ADVANCED PSYCHOPHARMACOLOGY

Psychology 572                       	                                 
Spring, 2004
Dr. John M. Morgan                    Tuesday & Thursday, 
8am to 9:20
                                                                      
Natural Resources 201

	This paper discusses various aspects of the class of 
drugs knows as "atypical" antipsychotics, used primarily to 
treat schizophrenia. The authors describe the brain activity 
of the drugs, the main effects and body changes, and the 
accompanying side effects. 


Atypical Antipsychotic drugs:  Their chemistry, route of 
access, synaptic transmitters affected, and affected ion 
channels.
Denise Thornton

	In order for drugs to have an effect on behavior, 
neurons must be affected directly or indirectly.  Neurons, 
or nerve cells, specialize in communication.  Neurons are 
composed of three parts; the soma (or cell body), the 
dendrites and the axon.  The soma contains the cell's 
nucleus.  Dendrites are tendril-like structures that extend 
from the soma.  Dendrites respond to impulses from other 
neurons and send them into the soma.  Axons are long 
structures (up to three feet long) which carry the impulse 
to the next cell. Bundles of axons that appear to be a 
single structure are what we call nerves.  
	The dendrites may receive hundreds of impulses 
which the neurons combine into one signal as it moves along 
the axon.  The axon can send the signal to up to 10,000 
other cells.  The electrical impulses are communicated from 
one neuron to the next by chemicals called 
neurotransmitters.  These chemicals are released by the 
terminal button, located at the end of each axon.  Each 
neurotransmitter fits into a receptor that is shaped exactly 
for reception of that specific type of neurotransmitter.  
The function of each neurotransmitter is dependent on its 
receptor.  A neurotransmitter may inhibit a neuron, excite 
another neuron, and be ineffective in yet another neuron, 
depending on the receptor (Kalat).
	Inhibitory receptors cause potassium ions to cross the 
cell membrane and hyperpolarize the cell.  This results in 
lowering the chances that the nerve will trigger again.  If 
the receptor is excitatory, sodium ions enter the cell 
membrane through ion channels causing depolarization.  
Sufficient depolarization causes the neuron to send another 
impulse down the axon.
	There are several types of dopamine (DA) receptors in 
the brain, but they are categorized in families as either D1 
receptors or D2 receptors. The D2 family includes D3 and D4 
receptors. 
	Neuroleptics, also called antipsychotics, are defined 
as drugs used in the treatment of psychotic disorders.  
There are currently two categories of neuroleptics, typical 
and atypical, (also called conventional and novel and first 
generation neuroleptics and new antipsychotics).  The 
typical antipsychotic drugs were developed in the 1950s.  
Chlorpromazine (Thorazine) was being used to suppress 
autonomic body reactions that interfered with surgery.  It's 
usefulness in treating psychosis was discovered by 
psychiatrist Jean Delay in 1952.  Chlorpromazine became the 
first typical antipsychotic (Schatzburg, et al.).  
	There are two classifications of symptoms of 
schizophrenia; positive symptoms and negative symptoms.  
Positive symptoms are those that we would like to eliminate.  
Positive symptoms include delusions, hallucinations, and 
disorganized thinking and behavior. Negative symptoms are 
the absence of desirable behaviors.  Negative symptoms 
include diminished speech, an inability to initiate or 
participate in focused activities, and flat affect(Palfai & 
Jankiewicz).  The typical antipsychotics are effective at 
treating positive symptoms.  These were the only type of 
antipsychotics available in the United States for many 
years, until 1990.
	All neuroleptics developed since 1990 are atypical.  
The first of these atypical drugs to be available in the 
United States is clozapine.  Several newer atypical 
antipsychotics have been developed since then; risperidone, 
olanzapine, quetiapine, sertindole, and ziprasidone.  
Atypical antipsychotics are effective at treating both 
positive and negative symptoms. The medicines help control 
the abnormal thinking associated with schizophrenia. They 
also improve the social withdrawal and lack of emotion that 
make people with schizophrenia seem different even when they 
are not having hallucinations or delusions.
	Atypical agents produce less D2 receptor blockade yet 
effectively antagonize other dopamine (principally D1 and 
D4) and the serotonin 5HT2 receptor subtypes. The atypical 
antipsychotics have a strong affinity for D4 receptors, but 
also strongly block 5-HT2 receptors.  Some serotonergic 
systems modulate dopamine systems.  These systems are able 
to raise DA activity at some sites while lowering DA 
activity at other sites rather than simply blocking DA 
receptors. . Whereas typical antipsychotic drugs block 
dopamine D2 receptors in the limbic system and striatum, 
accounting for both their effect on positive symptoms and 
their extrapyramidal effects, atypical agents produce less 
D2 receptor blockade yet effectively antagonize other 
dopamine (principally D1 and D4) and the serotonin 5HT2 
receptor subtypes (Keltner & Folks).  This results in 
effectively influencing negative symptoms while avoiding 
adverse side effects (Palfai & Jankiewicz). Negative 
symptoms are thought to be related to a hypodopaminergic 
process and serotonin inhibits dopamine.  Atypical 
antipsychotics antagonize 5HT2 receptors in the cortex that 
are presumed to block the inhibiting nature of serotonin 
neurons on dopamine, thus increasing frontal lobe dopamine 
levels.  This liberation of dopamine helps "normalize" 
frontal lobe function (Keltner & Folks).
	Atypical antipsychotics have the following 
characteristics:
		Reduced or no risk for EPSEs (reduced D2 
antagonism in nigrostriataltract)
		Increased effectiveness for negative and/or 
cognitive symptoms
		No elevation in prolactin (reduced D2 antagonism 
in tuberoinfundibular tract)
		Antagonization 5HT2
		Minimal risk for tardive dyskinesia 

