Pharm
Antipsychotic Medication
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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 Disorder
s (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 Effect
s (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
Gene
ral:
Extrapyramidal Side Effect
s (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
Gene
ration) -
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
,
Seizure
s, 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 Effect
s 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 Effect
s and
QT Prolongation
Gene
ric 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 Disorder
s
May be indicated in
Hallucination
s,
Delusion
s 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
Antidepressant
s 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 Effect
s,
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 Disorder
s 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
Gene
ral
See
Agranulocytosis
below
See
Extrapyramidal Side Effect
(EPSE)
Especially with high potency first generation agents and
Risperidone
(
Risperdal
)
All Antipsychotics can cause
Tardive Dyskinesia
Neuroleptic Malignant Syndrome
All Antipsychotics can cause
Neuroleptic Malignant Syndrome
Most common with
Clozapine
, but all other Atypical Antipsychotics have caused NMS
Anticholinergic
effects
Especially with Low potency first generation agents and
Clozapine
(
Clozaril
)
Sedation
Especially with Low potency first generation agents,
Clozapine
(
Clozaril
),
Olanzapine
(
Zyprexa
) and
Quetiapine
(
Seroquel
)
Hyperprolactinemia
See
Prolactin
Especially with all first generation Antipsychotics and
Risperidone
(
Risperdal
)
Postural Hypotension
Especially with low potency first generation Antipsychotics,
Clozapine
(
Clozaril
),
Quetiapine
(
Seroquel
), and
Risperidone
(
Risperdal
)
Seizure
s
Limited to
Overdose
and those predisposed to
Seizure
s (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 Inhibitor
s,
Beta Blocker
s,
Diuretic
s)
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
Arrhythmia
s)
Obtain history at baseline and readdress annually
Extrapyramidal Side Effect
s (EPSE) - all agents
Screen for
Tardive Dyskinesia
at each visit
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 Screen
ing (newer, atypical agents)
See adverse effects above
Fastin
g
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]
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