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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 (OCD), Depression, severe
Anxiety, and other conditions where thinking, compulsive behavior, or
impulsive behaviors are problems. Antipsychotics
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),
Tegretol (carbamazepine) and Lamictal (lamotrigine).
The
"atypicals" are Clozaril (clozapine), Risperdal (risperidone),
Zyprexa (olanzapine), Seroquel (quetiapine), Geodon (ziprasidone), Abilify
(ariprazole), Invega (paliperidone) plus the newest two - Saphris (asenapine)
and Fanapt (iloperidone).
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. Unfortunately, Moban is no longer being produced, at least
not in the US.
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 (except risperidone), 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 hypertension.
These side effects can be severe and may outweigh benefits. Some
doctors assert, and some studies support, that atypicals are not cost
effective for at least some 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
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 (but not) zero for low dose short term (weeks to months) use. The
risk of TD with the old "Typical" group is about 1 to 5% per
year (this means about 1 to 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,
use in non-psychotic conditions, 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, Abilify
and Geodon are probably close to the 0.5% risk while Seroquel and Zyprexa,
are at the 0.1% level. Clozaril treats or even reverses TD.
Antidepressants, anti-anxiety meds, sleeping meds, mood stabilizers, and
stimulants do not carry any TD risk at all. Tardive Dyskinesia (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 symptoms.
Neuroleptic
Malignant Syndrome (NMS) is a rare but potentially dangerous quasi
allergic like reaction that is fortunately rare with atypicals, especially
at lower doses. 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 (other than clozapine) 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 for Autism. Seroquel is an
alternative with moderate to strong sedation (sleep help), low EPS risk,
and mid-range weight gain risk. Geodon has the least sedation, mild
EPS risk, and no weight gain (this is a big plus in its favor). 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 not at lower
doses (checking an EKG may be useful if heart symptoms or high dose). Invega
is an extended release atypical related to Risperdal. Saphris and Abilify
are moderate re weight gain, EPS (movement disorder side effects) and
sedation. No atypicals (except clozapine) require regular blood or other
special testing and generally are easy to give. Geodon comes only in
capsules and tastes bad if split. Once
daily dosing is common for all antipsychotics although sometimes twice or
more doses a day for smoother effects. 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, diagnosis, what has been tried before, history of
response to other treatments, cost, is a split-able pill or liquid needed,
what effects are wanted, what effects are not wanted, and whether even the
side effect might be a benefit for this person.