The Treatment of
Psychotic Disorders
By: Siva Dantu
What is Psychosis
• “ a loss of contact with reality, usually including false beliefs
about what is taking place or who one is (delusions) and
seeing or hearing things that aren’t there (hallucinations)
• Treated with anti-psychotics
Disorders with Psychosis
•
•
•
•
•
Bipolar Disorder
Schizoaffective Disorder
Schizophrenic Disorder
Depression
Personality Disorders
• Schizotypal
• Schizoid
• Paranoid
Bipolar Disorder
Bipolar Disorder cont.
Two main different types:
• Bipolar I
• Manic around 1 week
• Depressive around 2 weeks
• Bipolar II
• Depressive
• Hypomanic
Treatments:
Mood Stabilizers:
- Lithium
Antipsychotics
Schizophrenia
• What is Schizophrenia?
• http://www.youtube.com/watch?v=bih7RTB9u04
Schizophrenia cont.
Symptoms:
• Delusions
• Hallucinations
• Disorganized speech and behavior
• Negative Symptoms
• Blunted affect
• Alogia
• Avolition
Schizophrenia cont.
• Delusions
•
•
•
•
Religious
Persecutory
Grandiose
Control
• Instertion
• Withdrawal
• Broadcasting
Hallucinations
- Visual
- Auditory
- Olfactory
- Tactile
Schizoaffective Disorder
• Spectrum
• The differences between Schizoaffective and…
• Schizophrenia
• Bipolar Disorder
Schizoaffective Disorder cont.
• Treatment:
• Mood Stabilizers
• Antipsychotics
• http://www.youtube.com/watch?v=htwAXZw_gkA
Psychotic Disorders
• Hereditary?
• Substance Induced?
• PCP
• Cocaine
• Cannabis
Antipsychotics
Or neuroleptics
Chlorpromazine
History
- Was the first antipsychotic used
- Around 1952- French doctor
- Revolutionary
- Only existed electroconvulsive therapy and psychotherapy
- Used in anesthesia
- Sedative effects
Antipsychotics: Chlorpromazine
cont.
Chlorpromazine
• Mechanism of Action
- Dopamine
- EPS
- Histamine
- Weight gain
- Sedative effect
- Alpha 1 adrenergic
- orthostatic hypotension
EPS: extrapyramidal symptoms
• Dystonias
• Involuntary convulsion of muscles
• Development of Parkinson’s syndrome
• Dyskinesias
• Involuntary body of facial movements
• 20% eventually developed
Phenothiazine-Derived Drugs
• All are derivatives from the
phenothiazine tricyclic compound
• 3 different classes
• Aliphatic
• Piperidines
• Piperazines
Aliphatic Phenothiazines
Chlorpromazine
Promazine
Triflupromazine
Piperidine Phenothiazines
Mesoridazine
Thioridazine
Piperazine Phenothiazines
Fluphenazine
Perphenazine
Butyrophenones
Haloperidol
Benperidol
Problems with Typical
Antipsychotics
• Solves no negative symptoms
• EPS are very troublesome
• Glutamatergic vs. Dopaminergic
Discovery of Clozapine
• History
• Comparison study of angles between anti-depressants and
psychotics
• The group found clozapine. Consequently didn’t work with the
theory
• In clinical trails Clozapine didn’t exhibit EPS
• Also solved many negative symptoms
Clozapine cont.
• Slow acceptance
• Precaution
• Agranulocytosis
Clozapine Mechanism of Action
• Weaker D2 receptor binding
• Stronger serotonin antagonist
• Postsynaptic 5-HT2 receptors
JUST LIKE CHLORPROMAZINE BECAME A MODEL OF ATYPICAL
ANTIPSYCHOTICS TODAY
Other atypical antipsychotics
Risperadome – less harmful , weaker affinity for D2
Other atypical antipsychotics
cont.
Olanzapine- much less is needed
100 fold stronger antagonist alpha 2 andrenergic
Third Generation
Antipsychotics
• Aripiprazole (Abilify)
• Partial agonist
• Partial 5HT1 receptor
References
http://en.wikipedia.org/wiki/Antipsychotic
http://www.nlm.nih.gov/medlineplus/ency/article/001553.html
http://www.nimh.nih.gov/health/topics/schizophrenia/index.shtml
http://www.mayoclinic.com/health/schizoaffective-disorder/DS00866
http://www.nimh.nih.gov/health/publications/bipolardisorder/complete-index.shtml
Hippius, H. (1989). The History of clozapine. Psychopharmacology, 99,
S3-S5.
Leonard, B. (2003). Fundamentals of psychopharmacology. Chichester,
England: John Wiley & Sons Ltd.
Meyer, J, & Simpson, G. (1997). From Chlorpromazine to olanzapine: a
brief history of antipsychotics. Psychopharmacology, 48(9), 1137-1139.
Shen, Winston. (1999). A History of antipsychotic drug development.
Comprehensive Psychiatry, 40(6), 407-414.
Required Reading
Goodman and Gilman’s Pharmacological Basis of Therapeutics,
Chapter 18, pp. 461-467.
Questions
1. What are the biggest differences that separate a typical
from an atypical antipsychotic?
2. Why isn’t clozapine in the medical market today?
3. Draw one drug from each of the three different types of
phenothiazines and point out what makes each structurally
different.
4. What is the main receptor that had been related to
psychosis and discuss how this idea is changing.