	Clozapine has several side effects with the most 
serious being increased risk of seizures and 
agranulocytosis, lowering the white cell count and the 
immune system, which has a fatality rate as high as 30% 
(mentalhealth.com).  Clozapine has less of the side effects 
seen in conventional antipsychotics, including few 
extrapyramidal motor disturbances, no tardive dyskinesia, 
and no release of the hormone Prolactin (Palfai & 
Jankiewicz).  Patients being treated with clozapine must 
have weekly or biweekly blood level checks to monitor 
agranulocytosis.  Because of these serious side effects, 
clozapine is often only used as a last resort for patients 
resistant to other drugs.  Between 30% and 50% of patients 
respond poorly to other antipsychotics and 30% to 60% 
experience extrapyramidal symptoms.  Clozapine is often the 
drug of choice for these patients. 
	Orally administered clozapine (the gold standard of 
atypical antipsychotics) is absorbed at a rate of 90 to 95%.  
Clozapine is subject to first-pass metabolism, resulting in 
an absolute bioavailability of 50 to 60%.  Concentrations of 
clozapine in the blood show large differences between 
individuals, with peak concentrations appearing about 2.5 
hours after consuming the drug.  Clozapine is largely (95%) 
bound to plasma proteins.  Only trace amounts of the 
unchanged drug are found in urine and feces due to its being 
broken down by the body's organs. About 80% of the dosage is 
expelled through urine and feces (Mentalhealth.com). 
Clozapine is metabolized by the cytochrome P450 1A2 and 2D6 
systems. (American Family Physician).

