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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