Schizophrenia & Psychosis

Increased dopamine in the mesolimbic pathway

Negative Signs and Symptoms – (Normal behaviors that are missing)

Loss of interest in everyday activities Lack of emotion Inability to plan or carry out activities Poor hygiene Social Withdrawal Loss of motivation (avolition) Poverty of speech (alogia)

Positive Signs and Symptoms Hallucinations

o Hearing voices Delusions

o Are beliefs the patient has, but without a basis in reality Thought disorders, or difficulty speaking and organizing thoughts, such as

stopping in mid-sentence or jumping together meaningless words Difficulty paying attention

Natural Products Fish Oils

o ADHDo Depressiono Triglycerideso Psychosis

Do not recommend cod liver oil due to risk of vitamin A toxicity

Medications that can cause psychotic symptoms Amphetamines Methamphetamine Cannabis Cocaine Phencyclidine Lysergic acid diethylamide (LSD) and other hallucinogenics Anticholinergics (centrally-acting, high doses) Dopamine or dopamine agonists used for Parkinson’s disease

o Requip, Mirapex, Sinemet Interferons Steroids (typically with lack of sleep – ICU psychosis) Stimulants including ADHD drugs, modafinil

Pharmacotherapy Patient should have an adequate trial period of 4-6 weeks to determine

response.

Second generation Antipsychotics are typically used first, however some patients still need first generation antipsychotics.

ODT’s contain phenyllanineo Do not dispense to pts with PKU

Long Acting Injections Haloperidol – Haldol(1st)

o Decanoate Once a MONTH

Risperidone – Risperidalo Consta

Every 2 WEEKS Paliperidone

o Invega Susteena Once a MONTH

Orally disintegrating Tablets Clozapine - Clozaril Olanzapine - Zyprexa Risperidone - Risperidal Asenapine - Saphris

Acute IM Injections – May be mixed with a Benzodiazepine Zispiradone – Geodon Haloperiodol – Haldal Olanzapine - Zyprexa

First Generation Antipsychotics

High-potency FGA’s (Haloperidol) are associated with: A high risk of EPS effects

o TD – may be irreversible Facial Movements More in elderly females

o Dystonias Prolonged muscle contractions More in younger males Can use benedryl or benztropine as prophylaxis therapy

o Akathisia Consistent urges to move

o Dyskinesias Abnormal movements

Moderate risk of sedation Low risk of orthostatic hypotension, tachycardia and anticholinergic effects Moderate risk of weight gain Low risk of metabolic effects High risk of sexual side effects Cardiovasular complications

o QT prolongation (Thioridazine) is associated with highesto Orthostasis

Low-potency FGA’s are associated with: Lower risk of EPS High degree of sedation High risk of orthostatic hypotension and tachycardia High risk of anticholinergic effects Moderate risk of weight gain Low risk of metabolic effects High risk of sexual side effects

Chlorpromazine (lower potency)Thioridazine - Mellaril

Black Box Warningo QT Prolongation

LoxapinePerphenazineFluphenazine

Available in 2-week deconoate (Prolixin) Haloperidol – Haldol (higher potency)

Class - Butyrophenone Also used for tics and vocal outbursts due to Tourette syndrome Formulations

o Tab o Solutiono IV o Deconoate (monthly), o IM (only for conversion from PO)

Use 10-20x the oral doseTrifluoperazine

Thiothixene

Second Generation Antipsychotics (SGA’s)

Clozapine – Clozaril FazaClo - ODT Side Effects

o Agranulocytosis o Seizures o Myocarditiso Metabolic issues

A clozapine trial should be considered for a patient who has had no or poor response to two trials of antipsychotics medication or significant ADRs\

Start at 25mg and titrate Decreased risk of EPS REMS requirements

o Patient must register with Clozaril Registry Only pharmacies using Registry can fill this drug:

o WBC must be >3,500 and ANC must be >2000 Monitor WBC and ANC weekly for 6 months, then Q 2 weeks x

