1. 1 in 100 people have had a schizophrenia episode. more than 2
1 in 100 people have had a schizophrenia episode... more than 2.2 million Americans.
Previously- talked about 1/3 rule
1/3 take meds and get better; 1/3 take med but have ups and downs; 1/3 medication does little to help
NEW MEDS PROBABLY HAVE CHANGED THESE NUMBERS!!

2. Slight diversion – how to study whether genetics plays a role in a disorder?
twin studies
look at monozygotic (1 egg) twins – 99% genes in common vs dyzgotic twins – 50% genes in common

4. Other ways to look at role of genetics
Adoption studies
allows you to look at role of environment vs genes

5. Adoption Studies – 2 potential scenarios
biological parent
(shares 50% genes)
adoptive parent
(shares env)
child
has schizophrenia
normal home
increased incidence of schizophrenia

6. Adoption Studies – 2 potential scenarios
biological parent
(shares 50% genes)
adoptive parent
(shares env)
child
normal home
has schizophrenia
increased incidence of schizophrenia

8. Symptoms of schizophrenia
positive and negative symptoms
positive symptoms –
things that you can see; hallucinations, delusions, etc
negative symptoms – things that are absent
social withdrawal

9. The Way We Used to Think About Schizophrenia
positive symptoms – could be treated medically
negative symptoms – would not respond to drugs but rather was brain damage as a consequence of whatever schizophrenia did to the brain

10. Recent History in Pharmacotherapy of Schizophrenia
First drugs to treat schizophrenia appeared in early 1950’s – major impact!
called traditional neuroleptics, antipsychotics
treat the positive symptoms
Now – atypical neuroleptics – 1989 – 1999
treat positive and negative symptoms

11. Recent txt history
1950’s – chlorpromazine (Thorazine) and haloperidol (Haldol)
still the most widely used and cheapest way to treat positive symptoms
Other Uses for chlorpromazine
nausea and vomiting, chronic hiccups, severe itching, manage psychotic component in acute mania, to treat alcohol hallucinosis

12. What is the main mechanism of action?
Blocking DA receptors
Resulted in the DA theory for schizophrenia
D2 receptor subtype important
how well the drug binds to D2 receptor is clearly linked to reduction in positive symptoms

13. Evidence for the DA Theory for Schizophrenia
drugs that block DA;
drugs that increase DA activity
l-dopa
used to treat Parkinsons Disease
potential side effect:
amphetamine and cocaine
acute psychosis

14. So where are the DA pathways in the brain?
mesolimbic DA pathway –
important for reward and probably some of the positive symptoms associated with schizophrenia
nigrostriatal DA pathway –
important for movement (pathway for Parkinsons Disease)

15. So what are some of the side effects with antipsychotic drugs?
a lot of problems related to movement

16. Parkinson like symptoms brought on by medication ~ 20%
characteristics: rigidity, tremor, difficulty initiating movement, flat affect
dystonia – spastic contractions of discrete muscle groups ~ 10%
occurs most commonly in neck, eyes and torso; causes great distress

17. akathisia-
complain of an inner sensation of restlessness and an irresistible urge to move various parts of body (often seen as pacing and inability to sit still)
20 – 25% of patients show it
frequent cause of noncompliance

18. tardive dyskinesia
probably most serious of the movement disorders;
involuntary movement disorder caused by sustained exposure to antipsychotic medication
most commonly affects oral facial region – so tongue protrusions, lip smacking, neck jerking, etc
until recently considered a permanent effect

19. Is it only DA that is affected by these drugs?
NO! – these drugs have effects on multiple other neurotransmitters that also have significant side effects

20. 1 in 3 patients who start an antipsychotic will either switch medications or discontinue their medication within a year.
Why do they discontinue? At least 1/3 appear to discontinue because of the side effects of the medication.

21. Sedation- most common single side effect of antipsychotic medication
Common side effects
Sedation- most common single side effect of antipsychotic medication
often most pronounced early in treatment
variety of adverse effects, can occur in 10 – 50% of treated patients
some patients experience problems with thermoregulation
weight gain: up to 40% treated patients gain significant weight

22. atypical neuroleptics
first atypical neuroleptic was clozapine
people who had not been able to leave hospital for 25 years were suddenly better!

23. atypical neuroleptics
first atypical neuroleptic was clozapine
effective in proportion of patients that were unresponsive to previous medication

24. atypical neuroleptics
first atypical neuroleptic was clozapine
effective in proportion of patients that were unresponsive to previous medication
reduced negative symptoms

25. atypical neuroleptics
first atypical neuroleptic was clozapine
effective in proportion of patients that were unresponsive to previous medication
reduced negative symptoms
reduced tardive dyskinesias

26. atypical neuroleptics
first atypical neuroleptic was clozapine
effective in proportion of patients that were unresponsive to previous medication
reduced negative symptoms
reduced tardive dyskinesias
risky side effects – agranulocytosis (potentially lethal drop in white blood cells ~ 1% of people on drug)

27. consequence Initially, clozapine cost 36,000/year. now off patent
required contract with nurses that would take weekly blood tests
subsequent costs ~ 12,000/year
now off patent

28. Since clozapine
5 new atypicals on the market – the most recent in 2002; one still in clinical trials
none are as effective as clozapine for treating tardive dyskinesias
all expensive

29. What is different about these atypicals?
good question – some say the drugs bind to D2 receptors but also to a certain type of 5HT receptors
some say these drugs do not bind quite as well to D2 receptors as the more traditional ones

30. atypical neuroleptics
clozapine – Clozaril – 1989 – generic 1998
risperidone – Risperdal
olanzapine – Zyprexa
quetiapine – Seroquel
ziprasidone – Geodon -
aripiprazole (Abilify)- approved 11/2002
$13.00/pill?
iloperidone (Zomaril)
Novartis – phase III program including those with schizoaffective and comorbid polysubstance use
action on all monoaminergic receptor systems