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 ADHD o Depression o Triglycerides o 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 Parkinsons 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. ODTs contain phenyllanine o Do not dispense to pts with PKU

Long Acting Injections Haloperidol Haldol(1st) o Decanoate Once a MONTH Risperidone Risperidal o 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 FGAs (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 highest o Orthostasis

Low-potency FGAs 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 Warning o QT Prolongation Loxapine Perphenazine Fluphenazine 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 Solution o IV o Deconoate (monthly), o IM (only for conversion from PO) Use 10-20x the oral dose

Trifluoperazine Thiothixene

Second Generation Antipsychotics (SGAs)

Clozapine Clozaril FazaClo - ODT Side Effects o Agranulocytosis o Seizures o Myocarditis o 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 effects Olanzapine Zyprexa o Zydis ODT o IM injection for acute agitation o Relprevv injection suspension o Lasts 2-4weeks, restricted use REMS o Can cause coma or delirium after injection o Side Effects o Sedation o Weight Gain o Increased Lipids and Glucose o EPS o Monitor for metabolic effects o Lowest risk for Cardiac issues Risperidone Risperdal o Formulations o Tabs o Oral solution Mix with all drinks except Cola or tea o ODT Risperdal M-Tabs o Injection Risperdal Consta

 2 week injection o Side effects o EPS High Risk o Prolactin o Sexual dysfunction o Orthostasis o Weight gain, increased lipids, and glucose o QT prolongation Quetiapine Seroquel, Seroquel XR o Take once daily at night o Must have eye exam for cataracts at beginning of therapy o Drug of choice for pts with Parkinsons o 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 injection o Watch for QT Prolongation o Contraindicated with QT risk o No metabolic issues Aripiprazole Abilify o Also 5HT1a partial agonist o IM injection and ODT o No metabolic issues or QT risk o Side effects o Anxiety o Insomnia o Constipation o Least Sedating Paliperidone Invega o Active metabolite of Risperidone o Available in OROS delivery system o Invega Sustenna o Long acting Monthly injection o Side Effects o Increased Prolactin o High risk of EPS o Tachycardia, Headache, Sedation, Anxity o Prolongs QT interval

o Metabolic issues Ilooperidone Fanapt o Prolongs QT interval o Must titrate slowly Asenapine Saphris o Only Sublingual formulation o No food/drink for 10 min after dose o Side effects o Somnolence o Tongue/mouth numbness o EPS o Prolonged QT interval Lurasidone Latuda o Side effects o QT risk o Metabolic issues Agents that cause QT prolongation/Arrhythmias Ziprasidone - Geodon Risperidone - Rispiradal Paliperione - Invega Iloperidone Asenapine - Saphris Lurasidone - Latuda Thioridizine (BBW) SGAs are associated with: Weight gain and metabolic effects( lipids, glucose levels) o Clozapine - Clozaril o Olanzapine Zyprexa (highest Risk) o Quetiapine - Seroquel o Risperidone - Risperidal o 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 SGAs 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