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Antipsychotic Medication
Aka: Antipsychotic Medication, Antipsychotic, Anti-Psychotic, Neuroleptic, Atypical Antipsychotic
- See Also
- Extrapyramidal Side Effect
- Neuroleptic Malignant Syndrome
- Indications
- Psychosis (e.g. Schizophrenia)
- Sedation in Excited Delirium
- Especially Haloperidol, Olanzapine, Ziprasidone
- Other uses
- Antipsychotics should primarily be used for Psychotic Disorders (see precautions below)
- Refractory Major Depression adjunct
- Atypical Antipsychotics, especially Quetiapine, Aripiprazole
- Bipolar Disorder adjunct
- Atypical Antipsychotics, especially Quetiapine, Olanzapine, Aripiprazole
- Refractory Obsessive Compulsive Disorder adjunct
- Atypical Antipsychotics, especially Risperidone, Aripiprazole
- Autism related severe maladaptive behaviors
- Atypical Antipsychotics, especially Risperidone, Aripiprazole, Olanzapine
- Efficacy: Newer low potency agents
- Atypicals are only slightly better than high potency agents
- Similar efficacy in control of Psychosis
- Slightly less Extrapyramidal Side Effects (EPSE)
- Clozapine has much less EPSE, but has diabetes risk
- Higher weight, lipid and diabetes related conditions
- Compliance is similar for both types of agents
- Atypical Antipsychotics are much more expensive
- References
- Barry (2003) Am Fam Physician 68(5):943-4 [PubMed]
- Leucht (2003) Lancet 361:1581-9 [PubMed]
- Preparations: D2 Antipsychotic Agents - High Potency
- General: Extrapyramidal Side Effects (EPSE) with all
- Haloperidol (Haldol) or Haloperidol decanoate
- Typical dose: 10-15 mg/day
- Perphenazine (Trilafon)
- Well tolerated with similar efficacy to other agents
- Lieberman (2005) N Engl J Med 353:1209-23 [PubMed]
- Thiothixene HCl (Navane)
- Typical Dose: 10 mg three times daily
- Maximum Dose: 60 mg per day
- Fluphenazine HCl (Prolixin)
- Typical Dose: 2.5 mg orally twice daily starting to 10-20 mg/day
- Maximum Dose: 40 mg orally or 100 mg IM per day
- Trifluoperazine (Stelazine)
- Preparations: D2 Antipsychotic Agents - Medium Potency
- Loxapine (Loxitane)
- Molindone (Moban)
- Preparations: D2 Antipsychotic Agents - Low Potency
- Strong Anticholinergic effects with both agents
- Chlorpromazine HCl (Thorazine) - not available in U.S.
- Anticholinergic Symptoms
- Alpha adrenergic blockade (Hypotension)
- Sedation
- Dosing: 400 mg/day (maximum 1000 mg/day)
- Thioridazine HCl (Mellaril) - not available in U.S.
- Anticholinergic Symptoms
- Alpha adrenergic blockade (Hypotension)
- Sedation
- Dosing: 200-300 mg/day (maximum 800 mg/day)
- Preparations: Atypical Antipsychotics (Second Generation) - Serotonin-Dopamine Antagonists
- Dibenzodiazepine (Clozapine, Clozaril)
- Typical maintenance dose: 150-225 mg twice daily (300-600 mg/day)
- Oldest second generation Antipsychotic (introduced in 1989)
- Most adverse side effect profile of second generation agents
- Agranulocytosis (unique to Clozapine and FDA limits prescribers due to this effect)
- Causes Anticholinergic effects, sedation, Postural Hypotension, Seizures, weight gain, dyslipidemia
- Severe CNS depression in Overdose
- Illoperidone (Fanapt, Fanapta, Zomaril)
- Typical maintenance dose: 6-12 mg orally twice daily
- Higher risk of QTc Prolongation
- Lurasidone (Latuda)
- Typical maintenance dose: 40-160 mg/day
- Significant CNS depression in Overdose
- Olanzapine (Zyprexa)
- Typical maintenance dose: 10-20 mg/day
- Agitation: 10-20 mg oral or IM
- May cause elevated Creatine Kinase (CK)
- Significant CNS depression in Overdose
- Paliperidone (Invega)
- Sustained release formulation of the active metabolite of Risperidone
- Typical maintenance dose: 3-6 mg/day (maximum: 12 mg/day)
- Also available as long acting formulation
- Initial dose: 234 mg IM
- Next dose: 156 mg IM at 1 week after initial dose
- Next dose: 39 to 234 mg IM monthly, at 1 month after second dose
- Quetiapine (Seroquel)
- Typical maintenance dose: 250-600 mg/day
- May cause Tachycardia
- Severe CNS depression in Overdose
- Risperidone (Risperdal)
- Typical maintenance dose: 3-6 mg/day
- Agitation: 4 mg orally daily
- May cause Dystonia
- Ziprasidone (Geodon)
- Typical maintenance dose: 40-80 mg/day
- Agitation: 10 mg IM every 2 hours or 20 mg IM every 4 hours
- Higher risk of QTc Prolongation
- Significant CNS depression in Overdose
- Aripiprazole (Abilify)
- Typical maintenance dose: 10-30 mg/day
- Significant CNS depression in Overdose
- Caplyta (lumateperone)