Effects of Antipsychotic Drugs on Selected Neurotransmitter 
Receptors:
Receptor:        Effects of receptor blockade
D1, D5: 	 antipsychotic effect
D2: 		 mesolimbic tract, antipsychotic effect (all 
antipsychotic drugs antagonize this receptor) nigrostriatal 
tract, extrapyramidal side effects (EPSEs); 
tuberoinfundibular tract, prolactin elevation and associated 
effects; mesocortical tract, ?secondary negative symptoms 
D3: 		 ?antipsychotic effect on negative symptoms
D4: 		 ?antipsychotic effect on positive symptoms
5HT1:    	 ?mood, cognitive symptoms
5HT2A: 	 ?antipsychotic effect on negative symptoms; 	
		 ?reduction in EPSEs
5HT2c: 	 weight gain
5HT3:	 ?nausea
M: 		 can restore acetylcholine/dopamine balance and 	
		 relieve EPSEs;	anticholinergic side effect
H1: 		 sedation, orthostasis, weight gain
Alpha-1:   orthostasis, dizziness, sedation, 
		 ?antipsychotic effect
Alpha-2:	 sexual dysfunction
GABA: 	 lowers seizure threshold
(Keltner & Folks)

	
Areas of Concentration for Dopamine Receptor Subtypes
D1:  Found in motor neurons in the basal ganglia and may be 
the principal dopamine-stimulating receptor fro motor 
function. It has no direct role in controlling psychotic 
symptoms. It does influence D2 receptor function.
D2:  Located in neurons of both the limbic and motor 
centers.  Dopamine stimulation D2 receptors activate 
psychomotor pathways. Overactivation is thought to be the 
cause of positive symptoms.
	D2 receptors are modulated when the D1 receptor is 
blocked, but this does not occur in schizophrenia
D3 and D4:  Found primarily in limbic centers.  Dopamine 
stimulation of D3 may suppress behavior; overstimulation D3 
may be associated with negative symptoms.  D4 receptors are 
located on neurons that influence thought processes and may 
be related to positive symptoms.
D5:  Found only in the limbic regions, including hippocampal 
gyrus and nucleus accumbens.  May be an important dopamine-
stimulating receptor for behavior.
(Keltner & Folks). 	
References

Kalat, J. W. Biological Psychology. Brooks/Cole Publishing.
Keltner, N.L. & Folks, D.G. (2001).  Psychotropic Drugs 
Third Edition. St. Louis: Mosby, Inc. 
Mentalhealth.com.  www.mentalhealth.com
Motsinger, C.D., Perron, G.A., & Lacy, T.J. (2003) American 
Family Physician
Palfai, T. & Jankiewicz, H. (2001). Drugs and Human 
Behavior. NY: McGraw-Hill.
Schatzberg, A.F., Cole, J.O., & DeBattista, C. (2003).  
Manual of clinical                                                                     
psychopharmacology. Washington, D.C.:American Psychiatric 
Publishing.


Physiological (Whole Body) Changes and Primary Behavior 
Changes
Teresa Gauthier


       There are two main categories of antipsychotic drugs.  
Those made available in the United States between 1950 and 
1990 are referred to as traditional or typical 
antipsychotics, while the group of drugs developed and 
released since 1990 are called atypical antipsychotics.  The 
second group, atypical antipsychotics, consists of the 
following drugs: clozapine (Clozaril), first introduced in 
1960 but not released until 1990 because of its potentially 
fatal side effect, agranulocytosis, followed by risperidone 
(Risperdal) in 1994, then olanzapine (Zyprexa) in 1996, 
quetiapine (Seroquel) in 1997, and, finally, ziprasidone 
(Zeldox) in 2000 (Keltner & Folks, 2001).
       The primary features distinguishing atypical from 
typical antipsychotics are as follows: (1) The absence of 
extrapyramidal motor disturbances (EPS) and other motor 
disturbances; (2) the ability to effectively reduce 
schizophrenic symptoms in patients who do not respond well 
to typical antipsychotics; and (3) an increased ability to 
reduce the negative symptoms of schizophrenia (Grilly, 
1998).
       Traditional or typical antipsychotics have been 
effective in treating the positive symptoms of 
schizophrenia, while the negative symptoms have been more 
responsive to the newer atypical drugs.  Listed below are 
the positive and negative symptoms of schizophrenia (Keltner 
& Folks, p. 84): 

Positive symptoms: Abnormal thought form, agitation, 
tension, associational disturbances, bizarre behavior, 
conceptual disorganization, delusions, excitement, feelings 
of persecution, grandiosity, hallucinations, hostility, 
ideas of reference, illusions, insomnia, and suspiciousness. 
 
