The Treatment of Psychotic DisordersBy: 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:- LithiumAntipsychotics

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

AntipsychoticsOr 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

ChlorpromazinePromazine

Triflupromazine

Piperidine Phenothiazines

Mesoridazine Thioridazine

Piperazine Phenothiazines

FluphenazinePerphenazine

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

Referenceshttp://en.wikipedia.org/wiki/Antipsychotichttp://www.nlm.nih.gov/medlineplus/ency/article/001553.htmlhttp://www.nimh.nih.gov/health/topics/schizophrenia/index.shtmlhttp://www.mayoclinic.com/health/schizoaffective-disorder/DS00866http://www.nimh.nih.gov/health/publications/bipolar-disorder/complete-index.shtmlHippius, 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.