1. Antipsychotic Medications

2. Illnesses in which a client might experience Psychosis
Schizophrenia, Substance-induced psychosis, schizophreniform, schizoaffective, delusional disorder, brief psychotic, shared psychosis, psychosis due to a medical condition, Mania, depression, cognitive disorders, and Alzheimer’s dementia

3. Types of Psychosis
Paranoid Psychosis: Paranoid projections, hostile belligerence and grandiose expansiveness
Disorganized-Excited Psychosis: Conceptual disorganization (giving answers that are irrelevant, drifting off subject, etc), Disorientation (time, place…), Excitement (expression of feeling without restraint, excess speech, restlessness, etc>)

4. Type of Psychosis (cont)
Depressive Psychosis: Retardation, apathy (Slowed speech/Movements, indifference to future, poor recent memory and blocking speech), anxious self-punishment and blame (feeling fully unworthy and sinful, guilt and remorse, etc.).

5. As we will see…
There are four main pathways for Dopamine (Draw page 375 on Board)
The Mesolimbic Pathway #1
The Mesocortical Pathway #2
The Nigrostriatal Pathway #3
The Tuberoinfundibular Pathway #4

6. Symptoms
Positive Symptoms: Delusions, hallucinations, disorganized speech, disorganized/catatonic/agitated behavior
Schizophrenia, bipolar, schizoaffective, psychotic depression, Alzheimers
Seems to occur from EXCESS activity of Dopamine in the Mesolimbic dopamine pathway #1
Negative Symptoms: Affective flattening, alogia (restricted thought and speech), avolition (restriction in initiating goal related behavior), anhedonia (lack of pleasure), attentional impairment
Schizophrenia, depression
Seems to occur from TOO LITTLE dopamine in the mesocortical pathway #2

7. Thorazine and Conventional Neuroleptics
Used in 1952 as postoperative sedative
Blocks Dopamine D2 Receptors (causing upregulation of receptors, thus less dopamine in synapse)
However, the D2 receptors in the mesolimbic pathway #1 are not the only ones that get blocked, all D2 receptors get blocked in the entire brain. Thus the D2 receptors in the mesocortical pathway #2 also get blocked (where DA may already be deficient) Thus negative symptoms can worsen with tx

8. Side effects of Neuroleptics
Due to blocking D2 in the nigrostriatal DA pathway #3 cause Extrapyramidal Side Effects (EPS)
Parkinson’s like: slowed movements, decreased facial expressions, tremor and shuffling gate
Dystonic effects: Sustained muscle spasms
Akathisia: Intense feelings of restlessness
Due to blocking D2 in the Tuberoninfundibular pathway #4
Breast secretions and irregular periods
Due to muscarinic cholinergic receptor blocking
Anticholinergic, Antiandrenergic, Tardive Dyskinesia, weight gain, seizures, Temperature disregulation
Fever, confusion and rigidity are cluster of symptoms that may lead to coma or death

9. If these occur, get physician Involved
Confusion
Falls
Inability to Urinate
Severe constipation
Rash
High Fever
Involuntary movement
Jaundice
Severe Sedation
Severe restlessness
Muscle spasms

10. Atypical Antipsychotics
Clozapine, risperidone, olanzapine, quetiapine, and ziprasidone
Strong 5HT 2A receptor and weaker Dopamine D2 blockers (SDAs) thus
Low extrapyramidal symptoms
Efficacy with negative symptoms as well as positive symptoms
5HT inhibits dopamine release to different degrees in the four different dopamine pathways

11. We can’t go into each pathway…
We can’t go into each pathway….but please refer to chapter11 of Essential Psychopharmacology if you want the specifics. But to sum it up…
In conventional neuroleptics…dopamine blockade occurs at every pathway resulting in improved positive symptoms, but worsened negative symptoms and tough side effects
In atypical antipsychotics….Dopamine blockade wins the “tug of war” where it must win (improved positive symptoms) and Dopamine release occurs where needed due to the interaction of 5HT and Dopamine
Due to the chemistry of the 5 most common atypical drugs, each has its “benefits” and “drawbacks” concerning which side effects are best managed

12. Clozapine-MOST EFFECTIVE
Few EPS, no TD, no elevated prolactin
Can cause life threatening Agranulocytosis (blood count lowers) and risk of seizures at higher doses
Is sedating and causes weight gain
Greatest efficacy, but highest side effects of atypical antidepressants

13. Risperidone
Good at low doses, but mimics conventional neuroleptics at higher doses
Used with elderly, children and adolescents due to low dose needs
Elevates Prolactin
May improve cognitive functioning in Alzheimer’s and may improve mood in schizophrenia, manic and depressive phases of bipolar
Does not block histamine 1 receptors, so less weight gain

14. Olanzapine Usually no EPS- even at high doses Expensive
So used with more severe cases
Expensive
Weight gain, moderate sedation, low prolactin, low TD
Improved mood in bipolar and improved cog functioning in schizophrenia and dementia

15. Quetiapine Virtually no EPS at any dose, no Prolactin
Thus good for patients with Parkinson’s and Psychosis
Weight gain, may cause cataracts (animal studies)
Mood and Cog func. Bipolar, Dementia, Schizophrenia

16. Ziprasidone Low EPS, low Prolactin No weight gain
Antidepressant and anxiolytic properties due to additional inhibition of 5HT and NE reuptake
Cog and Mood: Bipolar, schizophrenia, Dementia

17. Additional Facts Atypical Antipsychotics
Seem to act differently in different patients, unlike the more conventional drugs
Optimal doses change dependent on patient
May not work as fast as conventional neuroleptics for acutely psychotic, aggressive, agitated patients that require rapid sedation
So use conventional or use benzos as adjuncts
Consider use of conventionals in intravenous injections
Monthly injections available for conventionals (no atypical injections available at this time)
Most patients receive more than one antipsychotic in clinical treatment

18. So how do you choose
Match drug effects and side effects to symptoms and comorbid disorders
Match enzyme metabolizing properties with desired effects and other drugs being taken
Consider time needs
What has worked in the past; with family members