Antipsychotic Medications

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

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>)

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.).

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

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

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

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

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

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

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

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

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

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

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

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

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

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