LaGenia Bailey, Pharm.D.
Spring 1998

Schizophrenia and Anti-Psychotics

Schizophrenia

1. Introduction
2. Biologic Theories
3. Diagnosis

Antipsychotic Drug Therapy

1. Introduction
2. Mechanism of Action
3. Indications
4. Agents, Dose, Potencies & Considerations for Use
5. Pharmacokinetics
6. Side Effects and Adverse Reactions
7. Atypical Antipsychotics

Case Study

Goals

1. Educate a patient and the patient's family members regarding the use of an antipsychotic medication, including an assesment for what the patient/family knows, name, indication, dosing, time for response of symptoms, expectations, side effects and time course for side effects, treatment of side effects, length of treatment for side effects, coping for side effects, length of therapy

2. Recommend appropriate drug therapy for a patient with schizophrenia taking into account, history, medical illness, laboratory abnormalities, age, other etiologies of symptoms, family history, compliance, risk factors for side effects, target symptoms, severity of symptoms, and drug interactions.

3. Recommend the monitoring parameters in a specific patient on a given antipsychotic agent, including responsiveness, dosage adjustments, plasma concentrations, drug interactions, side effects, compliance, and drug interactions.

4. Assess the patient for side effects, responsiveness to a given medication.

Objectives

1. Describe the mechanism of action of the antipsychotic agents and how this applies to both therapeutic responsiveness and genesis of side effects.

2. List each neurotransmitter system effected by the antispychotics as well as the clinical implications of the antipsychotic's effect on that given neurotranmitter system.

3. List the effects of the activation of dopamine type 1 and 2 receptors.

4. Given a dosage of one agent be able to convert that dosage into a dosage of any other agent based on chlorpromazine equivalents.

5. Know the trade and generic names of each agent and the dosage form availability as well as dosages ranges and appropriate starting dosages for each agent.

6. Know the risk factors, onset, and treatment of the side effects of the antipsychotic agents.

7. Based on pharmacokinetic variables, estimate the time to steady state, appropriate level determination, effects of different physiologic variables such as age and smoking status in the evaluation of a given antipsychotic agent and variations between routes of administration (Depo, Po, IM)

8. Given a case study, evaluate the case for the necessity of plasma monitoring of an antipsychotic agent.

9. List the differences in decanoate dosage forms and given an oral dose of either haloperidol or fluphenazine, recommend guidelines for conversion from an oral form of the drug to a decanoate injection in both a psychiatrically stable and unstable patient.

10. Identify potential drug interactions when given a medication prescribed concurrently with an antipsychotic agent and the clinical significance of that interaction.

11. List the antipsychotic agents in order in regards to classification as either high or low potency agents and the ability of the agents to cause the following effects: anticholinergic effects, sedation, orthostatic hypotension, acute and chronic extrapyramidal effects.

12. Describe the characteristics, onset, and treatment for the extrapyramidal reactions and be able to counsel the patient as to what these reactions are, onset, development of tolerance, and treatment in lay terminology.

13. Recommend an antipsychotic treatment regimen for a patient with one or more of the following variables: elderly, seizures, cardiac disease, glaucoma, organic brain insult, or any of the other variable discussed in the readings, or in lecture.

14. List the cardiac effects of the antipsychotic agents and recommend a drug for treatment of a patient with cardiac disease as well as treatment for any cardiac effects that may be observed.

15. List the generic/trade name of the agents used to treat EPS, how they are used, side effects, and dosage ranges.

16. Describe the anticholinergic, opthomologic and other misc. side effects of the antipsychotic agents, how to manage these problems, and the patient teaching that accompanies each side effect.

17. List the incidence of tardive dyskinesia(TD), areas affected, as well as the diagnostic considerations and the necessary criteria for a diagnosis of TD. Be able to develop a monitoring and treatment plan for treatment once TD has been identified in a given patient.

18. Develop a treatment plan including, starting dosages, expected symptom resolution, time for dosage adjustment and dosage guidelines for those adjustments, monitoring parameters, treatment of side effects, patient education, dosages for PRN antipsychotic usage and definition of a therapeutic trial.

Readings:

Readings: *Required Reading

*Pharmacotherapy: A Pathophysiologic Approach 3rd Edition. Ch. 66. pp. 1367-1394

Other Highly Suggested Reading!!!!!!!:

Applied Therapeutics: 6th Edition. Ch. 75.

I. INTRODUCTION

A. EPIDEMIOLOGY

Prevalence:

0.5% - 1% incidence

Incidence:

1/10,000

10% of U.S. disabled population

7-20% of all psychiatric admissions(500,000 to 1 million per yr in the U.S.)

Economic Impact:

$ 22.7 Billion Dollars

2.5% of Total Annual Health Care Costs

 

B. GENETICS

Population	Lifetime risk of developing schizophrenia (%)
General population	1
Parent of a person with schizophrenia	5
Fraternal twins	10
Sibling of a person with schizophrenia	10
Child of one parent with schizophrenia	10-15
Child of two parents with schizophrenia	30-40
Identical twins	40-50

II. BIOLOGIC THEORIES

A. DOPAMINE HYPERACTIVITY HYPOTHESIS

1. Dopaminergic pathways

mesolimbic : midbrain to limbic system

mesocortical : midbrain to temporal & frontal lobes of the cerebral cortex

nigrostriatal : substantia nigra in the midbrain to the caudate nucleus in the basal ganglia

tuberoinfundibular : hypothalamus to the median eminence of the anterior pituitary

a. Dopaminergic Pathway Function

Dopamine Track	Function	Antipsychotic Drug Effect
Nigrostriatal	Extrapyramidal System	Movement disorder
Mesolimbic	Arousal, memory, stimulus processing, motivation	Relief of Psychosis
Mesocortical	Cognition, communication social function, response to stress	Relief of Psychosis, Akathisia?
Tuberoinfundibular	Regulates prolactin release	Increased prolactin Concentrations

2. Data primarily from antipsychotic usage

MOA: Antipsychotics block post synaptic dopamine receptors.

D1 and D2 receptors are associated with antipsychotic efficacy. Other (D1, D2, D3, D4, D5) dopaminergic receptors have been isolated but not characterized as to their action. D2 receptors are cited as responsible for antipsychotic induced movement disorders with D1 receptors modulating the intensity of these side effects. 65-70% of patients with schizophrenia respond to traditional (those with primarily D2 blocking action)antipsychotic agents. Newer atypical antipsychotic agents (i.e. Clozapine) have effects on multiple dopaminergic receptors and have been effective in patients whom traditional antipsychotics have been ineffective. Clozapine, olanzapine and risperidone are effective for negative symptoms as well.