6 months, then monthly metabolic effectsOlanzapine – Zyprexa

o Zydis – ODTo IM injection for acute agitationo Relprevv injection suspension

o Lasts 2-4weeks, restricted use REMSo Can cause coma or delirium after injection

o Side Effectso Sedation o Weight Gain o Increased Lipids and Glucose o EPS

o Monitor for metabolic effects o Lowest risk for Cardiac issues

Risperidone – Risperdalo Formulations

o Tabso Oral solution

Mix with all drinks except Cola or tea

o ODT – Risperdal M-Tabso Injection – Risperdal Consta

2 week injectiono Side effects

o EPS – High Risk o Prolactin o Sexual dysfunctiono Orthostasiso Weight gain, increased lipids, and glucose o QT prolongation

Quetiapine – Seroquel, Seroquel XRo Take once daily at nighto Must have eye exam for cataracts at beginning of therapy o Drug of choice for pts with Parkinsonso Seroquel XR

Taken at night without food or light meal o Side Effects

Sedation Orthostasis Weight gain Increased lipids, and glucose

o Low risk of EPS Ziprasidone – Geodon

o Available in acute injectiono Watch for QT Prolongation

o Contraindicated with QT risk o No metabolic issues

Aripiprazole – Abilifyo Also 5HT1a partial agonisto IM injection and ODTo No metabolic issues or QT risko Side effects

o Anxietyo Insomniao Constipation

o Least Sedating

Paliperidone – Invegao Active metabolite of Risperidoneo Available in OROS delivery systemo Invega Sustenna

o Long acting Monthly injectiono Side Effects

o Increased Prolactin

o High risk of EPS o Tachycardia, Headache, Sedation, Anxityo Prolongs QT intervalo Metabolic issues

Ilooperidone – Fanapto Prolongs QT intervalo Must titrate slowly

Asenapine – Saphriso Only Sublingual formulationo No food/drink for 10 min after doseo Side effects

o Somnolenceo Tongue/mouth numbnesso EPSo Prolonged QT interval

Lurasidone – Latudao Side effects

o QT risko Metabolic issues

Agents that cause QT prolongation/Arrhythmias Ziprasidone - Geodon Risperidone - Rispiradal Paliperione - Invega Iloperidone Asenapine - Saphris Lurasidone - Latuda Thioridizine (BBW)

SGA’s are associated with: Weight gain and metabolic effects( lipids, glucose levels)

o Clozapine - Clozarilo Olanzapine – Zyprexa (highest Risk)o Quetiapine - Seroquelo Risperidone - Risperidalo paliperidone - Invega

Agents that increase Prolactin levels – Can cause galactorrhea, gynecomastia, osteoporosis, irregular periods.

Risperidone - Risperidal Paliperidone - Invega

Agents with increased risks of Tardive Diskenisia

Risperidone - Risperidal Paliperidone - Invega Lowest risk:

o Quetiapine – Seroquel DOC for Parkinson Disease

o Clozapine - Clozaril

Risperidone is the only generic currently available SGA

MOA Primarily dopamine receptor blockers.

o All First Generation Antipsychotics All SGA’s block Dopamine2 and Serotonin2a receptors.

o Aripiprazole is a Dopamine and serotonin1a and partial agonist and serotonin2a antagonist

Black Box Warning Increased risk of mortality in elderly patients with dementia-related

psychosis, primarily due to an increased risk of stroke

Neuroleptic Malignant Syndrome (NMS)

Mainly first generation but also seen in second

Signs: Hyperthermia (high fever, with profuse sweating)

o May be placed in an ice bed Extreme muscle rigidity (called “lead pipe” rigidity)

o Lung muscles may lock up Mental status changes Other signs can include tachycardia and tachypnea and blood pressure

changes

Treatment Stop the antipsychotic! Provide supportive care Cool them down Dantrolene (muscle relaxant) is used but not necessarily beneficial