Negative symptoms: Alogia, anergia, anhedonia, asocial 
behavior, attention deficits, avolition, blunted affect, 
communication difficulties, difficulty with abstractions, 
passive social withdrawal, poor grooming and hygiene, poor 
rapport, and poverty of speech.

     The therapeutic effects of antipsychotic drugs, 
including physiological and behavioral changes, are 
numerous.  Clinical research has shown impressive evidence 
for the effectiveness of these drugs.  For example, 75% of 
all patients with positive symptoms of schizophrenia respond 
to antipsychotics.  Of those patients who do not respond to 
typical antipsychotics, 30% respond to clozapine or other 
atypical antipsychotics.  Generally, a positive response is 
noticed in 1 to 2 weeks, with continued improvement for up 
to 6 to 8 weeks (Keltner & Folks, 2001).  According to 
Preston and Johnson (2004), symptomatic improvement as a 
result of antipsychotic medication is first noticed as a 
decrease in agitation, arousal, and emotional dyscontrol, 
while symptoms such as hallucinations, thought disturbances, 
and poor reality testing generally take much longer to 
respond.  The specific physiological and behavior changes, 
or therapeutic effects, of antipsychotic drugs will be 
outlined in the paragraphs below (Keltner & Folks, 2001).
     The central nervous system (CNS) effects of 
antipsychotic drugs include psychomotor slowing, sedation, 
and emotional quieting.  The effect of emotional quieting 
allows the patient to better utilize other forms of 
therapeutic intervention, such as psychotherapy and 
psychoeducation.  In addition, the CNS effect of sedation is 
often helpful for patients with insomnia.
     Schizophrenic patients often suffer from perceptual 
disturbances.  Generally, the more bizarre the psychotic 
behavior, the greater the likelihood an antipsychotic drug 
will be beneficial to the patient.  Illusions and 
hallucinations usually diminish or go away completely with 
the use of antipsychotics.  Even if they do not completely 
go away, these drugs will help the patient understand that 
these perceptual disturbances are not real and that they can 
be tolerated without negatively influencing their behavior.
     Antipsychotic drugs may also decrease delusions, 
suspiciousness, and ambivalence.  Because these thought 
disturbances often cause frustration and behavioral 
consequences in schizophrenic patients, antipsychotic drugs 
have been found to be effective at simultaneously decreasing 
schizophrenic symptoms while increasing the patient's 
ability to communicate and cooperate with others.
     Individuals with schizophrenia are often hyperactive 
and agitated.  Antipsychotic drugs may help to slow or 
normalize their psychomotor activity.  Some drugs such as 
clozapine, risperidone, and olanzapine are inherently 
sedating, and this effect may be especially helpful for 
agitated and combative patients.
     Antipsychotic drugs can be effective in decreasing 
mental confusion in psychotic and schizophrenic patients.  
These symptoms are often considered by mental health 
professionals to be the most disabling.
     Schizophrenic patients often have a history of 
interpersonal disturbances, such as asocial behavior and 
social withdrawal.  Many have very few, if any, close 
personal relationships, and, in addition, they often have 
disturbed relationships with family members.  Additionally, 
these individuals tend to neglect their personal appearance 
and hygiene, and they are often unaware of their offensive 
behavior toward others.  Antipsychotic drugs may be 
effective in helping schizophrenic patients overcome some of 
these interpersonal difficulties.
     Depression is commonly found in individuals with 
schizophrenia and occurs most often after symptoms improve 
(i.e. postpsychotic depression).  Generally, depression is 
treated with antidepressants and psychotic symptoms with 
antipsychotics, but the atypical antipsychotic drug 
ziprasidone (Zeldox) has been found effective at treating 
both schizophrenia and depression since it blocks the 
reuptake of serotonin and norepinephrine.
     As mentioned earlier, there is a new group of 
antipsychotic drugs called atypical antipsychotics that are 
believed to have an improved therapeutic efficacy on both 
the positive and negative symptoms of schizophrenia with 
decreased side effects. Of this group, clozapine, 
resperidone, and olanzapine are most frequently prescribed.  
Clozapine has received approval for use in human subjects 
despite its rare but potentially fatal side effects.  A 
number of studies have shown its antipsychotic efficacy in 
otherwise unresponsive schizophrenic patients and its 
reduced association with EPS and tardive dyskinesia as 
compared to the typical antipsychotics.  These studies have 
shown that clozapine is effective in treating both positive 
and negative symptoms of psychosis, and it has also been 
shown to improve "functionality," including increased 
social, vocational, and interpersonal adaptation.  This 
particular improvement has resulted in few hospitalizations 
and in more patients increasing their educational level and 
reentering the workplace (Schatzberg & Nemeroff, 1998).
     Risperidone, another of the atypical antipsychotics, 
has been associated with improvement in quality-of-life 
scales, social functioning, reductions in hospital stays, 
and overall reductions in lifetime cost of illness.  In 
addition to reducing schizophrenic symptoms, risperidone has 
been shown to improve cognitive deficits in treatment-
resistant patients.  Because of risperidone's relative 
safety and few adverse side effects, studies have suggested 
its usefulness in the treatment of other psychotic 
disorders, including psychotic depression, psychotic 
dementias, and mania (Schatzberg & Nemeroff, 1998).  Other 
atypical antipsychotic drugs such as iloperidone, 
mazapertine, aripiprazole are currently under development, 
and, if proven successful, may eventually be released for 
use.  
     In conclusion, the constant search for more effective 
and better-tolerated antipsychotic drugs, combined with the 
ever-increasing sophistication of neurobiology, have led to 
the development of several new-generation atypical 
antipsychotic drugs.  In time, an entire series of even 
newer atypical antipsychotics will arrive on the market, 
further expanding our understanding of the pathogenesis and 
treatment of schizophrenia and other psychotic disorders.

