CHAPTER SEVEN Antipsychotic Medications The Evolution of Treatment Many readers may begin this chapter with some familiarity with antipsychotic medications. Others may think antipsychotic medications or the research related to them has not affected their lives. These latter readers may be wrong. Have you ever taken a prescription antihistamine such as Seldane or Allegra? Perhaps got over motion sickness with a compound that included promethazine? If so, your life has been affected by research into antipsychotics. As with so many other areas of research in psychotropic medication, antipsychotics and theories about their use have been developed through combined scientific effort, clinical research, market-driven agendas, and serendipity. Let's look at some history to introduce this topic. The primary source for the following is Healy (2002). THE CURRENT IMPACT OF ANTIPSYCHOTICS In a video designed for psychiatrists (Novartis Pharmaceuticals, 1998), a young man suffering from treatment-resistant schizophrenia is shown in an inpatient setting. Although his psychotic symptoms are temporarily under control, he is so incapacitated by medication side effects that he can barely walk across a small room. His movements are jerky contractions of muscle groups that he can hardly control. Anyone who has treated clients taking conventional antipsychotic medications knows that this young man is living a worst-case scenario in which the treatment is worse than the disorder being treated. The video progresses, showing the young man at monthly intervals as he is slowly weaned off the medications causing the side effects, and gradually titrated onto a new medication (clozapine). With each passing month, we see that the young man's psychotic symptoms remain under control but that he is gradually regaining control of his body. In the final video frame, we see the same young man enjoying a game of basketball and apparently having no problems with movement or symptoms of psychosis. This was one of the first videos promoting what we describe later as an atypical antipsychotic, and at the time of their development most of us believed that clozapine and drugs modeled after its molecular structure launched another revolution in psychopharmacology. It was hoped that (as was hoped in the SSRI revolution in antidepressants) the new antipsychotics would change the way psychotic disorders are treated as well as the quality of life that patients can expect during treatment. As we will see, although newer agents do work better for some but not all people with schizophrenia, the newer agents have problematic side effects similar in impact (if different in quality) as the older agents. Also, the claims that newer medications worked better than the older ones now seem to be untrue ( Jones et al., 2006; Lieberman et al., 2005). This chapter is divided into seven sections. The first is an overview of schizophrenia and the spectrum of symptoms being treated. The second focuses on th.

1. CHAPTER SEVEN
Antipsychotic Medications
The Evolution of Treatment
Many readers may begin this chapter with some familiarity with
antipsychotic medications. Others may think antipsychotic
medications or the research related to them has not affected
their lives. These latter readers may be wrong. Have you ever
taken a prescription antihistamine such as Seldane or Allegra?
Perhaps got over motion sickness with a compound that
included promethazine? If so, your life has been affected by
research into antipsychotics. As with so many other areas of
research in psychotropic medication, antipsychotics and theories
about their use have been developed through combined
scientific effort, clinical research, market-driven agendas, and
serendipity. Let's look at some history to introduce this topic.
The primary source for the following is Healy (2002).
THE CURRENT IMPACT OF ANTIPSYCHOTICS
In a video designed for psychiatrists (Novartis Pharmaceuticals,
1998), a young man suffering from treatment-resistant
schizophrenia is shown in an inpatient setting. Although his
psychotic symptoms are temporarily under control, he is so
incapacitated by medication side effects that he can barely walk
across a small room. His movements are jerky contractions of
muscle groups that he can hardly control. Anyone who has
treated clients taking conventional antipsychotic medications
knows that this young man is living a worst-case scenario in
which the treatment is worse than the disorder being treated.
The video progresses, showing the young man at monthly
intervals as he is slowly weaned off the medications causing the
side effects, and gradually titrated onto a new medication
(clozapine). With each passing month, we see that the young
man's psychotic symptoms remain under control but that he is
gradually regaining control of his body. In the final video
frame, we see the same young man enjoying a game of

