BREAKING BARRIERS AND IMPROVING

OUTCOMES IN SCHIZOPHRENIA A PHARMACIST’S EXPERIENCE

LAURA KHO SUI SAN

MPharm, BCPP

MasterChef US Season 3

Joshua Marks vs. Christine Ha

APRIL 2012

Masterchef US finale.

Lost to Christine Ha

SEPTEMBER 2012

Suffers PANIC ATTACK. First sign that something is wrong

JANUARY 2013 1st admission. Diagnosed with

BIPOLAR DISORDER with episodes of psychosis

JULY 2013 2nd admission. Diagnosed with

PARANOID SCHIZOPHRENIA

OCTOBER 2013 KILLED HIMSELF with a gunshot to the head

TIMELINE OF EVENTS

Joshua Marks

1987 - 2013

Homeless vagrant?

Drug addict?

Crazy man talking to himself in public?

John Nash 1928 - 2015

Mathematician Nobel Prize winner

Princeton University Paranoid Schizophrenia

Elyn Saks Professor of Law, Psychology, and Psychiatry Author, Speaker, Mental Health Advocate

Chronic Schizophrenia

OUTLINE

OUTLINE Schizophrenia : Disease and Prevalence Treatment Goals Pharmacological Treatment of Schizophrenia : Choice of Antipsychotics Side Effects of Antipsychotics

Tips for Non-Psychiatric Pharmacists

WHAT IS

SCHIZOPHRENIA?

Brain disorder

Interferes with a person's ability to : • Think clearly

• Manage emotions • Make decisions

• Relate to others

SCHIZOPHRENIA

WHAT ARE THE SYMPTOMS OF

SCHIZOPHRENIA?

SYMPTOMS

SCHIZOPHRENIA

NEGATIVE

AFFECTIVE

POSITIVE

COGNITIVE

POSITIVE

HALLUCINATIONS

DELUSIONS

DISORGANIZED thoughts

PARANOIA

NEGATIVE

BLUNTED affect

LOSS of interest, energy & emotions

Reduced SPEECH

Social WITHDRAWAL

COGNITIVE

Problems with :

MEMORY

ATTENTION

PLANNING

DECISION MAKING

AFFECTIVE

MOOD

ANXIETY

DEPRESSION

SUICIDALITY

Diagnosis of Schizophrenia

• DELUSIONS

• HALLUCINATIONS

• DISORGANIZED speech

• DISORGANIZED behavior

• NEGATIVE symptoms

• At least 2 symptoms persistent for 6 months • Delusion, hallucinations or disorganized speech must be present * DSM-V , American Psychiatric Association

WHAT IS THE PREVALENCE OF

SCHIZOPHRENIA?

1 in every 100 people will suffer from schizophrenia during their lifetime

15 – 25 25 - 35

AGE OF ONSET

TREATMENT GOALS

22

TREATMENT GOALS

SHORT-TERM LONG-TERM

Treat ACUTE symptoms

Functional Improvement

Prevent RELAPSE

Tolerability

QUALITY OF LIFE

Health & Wellness

Social Integration

Employment

COURSE OF ILLNESS IN SCHIZOPHRENIA After the first episode in schizophrenia , there is progressive

deterioration, loss in brain tissue, and treatment resistance with repetitive RELAPSES

Source : Black DW et al. Introductory Textbook of Psychiatry, 2001: 204-228

COURSE OF ILLNESS IN SCHIZOPHRENIA After the first episode in schizophrenia , there is progressive deterioration, loss in

brain tissue, and treatment resistance with repetitive RELAPSES

Source : Nasrallah HA, Smeltzer DJ. Contemporary diagnosis and management of the patient with schizophrenia. 2nd ed. Newton, PA: Handbooks in Health Care Co; 2011

Thompson et. al; PNAS (USA) 2001;98:11650–11655

25

Schizophrenia Brain vs Normal Adolescent

PROGRESSIVE GRAY MATTER LOSS IN EARLY

AND LATE SCHIZOPHRENIA

Thompson et. al; PNAS (USA) 2001;98:11650–11655

26

PHARMACOLOGICAL MANAGEMENT OF

SCHIZOPHRENIA

DOPAMINE HYPOTHESIS DOPAMINE SYSTEM PATHWAYS & CLINICAL FUNCTION

• SYMPTOM-driven treatment NOT cure

• MAINSTAY of treatment

• 2 classes : Typical Antipsychotics & Atypical Antipsychotics

• SIGNIFICANT SIDE EFFECTS

ANTIPSYCHOTICS

SYMPTOMS

SCHIZOPHRENIA

NEGATIVE

AFFECTIVE

POSITIVE

COGNITIVE

ANTIPSYCHOTICS • Effectively treat POSITIVE symptoms

• Not fully effective for NEGATIVE, COGNITIVE or MOOD symptoms

ANTIPSYCHOTICS

TYPICAL

ATYPICAL

ORAL

ORAL

LONG-ACTING DEPO INJECTIONS

(LAI)

LONG-ACTING DEPO INJECTIONS

(LAI)