3. Neurochemical Evidence

In Schizophrenia:

Decreased CSF Homovanillic Acid(HVA, Dopamine metabolite)

Post-Mortem studies:

Increases in dopamine concentrations found in the CNS

D-2 receptor density increase(may be due to antipsychotic use)

Antipsychotics:

Cause increase in levels of HVA, i.e. a negative feedback response to postsynaptic dopamine receptor blockade

Inhibit behavioral effects of apomorphine and amphetamine

Stimulant Effects:

Agents which increase presynaptic dopaminergic release may cause psychotic symptoms. i.e. amphetamine/cocaine, levodopa, methylphenidate

B. DOPAMINE DYSREGULATION HYPOTHESIS: "Hypofrontality" Theory

1. Negative symptoms: Traditional agents effect positive symptoms primarily. Negative symptoms are present many times regardless of the degree of response of the positive symptoms to drug therapy.

2. Neurochemical Evidence: Risperidone

Neuroimaging studies have demonstrated a dysfunction of many neurotransmitter systems. A subgroup of schizophrenic patients have shown central dopamine concentrations at low or normal concentrations. This decrease in dopamine in the frontal area of the brain may be responsible for negative symptoms.

Serotonin may modulate dopaminergic function(inhibitory effect) in these areas of the brain.

Risperidone: Blocks D2 receptors and 5HT2 receptors.

Risperidone has been successful in decreasing negative symptomatology.

Clozapine also has 5HT2 receptor effects. It also decreases negative symptomatology.

C. Other Neurotransmitter findings

1. SEROTONIN (5HT)

Serotonergic stimulation decreases dopaminergic release.

CSF 5-HIAA(serotonin metabolite) is lower in acute and paranoid patients and higher in chronic patients(may correlate with negative symptoms)

CSF 5-HIAA is inversely correlated with agitation and arousal

Cortical atrophy and large ventricle/brain ratios on CT scans are associated with lower CSF 5-HIAA

2. Gama-aminobutyric acid (GABA)

CSF GABA is lower in young drug-free schizophrenic patients

CSF GABA increases with duration of illness

CSF GABA is higher in patients with negative symptoms

Plasma GABA levels fluctuate or vary more in schizophrenics than in other groups

BZD's may help decrease psychotic and negative symptoms

3. Glutamate

Has an inhibitory effect on dopaminergic outflow, thus, psychosis may result from a deficiency of glutamate and subsequent dopaminergic overactivity. Model of Phencyclidine(Angel Dust) induced psychosis. Blockade of N-methyl-D-aspartic Acid(NMDA) action/glutamate receptors by PCP results in psychosis.

4. NOREPINEPHRINE

Brain NE & MHPG(metabolite) concentrations are increased in some brain areas

CSF NE is episodically elevated in drug-free pts.(state dependent)

CSF NE & MHPG decrease with neuroleptic treatment relative to clinical improvement

Plasma NE is elevated in chronic, drug-free, & and medicated pts.

Clonidine and propranolol may have antipsychotic augmenting effects in some patients

D. BRAIN MORPHOLOGY

1. CT & MRI

Lateral & third ventricular enlargement

10-50% of schizophrenics show an increase in vetricular brain ratio(VBR)

Increased cortical surface markings (thinning of the gyri and widening of the sulci)

2. PET Scans

Metabolic hypofunction of the frontal lobe and the basal ganglia

III. DIAGNOSIS

A. SCHIZOPHRENIA

a Bleuler's 4 A's

Autism(preoccupation with internal stimuli)

Inappropriate Affect(external manifestations of mood)

Associational Disturbances(Illogical or fragmented thought processes)

Ambivalence(simultaneous, contradictory thinking)

b. DSM-IV

A. Characteristic Symptoms:

Two or more of the following symptoms, each present for a significant portion of time during a 1-month period(or less if successfully treated)

1. delusions

2. hallucinations

3 disorganized speech

4. grossly disorganized or catatonic behavior

5. negative symptoms i.e. affective flattening, alogia, or avolition

Note: Only one Criterion A symptom is required if delusions are bizarre or hallucinations consist of a voice keeping up a running commentary on the person's behavior or thoughts, or two or more voices conversing with each other.

B. Social/Occupational Dysfunction: For a significant portion of the time since the onset of the disturbance, one or more major areas of functioning such as work, interpersonal relations, or self-care are markedly below the level achieved prior to the onset (or when the onset in adolescence, failure to achieve expected levels of accomplishment)

C. Duration: Continuous signs of symptoms for at least 6 months. This six month period must include at least one month of symptoms that meet criterion A.

D. Schizoaffective and Mood Disorder Exclusion: These disorders have been ruled out because either 1. no Major Depressive, Manic or Mixed Episodes have occurred concurrently with the active phase symptoms or 2. if mood episodes have occurred during active phase symptoms, their total duration has been brief relative to the duration of the active and residual periods.

E. Substance /general medical condition exclusion: The disturbance is not due to the direct physiological effects of a substance or a general medical condition

F. Relationship to a Pervasive Developmental Disorder: If there is a history of Autistic Disorder or another Pervasive Developmental Disorder, the additional diagnosis of Schizophrenia is made only if prominent delusions or hallucinations are also present for at least a month (or less if successfully treated).

B. DIAGNOSTIC CRITERIA FOR THE SUBTYPES OF SCHIZOPHRENIA (DSM-IV)(5 Types of Schizophrenia)

Paranoid Type:

Preoccupation with one or more delusions or frequent auditory hallucinations.

None of the following is prominent: disorganized speech, disorganized or catatonic behavior, or flat or inappropriate affect.

Disorganized Type:

All of the following are prominent:

Disorganized speech

Disorganized behavior

Flat or inappropriate affect

The criteria are not met for Catatonic Type

Catatonic Type:

A type of Schizophrenia in which the clinical picture is dominated by at least two of the following:

i) motoric immobility as evidenced by catalepsy(including waxy flexibility) or stupor

ii) excessive motor activity(that is apparently purposeless and not influenced by external stimuli)

iii) extreme negativism (an apparently motiveless resistance to all instructions or maintenance of a rigid posture against attempts to be moved) or mutism

iv) peculiarities of voluntary movement as evidenced by posturing (voluntary assumption of inappropriate or bizarre postures), stereotyped movements, prominent mannerisms, or prominent grimacing

v) echolalia or exhopraxia

Undifferentiated Type:

A type of Schizophrenia in which symptoms that meet Criterion A are present, but the criteria are not met for the Paranoid, Disorganized, or Catatonic Type.

Residual Type:

A type of Schizophrenia in which the following criteria are met:

i) Absence of prominent delusions, hallucinations, disorganized speech, and grossly disorganized

ii) There is continuing evidence of the disturbance, as indicated by the presence of negative symptoms or two or more symptoms listed in Criterion A for Schizophrenia, present in an attenuated form(eg. odd beliefs, unusual perceptual experiences)

C. PROGNOSTIC FACTORS

1. Schneider's First-Rank Symptoms of Schizophrenia

When present indicate a poor prognosis

• Audible thoughts
• Voices arguing
• Voices commenting on one's behavior
• Somatic passivity
• Thought withdrawal
• Thought insertion
• Thought broadcasing
• Experiences feelings not his/her own
• Experiences powerful influence not his/her own but actual performances of the act is his/hers
• Experiences actions under control of external influence
• Delusional perception

2. Positive and Negative Symptoms of Schizophrenia

Positive symptoms are present during acute exacerbations and are usually drug responsive thus are state dependent.