References

Grilly, D.M. (1998).  Drugs and human behavior.  Needham 
Heights, MA: Allyn and Bacon.  

Keltner, N.L., & Folks, D.G. (2001).  Psychotropic drugs.  
St. Louis, Missouri: Mosby, Inc.

Preston, J., & Johnson, J. (2004).  Clinical 
psychopharmacology made ridiculously simple.  Miami, Fl: 
MedMaster, Inc.

Schatzberg, A.F., & Nemeroff, C.B. (Eds.) (1998).  The 
american psychiatric press textbook of psychopharmacology.  
Washington, DC: American Psychiatric Press, Inc.        

The Side Effects of the Atypical Antipsychotic Medications
Marcella Strang

	The atypical antipsychotic medications have been 
utilized for their minimal side effect profile, when 
compared with traditional antipsychotic drugs. Many of the 
side effects are general to all drugs in this class, while 
other effects are specific to a particular drug. This paper 
will review the general side effects of antipsychotic drugs, 
and then will compare the specific medications' side effect 
profiles.
	The atypical antipsychotics comprise the following 
commonly prescribed medications: 
Generic		Brand Name
Clozapine		Cloraril
Risperidone	Risperdal
Olazapine		Zyprexa
Quetiapine	Seroquel
Ziprasidone	Geodon
Aripiprazole	Abilify

