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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, 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 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, depression, severe
anxiety, and other conditions where thinking, compulsive behavior, or
impulsive behaviors are problems.
Atypicals are often helpful medicines in treating behavioral and
neuro-psychiatric complications of dementia, head injuries, and strokes.
The newer “atypical” antipsychotics also work as mood
stabilizers. They are usually the best treatments for mania and are often
good for acute depression.
They also show promise in lessening recurrence of both mania and
depression like the classic mood stabilizers lithum, Depakote (valproic
acid), and Tegretol (carbamazepine).
The
“atypicals” are Clozaril (clozapine), Risperdal (risperidone), Zyprexa
(olanzapine), Seroquel (quetiapine), Geodon (ziprasidone), Abilify (ariprazole)
and Invega (paliperidone). Clozaril is used least despite potential
excellent benefits and no Tardive Dyskinesia risk because it has several
other possibly quite troublesome 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, mostly 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 medicine
chart Antipsychotics, page 2 provides the same categories
of important information about the atypical antipsychotic group. Atypicals
are newer, mostly still under patent, and are thus much more expensive
than the typicals.
Atypicals are usually preferred due to their generally 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 schizophrenia like apathy,
poor motivation, and alienation from society and also help mood.
Unfortunately, atypicals (except Geodon) may cause weight gain, increase
the risk of diabetes, may raise cholesterol and triglyceride levels, and
may overly 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 brief and often easily treated), and related effects. These short term
reversible EPS side effects can be reduced or prevented by changing the
antipsychotic medicine dose, changing the antipsychotic medicine to a
different one, stopping the antipsychotic, or 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 close to none 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 worsen even to disability. The best
treatment for TD is using Clozaril although 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 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 reversible and treatable false parkinsonian, acute
dystonia, and akathisia sympyoms. Neuroleptic malignant syndrome (NMS) is
a rare but potentially dangerous quasi allergic like reaction that is
fortunately extremely rare with atypicals. The greatly reduced risk of all
EPS, especially TD and NMS, is a big 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 with the older “typicals”.
Zyprexa
(olanzapine) may be the most effective but has the most sedation and
weight gain.
It also has the lowest EPS risk, next to its cousin clozapine.
Risperdal has been used the most in kids and is FDA approved fro Autism.
Seroquel is an alternative with more moderate to strong sedation and
mid-range weight gain risk. Geodon has the least sedation. Geodon and
Abilify have the least or no weight gain or “metabolic syndrome” risk.
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 and especially at
higher doses. Invega is a new delayed release atypical related to
Risperdal. No atypicals (except clozapine) require regular blood or other
special testing and generally are easy to give. Once daily dosing is
common, with Geodon 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 has rapidly stopped a potentially
dangerous situation that might have 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 low TD risk, its moderate sedation,
no problematic prolactin or heart effects, lower chance of weight gain,
convenient dosing and often good benefit is often worth consideration.
In
summary, the new atypical antipsychotics are welcome additions to our
treatment options. They are often rapidly helpful in crisis situations
where other lesser options have failed. I particularly like them for
severe impulsive aggression and rage or as boosters when other treatments
have been inadequate. 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 quite low, especially 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 comfortable
pace after things are calmer.