Negative symptoms are present both in the acute and residual stage of the illness and are generally not drug responsive thus are trait dependent.

Positive Symptoms	Negative Symptoms
Agitation, tension	Alogia
Associated disturbances	Amotivation
Delusions	Anhedonia
Hallucinations	Blunted Affect
Ideas of Reference	Poor grooming and hygiene
Illusions	Poor social skills
Insomnia	Poverty of Speech
Paranoia

3. Type I and Type II Schizophrenia

Type I = positive symptoms predominate: Usually apparent on initial presentation.

Type II = negative symptoms predominate: Usually apparent with chronic illnesss but may be present from the beginning.

4. Prognosticators of Outcome for Schizophrenia Treated with Antipsychotics

Feature	Good Prognosis	Poor Prognosis
Premorbid Functioning	High	Low
Precipitating factors	Present	Absent
Age at onset	Older than average	Younger than average
Onset of symptoms	Sudden	Insidious
Family History	Affective illness	Schizophrenia
Interpersonal Relationships	Married/stable home	Single
Affective Symptoms	Present	Blunted Affect
Behavioral Features	Positive symptoms	Negative symptoms predominate
CNS morphology	Normal	Ventricular enlargement, or central atrophy
Dopamine system	Hyperactive in limbic system	Hypoactive in frontal cortex
Response to typical neuroleptics	Good	Fair to Poor

ANTIPSYCHOTIC DRUG THERAPY

I. INTRODUCTION

II. MECHANISM OF ACTION

A. DOPAMINERGIC EFFECTS

1. General MOA

Antipsychotics produce a blockade of post-synaptic dopamine receptors

All antipsychotics, except haloperidol, block both D1 and D2 post synaptic receptors

Newer antipsychotics i.e. clozapine, may preferentially block D1 and D2 post synaptic receptors in the ventral tegmental (A-10) region of the brain(antipsychotic efficacy)...thus avoiding EPS type reactions which are reflective of blockade in the nigrostriatal (A-9) region of the brain.

2. Specific Dopamine Receptors

	D1 & D5	D2a	D2b	D3 & D4
Effects on cyclic AMP	Increases	Decreases	Increases phosphoinositide turnover	? Decreased
Agonists
Dopamine	Weak D1, Moderate D4	Moderate	Moderate	Potent
Apomorphine	Weak D1, Moderate D4	Potent	Potent	Potent
Antagonists
Phenothiazines	Weak	Potent	Potent	Potent D3, Moderate D4
Thioxanthenes	Potent	Potent	Potent	-
Butyrophenones	Weak	Potent	Potent	Weak
Clozapine	Weak	Weak	Weak	Weak D3, Potent D4

D-1 Receptors

Increase adenylate cyclase activity

Modulate intensity of movement disorders

Higher concentration found in the prefontal cortex than in the basal ganglia and mesolimbic tissue.

D-2 Receptors

Independent of or decrease adenylate cyclase activity

Antipsychotic activity correlated with D-2

Associated with direct pathogenesis of movement disorders such as parkinson's disease

Potency of the agents correlate with D-2 receptor affinity

B. POTENTIAL EFFECTS OF ANTIPSYCHOTICS ON NEUROTRANSMITTER SYSTEMS

DOPAMINERGIC

Extrapyramidal Dystonia

• Akathisia
• Pseudoparkinsonian
• Tardive dyskinesia

Hyperprolactinemia

• Galactorrhea
• Gynecomastia

ANTIMUSCARINIC-CHOLINERGIC

Visual

• Blurred Vision
• Narrow angle glaucoma

Gastrointestinal

• Dry mouth
• Constipation

Genitourinary

• Urinary retention
• Delayed or retrograde ejaculation

CNS

• Memory dysfunction
• Delirium

Cardiovascular

• Sinus tachycardia

Skin

• Decreased sweating

ANTIHISTAMINIC (H1)

• Sedation
• Hypotension

ANTI-ALPHA1- ADRENERGIC

• Postural hypotension, dizziness
• Reflex tachycardia

CALCIUM CHANNEL BLOCKADE

• Neuroleptic malignant syndrome
• Inhibition of ejaculation
• Arrythmias

NO KNOWN RECEPTOR MEDIATION

Hematologic

• Agranulocytosis

Gastrointestinal

• Anorexia
• Nausea and vomiting

CNS

• Seizures
• Depression

Visual

• Pigmentary retinopathy (thioridazine)

Skin

• Discoloration
• Photosensitivity

Immune

• Allergic Reactions

III. INDICATIONS

Schizophrenia

Psychosis of any kind

Bipolar Affective Disorder-manic phase

Depression-psychotic

Organic Brain Syndrome-(low dose)

Gilles de la Tourette syndrome

 

IV. AGENTS, DOSE, POTENCIES & CONSIDERATIONS FOR USE

(USUAL ORAL DOSE-MG/DAY)

*Elderly patients: use approximately one half of dosage listed.

Dosage forms available: T, tablet/capsule; L, liquid; I, injection; D, decanoate; S, suppository.

Note: The potency of antipsychotic agents refers to D-2 receptors only, thus when converting from one antipsychotic to another, caution must be utilized and the dosage tapered up to assess for side effects associated with other neurotransmitter systems.

A. SELECTION OF MEDICATION

Patient history

Target symptoms

Target symptoms must be documented in terms of severity and frequency in the chart before treatment is started and goals for pharmacotherapy should be explicitly stated.

Onset and Etiology of Symptoms(Differential Diagnosis)

Drug Induced Psychosis

• Amphetamine
• Cocaine
• Cannabis
• Phencyclidine
• Lysergic Acid Diethylamide
• Anticholinergics

Primary Psychiatric Disorders

• Brief Reactive psychosis
• Schizophreniform disorder
• Bipolar affective Disorder, manic type
• Mood disorder with psychotic features

Personality Disorders

• Schizotypal
• Schizoid
• Paranoid

Age

Medication and Family history

A comprehensive patient history should obtained including family and previous drug history of the patient.

Medical Illness

Drug Interactions

B. STABILIZATION OF PATIENT

Symptom Responsiveness

Most Responsive

• Combativeness and Hostility
• Tension and Hyperactivity
• Hallucinations
• Sleep
• Appetite
• Dress
• Delusions
• Social Skills
• Affect
• Realistic Planning
• Judgement
• Insight

Least Responsive

Severity of Symptoms

Age and Size of patient

Side Effects

Change of dosage

Therapeutic trial

Change of medication(therapeutic equivalence)

How long to maintain medication

AVOID POLYPHARMACY!!

