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?

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

Psychotic Disorders Hereditary? Substance Induced? PCP Cocaine Cannabis

Antipsychotics Or neuroleptics

Chlorpromazine History -Was the first antipsychotic used -Around 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 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), Shen, Winston. (1999). A History of antipsychotic drug development. Comprehensive Psychiatry, 40(6),

Required Reading Goodman and Gilman’s Pharmacological Basis of Therapeutics, Chapter 18, pp

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.