Antipsychotic Medications

Antipsychotics

Typical Antipsychotics

• Chlorpromazine (Thorazine): indicated for psychosis, Tourette's, schizophrenia; 1-40mg dosage; available in PO tablet, liquid, IM, IV, and deaconate formulations
• Mesoridazine (Serentil): typical antipsychotic
• Thioridazine (Mellaril): typical antipsychotic
• Loxapine (Loxitane): mid-potency antipsychotic
• Fluphenazine (Prolixin): mid-potency antipsychotic
• Haloperidol (Haldol): mid-potency antipsychotic; 1-40mg dosage; available in PO tablet, liquid, IM, IV, and deaconate formulations
• Perphenazine (Trilafon): mid-potency antipsychotic
• Pimozide (Orap): mid-potency antipsychotic
• Thiothixene (Navane): mid-potency antipsychotic
• Trifluoperazine (Stelazine): mid-potency antipsychotic

Atypical Antipsychotics

• Olanzapine (Zyprexa): FDA-approved for treatment of schizophrenia and mania in ages 13 and over; 10-20mg dosage; available in ODT, IM, and LAI formulations
• Asenapine (Saphris): FDA-approved for treatment of mania in ages 10 and up, schizophrenia, and bipolar maintenance; 10-20mg dosage; available in transdermal and SL formulations
• Risperidone (Risperdal): FDA-approved for schizophrenia, mania, irritability r/t autism, and bipolar maintenance; 2-8mg dosage; available in tablet, liquid, ODT, and LAI formulations
• Paliperidone (Invega): FDA-approved for management of schizophrenia in ages 12 and older; 6-12mg dosage; available in LAI formulation
• Ziprasidone (Geodon): DRESS FDA warning issued in 2014; 40-80mg dosage; available in IM formulation
• Iloperidone (Fanapt): FDA-approved for bipolar depression and schizophrenia; 12-24mg dosage; available in divided doses
• Lurasidone (Latuda): FDA-approved for bipolar depression, schizophrenia, and mania; must be taken with a small meal; 1.5-6mg dosage
• Lumeteperone (Caplyta): FDA-approved for schizophrenia; 42mg once-daily dosage; available in capsule formulation
• Pimavanserin (Nuplazid): FDA-approved for hallucinations and delusions r/t Parkinson's; 34mg daily dosage; available in capsule and tablet formulations

Antipsychotics

• Antipsychotics can cause side effects such as weight gain and sedation due to blockade of Histamine H1 receptors.
• Blockade of α1-adrenergic receptors can lead to Orthostatic Hypotension and Drowsiness.
• Metabolic side effects include weight gain, Dyslipidemia, Diabetes/Insulin resistance, and Hypertension.

Long-Acting Injectables (LAI)

• Dosing schedules for LAI:
  • Invega Sustenna: 4 weeks
  • Invega Trinzia: 12 weeks
  • Abilify Maintena: 4 weeks
  • Aristada: 4, 6, or 8 weeks
  • Risperdal Consta: 2 weeks
  • Risperdal Perseris: 4 weeks
  • Haldol Decanoate: 4 weeks
  • Prolixin Decanoate: 2 weeks

Typical Antipsychotics

• Also known as classical, conventional, or first-generation antipsychotics.
• Discovered in the 1950s, with therapeutic effects due to blockade of D2 receptors in the mesolimbic dopamine pathway.
• Mainly target positive symptoms of psychosis.
• Unfortunately, Typical antipsychotics block D2 receptors in all areas of the brain, leading to a multitude of side effects.

Atypical Antipsychotics

• Aripiprazole (Abilify)
• Asenapine (Saphris)
• Brexpiprazole (Rexulti)
• Cariprazine (Vraylar)
• Clozapine (Clozaril)
• Illoperidone (Fanapt)
• Lurasidone (Latuda)
• Olanzapine (Zyprexa)
• Paliperidone (Invega)
• Quetiapine (Seroquel)
• Risperidone (Risperdal)
• Ziprasidone (Geodon)
• Lumateperone (Caplyta)

Metabolic Risk

• High risk: Clozapine (Clozaril), Olanzapine (Zyprexa)
• Moderate risk: Risperidone (Risperdal), Paliperidone (Invega), Quetiapine (Seroquel), Iloperidone (Fanapt)
• Low risk: Ziprasidone (Geodon), Lurasidone (Latuda), Aripiprazole (Abilify), Asenapine (Saphris), Cariprazine (Vraylar)