IV. PHARMACOKINETICS

A. Typical Antipsychotics

Drug	Bioavail. (%)	Pb (%)	Vd (L/kg)	Plasma t1/2 (hours)	Plasma Conc (ng/ml)
Chlorpromazine	10-33	90-95	7-20	8-35	100-300
Fluphenazine	50	90-95		14-24	0.2-3.0
Haloperidol	40-70	92	10-35	12-36	3-15
Perphenazine	25		10-35	8-21	0.8-2.4
Thioridazine	25-33	99		9-30	200-800
Thiothixene	50	90-95		34	1.0-5.0

A. ABSORBTION

The antipsychotic agents exhibit variable absorption and a large amount of first pass metabolism. Intramuscular administration allows 4 to 10 times the availability of drug when compared to oral administration.

B. DISTRIBUTION

The antipsychotics are highly lipophillic and thus have large volumes of distribution. Most volumes of distribution range from 7 to 40 L/kg. The drugs accumulate in the fat over time. Due to this phenomena the half-lives of these agents are long, ranging from 10-30 hours. Thus, steady state usually takes approximately one week to occur. They are highly protein bound and cross the placenta and are excreted in the maternal milk supply.

C. METABOLISM

The agents are metabolized by microzomal oxidation and by conjugation in the liver.

D. EXCRETION

After oxidation or conjugation, metabolites are excreted primarily in the urine and to a small degree in the bile.

E. ANTIPSYCHOTIC PLASMA CONCENTRATIONS

Not for routine monitoring

Research is in progress in delineating concentration/response relationships.

4 to 10 fold concentration variance between patients for any one antipsychotic dosage

Clinical Utility: i. e. when to consider an antipsychotic level

Non-responding patient given an adequate dose and duration of therapy

Change in functioning in previously compliant and stable patient

To document level when response is seen

As a comparison to previous levels for compliance purposes

Monitor toxicity(unusual or severe adverse reactions)

Utilizatioin of higher that usual dosages

F. OTHER PHARMACOKINETIC VARIABLES

1. Age

2. Smoking

	DOSE (mg/day)	Clearance (L/min)
Smokers (N=23)	38+19	1.6+0.78
Non-smokers (N=27)	45+24	1.2+0.4

3. Drug Interactions

Interacting Compound	Mechanism	Clinical Outcomes
Antacids	Decrease GI absorption	Decrease efficacy
Oral Anticoagulants	Inhibit microsomal enzymes	Increase anticoagulant activity
Antidepressants	Inhibit microsomal enzymes	Increase plasma level of antipsychotics
Antichoinergics	Unknown	Decrease plasma levels
Barbiturates	Induction of microsomal enzymes	Decreasd plasma levels
Alcohol and other CNS depressants	Additive CNS effect	Increase sedation
Amphetamine	Antagonism dopamine blockade	Worsening of Levodopa psychosis
Anticonvulsants	Antipsychotic may lower seizure threshold	Seizures
Beta-blockers	Orthostatic hypotension	Exaggerate antihypertensive effects
Phenytoin	Decrease metabolism of phenytoin	Anticonvulsant toxicity
Oral hypoglycemics, Insulin	Antipsychotic may increase blood glucose	Titration of hypoglycemic agents
Rifampin, griseofulvin, phenylbutazone, carbamazepine	Increased metabolism	Decrease antipsychotic activity
Disulfiram, oral	Decrease metabolism	Increase

G. DEPO DOSAGE FORMS

1. Decanoate

Esterification of the hydroxyl group of the antipsychotic to a long chain fatty acid, then dissolved into sesame oil. These esters are sensitive to hydrolysis by water, thus vials are qs'ed with N2 as packing. Once the rubber stopper is punctured the decanoate bond is subject to degradation.

2. Rate-limiting step

Release from the muscle or absorption is the determining factor in onset and duration of action. Time to steady state is dependent on the half-life of the drug determined by absorption rate ka rather than hepatic metabolism ke.

3. Available agents

a. Fluphenazine

Fluphenazine Decanoate: duration is as much as two weeks longer than enanthate

t1/2 = 14 days

25mg/ml of preparation

Cpss = 4-8 weeks

Conversion from oral therapy to Injectable Therapy:

Fluphenazine decanoate

Stable Patients(who are not acutely psychotic):

After first injection the oral dosage may be discontinued abruptly unless the patient is acutely psychotic or has a history of rapid relapse upon d/c of medication. Many choose to taper the medication over the first month of therapy.

i. Multiply 1.2 times the oral dosage

ii. Round to the nearest 0.5 ml(12.5mg) of fluphenazine decanoate

iii. Administer q 1-2 weeks.

OR

i. Multiply oral dose/d times 7 days

i.e pt on 10mg/d of fluphenazine oral

10mg/day X 7 days = 70mg

ii. Divide by four: factor based on increased bioavailability of IM

70 div 4 = 17.5 mg

iii. Reduce by one third for a safety margin

17.5 - (1/3 X 17.5) = 11.7 mg

iv. Round off to nearest 12.5 mg (0.5 ml) and administer weekly (every other week in a stable patient)

Dose: 0.5 ml q week or q 2 weeks

Note: after 4-6 weeks(achieving steady state) the dosage interval should be increased to every 2-3 weeks to prevent accumulation of fluphenazine in the patient.

Dosage for an Acutely Psychotic Patient(Prolixin decanoate)

Conversion factor of 1.6

Round up to the higher 0.5 ml(12.5 mg) fluphenazine decanoate dose and administer q week.

After 4 weekly injections, increase dosage interval to q 2 weeks

Oral dosage may be d/c'd after the pm dosage the night prior to the first injection.

Note: after 4-6 weeks(achieving steady state) the dosage interval should be increased to every 2-3 weeks to prevent accumulation of fluphenazine in the patient.

b. Haloperidol Decanoate

t1/2 = 20 days

50mg/ml, 100mg/ml available

Cpss = 3 months

Note: MFG's recommend not more than 100 mg be given at initial dosing.

Take the po dose X 20.

Give this dosage IM over one week.

In four weeks reduce the dose by 25%

In 8 weeks reduce the dose by 50%.

i.e. Oral dose of 20 mg/day

20x 20 = 400 mg

 

Day 1: 100 mg IM Haldol Decanoate

Day 4: 150 mg IM Haldol Decanoate

Day 6 or 7: 150 mg IM Haldol Decanoate

Week four: (i.e. four weeks after day 1)

Give 300mg IM Haldol Decanoate

Week eight: Give 200mg IM Haldol decanoate and administer 200mg IM as the Maintenance dose every four weeks. Goal is to have the patient free of oral medication by 3 to four months of treatment.