• First-generation antipsychotics

• 1951: Chlorpromazine was the first agent

• Other examples : Haloperidol, Fluphenzaine, Flupenthixol

• Block D2 receptors → target POSITIVE symptoms

• SIDE EFFECT PROFILE : Higher risk of EPS

TYPICAL ANTIPSYCHOTICS

• Second-generation antipsychotics

• 1980’s : Risperidone first widely used atypical agent

• Other examples : Aripriprazole, Clozapine, Olanzapine, Quetiapine, Paliperidone

• Block D2, 5-HT, M and H receptors → target POSITIVE, NEGATIVE, COGNITIVE & AFFECTIVE symptoms

• SIDE EFFECT PROFILE : Minimal risk of EPS, Higher risk of other side effects

ATYPICAL ANTIPSYCHOTICS

Receptor Systems Affected by ATYPICAL Antipsychotics

Aripiprazole D2, 5-HT2A, 5-HT1A, 1, 2, H1

Asenapine D2, 5-HT2A, 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B,

5-HT2C, 5-HT5A, 5-HT6, 5-HT7, D1, D2, D3, D4, 1, 2A, 2B, 2C, H1, H2

Clozapine D2, 5-HT2A, 5-HT1A, 5-HT2C, 5-HT3, 5-HT6, 5-HT7, D1, D3, D4, 1, 2, M1, H1

Olanzapine D2, 5-HT2A, 5-HT2C, 5-HT3, 5-HT6, D1, D3, D4, D5, 1, M1-5, H1

Quetiapine D2, 5-HT2A, 5-HT6, 5-HT7, 1, 2, H1

Risperidone D2, 5-HT2A, 5-HT7, 1, 2

Sertindole D2, 5-HT2A, 5-HT2C, 5-HT6, 5-HT7, D3, 1

Ziprasidone D2, 5-HT2A, 5-HT1A, 5-HT1D, 5-HT2C, 5-HT7, D3, 1, NRI, SRI

LONG-ACTING DEPO INJECTIONS (LAI)

Typical :

• Fluphenzaine (Modecate®)

• Flupenthixol (Fluanxol®)

Atypical :

• Risperidone (Risperdal® Consta)

• Paliperidone (Invega Sustenna®)

Usually given every 2 – 4 weeks

LONG-ACTING DEPO INJECTIONS (LAI)

DRUG NAME (Trade Name)

VEHICLE Usual MAINTAINENCE dosing interval (weeks)

Fluphenazine decanoate (Modecate)

Sesame oil 4-6

Flupenthixol decanoate (Fluanxol)

Coconut oil 2-4

Haloperidol decanoate (Haldol)

Sesame oil 4

Zuclopenthixol decanoate (Clopixol)

Coconut oil 2-4

Risperidone LAI (Risperdal Consta)

Aqueous suspension

2

Paliperidone palmitate (Invega Sustenna)

Aqueous suspension

4

LONG-ACTING DEPO INJECTIONS (LAI)

ADVANTAGES

• Improve ADHERENCE

• No first-pass metabolism

• Improved pharmacokinetic

profile

• Less stigmatizing than oral

medication

LONG-ACTING DEPO INJECTIONS (LAI)

DISADVANTAGES

• COST

• PAIN at injection site

• Patient & Caregiver

acceptance

• Harder to reverse side

effects

SELECTION OF ANTIPSYCHOTICS

EFFICACY ? • First-line :usually ATYPICAL AGENT

• Current evidence :

ALL antipsychotics are similarly effectively EXCEPT CLOZAPINE (the best!)

Choice of

Antipsychotic

• Side effects • Patient preference • Cost

The Schizophrenia Commission (2012)

SELECTION OF ANTIPSYCHOTICS

• Optimum STABILITY

• Minimum Medication

• Minimum SIDE EFFECTS

Choice of Antipsychotic

• Side effects • Patient preference • Cost

SIDE EFFECTS OF ANTIPSYCHOTICS

COMMON SIDE EFFECTS SYSTEMIC/METABOLIC

• Metabolic syndrome

• Hypersalivation

• AntiCHOLINERGIC side effects

• Cardiovascular

• Agranulocytosis

CNS

• ExtraPyramidal

Symptoms(EPS) • Hyperprolactinaemia

• SLEEP disturbances

• SEIZURES • Sexual dysfunction

• Acute dystonia • Pseudoparkinsonism • Akathisia • Tardive dyskinesia (TD)

EXTRAPYRAMIDAL SYMPTOMS (EPS)

Blockade of this pathway causes EPS

3 situations : DOSE-RELATED Start new antipsychotic

(Rapidly)Increase dose of antipsychotic

Acute DYSTONIA

“Sudden, involuntary muscle contractions or spasms.”

Uprolling eyeballs Head and neck twisted to one side.

More common in :

Young males

New patients

Those treated with TYPICAL antipychotics

Acute DYSTONIA

Acute DYSTONIA

HOW TO MANAGE : IM or Oral anticholinergic drugs (eg. Benzhexol, diphenhydramine)

Start low, go slow

Pseudoparkinsonism

“Adverse effect of drug that causes symptoms

resembling parkinsonism.”

Reversible

Can be mistaken for negative symptoms of schizophrenia.

