Conventional Conventional AntipsychoticsAntipsychotics

Concise Review for Concise Review for Non-Psychiatrists Treating Non-Psychiatrists Treating

Developmentally Disabled PopulationDevelopmentally Disabled Population

Presenter Presenter

S. Christopher Shim, M.D.S. Christopher Shim, M.D.Distinguished Fellow Distinguished Fellow

American Psychiatric AssociationAmerican Psychiatric Association

ObjectivesObjectives

Participants will have enhanced knowledge in:Participants will have enhanced knowledge in:

Different potencies of conventional anti-psychotic Different potencies of conventional anti-psychotic medicationsmedications

Safety and tolerability profiles of conventional Safety and tolerability profiles of conventional anti-psychotic medicationsanti-psychotic medications

Cautions of reduction and discontinuation of Cautions of reduction and discontinuation of conventional anti-psychotic medicationsconventional anti-psychotic medications

PotencyPotency

EfficacyEfficacy

Different Potency of TreatmentDifferent Potency of Treatment

High Potency AntipsychoticsHigh Potency Antipsychotics

BRAND NAME BRAND NAME GENERIC NAME GENERIC NAME EqEq

HaldolHaldol HaloperidolHaloperidol 22

ProlixinProlixin FluphenazineFluphenazine 22

Navane Navane ThiothixineThiothixine 44

Stelazine Stelazine TrifluoperazineTrifluoperazine 55

OrapOrap PPimozideimozide 1.51.5

High Potency AntipsychoticsHigh Potency AntipsychoticsBenefits & RisksBenefits & Risks

Higher binding to D2 receptors:Higher binding to D2 receptors: Higher EfficacyHigher Efficacy More EPS (Extra Pyramidal Symptoms)More EPS (Extra Pyramidal Symptoms) Higher incidence of TD (Tardive Dyskinesia)Higher incidence of TD (Tardive Dyskinesia)

Less Cognitive ProblemsLess Cognitive Problems Less SedationLess Sedation Less Anti-cholinergic SE (Side Effects)Less Anti-cholinergic SE (Side Effects)

Less Cardiovascular SELess Cardiovascular SE

Low Potency AntipsychoticsLow Potency Antipsychotics

BRAND NAME BRAND NAME GENERIC NAMEGENERIC NAME Eq Eq

Mellaril Mellaril ThioridazineThioridazine 100100

Thorazine Thorazine ChlorpromazineChlorpromazine 100 100

Serentil Serentil MesoridazineMesoridazine 5050

Low Potency AntipsychoticsLow Potency AntipsychoticsBenefits & RisksBenefits & Risks

Lower binding to D2 receptors:Lower binding to D2 receptors: Lower EfficacyLower Efficacy Less EPS (Extra Pyramidal Symptoms)Less EPS (Extra Pyramidal Symptoms) Lower incidence of TD (Tardive Dyskinesia)Lower incidence of TD (Tardive Dyskinesia)

More Cognitive ProblemsMore Cognitive Problems More SedationMore Sedation More Anti-cholinergic SEMore Anti-cholinergic SE

More Cardiovascular SE and Other SEMore Cardiovascular SE and Other SE

Mid Potency AntipsychoticsMid Potency Antipsychotics

BRAND NAME BRAND NAME GENERIC NAMEGENERIC NAME EqEq

TrilafonTrilafon PerphenazinePerphenazine 8 8

Moban Moban Molindone Molindone 10 10

Loxitane Loxitane LoxapineLoxapine 10 10

Compazine Compazine ProchlorperazineProchlorperazine 15 15

Safety and TolerabilitySafety and Tolerability

Side Effect ProfilesSide Effect Profiles

Safety ProfilesSafety Profiles

Many Various Safety and Tolerability FactorsMany Various Safety and Tolerability Factors

Individual DifferencesIndividual Differences

Measure Benefits and Risks Measure Benefits and Risks

Preventions and TreatmentsPreventions and Treatments

Extra Pyramidal SymptomsExtra Pyramidal Symptoms

EPSEPS

EPS EPS (Extra Pyramidal Symptoms)(Extra Pyramidal Symptoms)

EPS include:EPS include: Acute Dystonias: happens within hours Acute Dystonias: happens within hours Parkinsonism: develops gradually (Days – Weeks)Parkinsonism: develops gradually (Days – Weeks) Tardive Dyskinesia: chronic developmentTardive Dyskinesia: chronic development Tardive Dystonia: chronic developmentTardive Dystonia: chronic development

Changes in Dopamine Receptor Blockade in the Changes in Dopamine Receptor Blockade in the Certain Areas of Brain (Substantia Niagra and Certain Areas of Brain (Substantia Niagra and Caudate Nucleus)Caudate Nucleus)

Parkinsonian SyndromeParkinsonian Syndrome

Parkinsonian SyndromeParkinsonian Syndrome TremorsTremors RigidityRigidity CogwheelingCogwheeling BradykinesiaBradykinesia AkinesiaAkinesia

May resemble Depression: May resemble Depression: Slowing in thinkingSlowing in thinking Decreased initiativeDecreased initiative Masked faceMasked face