V. SIDE EFFECTS AND ADVERSE REACTIONS

Summary:

A. EXTRAPYRAMIDAL REACTIONS

1. Acute Dystonic Reaction(Possible medical emergency)

a. Symptoms

Spasm of tongue(swollen tongue) or tongue protrusion, throat, face, eyes, neck(Torticollis) or back muscles

Oculogyric crisis (eyes roll back in head)

Trismus (face twisting to one side)

Opisthotonus (neck arching back, head reared back)

b. Characteristics

Onset: Sudden, 1 - 5 days after starting medication or an increase in dose

MOA: Sudden blockade of dopamine followed by a rapid fall of antipsychotic concentrations. Increased production, release and degredation of dopamine resulting from presynaptic dopaminergic autoreceptor blockade also with dystonic reactions. Thus, dystonias occur from a dysregulation of dopamine, rather than an absolute decrease in dopaminergic transmission.

At Risk Populations:

Younger individuals

Men more than women

Patients with brain insult, damage

High potency medications

• Haloperidol 16%
• Fluphenazine 11.7%
• Trifluoperazine 8.2%
• Thioridazine 0.6%

Children have more severe reactions involving the trunk and extremities

c. Treatment of Dystonic Reactions

Anticholinergic IM/IV

Cogentin 1-2 mg (15 min response IV, 30 min IM)

Benadryl 50 mg SLOW!!! IVP

Valium IV and Lorazepam(0.025-0.05 mg/kg IM)

Intubation if breathing is compromised

Maintenance anticholinergic medications may be necessary to prevent reoccurrence for 2-4 weeks and then may be subsequently tapered and discontinued.

2. Akathisia

a. Mechanism

Due to postsynaptic dopaminergic receptor blockade in non-striatal brain regions. Disregulation of gamma abminobutyric Acid or Norepinephrine may play a part in pathogenesis.

b. Symptoms

Feeling of inner restlessness

Motor restlessness

Inability to sit still with lack of causative factors

Feels driven with a compulsion to move

c. Characteristics

Onset: 6-60 days

Younger people

High potency medications

Rocking, pacing, standing up and sitting down

d. Treatment of akathisia

i. Decrease dosage: if symptoms are stable

ii. Change drug to lower potency agent or to an agent the patient has tolerated before without akathesia.

iii. Pharmacologic Treatments:

b-blocking agents:

• Propranolol (10 mg TID, max 90-180 mg/d)
• Naldolol: up to 80mg/day
• Metoprolol: up to 100mg/day

Clonidine: Mean dose of 0.43 mg/d

Benzodiazepines:

• lorazepam (1-3mg/d), clonazepam (0.5-2 mg/d)

Anticholinergic agents: especially if patient has acompanying pseudoparkinsonian symptoms.

3. Pseudoparkinsonian Reactions

a. Mechanism

Decrease in dopamine from the substantia nigra in the midbrain to the head of the caudate nucleus in the basal ganglia.

b. Symptoms

Akinesia, or Bradykinesia

Cogwheel Ridgidity

Tremor: more marked at rest

Postural Abnormalities

Others:

• masked facies
• posture
• slowing of movements

c. Characteristics

Onset, 5-90 days after initiation or increase in dose

Women, and patients of increased age are more at risk

Tolerance develops after 2 - 3 months

Seen primarily with high potency agents

• Haloperidol 30 - 40%
• Trifluoperazine - 15%
• Chlorpromazine - 7%

d. Treatment of pseudoparkinsonian reactions

Decrease dose if patient's target symptoms are stable

Change medication

Anticholinergic treatment

 

Antiparkinson/Anticholinergic Agents

DRUG	TRADE	TYPE	DOSE/DAY	INJECTION
Benztropine	Cogentin	Antihistamine, Anticholinergic	1 to 6	YES
Diphenhydramine	Benadryl	Antihistamine	25 to 200	YES
Trihexyphenidyl	Artane	Anticholinergic	1 to 10	NO
OTHERS:
Amantadine	Symmetrel	Dopamine agonist	100 to 300	NO
Biperiden	Akineton	Anticholinergic	2 to 6	YES
Ethopropazine	Parsidol	Antihistamine, Anticholinergic	50 to 600	NO
Orphenadrine	Disipal	Antihistamine	50 to 300	YES
Procyclidine	Kemadrin	Anticholinergic	1 to 10	NO

Dosing Guidelines:

Start low and monitor for side effects

Good patient education is critical

a. Prophylactic value:

If patient has a history of severe EPS on agent or one of higher potency or if the patient has multiple risk factors for the onset of EPS type reactions.

If patient is markedly psychotic and EPS may cause refusal of medication.

EPS is a significant cause of non-compliance in this patient popultion.

b. Maintenance therapy

90% of patients develop tolerance to EPS effects and thus don't require treatment with antiparkinsonian agents for greater than 3 months.

All patients should be given a antiparkinsonian free trial after 2 to 3 months of therapy.

Taper the medication slowly(generally weekly) and watch for reoccuring symptoms of EPS.

B. CNS EFFECTS

1. Sedation

2. Seizure threshold

3. Antipsychotic Tolerance and Dependence

4. Hypothalamic (excluding endocrine)

a. Poikilothermiaa

C. CARDIOVASCULAR SYSTEM

1. Tachycardia

Secondary to anticholinergic effects

2. Orthostatic Hypotension

Patients at risk

Elderly, diabetics, preexisting cardiovascular disease

a. Secondary to alpha-adrenergic blocking effects

• Local vasodilatory effects
• Central inhibitory effect on vasomotor center

b. Most often seen with low potency agents

c. Most develop tolerance in 2-3 months, however, may be persistent

d. Patient education: fluids, slow changes in posture, support hose.

e. Severe hypotension:

Pure alpha-adrenergic agent must be used such as norepinephrine (Levophed) or phenylephrine (Neo-Synephrine).

Agents with mixed alpha/beta adrenergic effects such as epinephrine (Adrenalin), or isoproterenol (Isuprel) should never be used for treatment of hypotension due to a paradoxical lowering of the person's blood pressure due to unopposed beta-adrenergic stimulation with possible cardiovascular collapse.

