The Treatment of Psychotic Disorders

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The Treatment of Psychotic Disorders

• By Siva Dantu

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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 arent there (hallucinations)
• Treated with anti-psychotics

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Disorders with Psychosis

• Bipolar Disorder
• Schizoaffective Disorder
• Schizophrenic Disorder
• Depression
• Personality Disorders
• Schizotypal
• Schizoid
• Paranoid

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Bipolar Disorder
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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

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Schizophrenia

• What is Schizophrenia?
• http//www.youtube.com/watch?vbih7RTB9u04

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Schizophrenia cont.

• Symptoms
• Delusions
• Hallucinations
• Disorganized speech and behavior
• Negative Symptoms
• Blunted affect
• Alogia
• Avolition

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Schizophrenia cont.

• Delusions
• Religious
• Persecutory
• Grandiose
• Control
• Instertion
• Withdrawal
• Broadcasting

• Hallucinations
• Visual
• Auditory
• Olfactory
• Tactile

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Schizoaffective Disorder

• Spectrum
• The differences between Schizoaffective and
• Schizophrenia
• Bipolar Disorder

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Schizoaffective Disorder cont.

• Treatment
• Mood Stabilizers
• Antipsychotics
• http//www.youtube.com/watch?vhtwAXZw_gkA

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Psychotic Disorders

• Hereditary?
• Substance Induced?
• PCP
• Cocaine
• Cannabis

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Antipsychotics

• Or neuroleptics

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Chlorpromazine

• History
• Was the first antipsychotic used
• Around 1952- French doctor
• Revolutionary
• Only existed electroconvulsive therapy and
  psychotherapy
• Used in anesthesia
• Sedative effects

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Antipsychotics Chlorpromazine cont.
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Chlorpromazine

• Mechanism of Action
• Dopamine
• EPS
• Histamine
• Weight gain
• Sedative effect
• Alpha 1 adrenergic
• - orthostatic hypotension

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EPS extrapyramidal symptoms

• Dystonias
• Involuntary convulsion of muscles
• Development of Parkinsons syndrome
• Dyskinesias
• Involuntary body of facial movements
• 20 eventually developed

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Phenothiazine-Derived Drugs

• All are derivatives from the phenothiazine
  tricyclic compound
• 3 different classes
• Aliphatic
• Piperidines
• Piperazines

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Aliphatic Phenothiazines
Chlorpromazine
Promazine
Triflupromazine
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Piperidine Phenothiazines
Thioridazine
Mesoridazine
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Piperazine Phenothiazines
Fluphenazine
Perphenazine
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Butyrophenones
Haloperidol
Benperidol
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Problems with Typical Antipsychotics

• Solves no negative symptoms
• EPS are very troublesome
• Glutamatergic vs. Dopaminergic

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Discovery of Clozapine

• History
• Comparison study of angles between
  anti-depressants and psychotics
• The group found clozapine. Consequently didnt
  work with the theory
• In clinical trails Clozapine didnt exhibit EPS
• Also solved many negative symptoms

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Clozapine cont.

• Slow acceptance
• Precaution
• Agranulocytosis

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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

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Other atypical antipsychotics
Risperadome less harmful , weaker affinity for
D2
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Other atypical antipsychotics cont.
Olanzapine- much less is needed
100 fold stronger antagonist alpha 2 andrenergic
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Third Generation Antipsychotics

• Aripiprazole (Abilify)
• Partial agonist
• Partial 5HT1 receptor

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References

• http//en.wikipedia.org/wiki/Antipsychotic
• http//www.nlm.nih.gov/medlineplus/ency/article/00
  1553.html
• http//www.nimh.nih.gov/health/topics/schizophreni
  a/index.shtml
• http//www.mayoclinic.com/health/schizoaffective-d
  isorder/DS00866
• http//www.nimh.nih.gov/health/publications/bipola
  r-disorder/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.

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Required Reading

• Goodman and Gilmans Pharmacological Basis of
  Therapeutics, Chapter 18, pp. 461-467.

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Questions

1. What are the biggest differences that separate a
   typical from an atypical antipsychotic?
2. Why isnt 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.