	The atypicals were developed in response to the 
significant side effects of "first-generation" antipsychotic 
medications. These effects, although significantly reduced 
in the atypical drugs, are still a risk factor for patients. 
As a treatment consideration, they deserve an explanation.
The major issues are the extrapyramidal side effects, 
and a condition known as "tardive dyskinesia". 
Extrapyramidal effects refer to four types of effects 
induced by antipsychotic medications: dystonia, akathisia, 
pseudoparkinsonism, and tardive diskenesia. Dystonia refers 
to involuntary muscle contractions that cause abnormal 
movements and postures, especially of the head, face and 
neck, and usually occur within 10 days of receiving 
medication or increased dosages. Akathisia consists of 
restlessness and inability to sit still, often accompanied 
by an inner feeling of agitation. Pseudoparkinsonism, much 
like classic Parkinson's disease, involves a general slowing 
down of movement, rigidity of the body, and lack of facial 
expression. Finally, tardive dyskenia consists of irregular, 
stereotyped movements of the tongue, mouth and face, 
accompanied by bizarre posturing of the body. Patients are 
frequently unaware of these actions. These effects, although 
frequently reversible, are a major deterrent to compliance 
with medication among patients (Schatzberg & Nemeroff, 
2001). 
Happily, the "second generation", atypical 
antipsychotics carry a substantially lower risk of these 
extrapyramidal symptoms. Atypicals are now the first line of 
defense in treating psychosis, supplanting the older, 
typical antipsychotics for most patients (Schatzberg, Cole, 
& DeBattista, 2003). 

General Side Effects

	Atypical antipsychotics have been associated with 
several disturbances of metabolism: obesity, onset of 
diabetes mellitus or diabetic ketoacidosis, and the 
development of hypertriglyceridemia (Lebovitz, 2003).

Weight gain

In general, all antipsychotic medications are 
associated with significant weight gain (ziprasidone and 
aripiprazole being the exceptions). However, the atypical 
antipsychotics are associated with significantly more weight 
gain than the typical neuroleptics. Among the atypicals, two 
drugs – clozapine and olazapine – appear to be the prime 
culprits. Weight gain is due to an increase in appetite and 
food intake, and involves an increase in fat rather than 
lean tissue (Lebovitz, 2003).
Weight gain is a major deterrent for patients, 
resulting in a high rate of noncompliance with treatment 
(Weiden, Mackell,& McDonnell, 2004). In response to this, 
psychosocial models have been developed in day-treatment 
formats to manage the effects of weight gain. Behavioral 
strategies have also been suggested, although limited data 
exists thus far to support their efficacy (Werneke, Taylor, 
Sanders, & Wessely, 2003).

Diabetic effects

	The atypical antipsychotics also appear to be 
associated with onset of type-II diabetes. Several studies, 
from the 1940's through the 1970's, have shown a high 
prevalence of type-II diabetes among schizophrenic patients. 
In fact, this condition is at least two to three times more 
prevalent in schizophrenia than in the general population. 
Recent data, however, suggest that the atypical drugs in 
particular may put patients at greater risk than older, 
typical drugs. A 1999 study at a veterans hospital found a 
9& higher rate of type-II diabetes onset in patients 
receiving atypical antipsychotic drugs. The highest rates 
were found in patients receiving clozapine, olanzapine, and 
quetiapine. In addition, patients may be at risk for 
diabetic ketoacidosis, a state of insulin deficiency 
(Lebovitz, 2003).

Hypertriglyceridemia

	Elevated levels of triglycerides, commonly referred to 
as high cholesterol, are another metabolic effect found in 
patients receiving atypical antipsychotics, especially 
olanzapine. This condition has been linked with heart 
disease and acute pancreatitis (Lebovitz, 2003).

Other general side effects

	Atypical antipsychotics, unlike their "first 
generation" cousins, do not produce major sedation. However, 
there is a sedative effect that can be unwelcome for many 
patients. In addition, the atypicals can result in 
akathisia, a general restlessness and inability to sit 
still. Akathisia can range from a general muscle tension to 
intense discomfort and agitation. In fact, this condition 
can easily be mistaken for psychotic agitation, resulting in 
increased medication and side effects. The author's of one 
psychiatric text warn clinicians to attend to patient 
feedback on drug effects, noting that overdosing patients 
with neuroleptics is much more common than underdosing 
(Schatzberg & Nemeroff, 2001).