2. basketball and apparently having no problems with movement or
symptoms of psychosis.
This was one of the first videos promoting what we describe
later as an atypical antipsychotic, and at the time of their
development most of us believed that clozapine and drugs
modeled after its molecular structure launched another
revolution in psychopharmacology. It was hoped that (as was
hoped in the SSRI revolution in antidepressants) the new
antipsychotics would change the way psychotic disorders are
treated as well as the quality of life that patients can expect
during treatment. As we will see, although newer agents do
work better for some but not all people with schizophrenia, the
newer agents have problematic side effects similar in impact (if
different in quality) as the older agents. Also, the claims that
newer medications worked better than the older ones now seem
to be untrue ( Jones et al., 2006; Lieberman et al., 2005).
This chapter is divided into seven sections. The first is an
overview of schizophrenia and the spectrum of symptoms being
treated. The second focuses on theories of neuroleptic
antipsychotic action. Section Three is an overview of the
side effects of first generation, neuroleptic medications. Section
Four is an introduction to the first atypical antipsychotic,
clozapine/Clozaril. Section Five covers the rest of the drugs
modeled on clozapine called serotonin-dopamine antagonists.
Section Six looks at newer compounds and theories of how to
create more effective antipsychotics. The final section looks at
psychological, cultural, and social issues relevant to
antipsychotic medications.
SECTION ONE: SCHIZOPHRENIA
Learning Objectives
• Have a sense of the complexity of theories of etiology for
schizophrenia.
• Be able to discuss why the name “schizophrenia” is not
terribly useful.
• Understand positive symptoms, primary negative symptoms
and secondary negative symptoms.

3. Schizophrenia “… definitely involves genetic factors the precise
genes and gene-environment interactions are yet to be clarified”
(Keshavan, Tandon, & Nasrallah, 2013, p. 4). As Stober et al.
(2009) concluded, “the phenotypic complexity, together with
the multifarious nature of the ‘group’ of ‘schizophrenic
psychoses’ limits our ability to form a simple and logical
biologically based hypothesis of the disease group” (p. 129).
Schizophrenia shares many heritable factors with Bipolar I
disorder, suggesting there may be an underlying genetic basis
for both disorders that runs on a continuum. At the more severe
end of the continuum, the person is afflicted with
schizophrenia; at the less severe end (if it is fair to use that
phrase in regard to any of these disorders), the person is
afflicted with Bipolar I Disorder (McIntosh et al., 2006).
Ultimately, though, schizophrenia is a disorder with a
heterogeneous presentation involving multiple genes that may
each have relatively small effects. Etiological factors also
include differences in brain structures (Hartberg et al., 2011),
white matter or the glial cells in the brain (Frances, 2013), and
neurochemical variables (although nothing as simple as
dopamine imbalance as was believed in the mid to late 20th
century). Prevalence among adults is thought to be between 1
and 1.5% of the adult population (American Psychiatric
Association, 2013). Keshavan (2013) has advocated eliminating
the name “Schizophrenia” because it conveys an inaccurate
characterization of the symptoms, has acquired a negative
connotation (like “lunacy”), and belies what we are learning
neurobiologically about the disorder. Keshavan et al. (2013)
have suggested an acronym “CONCORD,” which stands for
“youth onset conative, cognitive and reality distortion” (p. 1).
As Keshavan notes, we do not take lightly renaming a disorder
but the label of “schizophrenia” seems to be obsolete.
One of the most distressing aspects of schizophrenia is that it
seems to be correlated with premature death. Even more
disturbing is that we still have to discern if this is related to the
disorder, the medications people with the disorder take, or both.