Treatment of EPSTreatment of EPS

BRAND NAME BRAND NAME GENERIC NAME GENERIC NAME Dose Dose (mg)(mg)

AkinetonAkineton BiperidenBiperiden 2-62-6

ArtaneArtane TrihexyphenidylTrihexyphenidyl 5-155-15

CogentinCogentin Benztropine Benztropine 1-41-4

KemadrinKemadrin ProcyclidineProcyclidine 7.5-157.5-15

SymmetrelSymmetrel AmantadineAmantadine 100-300100-300

AkathisiaAkathisia

Restless PacingRestless Pacing

AkathisiaAkathisia

Akathisia:Akathisia: Inability to sit still Inability to sit still

A feeling of restlessness, A feeling of restlessness, A need to keep moving, A need to keep moving, An urge to raise the feet highAn urge to raise the feet high

Difficult to differentiate from Difficult to differentiate from illness-related behaviorsillness-related behaviors

AkathisiaAkathisia

Appear Anxious: Appear Anxious: May misidentify akathisia as anxietyMay misidentify akathisia as anxiety Anxiety can aggravate akathisiaAnxiety can aggravate akathisia

Treatment: Treatment: Lowering the dosage of the medicationLowering the dosage of the medication Anticholinergics: not always effectiveAnticholinergics: not always effective Propranolol: 10 to 80 mg/dPropranolol: 10 to 80 mg/d Clonidine: 0.1 to 0.8 mg/dClonidine: 0.1 to 0.8 mg/d

Neuroleptic Malignant SyndromeNeuroleptic Malignant Syndrome

NMSNMS

NMSNMS(Neuroleptic Malignant Syndrome)(Neuroleptic Malignant Syndrome)

A rare but potentially fatal complicationA rare but potentially fatal complication

Main clinical findings:Main clinical findings: HyperthermiaHyperthermia Severe muscular rigiditySevere muscular rigidity Autonomic instability: Autonomic instability:

Pulse/ BP/ Breathing/ SweatingPulse/ BP/ Breathing/ Sweating Changing levels of consciousnessChanging levels of consciousness Unstable vital signs Unstable vital signs

NMSNMS(Neuroleptic Malignant Syndrome)(Neuroleptic Malignant Syndrome)

Most common: Most common: When high potency antipsychotics are given When high potency antipsychotics are given

high dosages high dosages When depot forms are usedWhen depot forms are used When the dosage is escalated rapidlyWhen the dosage is escalated rapidly In young person than in mature personIn young person than in mature person

Twice as common in men as in womenTwice as common in men as in women

NMSNMS(Neuroleptic Malignant Syndrome)(Neuroleptic Malignant Syndrome)

Lab tests:Lab tests: Creatine Phosphokinase (CPK)Creatine Phosphokinase (CPK) AdolaseAdolase Liver TransaminasesLiver Transaminases Leukocytosis (increased WBC)Leukocytosis (increased WBC) Increased Myoglobin and MyoglobinuriaIncreased Myoglobin and Myoglobinuria

Mortality: 20 – 30 %Mortality: 20 – 30 % May be higher when depot forms are usedMay be higher when depot forms are used

NMSNMS(Neuroleptic Malignant Syndrome)(Neuroleptic Malignant Syndrome)

TreatmentsTreatments Stop the antipsychoticsStop the antipsychotics Supportive and symptomatic TXSupportive and symptomatic TX Medications:Medications:

Dantrolene (Dantrium): Dantrolene (Dantrium): IV, 0.8 to 2.5 mg/kg, Q 6h IV, 0.8 to 2.5 mg/kg, Q 6h A maximum IV dosage 10 mg/ kg/ dA maximum IV dosage 10 mg/ kg/ d When symptoms subside, PO 100 - 200 mg/ dWhen symptoms subside, PO 100 - 200 mg/ d

Bromocriptine (Parlodel):Bromocriptine (Parlodel): 20 -30 mg/ d in four divided doses20 -30 mg/ d in four divided doses

Amantadine (Symmetrel)Amantadine (Symmetrel)

Tardive DyskinesiaTardive Dyskinesia

T DT D

TDTD(Tardive Dyskinesia)(Tardive Dyskinesia)

Involuntary and persistent movement disorder Involuntary and persistent movement disorder that may occur later after long-term treatmentthat may occur later after long-term treatment

At least 10 – 20% of the patients (pts) treated At least 10 – 20% of the patients (pts) treated with the conventional antipsychotics for more with the conventional antipsychotics for more than a year experience TDthan a year experience TD

In chronically institutionalized pts who were In chronically institutionalized pts who were treated with conventional antipsychotics, the treated with conventional antipsychotics, the prevalence rate is between 15 and 20 %prevalence rate is between 15 and 20 %

A task report on TD by APA in 1992:A task report on TD by APA in 1992:

1.1. Abnormal movements are reduced by Abnormal movements are reduced by voluntary movements of the affected parts voluntary movements of the affected parts and increased by voluntary movements of and increased by voluntary movements of the unaffected partsthe unaffected parts