Labs & Monitoring

• Prior to initiation:
  • Weight/BMI/Waist circumference
  • EKG
  • CMP
  • CBC with diff
  • Fasting Lipid Panel
  • Blood pressure
• Monitoring:
  • BMI quarterly
  • Blood pressure, Lipids, and Glucose within 3 months, and then every 6 months
  • Prolactin as needed
  • CBC with diff as needed
  • Abnormal Involuntary Movement Scale periodically

Clozapine (Clozaril)

• First antipsychotic to be recognized as atypical
• Gold standard for efficacy in schizophrenia
• Only antipsychotic to demonstrate increased efficacy compared to other antipsychotics
• Only antipsychotic to be FDA approved for reducing the risk of suicide in schizophrenia and schizoaffective disorder
• Not a first-line treatment choice, usually reserved for treatment-resistant schizophrenia, due to unfavorable side effect profile
• May be very sedating
• Associated with excessive salivation, myocarditis

Risperdal (Risperidone)

• FDA approved for:
  • Schizophrenia ages 13 and up
  • Mania ages 10 and up
  • Irritability r/t Autism ages 5 and up
  • Bipolar maintenance
• Dosage: 2-8 mg for psychosis or mania; 0.5-2 mg for agitation in children
• Comes in tablet, liquid, ODT, and LAI formulations (Consta and Perseris)
• More typical at high doses, may be more likely to cause EPS
• Weight gain and sedation are common
• Common elevation of prolactin even at low doses

Invega (Paliperidone)

• Dosing: 6-12 mg; Sustained released, once a day dosing
• FDA approved for management of schizophrenia ages 12 and older
• The active metabolite of Risperdal
• Is not hepatically metabolized, eliminated via urinary excretion
• Possibly better tolerated, with less sedation, EPS, and orthostasis
• Comes in LAI form Invega Sustenna
• Dosing range of 80-160 mg in BMD, up to 200 mg in schizophrenia
• Comes in IM formulation

Geodon (Ziprasidone)

• DRESS (Drug Reaction with Eosinophilia) FDA warning issued in 2014
• Rare but serious skin condition
• Rash that may spread to other parts of the body, causing fever, swollen lymph nodes, swollen face, inflammation of organs, an increase in white blood cells, and death
• Symptoms often develop 11-30 days after initiation of treatment
• Dosage range: 5-15 mg for ASD, 15-30 mg for Schizophrenia/mania, 2-10 mg for depression
• Comes in Tablet, ODT, Oral solution, and 2 LAI formulations (Maintena and Aristada)
• Half-life of 75 hours
• Low level of EPS (except Akathisia), dyslipidemia, elevation of triglycerides, or insulin resistance, and weight gain

Abilify (Aripiprazole)

• D2 dopamine receptor partial agonist
• Theoretically reduces dopamine output when dopamine concentrations are high, improving positive symptoms
• Theoretically increases dopamine output when dopamine concentrations are low, improving cognition and negative symptoms
• Has 5HT1a partial agonist actions, may contribute to antidepressant actions
• Lacks D1, anticholinergic, and antihistamine properties
• May not deliver sufficient antipsychotic efficacy in difficult to treat patients
• No issues with hyperprolactinemia, and may even reverse hyperprolactinemia
• Reports of issues with impulse control including compulsive gambling, shopping, binge eating, and sexual activity

Caplyta (Lumateperone)

• FDA approved for schizophrenia, launched Q1 2020
• Dosed at 42 mg once a day with food
• Most common side effects are sedation and dry mouth
• Serotonin-dopamine antagonist
• Blocks serotonin 2a receptors, post-synaptic D2 receptors
• Affinity for serotonin reuptake pump
• Interactions at a myriad of other neurotransmitter receptors may contribute to efficacy
• Moderate binding affinity for D1 and D4 receptors

Nuplazid (Pimavanserin)

• A serotonin 2a/2c agonist/inverse agonist
• Inverse agonist and antagonist activity at 5HT2a receptors, and to a lesser extent 5HT2c receptors
• FDA approved for hallucinations and delusions r/t Parkinson's
• Dosing of 34 mg per day (comes in a 34 mg capsule and 10 mg tablet)
• Warning for QTc prolongation
• Common SEs are Peripheral edema, nausea, and confusion
• Should not worsen motor symptoms of Parkinson's