A concise version of pharmacotherapy pointers in Schizophrenia management based on the Malaysian Clinical Practice Guidelines

1. SCHIZOPHRENIA

2. A masterpiece of a movie
focusing on Schizophrenia

3.  Schizophrenia is a term used to describe a major psychiatric
disorder that alters an individual’s perception, thought, and
behaviour.
 Malaysia developed its National Mental Health Registry for
Schizophrenia in 2003.
 Incidence rate was 15.2 per 100,000;

4. RISK FACTORS
 Family h/o schizophrenia
 h/o obstetric complications
• Preeclampsia
• Extreme prematurity
• Hypoxia or ischemia during birth
• Cannabis abusers
 Individual living in higher level of urbanization
 Offspring of older fathers
 Unmarried mothers
 h/o childhood CNS infection
• (h/o or H/o = History of)

5. POSITIVE SYMPTOMS
Symptoms that appear to reflect the presence of mental features
which are not normally present
 Delusions, Hallucinations
 Disorganized speech/thinking (thought disorder or loosening of
associations)
 Grossly disorganised behaviour, Catatonic behaviours
 Other symptoms:
• Affected inappropriate to the situation or stimuli
• Unusual motor behaviour (e.g. pacing and rocking)
• Depersonalisation; Derealization

6. NEGATIVE SYMPTOMS
Symptoms that appear to reflect a diminution or loss of normal
emotional and psychological function; are less obvious but persist
even after resolution of positive symptoms;
 Affective flattening
• reduction in range and intensity of emotional expression (facial
expression, voice tone, eye contact, and body language);
 Alogia (poverty of speech)
• lessening of speech fluency and productivity, slowing or blocked
thoughts, often manifested as short, empty replies to questions;

7. Negative symptoms (contd’.)
 Avolition
• reduction, difficulty, or inability to initiate and persist in goal-directed
behaviour,
• Egs.: no longer interested in….
• going out and meeting with friends,
• activities that the person used to show enthusiasm for,
• anything (sitting in the house for many hours a day doing
nothing);

8. COGNITIVE SYMPTOMS
These refer to difficulties with concentration and memory.
 Disorganised and slow thinking
 Difficulty in understanding
 Poor concentration, poor memory
 Difficulty in expressing thoughts
 Difficulty integrating thoughts, feelings and behaviour

10. The phases of schizophrenia management
 Prodromal phase
 Acute phase – (Positive symptoms emerge; can be treated; but
negative symptoms persist);
 Relapse prevention
 Stable phase
 Poor response to treatment

11. SCHIZOPHRENIA MANAGEMENT
Should be comprehensive;
Includes individually-tailored medication regimen,
appropriate psychosocial and service level interventions;

12. Anti Psychotics available in Malaysia
Either in oral, intramuscular (IM) or long-acting depot IM
preparations;
Conventional APs
• Haloperidol; Trifluoperazine; Chlorpromazine; Fluphenazine;
Perphenazine; Zuclopenthixol; Sulpiride; Flupenthixol;
Atypical APs (AAPs)
• Clozapine; Ziprasidone; Risperidone; Aripiprazole; Olanzapine;
Paliperidone; Quetiapine; Amisulpride;

13. TREATMENT OF ACUTE PHASE OF SCHIZOPHRENIA
 APs
 Are the primary medications for treatment in schizophrenia;
 300 – 1000 mg chlorpromazine (CPZ) equivalents daily
(recommended optimal oral dose);
 All APs are different in their efficacy and side effects profile.
 Choice of APs depends on differences in side-effect profiles;
 APs should be used for at least 6 - 8 weeks with adequate
dosage before switching to other APs.
 Reasons to switch include lack of clinical response, intolerability
and drug interactions.
 The EPS produced by conventional APs are mostly dose-
dependent.

14. APs (contd’.)
 APs should be used at least 1-2 years for the first episode and for a
longer duration in those with chronic schizophrenia.
 If AP is to be withdrawn, it should be done gradually whilst
symptoms of potential relapse are monitored for at least two more
years.

15. AAPs
 Recommended to use lower end dose ranges;
 Are generally a/w lower risk of EPS than conventional APs such
as haloperidol;
 Have a different side effects profile (cause Metabolic Syndrome
- weight gain, dyslipidaemia and glucose intolerance);
In relapse prevention, standard doses (equivalent to 200 – 500
mg CPZ) should be used.

16. Malaysian CPG Recommendations (APs vs AAPs)
Choice of APs should be based on the agreement between
patients and clinician taking into account the relative benefits of
the drugs and their side-effect profile.
Patients who respond well to conventional APs without side
effects should not be changed to AAPs.
Oral AAPs (amisulpride or olanzapine) should be considered as
treatment options.
When there is a need to change APs due to EPS or lack of
efficacy, switching to AAPs provide no advantage in terms of
quality of life or cost.
Patients on AAPs should be monitored closely for emergence of
metabolic syndrome.

