1. BREAKING BARRIERS AND IMPROVING
OUTCOMES IN SCHIZOPHRENIA
A PHARMACIST’S EXPERIENCE
LAURA KHO SUI SAN
MPharm, BCPP

2. MasterChef US Season 3
Joshua Marks vs. Christine Ha

3. 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

4. Joshua Marks
1987 - 2013

5. Homeless vagrant?
Drug addict?
Crazy man talking to himself in public?

6. John Nash
1928 - 2015
Mathematician
Nobel Prize winner
Princeton University
Paranoid Schizophrenia

7. Elyn Saks
Professor of Law, Psychology, and Psychiatry
Author, Speaker, Mental Health Advocate
Chronic Schizophrenia

8. OUTLINE

9. OUTLINE
Schizophrenia : Disease and Prevalence
Treatment Goals
Pharmacological Treatment of
Schizophrenia : Choice of Antipsychotics
Side Effects of Antipsychotics
Tips for Non-Psychiatric Pharmacists

10. WHAT IS
SCHIZOPHRENIA?

11.  Brain disorder
 Interferes with a
person's ability to :
• Think clearly
• Manage emotions
• Make decisions
• Relate to others
SCHIZOPHRENIA

12. WHAT ARE THE SYMPTOMS OF
SCHIZOPHRENIA?

13. SYMPTOMS
SCHIZOPHRENIA
NEGATIVE
AFFECTIVE
POSITIVE
COGNITIVE

14. POSITIVE
HALLUCINATIONS
DELUSIONS
DISORGANIZED
thoughts
PARANOIA

15. NEGATIVE
BLUNTED affect
LOSS of interest,
energy & emotions
Reduced SPEECH
Social
WITHDRAWAL

16. COGNITIVE
Problems with :
MEMORY
ATTENTION
PLANNING
DECISION
MAKING

17. AFFECTIVE
MOOD
ANXIETY
DEPRESSION
SUICIDALITY

18. 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

19. WHAT IS THE PREVALENCE OF
SCHIZOPHRENIA?

20. 1 in every 100 people will suffer from
schizophrenia during their lifetime
15 – 25 25 - 35
AGE OF ONSET

21. TREATMENT GOALS

22. 22
TREATMENT GOALS
SHORT-TERM LONG-TERM
Treat ACUTE
symptoms
Functional
Improvement
Prevent
RELAPSE
Tolerability
QUALITY OF
LIFE
Health &
Wellness
Social
Integration
Employment

23. 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

24. 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

25. Thompson et. al; PNAS (USA) 2001;98:11650–11655
25
Schizophrenia Brain vs Normal Adolescent

26. PROGRESSIVE GRAY MATTER LOSS IN EARLY
AND LATE SCHIZOPHRENIA
Thompson et. al; PNAS (USA) 2001;98:11650–11655
26

27. PHARMACOLOGICAL MANAGEMENT OF
SCHIZOPHRENIA

28. DOPAMINE HYPOTHESIS
DOPAMINE SYSTEM PATHWAYS & CLINICAL FUNCTION

29. • SYMPTOM-driven treatment NOT cure
• MAINSTAY of treatment
• 2 classes : Typical Antipsychotics & Atypical
Antipsychotics
• SIGNIFICANT SIDE EFFECTS
ANTIPSYCHOTICS

30. SYMPTOMS
SCHIZOPHRENIA
NEGATIVE
AFFECTIVE
POSITIVE
COGNITIVE
ANTIPSYCHOTICS
• Effectively treat
POSITIVE
symptoms
• Not fully effective
for NEGATIVE,
COGNITIVE or
MOOD symptoms

31. ANTIPSYCHOTICS
TYPICAL
ATYPICAL
ORAL
ORAL
LONG-ACTING
DEPO INJECTIONS
(LAI)
LONG-ACTING
DEPO INJECTIONS
(LAI)

32. • 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

33. • 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

34. 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

35. LONG-ACTING DEPO INJECTIONS (LAI)
 Typical :
• Fluphenzaine (Modecate®)
• Flupenthixol (Fluanxol®)
 Atypical :
• Risperidone (Risperdal®
Consta)
• Paliperidone (Invega
Sustenna®)
 Usually given every 2 – 4
weeks

36. 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 Aqueous 4

37. LONG-ACTING DEPO INJECTIONS (LAI)
ADVANTAGES
• Improve ADHERENCE
• No first-pass metabolism
• Improved pharmacokinetic
profile
• Less stigmatizing than oral
medication

38. LONG-ACTING DEPO INJECTIONS (LAI)
DISADVANTAGES
• COST
• PAIN at injection site
• Patient & Caregiver
acceptance
• Harder to reverse side
effects

39. 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

40. The Schizophrenia Commission (2012)

41. SELECTION OF ANTIPSYCHOTICS
• Optimum STABILITY
• Minimum Medication
• Minimum SIDE EFFECTS
Choice of
Antipsychotic
• Side effects
• Patient preference
• Cost

