Schizophrenia is a mental disorder characterized by abnormalities in thinking, emotion, and behavior. The symptoms can be divided into positive (e.g. hallucinations), negative (e.g. social withdrawal), and cognitive symptoms. The phases include a prodromal phase with declining functioning, a psychotic phase with clear symptoms, and a residual phase with milder symptoms. Treatment involves antipsychotic medications and hospitalization may be needed for severe symptoms or risk of harm. Clozapine is effective for treatment-resistant schizophrenia.

1. SCHIZOPHRENIA
Schizophrenia is characterized by a
constellation of abnormalities in thinking,
emotion and behavior. There is no single
symptoms that is pathognomonic ,and there
is a heterogenous clinical presentation.

2. EPIDEMIOLOGY
ETIOLOGY
TYPES OF SCHIZOPHRENIA
SYMPTOMS OF SCHIZOPHRENIA
PHASES OF SCHIZOPHRENIA
HYPOTHESIS OF SCHIZOPHRENIA
COMPLICATION
MANAGEMENT

7. The symptoms of schizophrenia can be
divided into positive, negative and cognitive
symptoms.

8. PHASES OF SCHIZOPHRENIA
•Decline in functioning that precedes the first psychotic
episode. Patient started socially withdrawn and irritable.
Patient may have physical complaints, declining
school/work performances ,and/or newfound interest in the
religion or the occult
1) Prodromal phase :
•Perceptual disturbances ,delusion and disordered thought
process/content
2)Psychotic
•Occurs following an episode of active psychosis. It is marked
by mild hallucination or delusion, social withdrawn and
negative symptoms
3)Residual

12. OTHER DOPAMINE PATHWAY
AFFECTED BY ANTIPSYCHOTICS
• Tuberoinfundibular :blocked by antipsychotics,
will cause hyperprolactinaemia,which may lead
to gynacomastia,galactorrhea,sexual
dysfunction,menstrual irregularities
• Nigostriatal : blocked by antipsychotics,will cause
Parkinsonism/EPSE such as tremor,rigidity
,slurred speech,akathisia,dystonia and other
abnormal movement

16. DIAGNOSIS

17. MANAGEMENT

18. THE NEED FOR HOSPITAL
ADMISSION
• High risk of suicide or homicide.
• Other illness-related behaviour that endangers
relationships,reputation, or assets.
• Severe psychotic, depressive, or catatonic symptoms.
• Lack of capacity to cooperate with treatment.
• Lack or loss of appropriate psychosocial supports.
• Failure of outpatient treatment.
• Non-compliance with treatment plan (e.g. depot medication)
• Significant changes in medication for patient at high risk of
relapse (including clozapine ‘red’ result.
• Need to address comorbid conditions (e.g. inpatient detoxication,
physical problems, serious medication side-effects)

22. INITIAL
TREATMENT
OF ACUTE
PSYCHOSIS
Emergency treatment of behavioural disturbance
 • Attempts to defuse the situation should be
attempted, whenever possible.
 • Reassurance and the offer of voluntary
oral/intramuscular medication is often
successful.
 • The content of delusions and hallucinations is
of poor diagnostic value, but may better predict
violence/behavioural disturbance.
 • Act decisively and with sufficient support to
ensure restraint and forcible administration of
medication proceeds without unnecessary delay
or undue risk to the patient or staff.
 • Do not attempt to manage severe violence on
an open ward when secure facilities with
appropriately trained staff are available
elsewhere.

23.  Rapid tranquillisation is the pharmacological management of the acute
behavioural disturbances in schizophrenia i.e. agitation, aggression and
potentially violent behaviour.
 Oral medication should be offered before parenteral medication
 IM preparations that can be used for rapid tranquillisation are lorazepam,
midazolam, haloperidol, olanzapine, ziprasidone and zuclopenthixol acetate.
Wherever possible, a single agent is preferred
 When rapid tranquillisation is urgently needed, a combination of IM haloperidol
plus lorazepam or IM haloperidol plus promethazine should be considered.
 IV diazepam should be used for management of violent behaviour rather than IM
diazepam due to its erratic absorption
 The aim of rapid tranquillisation is to achieve sedation in order to minimise the
risk of harm to the patients and others.
 When using parenteral preparation for rapid tranquilisation, emergency
resuscitation equipments and drugs should be readily available. There should be
close monitoring of vital signs (blood pressure, pulse rate, respiratory rate and
temperature).
 While the patient is being restrained and sedated, precautions should be taken
to avoid over-sedation and failure to detect an underlying medical condition.

