finger tapping and tongue examination but are less
aware of the way I watch them walk, sit, stand, and how I look for other
subtle early signs of Tardive Dyskinesia. I am also watching and listening
for signs of the fully reversible and fully treatable false parkinson’s,
acute dystonia, and akathisia.
Although not yet certain, it appears the chances of the allergic like
uncommon neuroleptic malignant syndrome (NMS) is rare with atypicals. The
greatly reduced risk of all EPS, especially TD and NMS, is my favorite
advantage of the atypicals and makes the often impressive benefits and
advantages of this family of medicines more available for more situations
and more patients with far less risks than before.
Risperdal and Zyprexa are the 2 most tried and true atypicals for both
adults and kids. Seroquel is an alternative with more moderate sedation
and weight gain. Geodon has the least sedation. Geodon and Abilify have
the least or no weight gain. Risperdal and less so Geodon can increase the
hormone prolactin which can lead to breast engorgement and discharge.
Geodon has a tendency to mildly slow heart conduction but this is rarely a
problem. No atypicals require regular blood or other special testing and
generally are easy to give. Once daily dosing is common, with Geodon and
Seroquel more often given twice a day. All work rapidly, often the first
day or in the first week. I have seen many situations where an atypical
antipsychotic medicine, especially Risperdal or Zyprexa, has rapidly
prevented or stopped a potentially dangerous situation that would have
likely otherwise gone on to hospitalization, arrest, or serious harm. So
which is best? As usual, that depends on matching the medicine to the
patient, the target symptoms, what effects are wanted and what effects are
not wanted. Abilify, with its low EPS and very low TD risk, its moderate
sedation, no problematic prolactin or heart effects, little to no weight
gain, and good benefit is becoming, although the newest, a top choice.
In summary, the new atypical antipsychotics are wonderful additions to our
treatment options. They are often rapidly helpful in crisis situations
where other lesser options have failed. I particularly like them for
extreme impulsive aggression and rage. Low to moderate doses are usually
enough. They are quite safe and easy to use. Although the risk of Tardive
Dyskinesia makes them “big guns” the risk of TD is zero on a short
term basis. They are also easier and safer to use than other “big
guns” like Tegretol, Depakote, Lithium, and the older typical
antipsychotics. It is important to remember that we don’t often use
antipsychotic medicine for aggression unless the situation is severe,
other attempts have failed, and they won’t be kept unless they are very
helpful. Then we can decide how long to keep them at a more leisurely pace
after things are calmer.