42. SIDE EFFECTS
OF ANTIPSYCHOTICS

43. COMMON SIDE EFFECTS
SYSTEMIC/METABOLIC
• Metabolic syndrome
• Hypersalivation
• AntiCHOLINERGIC side
effects
• Cardiovascular
• Agranulocytosis
CNS
• ExtraPyramidal
Symptoms(EPS)
• Hyperprolactinaemia
• SLEEP disturbances
• SEIZURES
• Sexual
dysfunction

44. • Acute dystonia
• Pseudoparkinsonism
• Akathisia
• Tardive dyskinesia (TD)
EXTRAPYRAMIDAL SYMPTOMS (EPS)

45. Blockade of
this pathway
causes EPS

46. 3 situations : DOSE-RELATED
Start new antipsychotic
(Rapidly)Increase dose of
antipsychotic

47. Acute DYSTONIA
“Sudden, involuntary muscle
contractions or spasms.”
Uprolling eyeballsHead and neck
twisted to one side.

48. More common in :
 Young males
 New patients
 Those treated with
TYPICAL
antipychotics
Acute DYSTONIA

49. Acute DYSTONIA
HOW TO MANAGE :
 IM or Oral anticholinergic
drugs (eg. Benzhexol,
diphenhydramine)
 Start low, go slow

50. Pseudoparkinsonism
“Adverse effect of drug
that causes symptoms
resembling parkinsonism.”
Reversible
Can be mistaken for
negative symptoms of
schizophrenia.

52. Management of
Pseudoparkinsonism
 REDUCE dose
 SWITCH to another
antipsychotic
 Oral anticholinergic
(eg. benzhexol)

53. AKATHISIA
“A feeling of
INNER RESTLESSNESS”
 Cannot sit still
 Foot stamping
when seated
 Constantly pacing
up and down
 Rocking from foot to
foot

54. Management of AKATHISIA
 REDUCE dose
 SWITCH to another
antipsychotic
 Low-dose beta-
blocker. eg
propranolol 20-80
mg/day
 Benzodiazepines

55. Tardive Dyskinesia (TD)
“Repetitive,
involuntary,
purposeless
movements.”
“Worsen under stress.”

56.  Grimacing
 Tongue
protrusion
 Lip smacking
 Excessive eye
blinking
 Choreiform hand
movements (e.g.
pill rolling)
Can lead to difficulty breathing,
eating or speaking!

57. 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

58. Management of Tardive Dyskinesia
(TD)
 REDUCE to lowest
possible dose
 SWITCH to another
antipsychotic (e.g.
clozapine)
Tab. BENZHEXOL
can WORSEN TD!

59. Blockade of this
pathway causes
↑ prolactin

60. Hyperprolactinaemia
Serum prolactin ˃ 25mcg/L
(10-25 mcg/L)
Not always symptomatic
 Gynecomastia
 Galactorrhea
 Menstrual abnormalities
 Sexual dysfunction

61. Hyperprolactinaemia
Potent D2 blockers:
Haloperidol
Risperidone
Paliperidone
Amisulpiride
REDUCE dose
SWITCH drug
AUGMENT with aripiprazole

62. METABOLIC

63. METABOLIC
Insulin RESISTANCE
↑ blood sugar
Weight GAIN ˃5%
Of initial weight
DYSLIPIDEMIA
↑ cholesterol, LDL
and mostly TGs

64. METABOLIC
Common in ATYPICAL ANTIPSYCHOTICS
CLOZAPINE
OLANZAPINE
QUETIAPINE

65. MANAGEMENT
Monitor, monitor, monitor…….
Lifestyle modifications
If weight gain >5% of initial weight,
suggest switching to another
weight-neutral AP. e.g. Aripiprazole

66. 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

67. Hypersalivation
• Antipsychotics
[CLOZAPINE ]
• Drooling, especially at
NIGHT
• Usually at initiation
• May be persistent

68. 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

69. TIPS FOR NON-PSYCHIATRIC
PHARMACISTS

70. 1. HAVE EMPATHY

71. “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

72. 2. ENGAGE

73. ENGAGEWITH
YOUR PATIENT
Establish trust
Build rapport

74. 3. EMPOWER

75. EMPOWERINGYOUR 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

76. EMPOWERINGYOUR PATIENT
I. PATIENT EDUCATION
IB. CONTINUING Medication
 Emphasize, emphasize, emphasize
 Continue medication even if you feel
well
 Goal : Prevent relapse

77. EMPOWERINGYOUR PATIENT
II. SIDE EFFECTS Management
• Reassurance
• Caution about side effects
• Address side effects quickly &
effectively

78. EMPOWERINGYOUR 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)

79. EMPOWERINGYOUR PATIENT
IV. LIFESTYLE Message
 Set realistic and achievable goals :
• Diet
• Exercise
• Smoking cessation

80. EMPATHIZE
ENGAGE
EMPOWER

81. THANKYOU!

82. 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