17. Malaysian CPG Recommendations (Neg. Symptoms)
APs + antidepressants combo can be used in treatment of
persistent negative symptoms.
Olanzapine, quetiapine and risperidone are superior to
conventional APs in the treatment of persistent negative
symptoms.
All APs are equally effective in treatment of persistent
cognitive symptoms.
Clozapine is superior in the treatment of persistent
aggression.
Clozapine is indicated in the treatment of persistent suicidal
thoughts or behaviours.

18. Malaysian CPG Recommendations
(Violent Behaviour)
According to NICE, violent behaviour can be managed
without the prescription of unusually high doses of APs.
Violent behaviour can be adequately controlled with
standard doses of APs using minimum effective dose.
Oral medication should be offered before parenteral
medication.
 The IM route is the preferred choice when parenteral
treatment is indicated.
( NICE = National Institute for Clinical Excellence)

19. Malaysian CPG (Rapid tranquilization)
 The p’cological management of acute behavioural disturbances in
schizophrenia (agitation, aggression and potentially violent
behaviour).
 Aim: to achieve sedation in order to minimize the risk of harm to
the patients and others;
 When using parenteral preparation for rapid tranquilization,
emergency resuscitation equipments and drugs should be readily
available.
 Closely monitor vital signs (BP, PR, RR, and temp.).
 While the patient is being restrained and sedated, take
precautions to avoid over-sedation and failure to detect an
underlying medical condition.

20. Rapid Tranquilization (contd’.)
 Medications used in rapid tranquilisation include oral and
parenteral preparations.
 If patient fails to take oral medication, parenteral preparations may
prove to be mandatory.
 The use of IM chlorpromazine is a/w hypotension and
cardiotoxicity, and therefore not recommended.
 IM haloperidol + IM lorazepam combo may produce a faster
response than IM haloperidol monotherapy.

21. Malaysian CPG Recommendation
(Schizophrenia relapse)
Relapse: hospitalization for psychopathology or a 20% increase
in PANSS score, increased level of care; self-injury, suicide or
homicidal ideation or violent behaviour; or a Clinical Global
Impression (CGI) rating > 6.
APs are the mainstay of treatment for relapse prevention.
There is no difference in efficacy in relapse prevention amongst
all APs.
Depot preparations may be considered when treatment
adherence issue arises.

22. Schizophrenia relapse (contd’.)
 APs treatment should be part of an overall management plan that
includes psychosocial and service level intervention.
 Monotherapy should be used wherever possible.
 Conventional APs should not be combined with AAPs except
during the short switching period.

23. DEPOT ANTIPSYCHOTIC TREATMENT
 Depot APs refer to long-acting injectable preparations of APs
which are used in the long-term pharmacological treatment of
schizophrenia.
 Depot APs available in Malaysia:
• Fluphenazine decanoate
• Zuclopenthixol decanoate
• Flupenthixol decanoate
• Risperidone

25. Positive and Negative Syndrome Scale (PANSS)
 Medical scale used to measure severity of symptoms in
schizophrenic patients;
 Created in 1987 by Stanley Kay et al.
 Interviewer administered test; takes around 40-45 mins. to
complete;
 Rating is from 1 to 7 on 30 different symptoms;
 3 domains:
• Positive scale (7 symptoms);
• Negative scale (7 symptoms);
• General Psychopathology scale ( 16 symptoms);
 Score range: 30 – 210

26. Positive and Negative Syndrome Scale (PANSS)
 PANSS items are rated on a 7-point scale.
 (1 = absent, 2 = minimal, 3 = mild, 4 = moderate,
5 = moderate severe, 6=severe, and 7=extreme);
 Since the absence of symptoms is equal to 1 point, the lowest
possible total score on both PANSS scales ( Positive and
Negative) is 7.

27. Clinical Global Impression (CGI)
 Is a 3-item observer-rated scale that measures…
• Illness severity (CGIS),
• Global improvement or change (CGIC), and
• Therapeutic response.
 Illness severity and improvement sections are used more
frequently than the therapeutic response section in both clinical
and research settings.
 Rated on a 7-point scale;
 CGIS: 1 (normal) to 7 (amongst the most severely ill patients);
 CGI-C: 1 (very much improved) to 7 (very much worse);

28. CGI (contd’.)
 Treatment response:
• take account of both therapeutic efficacy and treatment-related
adverse events;
• range from 0 (marked improvement and no side-effects) and 4
(unchanged or worse and side-effects outweigh the therapeutic
effects).

31. THE END

32. REFERENCE:
Malaysian Clinical Practice Guidelines –
Management of Schizophrenia 2018 – 2nd edition