- Low risk of weight gain, Diabetes Mellitus, Extrapyramidal Side Effects and QT Prolongation
- Moderately sedating, FDA approved only for Schizophrenia and is very expensive ($1300/month)
- Single dose: 42 mg once daily with food
- Saphris (asenapine sublingual)
- Low to moderate risk of weight gain, and low risk of Diabetes Mellitus, Extrapyramidal Side Effects and QT Prolongation
- Generic in 2020
- Secuado (asenapine patch)
- First Antipsychotic patch released at the same time asenapine will become generic
- Start dosing at 3.8 mg and increase to 5.7 mg after 1 week if needed (higher doses do not appear more effective)
- Costs $1200/month
- Preparations: Atypical Antipsychotics long acting injectables
- Background
- Consider injectable agents in non-compliant patients
- Most require insurance preauthorization or formulary selection
- Injectables cost >$1000/month
- Invega Trinza IM every 3 months
- Start with Invega Sustenna for at least 4 months before starting Invega Trinza
- Invega Sustenna IM every month
- Start with 2 injections spaced one week apart, then monthly
- Abilify Maintena IM every month
- Overlap with oral Abilify for the first 2 weeks (then discontinue oral form)
- Zyprexa Relprevv IM every 2-4 weeks
- No overlap needed with oral form
- Risperdal Consta IM every 2 weeks
- Overlap with oral Risperdal for the first 3 weeks (then discontinue oral form)
- References
- (2015) Presc Lett 22(9): 53
- Precautions
- Antipsychotics (both new and old) should primarily be used for Psychotic Disorders
- May be indicated in Hallucinations, Delusions or Dangerous Behavior outside of psychotic diagnosis
- May be appropriate as a low dose adjunct in severe refractory depression
- Trial on at least 2 different standard Antidepressants or combinations before adding Antipsychotics
- However should not be first-line therapy for non-psychotic conditions
- Not recommended in Insomnia
- Antipsychotics have potential for serious adverse effects (See adverse effects below)
- All Antipsychotics may cause Extrapyramidal Side Effects, QT Prolongation, sedation with fall risk
- Atypical Antipsychotics also risk weight gain and Diabetes Mellitus
- Atypical Antipsychotics increase mortality in Dementia (NNH 50-100 in 8-12 weeks)
- Taper off gradually when stopping medication
- Abruptly stopping may induce Movement Disorders and gastrointestinal symptoms
- Taper by 50% or less per week
- References
- (2015) Presc Lett 22(7):37-8
- (2016) Presc Lett 23(3): 17
- Adverse Effects: General
- Agranulocytosis
- See below
- Extrapyramidal Side Effect (EPSE, e.g. Akathisia, Dystonia, Parkinsonism)
- See Extrapyramidal Side Effect
- Especially with high potency first generation agents and Risperidone (Risperdal)
- All Antipsychotics can cause Tardive Dyskinesia
- Extrapyramidal Side Effect are less common with Quetiapine (Seroquel) and Ziprasidone (Geodon)
- Neuroleptic Malignant Syndrome
- All Antipsychotics can cause Neuroleptic Malignant Syndrome
- Most common with Clozapine, but all other Atypical Antipsychotics have caused NMS
- Anticholinergic effects
- May present with Constipation or Xerostomia
- Especially with Low potency first generation agents and Clozapine (Clozaril)
- Less common with Asenapine (Saphris) and Lurasidone (Latuda)
- Sedation
- Especially with Low potency first generation agents
- Most common with Clozapine (Clozaril), Olanzapine (Zyprexa) and Quetiapine (Seroquel)
- Aripiprazole (Abilify) may cause Insomnia
- Hyperprolactinemia
- See Prolactin
- Especially with all first generation Antipsychotics and Risperidone (Risperdal), Paliperidone (Invega)
- Prolactin is not significantly affected by Aripiprazole (Abilify) or Quetiapine (Seroquel)
- Postural Hypotension
- Especially with low potency first generation Antipsychotics
- Occurs more often with Clozapine (Clozaril), Quetiapine (Seroquel), and Risperidone (Risperdal)
- Seizures
- Limited to Overdose and those predisposed to Seizures (agents lower Seizure threshold)
- Most common with Clozapine (3% of cases) and to a much lesser extent Risperidone
- Sexual Dysfunction
- Especially with all first generation Antipsychotics and Risperidone (Risperdal)
- Myocarditis
- Most common with Clozapine (and Chlorpromazine)
- Most cases occur within first 4-8 weeks (and mild, asymptomatic cases may occur in up to 66% on Clozapine)
- Fulminant Myocarditis has a high mortality (50%)
- Treated as Cardiomyopathy (ACE Inhibitors, Beta Blockers, Diuretics)
- Ventricular Arrhythmia (including Cardiac Arrest)