Specific drug side effects

Clozapine (Clozaril)

	The most serious potential side effect, though rare, is 
a condition known as agranulocytosis, a disturbance in the 
levels of white blood cells. This condition has been 
reported in less than 2% of patients in the U.S. Because it 
can be fatal, close monitoring through weekly blood draws is 
required. The expense of monitoring contributes to the cost 
of treatment. Many patients and their families, however, 
consider the benefits of clozapine to be worth the risk and 
expense (Schatzberg, et al.,2003).

	Several other side effects have been linked to 
clozapine. Some cardiovascular effects have been reported, 
including very low blood pressure and irregular heartbeat. A 
small number of patients develop unpleasant gastro-
intestinal distress, and flu-like symptoms with passing 
fevers, early in treatment. Hypersalivation at night is 
common, and can result in wet pillowcases. Eneuresis (bed 
wetting) can occassionally occur. In addition, drug 
interactions can occur with fluvoxamine, especially when 
combined with lithium. This has resulted in several cases of 
NMS (neuroleptic malignant syndrome), a potentially deadly 
interference with bodily regulation (Schatzberg,et al, 
2003). 

Risperidone (Risperdal)

Risperdal has a mixed side effect profile. It has been 
linked with higher rates of extrapyramidal effects than the 
other atypicals, and a higher probability of raising 
proactin levels (also similar to the 'typical' 
antispychotics). However, it appears to be the least likely 
to cause the metabolic disturbances of the other atypicals, 
such as onset of diabetes (Schatzberg, et al, 2003).

Olanzapine (Zyprexa)

This drug carries a high risk for weight gain, as mentioned 
earlier. It tends to produce more sedation, and slightly 
more chance of akathisia, depending on the dose. Olanzapine 
also has some anticholinergic effect, meaning constipation 
and dry mouth (Schatzberg, et al.,2003).

Quetiapine (Seroquel)

Common side effects include sleepiness and dizziness. Weight 
gain tends to be less than with olanzapine and clozapine, 
but more than with geodon or risperdone. There is some 
warning of cataract risk, and possible risk of problems with 
liver enzymes (Schatzberg, et al.,2003).

Ziprasidone (Geodon)

This drug, one of the newest of the atypicals, is 
distinguished by its weight-neutral profile. This means it 
does not appear to cause any significant weight gain. This 
recommends it for many patients who struggle with obesity. 
Common side effects include drowsiness, stomach upset, 
dizziness, constipation, and nausea. Ziprasidone may also be 
associated with irregular heart rhythms, so patients with a 
history of heart problems may need to be monitored 
(Schatzberg, et al.,2003).

Apriprazole (Abilify)

This drug, one of the newest on the market, has the least 
amount of data available. So far, it does not appear to 
cause weight gain or to have a significant effect on the  
heart. It may, however, have a greater tendency to cause 
akathisia (restlessness,tension). Common side effects 
include nausea, tremor, insomnia, headache and agitation 
(Schatzberg, et al. 2003).

References:

Lebovitz, H.E.  Metabolic consequences of atypical 
antipsychotic drugs. Psychiatric Quarterly, 2003, 74 (3), 
277-288.

Schatzberg, A.F., Cole, J.O. & Debattista, C. (2003). Manual 
of clinical pharmacology. Washington, D.C.: American 
Psychiatric Publishing.

Schatzberg, A.F. & Nemeroff, C.B. (2001). Essentials of 
clinical psychpharmacology. Washington, D.C.: American 
Psychiatric Publishing.

 Weiden, P.J., Mackell, J.A. & McDonnell, D.D. Obesity as a 
risk factor for antipsychotic noncompliance. Schizophrenia 
Research,  2004, 66(1), 51-57.

Werneke, U.T., Taylor, D., Sanders, T.A. & Wessely, S. 
Behavioral management of antipsychotic-induced weight gain: 
A review. Acta Psychiatrica Scandinavica, 2003, 108(4), 252-
259.

Copyright © 2004, Dr. John M. Morgan, All rights reserved - This page last edited 1-3, 2004
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