4. Joukamaa and colleagues (2006) did a 17-year follow up of 99
people with schizophrenia. Of the 99, 39 died in that 17 years.
Adjusted for age and sex and other diseases, the risk for
premature death was significantly higher than expected. The
deaths also increased as the number of neuroleptics taken
increased. Even though we have agents to treat the symptoms of
schizophrenia, as noted above, they do not really differ much
from one another in general effectiveness and what is needed is
that we understand the mechanisms underlying the illness and
its progression. Until we can accomplish this, we will remain
stuck in symptom management (Kane & Correll, 2010).
The Spectrum of Symptoms in Schizophrenia
In DSM-5 (APA, 2013), the category Schizophrenia and Other
Psychotic Disorders of DSM-IV has been changed to
Schizophrenia Spectrum and Other Psychotic Disorders. Many
aspects of the DSM-5 were designed to reflect the International
Classification of Mental and Behavioural Disorders (ICD-10)
(WHO, 1992), which includes Schizotypal Personality Disorder
under the Schizophrenia heading. So in DSM-5, the spectrum of
disorders also contains a spectrum of symptoms. The spectrum
of symptoms in schizophrenia includes both positive and
negative symptoms. This concept derives from the work of the
19th-century neurologist John Hughlings Jackson. Positive
symptoms of schizophrenia are things the client experiences but
likely should not be experiencing, such
as hallucinations, illusions, delusions, and paranoia. Clients
with positive symptoms usually lack insight into the sense
outsiders have that these experiences are not real or normal and
frequently cannot distinguish between them and the consensual
reality shared by most others.
Negative symptoms of schizophrenia are deficits in the client's
functioning expressed as things like anhedonia (lack of pleasure
in life), isolation, withdrawal, flat or restricted affect, and
reduced motivation. These negative symptoms severely affect
quality of life for afflicted clients and can be exacerbated by
certain antipsychotic medications clients are given to control

5. the positive symptoms. In addition to the positive and negative
symptoms, clients suffering from schizophrenia experience
conceptual disorganization, which used to be called ” thought
disorder.” This disorganization can range from concrete
thinking to severe loose associations and word salad. These
symptoms may also severely reduce clients’ quality of life
(Thaker & Tamminga, 2001). From an integrative perspective,
all these symptoms need to be addressed. Although
pharmacological interventions are the first line of treatment for
schizophrenia, it is also important to include psychosocial and
educational components (American Psychiatric Association,
2000a).
Gelman (1999) divides the history of medicating psychotic
disorders into four periods. The first period encompasses the
1950s and 1960s and began with the appearance of
chlorpromazine (Thorazine). In this period, the mechanisms of
action for chlorpromazine were not known, and although many
people believed this drug would usher in an age of
deinstitutionalization, others felt it would likely just make
hospital wards more manageable.
The second period begins in the early 1960s with the emphasis
(begun in the Kennedy administration) of community care
versus hospital care. At this time, the National Institute of
Mental Health was labeling antipsychotics “antischizophrenic.”
At this time, psychological explanations for mental disorders
were dropped in favor of medical model theories. Some writers
at the time (Swazy, 1974) even posited that chlorpromazine was
a “magic bullet” for schizophrenia (which it never was). This
second period ends in the 1980s with the disappearance of such
overly optimistic views. By the 1970s, clinicians accepted that
neuroleptics could produce “alarming side effects, non-profound
benefits in most cases, and no benefit at all in many” (Gelman,
1999, p. 7).
The third period, encompassing the 1980s and early 1990s,
found many clinicians still clinging to the vague medical model
notion of a chemical imbalance as causing schizophrenia despite

6. the theory being increasingly falsified. Although researchers
and clinicians began to understand schizophrenia as a complex,
overdetermined disorder, many psychiatrists continued to follow
the chemical imbalance theory (old habits die hard and it is
easier to feign certainty than to live in ambiguity). Research
during this period birthed the atypical antipsychotics, and for
many psychiatrists these drugs seemed to continue to support
the chemical imbalance theory, although they operate very
differently from the neuroleptics that actually spawned the
theory. Neuroleptics block dopamine-2 (D2) receptors whereas
the atypicals block mostly serotonin receptors and some D2
receptors but not as many as neuroleptics. That these drugs that
massively block serotonin receptors work as well as
neuroleptics that block D2 receptors calls into question how
schizophrenia could possibly be just a dopamine imbalance.
The fourth and current period began in the mid-1990s and
continues to the present. This period is marked by new imaging
technology that allows neurologists and psychopharmacologists
to more closely examine the brain and the effects of
medications on the brain. During this period, researchers will
likely continue to construct newer theories to account for the
action of antipsychotic medications.
Review Questions
• What are some of the variables currently considered as
important to the etiology of schizophrenia?
• Why is the label “schizophrenia” inaccurate and what could
replace it?
• Describe positive symptoms, primary negative symptoms, and
secondary negative symptoms.
SECTION TWO: THEORIES OF NEUROLEPTIC ACTION
FROM THE MEDICAL MODEL PERSPECTIVE
Learning Objectives
• Understand the dopamine hypothesis of schizophrenia and how
it has been falsified.
• Be able to describe the primary dopamine tracts in the brain
and how neuroleptic medications are thought to work.