3. EKG Changes

a. Increased HR

b. Prolonged QT and PR intervals

c. Depressed T waves

d. Depression of the ST segment

e. These changes are not usually clinically significant

4. Antiarrhythmic and arrhythomogenic effects

a. Quinidine-like activity

b. RBBB, left anterior hemiblock, transient complete heart blockage may be seen

c. Prior cardiac disease increases risk of sudden death

d. Avoid usage of low potency agents in people with heart disease

D. ANTICHOLINERGIC EFFECTS (Antiparkinsonian agents may worsen this problem)

• Dry mouth
• Constipation
• Nasal dryness
• Dry skin
• Urinary hesitancy/retention
• Tachycardia
• Blurred vision
• Inhibition/retrograde ejaculation

1. Treatment

a. Decrease dosage if condition stable

b. Supportive

• Hydration: Specify amount!!! i.e 8-10 glasses of water per day
• Ice chips, sugarless gum or candy
• Increase exercise
• Increase fiber content in food
• Lotions
• Decreased exposure to wind and sun
• Bulk-forming laxative
• Artificial Tears

c. Change of medication to a higher potency agent

E. OPTHOMOLOGIC EFFECTS

1. Blurred Vision

2. Glaucoma

a. Exacerbation of narrow angle glaucoma

b. Increase in intraocular pressure

3. Pigmentary Retinopathy

a. Thioridazine (Mellaril)

b. Brownish discoloration of vision

c. Risk

Reported with dosages of 800mg/day or more, questionable at dosages of 600mg/d.

d. Morbidity-may lead to blindness if drug not stopped and progression allowed

F. HEMATOLOGIC EFFECTS

1. Agranulocytosis

a. CPZ 1/10,000, Primarily seen with low potency medications

b. Toxic effect on granulopoiesis in bone marrow

c. Risk

• Increased age
• Female
• Debilitation

d. Leucopenia may occur more frequently

e. See within the first 6 weeks, monitor for clinical symptoms i.e. sore throat, cold/flu

2. Clozapine

0.8-2% risk of agranulocytosis

G. ENDOCRINE

1. Women:

Galactorrhea/Gynecomastia (up to 57%)

Mentral Irregularities or Ammenorrhea (up to 97%)

MOA-Blockade of prolactin inhibitory factor (dopamine) in the tuberoinfundibular pathway leading to the pituitary

2. Metabolic Effects

a. Glucose metabolism

b. Weight Gain

Food intake increase, fluid retention

55% of patients on depot maintenance "clinically significant weight gain

H. DERMATOLOGIC SIDE EFFECTS

1. PHOTOSENSITIVITY

a. Sunburn-photosensitivity reactions are very common, esp. with CPZ. Thought to be due to free radical production. Use of a block sunscreen very important.

b. A blue/grey or purplish hyperpigmentation by lower potency agents, esp CPZ may be seen with higher dosages for extended periods of time.

c. Contact dermatitis: May be seen in medical personel or patients--mixing oral concentrates with a volume of liquid and advising the patient to swallow the liquid quickly may reduce this problem.

I. NEUROLEPTIC MALIGNANT SYNDROME

1. Risk:

• High Potency antipsychotic agents
• Dehydration
• Injectable antipsychotics

2. Mortality : 5-20%

3. Incidence: 0.5-1.5%

4. NMS Presentation

• Lead pipe rigidity
• EPS unresponsive to anticholinergic agents
• Fever
• Leukocytosis
• Akinesia
• Diaphoresis
• Sweating
• Increase in CPK
• Myoglobinuria
• Mental status changes, stupor, coma
• Death due to :

• Pulmonary Failure
• Renal Failure
• Aspiration Pneumonia

5. Treatment for NMS

Discontinue medications

Supportive therapy(hydration, benzodiazepines)

Dantrolene Sodium

Bromocriptine

J. TARDIVE DYSKINESIA (Characterized as an EPS reaction)

1. INCIDENCE AND PREVALENCE

10 to 20% of patients on antipsychotics for longer than one year

Elderly

Women

2. PATHOPHYSIOLOGY

"Dopamine Supersensitivity Hypothesis"

Functional overactivity of extrapyramidal mechanisms mediated by dopamine

3. RISK FACTORS

Age

Average daily dose

Female Gender

Organic Disorder

Pseudoparkinsonian reactions?

Prolonged anticholinergic usage?

4. PRESENTATION

Face: eye blinking, tremors, oralingual pouting, puckering, smacking, chewing, sucking, tongue protrusion and tremor, and choreoathetoid tongue movements.

Neck and Trunk: head nodding, retrocollis, spasmotic torticollis, torsion movements of trunk, axial hyperkinesia and rocking movements.

Upper Extremities: ballistic movements, chorea and athetosis of fingers, wrists and arms. Pill rolling movements, caressing and rubbing of face and hair, and rubbing of thighs.

Lower Extremities: rotation and/or flexion of ankles, toe movements, stamping movements both sitting and standing, crossing and uncrosssing of legs, and restless legs.

5. DIAGNOSTIC CONSIDERATIONS

Other abnormal movements: habit spasms, tics of unknown cause, psychotic mannerisms, manifestations of senescence.

Other neurologic syndromes:

1. Neuroleptic withdrawal-emergent dyskinesia or other transient dyskinesias associated with neuroleptic initiation.
2. Late and persistent TD.
3. Spontaneous oral dyskinesias of advance age or senility
4. Oral dyskinsias related to dental conditions or prostheses
5. Idiopathic torsion dystonia
6. Focal dystonias
7. Huntington's disease (both psychiatric disorder and dyskinesia may be present)
8. Gilles de la Tourette's Syndrome
9. Wilson's Disease (hepato-cerebral-linticular degeneration due to abnormal copper metabolism), maganism, and other disorders due to heavy metal poisoning(both psychiatric disorder and dyskinesia may be present)
10. Fahr's syndrome and other disorders with calcification of the basal ganglia.
11. Postanoxic, postencephalitic and encephalitic extrapyramidal syndromes
12. Rheumatic chorea (Sydenham's chorea, St. Vitus' dance).
13. Drug intoxiciations involving L-dopa and amphetamines, less commonly anticholinergics, antidepressants, lithium and phenytoin.
14. CNS complications of systemic metabolic disorders (renal failure, hypoglycemia).
15. Brain neoplasm (thalamic, basal ganglia).

6. AIMS (Abnormal Involuntary Movement Scale)

Positive rating if +3 in one body area or rating of +2 in two different body areas with at least 3 months of exposure to antipsychotic agents and no other diagnostic considerations (including withdrawal dyskinesia or akathisia).

7. GUIDELINES

a. Indications: Chronic psychosis, proven exacerbation off of antipsychotic medication.

b. Lowest effective dosage.

c. Reevaluate patient and document indications per visit and attempt dosage reduction..

d. Advise patient and family of benefits and risks. Talk to family and patient about TD (what to look for) so that detection may occur early.

e. Abnormal involuntary movement rating scale (AIMS) every 6 months, and then every 1 to 3 months if any movement disorder is detected.

f. At the earliest sign of dyskinesia attempt to taper the medication and wait for remission as long as psychiatric status permits, reduce the dosage, change to a less potent agent. Consider the use of an alternative agent.

8. TREATMENT

Prevention is the hallmark of treatment

Avoid unnecessary exposure to antipsychotics

Encourage patient to avoid drug and alcohol use

Lowest dose, shortest time

Routine exam for dyskinetic movement(AIMS)

Baseline rating and q 6 months after

Lower dosage and consider D/C if early signs develop

Positive rating if +3 in one body area or rating of +2 in two different body areas with at least 3 months of exposure to antipsychotic agents and no other diagnostic considerations.

If positive rating, TD must be assessed q 1 - 3 months depending on severity.

