schizophrenia

Lecture learning outcomes

• Describe signs and symptoms of Schizophrenia
• Discuss Pathophysiology, epidemiology, and the course of
the illness
• Describe the diagnostic criteria
• Recognize Goals of treatment
• Describe and understand the Modalities of treatment for
patients with schizophrenia
• Know drugs used in the treatment of schizophrenia with
regards to MOA, adverse effects, drug interactions,
monitoring parameters, initial doses and target doses……
• Recommend a therapeutic plan for schizophrenic patients
 Meet the patient
• John P is a 25-year-old male with the diagnosis of
schizophrenia. He was born on winter season,
and was a healthy child, but his parents report
that he was a bedwetter and seemed slower to
develop than his brothers and sisters. A maternal
uncle has also been diagnosed with
schizophrenia.
• John had 2 brief hospitalizations in his late teens
that were precipitated by anger at his boss,
depression and voices discussing in his head.
 Meet the patient
• John smokes marijuana and tobacco frequently to
calm himself; he also drinks vodka.
• John's parents support him financially. His
brothers and sisters are angry and frightened of
him. They are particularly upset by his lack of
interest in the outside world, self care neglect,
poverty of speech , emotional blunt and social
withdrawal.
• John has working difficulties.
 Definitions
• Psychosis :
Variety of severe mental disorders
With marked dissociation of thoughts, affect
and behavior
 Definitions CONT’d
• Schizophrenia:
 It is a psychiatric diagnosis
 Mental disorder
Episodic rather than continuous psychotic
symptoms
Abnormalities in the perception or expression
of reality.
 Epidemiology
• 0.5% of the population
• Male = female
• Onset: Late teen – early adulthood
 Etiologies
• Genetic basis

• Prenatal causes:
Prenatal developmental damage
• Environmental:
 Winter birth
 Cannabis use
 Pathophysiology
• Anatomical abnormalities of the brain:
enlargement of the ventricles
decreased brain volume in medial temporal areas.
• Neurochemical theories:
Dopamine activity hypothesis
 Hypoactivity in the mesocortical system 
negative symptoms
 hyper activity in the mesolimbic system 
positive symptom
Involvement of glutamate and 5-HT
 Clinical presentation
• Positive symptoms= psychotic symptoms:
hallucinations, which are usually auditory;
delusions;
disorganized thoughts and behavior.
 Clinical presentation
• Negative symptoms:
decrease in emotional range,
 poverty of speech,
loss of interests
and loss of drive.
 Clinical presentation CONT’d
• Cognitive symptoms:
deficits in working memory
deficits in attention
deficits in executive functions (the ability to
organize and abstract).
 Clinical presentation CONT’d
• Mood symptoms:
Cheerful or Sad
They often are depressed.
 Diagnosis
• Rule out general medical condition or use of a
substance.
• Use DSM-V-TR
• Presence of impairment of social
/occupational functioning
 DSM-V-TR criteria
• 2 of the following symptoms: delusions,
hallucinations, disorganized speech,
disorganized or catatonic behavior, or negative
symptoms.
OR
• 1 symptom if the delusions are bizarre or if
auditory hallucinations
AND
• For a duration of at least 1 month
 Course of the illness
• Most of the deterioration occurs in the first 5-
10 years of the illness
• Is usually followed by decades of relative
stability,
• A return to baseline is unusual.
• Symptoms remit somewhat in older patients.
• Positive symptoms remit >> cognitive and
negative symptoms.
 Complications
• Premature mortality:
Suicide
Self harm
Cardiovascular complications

• Substance misuse

• Social disability
 Back to the case
• Is the clinical presentation of John suggestive
of schizophrenia?
• What are the predisposing factors in John’s
case?
 Managing the patient
• John sees a psychiatrist for 15 minutes every 2
months but sometimes misses his
appointment. He has a social worker whom he
sees often. He found the hospital stays
unhelpful. He was treated with haloperidol,
which gave him muscle cramps; he was then
treated with olanzapine and gained 10 kg and
developed diabetes mellitus.
 The questions
• Is John’s Condition Appropriately Managed?
• What is Haloperidol? Is muscle cramps a side
effect of this drug?
• What is olanzapine? Is DM a Side effect of
olanzapine?
• How shifting from one drug to the other
should be done?
 Management Arms

