Conventional Antipsychotics

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Conventional Antipsychotics

• Concise Review for
• Non-Psychiatrists Treating
• Developmentally Disabled Population

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Presenter

• S. Christopher Shim, M.D.
• Distinguished Fellow
• American Psychiatric Association

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Objectives

• Participants will have enhanced knowledge in
• Different potencies of conventional
  anti-psychotic medications
• Safety and tolerability profiles of conventional
  anti-psychotic medications
• Cautions of reduction and discontinuation of
  conventional anti-psychotic medications

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Potency

• Efficacy

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Different Potency of Treatment
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High Potency Antipsychotics

• BRAND NAME GENERIC NAME Eq
• Haldol Haloperidol 2
• Prolixin Fluphenazine 2
• Navane Thiothixine 4
• Stelazine Trifluoperazine 5
• Orap Pimozide 1.5

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High Potency AntipsychoticsBenefits Risks

• Higher binding to D2 receptors
• Higher Efficacy
• More EPS (Extra Pyramidal Symptoms)
• Higher incidence of TD (Tardive Dyskinesia)
• Less Cognitive Problems
• Less Sedation
• Less Anti-cholinergic SE (Side Effects)
• Less Cardiovascular SE

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Low Potency Antipsychotics

• BRAND NAME GENERIC NAME Eq
• Mellaril Thioridazine 100
• Thorazine Chlorpromazine 100
• Serentil Mesoridazine 50

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Low Potency AntipsychoticsBenefits Risks

• Lower binding to D2 receptors
• Lower Efficacy
• Less EPS (Extra Pyramidal Symptoms)
• Lower incidence of TD (Tardive Dyskinesia)
• More Cognitive Problems
• More Sedation
• More Anti-cholinergic SE
• More Cardiovascular SE and Other SE

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Mid Potency Antipsychotics

• BRAND NAME GENERIC NAME Eq
• Trilafon Perphenazine 8
• Moban Molindone 10
• Loxitane Loxapine 10
• Compazine Prochlorperazine 15

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Safety and Tolerability

• Side Effect Profiles

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Safety Profiles

• Many Various Safety and Tolerability Factors
• Individual Differences
• Measure Benefits and Risks
• Preventions and Treatments

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Extra Pyramidal Symptoms

• EPS

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EPS (Extra Pyramidal Symptoms)

• EPS include
• Acute Dystonias happens within hours
• Parkinsonism develops gradually (Days Weeks)
• Tardive Dyskinesia chronic development
• Tardive Dystonia chronic development
• Changes in Dopamine Receptor Blockade in the
  Certain Areas of Brain (Substantia Niagra and
  Caudate Nucleus)

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Parkinsonian Syndrome

• Parkinsonian Syndrome
• Tremors
• Rigidity
• Cogwheeling
• Bradykinesia
• Akinesia
• May resemble Depression
• Slowing in thinking
• Decreased initiative
• Masked face

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Treatment of EPS

• BRAND NAME GENERIC NAME Dose
• (mg)
• Akineton Biperiden 2-6
• Artane Trihexyphenidyl 5-15
• Cogentin Benztropine 1-4
• Kemadrin Procyclidine 7.5-15
• Symmetrel Amantadine 100-300

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Akathisia

• Restless Pacing

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Akathisia

• Akathisia Inability to sit still
• A feeling of restlessness,
• A need to keep moving,
• An urge to raise the feet high
• Difficult to differentiate from illness-related
  behaviors

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Akathisia

• Appear Anxious
• May misidentify akathisia as anxiety
• Anxiety can aggravate akathisia
• Treatment
• Lowering the dosage of the medication
• Anticholinergics not always effective
• Propranolol 10 to 80 mg/d
• Clonidine 0.1 to 0.8 mg/d

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Neuroleptic Malignant Syndrome

• NMS

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NMS(Neuroleptic Malignant Syndrome)

• A rare but potentially fatal complication
• Main clinical findings
• Hyperthermia
• Severe muscular rigidity
• Autonomic instability
• Pulse/ BP/ Breathing/ Sweating
• Changing levels of consciousness
• Unstable vital signs

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NMS(Neuroleptic Malignant Syndrome)

• Most common
• When high potency antipsychotics are given high
  dosages
• When depot forms are used
• When the dosage is escalated rapidly
• In young person than in mature person
• Twice as common in men as in women

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NMS(Neuroleptic Malignant Syndrome)