Medication Trial

VI. ATYPICAL ANTIPSYCHOTICS

A. Clozapine (Clozaril^R)

1. Historical data:

Dibenzodiazepine antipsychotic in Europe since the late 70's..

Phase I testing in the US in 1972

1975: 35 cases of agranulocytosis reported

Evaluation suspended from 1976-1982

Phase II testing initiated in 1985 with NDA in 1987 for txt-resistant schizophrenia

Approved for use in the U.S. in 1990 for treatment resistant schizophrenia

Effective for both the positive and negative symptoms of schizophrenia

2. Pharmacology:

"Broad spectrum antagonist with affinity for dopamine (D1(stimulate adenylate cyclase activity), D2(independent of , or inhibit adenylate cyclase activity), serotonin, histamine (H1), norepinephrine, and acetylcholine receptors.

3. Theories concerning actions:

a. Selectivity for limbic dopamine receptors versus striatal dopamine receptors

b. Modulation differences between D1 and D2 receptors in the extrapyramidal, limbic and mesocortical systems. Clozapine has similar affinity for both in vitro for both the D1 and D2 receptor, however it is structurally similar to the D1 specific antagonist SCH-23390 and may functionally provide increased activity at the D1 receptor.

c. Does not induce cataplexy or block apomorphine induced gnawing behavior in rats (markers for EPS side effects)

d. Does not increase abundance or sensitivity of dopamine receptors

e. Atypical antipsychotic in that clozapine causes only minimal elevations of prolactin(D2 receptor association), has very few parkinsonian side effects, and is not associated with T.D. or dystonia.

4. Indications:

a. Refractory Schizophrenia: Antipsychotic trial of two different agents with CPZ equivalents of 1000mg/d or more for a period of 6 weeks

b. Intolerance to side effects: Severe, intolerable extrapyramidal side effects. (T.D. or drug-induced parkinsonism.)

5. Adverse Effects:

Agranulocytosis:

0.8 - 2%, usually within the first months of therapy, recovery within 4 weeks without sequelae with close monitoring. Approximately 3 % have leukopenia. Most commonly occurs during the first 18 weeks of therapy but may occur at any time. Without close monitoring, greater than 30% mortality.

Seizures: dose related

1 - 2% in patients receiving < 300mg/day;

3 - 4% in those receiving 300 - 600mg/day;

and 5% in those receiving > 600mg/day.

Other more common side effects: sedation(40%), sialorrhea(31%), tachycardia (25%), dizziness(19%), hypotension(9%), hypertension(4%), constipation(14%), hyperthermia (5%,) (low fever is generally transient, evaluate for decreased WBC, infection or NMS)

Less Common: sexual dysfunction, chest pain, akathisia, rigidity, musculoskeletal problems

6. Drug interactions/Contraindications

History of myeloproliferative disorder or of drug induced granulocytopenia or agranulocytosis

Any drug with potential for bone marrow supression(carbamazepine, propylthiouracil, sulfonamides, captopril, anticonvulsants, chemotherapy, etc.)

CNS depressants including benzodiazepines, anesthetics, opiates, sedative-hypnotics

Antimuscarinic drugs

7. Dosing:

Start with 12.5 mg once daily, increase by 25 mg per day as tolerated over 2 weeks to 300 to 450mg/day.

Response range: 300 to 600mg/day.

Maximal dose 900mg/day.

Clozapine 50mg is equivalent to chlorpromazine 100mg clinically.

Clozapine is available in 25mg and 100mg tablets

If patients go without clozapine for longer that 48 hours the dosage must be retitrated due to the risk of respiratory depression with reinitiation of high dosages.

8. Response:

3-6 month trial

30% respond after 6 weeks of therapy

60% after 6 months of therapy.

9. Monitoring:

LABS

CBC with differential will be drawn every week and checked prior to the patient receiving their clozapine prescription.

LEUKOPENIA DEFINITION

WBC < 3500/mm3

OR

a drop over 3 consecutive weeks to a

WBC count below 5000/mm3.

Monitor CBC with Differential twice per week if:

WBC greater than 3000/mm3 but qualifies as above

Granulocyte count greater than 1500/mm3

Discontinue clozapine if:

WBC less than 3000/mm3 and granulocyte count less than 1500/mm3

Consultation with Hematology and Infectious Disease services

Hospitalization:

If granulocytes drop below 1500/mm3 the patient must be hospitalized with consideration given to bone marrow aspiration and analysis and start neutropenia precautions. The patient may never be rechallenged with clozapine.

10. Withdrawal:

Withdrawal symptoms such as diaphoresis, flushing, diarrhea, hyperactivity, and rebound psychosis have been reported, thus a one to two week taper is suggested. Abrupt discontinuation may be necessary due to drops in the blood count. In this instance, withdrawal symptoms may be treated symptomatically.

11. Patient Education:

Educate patient/family about signs/symptoms of agranulocytosis, and other side effects associated with clozapine.

Compliance with weekly visits and blood draws

Importance of notifying CTT immediately if they experience fever, chills, lethargy, infection , weakness, sore throat, urinary tract infection, flu-like symptoms or other signs of infection. Phone numbers for contact people on a 24 hour basis.

B. Risperidone (Risperdal^R)

1. Pharmacology:

A benzisoxazole Deriviative.

Selective monoaminergic antagonist with high affinity for 5HT2, D2, alpha1 and alpha2, and H1 receptors.

2. Indications: Same as traditional agents:

Schizophrenia: risperidone's main advantage over traditional agents is that the evidence for benefit in the treatment of negative symptoms of schizophrenia.

It is not indicated for patients who are treatment resistant to traditional antipsychotic agents as is clozapine. Many people are tried on risperidone who have not responded to other medications, but this is not it's primary indication.

3. Adverse Effects:

Different due to high incidence of insomnia, agitation, anxiety, runny nose, headache, otherwise similar to traditional agents. EPS occurs in 17%(similar to placebo) of patients on 10mg/d or less and in 34% in patients on 16 mg/d.

4. Dosing

Old Recommendations:

Immediately d/c the previous antipsychotics

Day 1: Start with 1 mg BID

Day 2: Increase to 2 mg BID

Day 3: Increase to 3 mg BID

Elderly/debilitated pts: begin with 0.5 mg BID and increase more slowly as tolerated.

New Recommendation:

Taper the old antipsychotic slowly

Package insert still reads as previous.

Jansen PR...new recommendation is to begin at 1-2 mg and titrate to patient response.

Further dosage increases should not occur more frequently than once per week.

Mean dosage patients do best at a dosage of 6mg/day.

Dosage Range: 4-16 mg/day.

Elderly may need less.

C.Olanzapine (Zyprexa(r))

1. Pharmacology:

Thienobenzodiazepine Class

Selective monoaminergic antagonist with high affinity binding for for 5HT2A/2C, D1-4, Muscarinic1-5, alpha1, and H1 receptors. Binds weakly to GABAA, BZD, and Beta adrenergic receptors.