Management of

Pseudoparkinsonism

REDUCE dose

SWITCH to another

antipsychotic

Oral anticholinergic (eg. benzhexol)

AKATHISIA

“A feeling of

INNER RESTLESSNESS”

Cannot sit still Foot stamping

when seated

Constantly pacing up and down

Rocking from foot to

foot

Management of AKATHISIA

REDUCE dose SWITCH to another

antipsychotic

Low-dose beta-blocker. eg

propranolol 20-80 mg/day

Benzodiazepines

Tardive Dyskinesia (TD)

“Repetitive, involuntary, purposeless movements.”

“Worsen under stress.”

Grimacing Tongue

protrusion Lip smacking Excessive eye

blinking Choreiform hand

movements (e.g. pill rolling)

Can lead to difficulty breathing, eating or speaking!

More common in : Elderly females Prior history of acute EPS earlier in treatment

Tardive Dyskinesia (TD)

The result of PROLONGED use or HIGH-DOSE

antipsychotics

Management of Tardive Dyskinesia (TD)

REDUCE to lowest

possible dose

SWITCH to another

antipsychotic (e.g. clozapine)

Tab. BENZHEXOL can WORSEN TD!

Blockade of this pathway causes

↑ prolactin

Hyperprolactinaemia

Serum prolactin ˃ 25mcg/L (10-25 mcg/L)

Not always symptomatic

Gynecomastia Galactorrhea Menstrual abnormalities Sexual dysfunction

Hyperprolactinaemia

Potent D2 blockers: Haloperidol Risperidone Paliperidone Amisulpiride

REDUCE dose SWITCH drug AUGMENT with aripiprazole

METABOLIC

METABOLIC

Insulin RESISTANCE ↑ blood sugar

Weight GAIN ˃5% Of initial weight

DYSLIPIDEMIA ↑ cholesterol, LDL and mostly TGs

METABOLIC

Common in ATYPICAL ANTIPSYCHOTICS

CLOZAPINE

OLANZAPINE

QUETIAPINE

MANAGEMENT

Monitor, monitor, monitor…….

Lifestyle modifications

If weight gain >5% of initial weight, suggest switching to another weight-neutral AP. e.g. Aripiprazole

Ref: American Diabetes Association. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004;27:596-601

MANAGEMENT Monitor, monitor, monitor…….

Source : American Diabetes Association. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004;27:596-601

Hypersalivation

• Antipsychotics

[CLOZAPINE ] • Drooling, especially at NIGHT • Usually at initiation • May be persistent

HYPERSALIVATION

How to Manage?

BENZHEXOL (Take before 7pm for

nighttime relief)

DAYTIME : CHEW sugarless gum to aid swallowing

OFF-LABEL USE: ATROPINE 1% eye drops

TIPS FOR NON-PSYCHIATRIC PHARMACISTS

1. HAVE EMPATHY

“Your son has

schizophrenia,” I told the

woman. “Oh, my God, anything but that,”

she replied. “Why couldn’t he

have leukaemia or some other

disease instead?”

“But if he had leukaemia he might

die,” I pointed out.

“Schizophrenia is a much

more treatable disease.”

“

” - E. Fuller Torrey, Surviving Schizophrenia: A Manual for Families, Patients, and Providers

2. ENGAGE

ENGAGE WITH

YOUR PATIENT

Establish trust

Build rapport

3. EMPOWER

EMPOWERING YOUR PATIENT

I. PATIENT EDUCATION

IA. STARTING Medication

• NOT Miracle drug

• Will take 2-4 weeks to start working

• Full effect may take longer

• Be patient

EMPOWERING YOUR PATIENT

I. PATIENT EDUCATION

IB. CONTINUING Medication

Emphasize, emphasize, emphasize

Continue medication even if you feel well

Goal : Prevent relapse

EMPOWERING YOUR PATIENT

II. SIDE EFFECTS Management

• Reassurance

• Caution about side effects

• Address side effects quickly & effectively

EMPOWERING YOUR PATIENT

III. FACILLITATE ADHERENCE

Simplify medication regime Work with patient’s daily routine Utilize memory aids

• Pillboxes are not for everyone • Link medication-taking to daily

activity eg meal times. (Remember Pavlov’s experiments)

EMPOWERING YOUR PATIENT

IV. LIFESTYLE Message

Set realistic and achievable goals : • Diet • Exercise • Smoking cessation

EMPATHIZE

ENGAGE

EMPOWER

THANK YOU!

REFERENCES • American Psychiatric Association. Diagnostic and Statistical Manual of

Mental Disorders (DSM-IV-TR). 4th ed. Washington, DC: American Psychiatric Press; 2000.

• American Diabetes Association. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004;27:596-601

• Black DW et al. Introductory Textbook of Psychiatry, 2001: 204-228

• The Schizophrenia Commission (2012) The abandoned illness: a report from the Schizophrenia Commission. London: Rethink Mental Illness.

• Nasrallah HA, Smeltzer DJ. Contemporary diagnosis and management of the patient with schizophrenia. 2nd ed. Newton, PA: Handbooks in Health Care Co; 2011