7. • Know the four classes of extrapyramidal side effects (EPS).
• Know two classes of medications regularly used to treat EPS.
In this section, we outline the mechanism of action in typical
antipsychotics (neuroleptics), detail their common side effects,
and discuss how to deal with side effects. It is interesting that
neuroleptics, and chlorpromazine/Thorazine in particular, were
widely used before their mechanisms of action were isolated. As
you are now aware, this is not unusual in the history of
psychopharmacology, and the neuroleptics were being used on a
global scale before their mechanisms of action were identified.
The Dopamine Hypothesis of Schizophrenia
The dopamine hypothesis of schizophrenia (the first “chemical
imbalance” theory for the disorder) actually was formulated in
the 1960s but had no impact on the field of psychiatry until the
1970s. The hypothesis proposed that schizophrenia was caused
by an undefined problem in dopamine transmission. The
hypothesis grew out of the realization that
chlorpromazine/Thorazine and haloperidol/Haldol both seemed
to interrupt dopamine transmission and decrease the symptoms
of schizophrenia. Equally, abuse of amphetamine drugs that
stimulate dopamine can cause symptoms indistinguishable from
schizophrenia in some but not all people. As you may recall
from Chapter Five, this is similar to the amine hypothesis of
depression. It posits a simple (too simple) cause-and-effect
relationship from observations of medical trials. As in other
cases, though, the reality is far more complex, and emotional
defense of the simple dopamine hypothesis today carries the
same authority as emotional proclamations espoused by the Flat
Earth Society.
So how was the dopamine hypothesis developed, and what
relevance has it for mental health clinicians? Since the early
administration of chlorpromazine/Thorazine, researchers had
noted that the drug caused symptoms similar to those in
Parkinson's disease (so named for James Parkinson, who
outlined the symptoms in 1812). Carlsson and Lindqvist (1963)
proposed the first variation on the dopamine hypothesis, but

8. remember that at the time people knew little about
neurotransmitters and nothing at all about neurotransmitter
receptors. Arvid Carlsson discovered dopamine in the central
nervous system, where, researchers learned, dopamine was also
a precursor to norepinephrine. Studies with reserpine/Serpalan
demonstrated that it depleted norepinephrine and serotonin from
the brain, but when these neurotransmitters were replaced they
did not counter the effects of the reserpine/Serpalan. Carlsson
and his colleagues, hot off their discovery that dopamine was
also present in the brain, assumed that dopamine too was
depleted by reserpine and discovered that giving research
animals a precursor for dopamine (levodopa/Carbidopa) did in
fact reverse the effects of reserpine/Serpalan. Thus was born the
first variation of the dopamine hypothesis—that psychoses were
somehow related to deficiencies in dopamine.
The first response to this theory was that it did not make sense,
because chlorpromazine/Thorazine did not empty the
presynaptic neuron of dopamine (recall that researchers had not
yet learned about receptors). Carlsson and Lindqvist (1963)
demonstrated that chlorpromazine/Thorazine and
haloperidol/Haldol acted on the postsynaptic neurons. Only
after Solomon Snyder and Candace Pert confirmed the presence
of receptors could researchers make the conceptual leap linking
the effects of chlorpromazine/Thorazine to dopamine receptors.
Snyder, Banerjee, Yamanura, and Greenberg (1974) also
demonstrated that there were many dopamine receptors, and
subsequent research showed that antipsychotic drugs had a
particular affinity for binding at the dopamine-2 (D2) receptor.
This paved the way for the inordinate focus on receptors in
today's pharmacologic research. Researchers concluded that
neuroleptic drugs such as chlorpromazine/Thorazine and
haloperidol/Haldol blocked the D2 receptors, preventing
dopamine from binding at those receptors and exerting an
effect. Thus, decreasing dopamine activity in this manner
lessened symptoms of schizophrenia in many patients. When
researchers assumed that people suffering from Parkinson's