• Lab tests
• Creatine Phosphokinase (CPK)
• Adolase
• Liver Transaminases
• Leukocytosis (increased WBC)
• Increased Myoglobin and Myoglobinuria
• Mortality 20 30
• May be higher when depot forms are used

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NMS(Neuroleptic Malignant Syndrome)

• Treatments
• Stop the antipsychotics
• Supportive and symptomatic TX
• Medications
• Dantrolene (Dantrium)
• IV, 0.8 to 2.5 mg/kg, Q 6h
• A maximum IV dosage 10 mg/ kg/ d
• When symptoms subside, PO 100 - 200 mg/ d
• Bromocriptine (Parlodel)
• 20 -30 mg/ d in four divided doses
• Amantadine (Symmetrel)

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Tardive Dyskinesia

• T D

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TD(Tardive Dyskinesia)

• Involuntary and persistent movement disorder that
  may occur later after long-term treatment
• At least 10 20 of the patients (pts) treated
  with the conventional antipsychotics for more
  than a year experience TD
• In chronically institutionalized pts who were
  treated with conventional antipsychotics, the
  prevalence rate is between 15 and 20

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A task report on TD by APA in 1992

• Abnormal movements are reduced by voluntary
  movements of the affected parts and increased by
  voluntary movements of the unaffected parts
• The movements are increased by emotional arousal
  and decreased by relaxation and volitional effort

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A task report on TD by APA in 1992

• Some movements are at least moderate in one body
  area or mild in at least two body area
• The movements should be present for at least 4
  weeks
• The patient should have a history of at least 3
  months of total cumulative antipsychotic exposure

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Risk Factors of TD

• Children
• Elderly person especially elderly women
• African Americans
• Patients with mood disorders
• The potency of antipsychotic
• The dosage of antipsychotic
• The amount of time of using antipsychotic
• Patients who are vulnerable to acute EPS

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Cardiovascular Effects

• Heart Effects

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Cardiovascular Effects

• Prolonged QTc intervals
• Low Potency Conventional Antipsychotics
• Mellaril (Thioridazine)
• Thorazine (Chlorpromazine)
• With QTc intervals exceeding 0.440 seconds, the
  risk of sudden cardiac death increases because of
  ventricular tachycardia or ventricular
  fibrillation

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Cardiovascular Effects

• Malignant Arrhythmias (torsade de pointes)
• In pts with pre-existing prolongation of the QTc
  intervals
• In pts with increased QTc intervals during the Tx
• Sudden Cardiac Death
• Temperature increase in highly agitated pts,
  particularly when restrains are used
• Treatment (Tx)-resistant pts in long-term Tx unit
  who show violence and disruptive behaviors may
  have higher risk

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Other Safety Profiles

• Various Different Side Effects

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Eye Effects

• High dosage of Mellaril (Thioridazine), above
  1,000 mg/d, can result in retinal pigmentation
  that may lead into serious irreversible visual
  impairment or blindness
• Early sign may be nocturnal confusion
• Mellaril should not be prescribed at the doses
  over 800 mg/d
• Thorazine (Chlorpromazine) may be associated with
  granular deposits in the anterior lens and the
  posterior cornea

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Skin Effects

• Low Potency Conventional Antipsychotics,
  especially Thorazine (Chlorpromazine), are
  associated with an uncommon discoloration of the
  skin.
• The skin areas that are exposed to sunlight,
  particularly the face and the neck, develop
  blue-gray metallic discoloration.

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Miscellaneous Effects

• Orthostatic BP changes
• More common with the low potency antipsychotics
• Prolactin elevation
• More common with the high potency antipsychotics
• Anti-cholinergic effects
• More common with the low potency antipsychotics

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Cautions

• Reduction or Discontinuation of
• Conventional
• Antipsychotic Medications

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Reduction of Conventional Antipsychotic
Medications

• Typically, reduction should be done gradually
• The reason for the medication reduction should be
  discussed among the IDT members and with a
  psychiatrist
• Prior to the reduction, review the clients past
  history and discuss with the psychiatrist

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Reduction of Conventional Antipsychotic
Medications

• The required medication reduction by regulatory
  reasons does not necessarily mean that the
  medication has to be reduced regardless of the
  clients clinical condition.
• It may be very difficult to cut down the lower
  dosage of conventional antipsychotic medications.

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Discontinuation of Conventional Antipsychotic
Medications

• The benefits and risks of stopping the medication
  verse continuation of the medication need to be
  reviewed.
• Justifications of continuation of the medication
  should be discussed and documented.

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Thank you !
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