2. Pharmacokinetics:

Well absorbed: Peak conc. 6 hours

High first pass effect: 40% metabolized before reaching the systemic circulation

PB: 93%

Vd: 1000 L

T1/2: 21-54 hours displaying linear kinetics

Major Metabolic Pathway: CYP1A2 and 2D6; Minor: CYP 2D6

3. Indications: Same as traditional agents:

Management of Psychotic Disorders: olanzapine's main advantage over traditional agents is that the evidence for benefit in the treatment of negative symptoms of schizophrenia. The drug has not been systematically evaluated in trials longer than 6 weeks.

4. Adverse Effects:

Significant difference from placebo for the occurrence of Akathisia at dosages of olanzapine of 10 mg or more and for any extrapyramidal event at dosages of 15 mg or more.

(Other Side Effects, see insert)

5. Dosing:

Starting dosage: 5 or 10 mg in once per day dosing

Dosages of 5mg may decrease the risk for orthostatic hypotension

Efficacy at dosages of 10-15 mg/day

Available: 5mg, 7.5mg and 10 mg tablets

Special populations: Elderly, debilitated or patients who have a predisposition to hypotension should be started at 5 mg per day dosing.

D. Quetiapine(Seroquel(r))

1. Pharmacology:

Dibenzothiazepine class

An antagonist with affinity binding for 5HT1A/2, D1-2, alpha1-2, and H1 receptors. No affinity for the BZD or muscarinic receptors.

2. Pharmacokinetics:

Rapidly absorbed with peak concentrations within 1.5 hours. 100% bioavailable.

PB: 83% at therapeutic dosages

Vd: 10+ 4 L/kg

T1/2: 7 hours

Major Metabolic Pathway: CYP3A4

3. Indications: Same as traditional agents:

Management of Psychotic Disorders: quetiapine's main advantage over traditional agents is that the evidence for benefit in the treatment of negative symptoms of schizophrenia. The drug has not been systematically evaluated in trials longer than 6 weeks.

4. Most Common Side Effects:

Somnolence, constipation, weight gain, orthostasis, agitation, dry mouth, increased LFT's, dizziness.

5. Dosing:

Starting dosage: 525 mg bid

Increase dosage in increments of 25-50 mg bid or tid on the second or 3 day as tolerated.

Range: 150-750 mg/day

Available: 25mg, 100mg and 200 mg tablets

CASE

CC GH is a 25 y.o. WM admitted to the psychiatric unit. His chief complaint consists of the following: I'm captain Kirk's assistant on the star ship enterprise". The family reports the patient has been spending more time alone in his room watching Star Trek reruns. he often gets so excited when the cast on the show is in danger that he has broken several pieces of furniture in the house. He seems to be fighting someone.

PMH: The patient has two previous admissions to the psychiatric hospital-Diagnosis: Chronic undifferentiated schizophrenia. He was treated with haloperidol (HALDOL) 10 mg bid with a good response.

MSE: Gh appears his stated age. His hygiene and grooming are poor with disheveled clothing and a noticible body odor. His motor activity is increased and he seems distracted, and responding internal stimuli. Mood-Euthymic, Affect-blunted. Oriented x 0. The patient states that it is the star date 2370, that he is James T. Kirk's assistant, and that he is on the planet vulcan. He admits to auditory hallucinations stating that the crew is in danger and that he must save them. Reports the radio and TV talking to him, and is exibiting looseness of association.

FH: 4th of seven siblings, one other brother with schizophrenia

SH: Smokes 3 ppd since age 25, 2 six packs of beer every weekend, no drug of abuse reported including PCP, LSD, Marijuana, Amphetamine, or Cocaine.

Current admission:. On the second day of admission the patient was put in restraints for one hour after accusing the staff of being romulans (aliens), and throwing a chair down the hallway at one of the psychiatric assistants.

1. List the patient's target symptoms.(Positive and Negative)

+ Symptoms	- Symptoms
Paranoid Delusions	Poor hygiene and grooming
Graniosity	Blunted affect
Ideas of reference	Withdrawal
Hallucinations
Agitation with violence and increased motor activity
Looseness of Associations
Responding to internal stimuli

2. Please recommend an antipsychotic medication for this patient?(Include drug, dose, route, schedule)?

Haloperidol 10 mg, po, BID or Haloperidol 5mg, po, QID

3. If the symptoms of Auditory Hallucinations do not respond- when would you recommend changing the dose? (2pts)

Change dose q 7-10 days if agitation has reponded but patient is still hallucinating with no improvement in psychosis.

4. The patient experiences a dystonic reaction specifically Torticollis. Recommend a drug to treat this adverse reaction. Be specific, include the name, dosage, route of the medication you recommend. How would your treatment differ for a pseudoparkinsonian reaction?(2 pts)

Dystonic Reaction: Cogentin 1-2 mg, IM, stat

Pseudoparkinsonian: Cogentin 0.5 - 1 mg, po, BID

5. What other common side effects would you recommend monitoring for in this patient? (3pts)

Cardiovascular-Hypotension, Tachycardia

EPS-akathisia, pseudoparkinsonian reactions, dystonic reactions

Sedation

Anticholinergic effects

Tardive dyskinesia

FYI : A patient education example

How would you explain the purpose (cogentin) of he above medication to the patient?

Your doctor mentioned you had a muscle cramp. What happened? (the patient tells you that his head twisted to the side the that his tongue felt stiff). The muscle cramps you describe are a reaction to the medication which is a side effect. It is not an allergic reaction to the medicine and it is not a seizure, just a cramp. The type of muscle cramps that happen from haldol are cramps in the face, neck, tongue and sometimes in other parts of the body. They happen usually when first starting the medication, usually the first week, or after an increase in the dosage of the medication. Many people find them scary, especially if they don't know what is happening. Now that you know what they are, lets talk about treatment for them and how to prevent them from happening again.

Did the nurse give you medication for the muscle cramp? (the patient states he got an injection of cogentin and is taking 1mg twice a day now)

Cogentin treats the cramps and prevents them from happening again.

After you have been on cogentin for approximately 2-4 weeks your doctor may begin to taper the medication. By this time your body has a chance to get used to the medication and the muscle cramps should not happen again. After the doctor has decreased the cogentin and stopped it the only medication you may have to take is haldol. Cogentin has drying type side effects which are: ..dryness of the mouth, the skin, constipation, dry eyes, .straining when starting to urinate, and blurred vision. If any of these side effects occur-let your doctor know. There are wayswe can talk about to help decrease these side effects without having to stop the medication.

If you go off of your medication and another doctor trys to start medication, be sure to tell him/her about these muscle cramps so they know you have had one before.

What questions do you have?

Just to make sure I didn't leave anything out--please tell me what you learned about cogentin and muscle cramps from haloperidol.

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