Non
Pharmacological Pharmacological
Non Pharmacological Management
Psychotherapy
Social support
ECT
 Pharmacological Management
• Corner stone
• Use of antipsychotic drugs
 Evidence Based Medicine
part one : efficacy
• Antipsychotic drugs are equally effective in controlling
positive symptoms exception Clozapine >>>
• SGA are more effective in improving negative
schizophrenic symptoms
• Selection is based on patient response history and
patient preference:
If first episode: SGA
If NOT use previously use Antipsychotic drugs
• Start low doses and gradual increase
• 4-6 weeks on the maximal dose:
Response
Partial – non response (see algorithm)
 EBM part Two : Safety
EPS +Hyperprolactenemia

FGA

Low potency
FGA
SGA
 EBM part Two : Safety
Weight gain
Clozapine
olanzapine

FGA
Other SGA
EBM part Two : Safety
Metabolic Changes

• Clozapine
• Olanzapine
• Quetiapine
 EBM part Two : Safety
Anticholinergic side effects and
sedation
Clozapine
Low potency FGA
Chlorpromazine

Other SGA
 Suggested pharmacotherapy algorithm for treatment of schizophrenia. Schizophrenia should be treated in the context of an interprofessional model that
addresses the psychosocial needs of the patient, necessary psychiatric pharmacotherapy, psychiatric co-occurring mental disorders, treatment adherence,
and any medical problems the patient may have. See the text for a description of the algorithm stages. (Data from references 26,27,28,29,30.)

Source: Schizophrenia, Pharmacotherapy: A Pathophysiologic Approach, 10e

Citation: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. Pharmacotherapy: A Pathophysiologic Approach, 10e; 2017 Available
at: https://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146064659 Accessed: April 12, 2017
Copyright © 2017 McGraw-Hill Education. All rights reserved
• 40% of the patients are poorly controlled=
antipsychotic –resistant patients: Augmentation
therapy can be considered in these patients
• After response is seen: continue treatment for at
least 6 months
• Chronic therapy is usually required
• Depot formulations are often used for
maintenance therapy for non compliant patients
 Back to the case
• The psychiatrist would like to switch him to
long-acting injectable antipsychotic treatment,
but John is afraid of injections and isn't sure
that he needs medication.
• How the shift should be achieved?
 Side effects
- Extrapyramidal motor disturbances
- Endocrine disturbances: hyperprolactemia
- Anticholinergic side effects
- Cognitive/memory impairment
- Hypotension, reflex tachycardia
- Cardiotoxicity
- Sedation
- Weight gain,
- Metabolic disturbances:
- Idiosyncratic and hypersensitivity reactions: jaundice,
leucopenia and agranulocytosis (Clozapine), urticarial
skin reactions AND neuroleptic malignant syndrome
Extrapyramidal motor disturbances
 Major problem of antipsychotic drug
treatment.
Two main types of disturbance occur:
– acute, reversible dystonias and Parkinson-like
symptoms
– slowly developing tardive dyskinesia, often
irreversible.
 Acute symptoms
• Pathophysiology the direct consequence of
block of nigrostriatal dopamine receptors.
• Acute symptoms:
Acute Dystonia

Akathesia

 Pseudoparkinsonism
 Tardive dyskinesia
• Tardive dyskinesia :
• Involuntary movements of face and limbs,
appearing after months or years of
antipsychotic treatment.
• Phathophysiology: It may be associated with
proliferation of dopamine receptors (possibly
presynaptic) in corpus striatum.
• Treatment is generally unsuccessful
 Trends in Prescribing of SGAs in
General Practice in England
450,000

400,000

350,000

300,000

250,000
Items

200,000

150,000

100,000

50,000

0
Jun-04

Sep-04

Dec-04

Mar-05

Jun-05

Sep-05

Dec-05

Mar-06

Jun-06

Sep-06

Dec-06

Mar-07

Jun-07

Sep-07

Dec-07

Mar-08

Jun-08

Sep-08

Dec-08

Mar-09

Jun-09
Quarter to

Quetiapine Amisulpride Risperidone Olanzapine Other SGAs

© Copyright NHSBSA 2009

• “Although none of us know to what
extent our perceptions of the world is
merely a construct of our own minds,
persons with schizophrenia are
confronted with this existential
dilemma throughout most of their
lives.”
Thank you