- Antipsychotic agent Relative Risk: 3.2
- Effects
- Antipsychotics may prolong QTc at standard doses
- Increases risk of Torsades and sudden death
- QRS Widening may also be seen with Antipsychotics in Overdose
- Precautions
- See Prolonged QT Interval due to Medication
- Consider obtaining baseline EKG before starting therapy
- Consider Electrolyte and Magnesium monitoring with high risk agents (e.g. Thioridazine)
- Avoid concurrent use of other medications prolonging QT Interval
- See Prolonged QT Interval due to Medication
- Risk factors
- Elderly
- Female patients
- Hypokalemia
- Bradycardia
- Underlying cardiac disease
- Congenitally-acquired QTc Prolongation (very high risk)
- Antipsychotics that prolong QTc (from highest to lowest risk)
- Thioridazine (Mellaril)
- Ziprasidone (Geodon)
- Iloperidone (Fanapt)
- Haloperidol (Haldol)
- Quetiapine (Seroquel)
- Risperidone (Risperdal)
- Clozapine (Clozaril)
- Olanzapine (Zyprexa)
- Paliperidone (Invega)
- Can also prolong the QT Interval (but was released after this study)
- Aripiprazole and Lurasidone are lowest risk for QTc Prolongation
- Antipsychotics that predispose to sudden death
- Typical Antipsychotics (first generation) have been associated with Torsades and Sudden Cardiac Death
- Olanzapine, Risperidone and Quetiapine are not associated with Sudden Cardiac Death
- References
- Hennessy (2002) BMJ 325:1070-2 [PubMed]
- Stroup (2007) Am J Psychiatry 164(3): 415-27 [PubMed]
- Titier (2005) Drug Saf 28: 35-51 [PubMed]
- Adverse Effects: Second generation agents (atypicals)
- Weight gain and risk of Metabolic Syndrome or Diabetes Mellitus
- Highest risk with Clozapine (Clozaril) and Olanzapine (Zyprexa)
- Lowest risk with Ziprasidone (Geodon) and Aripiprazole (Abilify), as well as Lurasidone (Latuda)
- Weight gain with all second generation agents except Aripiprazole (Abilify) and Ziprasidone (Geodon)
- Also occurs with low potency first generation Antipsychotics (Chlorpromazine, Thioridazine)
- Adverse Lipid effects
- Serum Triglyceride increase most with Clozapine (Clozaril), Olanzapine (Zyprexa), Quetiapine (Seroquel)
- HDL Cholesterol decrease is variable
- Monitoring
- Agranulocytosis
- White Blood Cell Count <1.5 (and Granulocyte count <0.5)
- Occurs in 1% per year on Clozapine
- High mortality risk (up to 35%), especially in first 6 months, but can occur years after starting
- Can occur with nearly all the second generation agents (Atypical Antipsychotics)
- Exceptions: Does not appear to occur with Lurasidone and Paliperidone
- However only Clozapine requires scheduled Complete Blood Count
- Clozapine has unique monitoring parameters (prescription only allowed by U.S. centers following protocol)
- Highest risk of Agranulocytosis
- Monitoring includes Complete Blood Count (CBC)
- CBC weekly for 6 months, bimonthly for 6 months, then monthly
- Medical history and Family History (including cardiovascular risks and Arrhythmias)
- Obtain history at baseline and readdress annually
- Extrapyramidal Side Effects (EPSE) - all agents
- Screen for Tardive Dyskinesia at each visit
- Perform Abnormal Involuntary Movement Scale (AIMS) at least every 6 months
- https://dmh.mo.gov/media/21821/download
- Screen for other EPSE symptoms
- Educate about Neuroleptic Malignant Syndrome
- Obesity Monitoring (all Antipsychotics)
- Calculate BMI baseline, monthly for 3 months and then every 3 months thereafter
- Measure Waist Circumference annually
- Blood Pressure
- Obtain baseline, every 3 months and then annually
- Diabetes Mellitus Screening (newer, atypical agents)
- See adverse effects above
- Fasting Serum Glucose, 3 months and then annually
- Consider Hemoglobin A1C at four months after starting agent
- Screen for Polyuria and polydipsia at each visit
- Hyperlipidemia (Newer, atypical agents)
- Lipid profile baseline and at 3 months
- Repeat lipids every 6 months if abnormal
- May decrease frequency to every 2-5 years if normal
- References
- Marder (2004) Am J Psychiatry 161: 1334-49 [PubMed]
- References
- Glauser and Peters (2016) Crit Dec Emerg Med 30(4): 17-27
- Gardner (2005) CMAJ 172(13): 1703-11 [PubMed]
- Geddes (2000) BMJ 321:1371-6 [PubMed]
- Glick (2001) Ann Intern Med 134: 47-60 [PubMed]
- Haddad (2007) CNS Drugs 21(11): 911-36 [PubMed]
- Holder (1014) Am Fam Physician 90(11): 775-82 [PubMed]
- Lieberman (2005) N Engl J Med 353:1209-23 [PubMed]
- Muench (2010) Am Fam Physician 81(5): 617-22 [PubMed]
- Tandon (2011) J Clin Psychiatry 72(suppl 1): 4-8 [PubMed]