2.2. The movements are increased by emotional The movements are increased by emotional arousal and decreased by relaxation and arousal and decreased by relaxation and volitional effortvolitional effort

A task report on TD by APA in 1992:A task report on TD by APA in 1992:

3.3. Some movements are at least moderate in one Some movements are at least moderate in one body area or mild in at least two body areabody area or mild in at least two body area

4.4. The movements should be present for at least 4 The movements should be present for at least 4 weeksweeks

5.5. The patient should have a history of at least 3 The patient should have a history of at least 3 months of total cumulative antipsychotic months of total cumulative antipsychotic exposureexposure

Risk Factors of TDRisk Factors of TD

ChildrenChildren Elderly person: especially elderly womenElderly person: especially elderly women African AmericansAfrican Americans Patients with mood disordersPatients with mood disorders The potency of antipsychoticThe potency of antipsychotic The dosage of antipsychoticThe dosage of antipsychotic The amount of time of using antipsychoticThe amount of time of using antipsychotic Patients who are vulnerable to acute EPSPatients who are vulnerable to acute EPS

Cardiovascular EffectsCardiovascular Effects

Heart EffectsHeart Effects

Cardiovascular EffectsCardiovascular Effects

Prolonged QTc intervalsProlonged QTc intervals

Low Potency Conventional AntipsychoticsLow 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

Cardiovascular EffectsCardiovascular Effects

Malignant Arrhythmias (torsade de pointes)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 DeathSudden Cardiac Death Temperature increase in highly agitated pts, particularly Temperature increase in highly agitated pts, particularly

when restrains are usedwhen restrains are used Treatment (Tx)-resistant pts in long-term Tx unit who Treatment (Tx)-resistant pts in long-term Tx unit who

show violence and disruptive behaviors may have higher show violence and disruptive behaviors may have higher riskrisk

Other Safety ProfilesOther Safety Profiles

Various Different Side EffectsVarious Different Side Effects

Eye EffectsEye Effects High dosage of Mellaril (Thioridazine), above High dosage of Mellaril (Thioridazine), above

1,000 mg/d, can result in retinal pigmentation 1,000 mg/d, can result in retinal pigmentation that may lead into serious irreversible visual that may lead into serious irreversible visual impairment or blindnessimpairment or blindness

Early sign may be nocturnal confusionEarly sign may be nocturnal confusion

Mellaril should not be prescribed at the doses Mellaril should not be prescribed at the doses over 800 mg/dover 800 mg/d

Thorazine (Chlorpromazine) may be associated Thorazine (Chlorpromazine) may be associated with granular deposits in the anterior lens and with granular deposits in the anterior lens and the posterior corneathe posterior cornea

Skin EffectsSkin Effects

Low Potency Conventional Antipsychotics, Low Potency Conventional Antipsychotics, especially especially Thorazine (Chlorpromazine), are Thorazine (Chlorpromazine), are associated with an uncommon discoloration associated with an uncommon discoloration of the skin. of the skin.

The skin areas that are exposed to sunlight, The skin areas that are exposed to sunlight, particularly the face and the neck, develop particularly the face and the neck, develop blue-gray metallic discoloration.blue-gray metallic discoloration.

Miscellaneous EffectsMiscellaneous Effects

Orthostatic BP changesOrthostatic BP changes More common with the low potency antipsychoticsMore common with the low potency antipsychotics

Prolactin elevationProlactin elevation More common with the high potency antipsychoticsMore common with the high potency antipsychotics

Anti-cholinergic effectsAnti-cholinergic effects More common with the low potency antipsychoticsMore common with the low potency antipsychotics

CautionsCautions

Reduction or Discontinuation of Reduction or Discontinuation of ConventionalConventional

Antipsychotic MedicationsAntipsychotic Medications

Reduction of Conventional Reduction of Conventional Antipsychotic MedicationsAntipsychotic Medications

Typically, reduction should be done gradually Typically, reduction should be done gradually

The reason for the medication reduction The reason for the medication reduction should be discussed among the IDT members should be discussed among the IDT members and with a psychiatristand with a psychiatrist

Prior to the reduction, review the client’s past Prior to the reduction, review the client’s past history and discuss with the psychiatrist history and discuss with the psychiatrist

Reduction of Conventional Reduction of Conventional Antipsychotic MedicationsAntipsychotic Medications

The required medication reduction by The required medication reduction by regulatory reasons does not necessarily mean regulatory reasons does not necessarily mean that the medication has to be reduced that the medication has to be reduced regardless of the client’s clinical condition. regardless of the client’s clinical condition.

It may be very difficult to cut down the It may be very difficult to cut down the lower dosage of conventional antipsychotic lower dosage of conventional antipsychotic medications.medications.

Discontinuation of Conventional Discontinuation of Conventional Antipsychotic MedicationsAntipsychotic Medications

The benefits and risks of stopping the The benefits and risks of stopping the medication verse continuation of the medication verse continuation of the medication need to be reviewed.medication need to be reviewed.

Justifications of continuation of the Justifications of continuation of the medication should be discussed and medication should be discussed and documented. documented.

Thank you !Thank you !

Q &Q & A A