9. disease were suffering from decreased dopamine activity, this
hypothesis further explained why people taking neuroleptics
might suffer Parkinsonian side effects. Although the drug they
were taking, not Parkinson's disease, had disrupted their
dopamine transmission, the result was the same.
This variation of the dopamine hypothesis was supported by
observations of amphetamine users as well. Researchers had
long known that heavy amphetamine users could develop
symptoms similar to those seen in schizophrenia. Because
amphetamines were later shown to increase dopamine in the
synaptic cleft, it made sense that if problems in dopamine
transmission could cause schizophrenia, drugs that artificially
increased dopamine levels might cause symptoms similar to
those of schizophrenia, just as decreased levels of dopamine
would cause symptoms similar to those of Parkinson's disease.
To summarize: It is now clear that neuroleptics (also
called typical antipsychotics) bind to a subfamily of dopamine
receptors called the D2 receptors. Here the drugs act
as antagonists, meaning they block the receptor but exert no
effect. They merely block dopamine molecules from binding.
The dopamine molecules would exert an effect if
they could bind, but they are prevented from doing so as long as
the person is taking a neuroleptic medication. The dopamine
hypothesis was a mainstay for understanding drug treatment for
schizophrenia until the 1990s.
The following two cases illustrate both (1) the use of
neuroleptics to treat disorders in the spectrum of schizophrenia
and (2) the reliance on the dopamine hypothesis as the
cornerstone for treating schizophrenia until the early 1990s.
This approach met with both success and failure, showing that
the dopamine hypothesis was too simplistic. Despite warnings
from researchers such as Solomon Snyder and Arvid Carlsson
that the hypothesis was merely a correlation and should not be
mistaken for a cause-and-effect relationship, by the 1970s the
dopamine hypothesis of schizophrenia was quite popular. It is
still espoused by some clinicians with great certainty today and

10. that is an error because we also know that agents that block
serotonin receptors and glutamate receptors can decrease
psychotic symptoms in some but not all people. The serotonin
hypothesis was developed by observing that drugs with strong
serotonergic agonism like lysergic acid diethylamide (LSD) can
cause psychotic-like hallucinations in some but not all users
(and these are actually usually visual unlike most psychotic
hallucinations) and (as noted above) newer antipsychotics
massively block serotonin and decrease psychotic symptoms in
some but not all people. Finally, the glutamate hypothesis is
that excessive release of excitatory neurotransmitters like
glutamate and acetylcholine causes deterioration in the frontal
cortex that causes the symptoms of schizophrenia. As Advokat,
Comaty, and Julien (2014) conclude “… none of these models
completely explains nor exactly mimics the phenotypic
presentation of behaviors associated with schizophrenia” (p.
340).
THE CASE OF COLIN
Colin, a 27-year-old father of four, began to notice that he
experienced strange thoughts, maybe voices, during his
workday. His wife noticed that he was more agitated and tense
at home, even impatient with the children. In his work as a
media specialist at a major university, Colin had a range of
responsibilities linked to a very tight schedule. His schedule
had become all but impossible with the layoff of his assistant
and he was under the most pressure he had ever been under in
his career. His immediate supervisor noticed his growing
disorganization at work and a gradual deterioration of his
performance. Colin insisted he was receiving messages that
preoccupied his mind and distracted him from his daily routine.
He became frightened and paranoid, and said people were out to
destroy him. He stopped sleeping and eating, and believed his
food was poisoned. Finally his wife called the emergency room
and was advised to bring Colin in as soon as possible. He
resisted her efforts, but finally agreed to go when his best friend
insisted he should to demonstrate to the world that he was not