32. ANTIPSYCHOTIC SIDE-EFFECTS
• Sedation- Avoid chlorpromazine/promazine. Prescribe high-
potency antipsychotics (e.g. haloperidol) or non-sedating SGA
(risperidone, amisulpride).
• Weight gain- Avoid phenothiazines, olanzapine and
clozapine. Prescribe haloperidol, fluphenazine.
• EPSEs -Avoid high-dose FGAs. Prescribe SGA.
• Postural hypotension Avoid phenothiazines. Prescribe
haloperidol, amisulpride, trifl uoperazine.

33. COMORBID DEPRESSION
• Depression can affect up to 70% of patients
in the acute phase but tends to remit along
with the psychosis.
• In the maintenance phase, post- psychotic
or post-schizophrenic depression occurs in
up to 1/3 of patients and there is some
evidence that TCAs (e.g. imipramine) may
be effective.
• Surprisingly,despite it being common
clinical practice, there are few studies
supporting other interventions such as
SSRIs.

34. RELAPSE PREVENTION
• Preventing relapse is a key quality indicator in the
management of people with schizophrenia in Malaysia
• •AP is the mainstay of treatment for relapse prevention.
• Amongst all APs, there is no difference in efficacy in relapse
prevention.
• Depot preparations may be considered when treatment
adherence issue arises.
• 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.

35. 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 are:
1) fluphenazine decanoate (modecate ®) = 25 mg every 2-4 weeks
2) flupenthixol decanoate (fluanxol ®) = 40 mg every 2-4 weeks
3) zuclopenthixol decanoate (clopixol ®) = 200 mg every 2-4 weeks
4) risperidone (risperdal consta ®) = 25-50 mg every 2 weeks
•Depot preparations could ensure continuous drug delivery, overcome
bioavailability problems and avoid the risk of overdose with oral
medications
•side effects at site of injection e.g. pain, oedema, pruritus and
sometimes a palpable mass.

36. OUTPATIENT TREATMENT
AND FOLLOW-UP
Medical
- MSE at every appointment.
- Enquire about side-effects and attitude to medication.
- Record any recent life events or current stresses.
- Enquire about suicidal ideas and, if appropriate, homicidal ideas.
- When symptoms appear unresponsive to treatment, review the history and provide
additional investigations/interventions as appropriate (e.g.clozapine).
-Conduct appropriate investigations where complications of illness or its treatment
arise (e.g. LFTs, FBC, U&Es, glucose), or where monitoring is indicated
Psychological
-Above all, try to provide supportive and collaborative treatment wherever possible.
-Provide education about schizophrenia and its treatment.
-Do not dismiss concerns, even if apparently based on delusional content.
- Offer to meet family members or carers where appropriate.

37. TREATMENT RESISTANT
SCHIZOPHRENIA
• Treatment resistant schizophrenia (TRS) has been defined as
failure of improvement of the target symptoms (positive, negative
and/or cognitive) despite an adequate trial of medication for at
least 6–8 weeks with adequate dosing, of at least two groups of
APs.
• Patients with refractory symptoms generally have more severe
functional impairments and are more likely to have abnormalities
of cerebral structure and neuropsychology
• The changes in presynaptic dopamine transmission usually seen
in schizophrenia are absent in TRS, but changes occur in anterior
cingulate glutamate activity. It is therefore not surprising that
other antipsychotics, which all have their main effects on
dopamine receptors, fail to work in people with TRS.

38. Clozapine mainly blocks D1 and D4 receptors; its effects on
D2 receptors are relatively less than traditional FGAs.
 The lower affinity of clozapine for D2 receptors may
partially explain its lack of EPSEs and
hyperprolactinaemia.
The superior efficacy of clozapine in treating resistant
schizophrenic patients may be due to its additional
blockade of 5HT2 receptors.
Antipsychotic activity also may be due to an increased
turnover of GABA in the nucleus accumbens, which
inhibits dopaminergic neurons.

40. CLOZAPINE : STARTING AND STOPPING
This is best done as either an inpatient
A normal leukocyte (WBC > 3500/mm3 , neutrophils >
2000/mm3 ) count
Baseline ECG
FBCs must be repeated at
- weekly intervals for 18wks
- and then fortnightly until 1 year
- continue monthly indefinitely thereafter.
max dose should not
exceed 900 mg/day

41. CLOZAPINE : SIDE EFFECTS
• Anticholinergic :Constipation, dry mouth, blurred vision,
difficulty passing urine.
• Anti-adrenergic: Hypotension, sexual dysfunction.
• Other: Sedation, weight gain, nausea, vomiting, ECG changes,
headache, fatigue, hypersalivation, tachycardia, hypertension,
drowsiness, dizziness