11. insane.
Colin was hospitalized for 18 days and prescribed 24 mg of a
typical antipsychotic called thiothixene/Navane. Colin also
participated in group and art therapy during his hospitalization.
On release, Colin continued the thiothixene/Navane (reduced to
12 mg a day) and began individual and couples therapy at a
mental health center. Colin continued both therapies for several
years, stopping the thiothixene/Navane after nine months. Ten
years after his hospitalization, Colin remains relatively stable
both at work and at home, leading an active and productive life.
Colin was never hospitalized again, nor did he decompensate to
such a state that he needed to go back on thiothixene/Navane or
into the hospital. This episode occurred in the early 1980s, and
the diagnosis at the time was Brief Reactive Psychosis
(what DSM-5 would label Brief Psychotic Disorder).
Colin's case also illustrates several of the perspectives we have
discussed in this book. He suffered from a brief but serious
cognitive impairment that included hearing voices, losing some
contact with reality, and becoming paranoid. From the medical
model perspective, Colin had psychotic symptoms and was
hospitalized for them. The neuroleptic, thiothixene/Navane, was
very helpful, and Colin never developed any serious side
effects. It is important to note that six months after his
recovery, Colin found a different position with more promotion
potential and less stress. As usual though, the medical model
perspective provides only part of the story. From the
psychological perspective, Colin experienced enormous pressure
to earn more money for his growing family at the same time he
learned of his parents’ divorce. He also learned there was little
promotion potential for him at work, and he began to sense a
growing stress with his wife. Culturally, Colin, as a second-
generation Irishman to the United States, was ashamed of the
dramatic nature of his psychological disorder and his need to
take a psychotropic medication. The influence of his family's
rigid interpretation of Catholic dogma made Colin ashamed to
share this experience with others. In addition, Colin felt a

12. covert stigmatization at work from his immediate supervisor,
who was Japanese and who failed to grasp the seriousness of
Colin's illness and to be empathic toward him during his
recovery. His supervisor also had a work ethic that seemed to
view an enormous workload as a source of pride rather than the
burden Colin felt it was.
Therapy was invaluable to Colin as he focused on some personal
issues that bothered him and also worked on many of the
difficulties in his marriage. Throughout the therapy, Colin
became alert to the signs that indicated that he could become ill
again and, as of this writing, he has had no further serious
problems.
THE CASE OF ETHEL
For many years, Ethel suffered from what DSM-IV called
Undifferentiated Schizophrenia accompanied with many
negative symptoms. Ethel's psychiatrist had prescribed 600 mg
of chlorpromazine/Thorazine daily. Because Ethel was single
and lived alone, it was very difficult for her case manager to
assess how compliant she was with her medication, including
her benztropine/Cogentin (taken to treat side effects from her
chlorpromazine/Thorazine). Over a period of two years, Ethel
had to be hospitalized six times, for periods ranging from eight
days to four weeks, because she was unable to function or care
for herself. Eventually, the pattern became clear: Ethel would
stop taking her chlorpromazine/Thorazine and gradually retreat
into a nonfunctioning catatonic state. During her last
hospitalization, the treatment team recommended
haloperidol/Haldol by injection on a monthly basis to assist her
with compliance. This strategy altered Ethel's response to her
illness. Although it remained essential for her to take her
benztropine/Cogentin orally, getting an injection once a month
at the mental health center ended her cycle of hospitalizations,
seemed to ease her negative symptoms, and allowed her to
participate in group activities sponsored by the center.
Neuroleptic therapy by injection was a strategy implemented for
noncompliant patients before the advent of the atypical

13. antipsychotics. This intervention was only partially successful,
because many clients remained resistant to treatment with all
neuroleptics and/or suffered such serious side effects that
neuroleptic treatment became a burden.
Side Effects of Neuroleptic Medication
Perhaps one of the greatest influences for the development of
newer antipsychotic medications was the side effects of the
neuroleptic medications. Table 7.1 lists the most common
neuroleptic drugs still in use today. Note that all these drugs are
associated in different degrees with the difficult side effects we
describe next.
To fully understand the side effects of neuroleptic antipsychotic
medications, we must look at four primary dopamine pathways
in the brain that are affected by these medications. Table
7.2 summarizes these pathways, and then we discuss each.
TABLE 7.1 Examples of Neuroleptic (Typical) Antipsychotics
TABLE 7.2 Four Primary Dopamine Pathways in the Brain
Name
Location
Mesolimbic pathway
Projects from the ventral tegmental area of the brain to the
limbic system. Plays a role in emotional behavior.
Mesocortical pathway
Projects from the ventral tegmental area of the brain all the way
to the cerebral cortex. Plays a role in cognition.
Nigrostriatal pathway
Projects from the substantia nigra of the brain stem to the basal
ganglia and is part of the extrapyramidal nervous system.
Tuberoinfundibular pathway
Projects from the hypothalamus to the pituitary and governs
prolactin release.
© Cengage Learning®
The Four Primary Dopamine Pathways in the Brain
The Mesolimbic Pathway
Without dispute, the mesolimbic pathway is most clearly
associated with the positive symptoms of schizophrenia. Stahl

14. (2013) has noted that the auditory hallucinations, delusions, and
even thought disorder symptoms of schizophrenia have been
correlated with this pathway. Stahl has suggested that perhaps
the dopamine hypothesis of schizophrenia should be renamed
the “mesolimbic dopamine hypothesis of positive psychotic
symptoms” (p. 374), because that more accurately describes the
correlation between neuroleptic medications acting at this brain
site and decreased symptoms. Obviously one problem in
medicating clients with schizophrenia is that the effects of the
medications (at least to date) cannot be isolated to this one
dopamine pathway.
The Mesocortical Pathway
The mesocortical pathway is related to cognition, but its role (if
any) in the symptoms of schizophrenia is undetermined. It does
appear that the blockade of the dopamine-2 receptors in this
pathway by neuroleptic medications causes an emotional
blunting (sometimes referred to as flat affect) and cognitive
problems that look like thought disorder. This has sometimes
been called neuroleptic-induced deficit syndrome (Stahl, 2013).
Neuroleptic-induced deficit syndrome is particularly
problematic, because it mirrors the negative symptoms of
schizophrenia that we discussed at the beginning of this chapter.
Part of the ongoing debate is whether neuroleptic medications
acting on this pathway actually exacerbate the negative
symptoms of schizophrenia and in turn degrade the client's
quality of life. Further, if clients have pronounced negative
symptoms before receiving neuroleptic medication, such
medications may make the symptoms worse.
The Nigrostriatal Dopamine Pathway
The nigrostriatal dopamine pathway as part of the
extrapyramidal nervous system governs motor movements. Any
deficiency of dopamine in this pathway causes a movement
disorder. Parkinson's disease is caused by a deficiency of
dopamine in this pathway, in turn caused by degeneration of
dopamine neurons in the pathway. What we describe later as
extrapyramidal symptoms are the Parkinsonian side effects that

15. result when neuroleptic medications block dopamine receptors
in this pathway and cause movement disorders. One of the more
serious disorders is tardive dyskinesia, or late-appearing
abnormal movement. Although the effects of neuroleptics on
this pathway and thus movement confirmed initial hypotheses
about the role played by dopamine in their mechanism of action,
such effects have also confirmed fears that for some clients the
treatment may be as difficult to live with as the symptoms.
The Tuberoinfundibular or Hypothalamic Pathway
Ironically, the physically shortest dopamine tract we will
discuss has the longest name. The …
Week 4
Respond to the following in a minimum of 175 words:
What is the diagnostic criteria for Schizophrenia? What is the
most effective drug therapy for people with schizophrenia who
are resistant to standard antipsychotic drugs?