Current treatment approaches and alternative treatment approaches for Schizophrenia

1. Current Treatment Approaches for
Schizophrenia
Guide : Dr. Sanjiv Singh
Presenting by: Avtar Singh Gautam
PT/ 367
Department:- Pharmacology and Toxicology
National Institute of Pharmaceutical Education and Research,
Hajipur

2. The word schizophrenia derived from Greek word literally means “Split-Mind”
Schizophre
nia
Schiz
o
Split
Phren Mind
Split from reality
Introduction

3. Schizophrenia is a serious mental disorder that affects how a person thinks,
feels, and behaves.
People with schizophrenia may seem like they have lost touch with reality.
They may hear voices other people don’t hear. They may think other people
are trying to hurt them.
Sometimes they don’t make any sense when they talk.

4. When does schizophrenia start and who gets it?
Start between the
age of 16 to 30
Imaging studies have shown
that men have 16 percent
smaller inferior partial lobule
in their
brain as compared to women
1.4:1
1% of the population
is affected with
schizophrenia
Research on the effects
of estrogen shows that it
reduces the
effects of dopamine in
the central nervous
system. If men are given
estrogen, their
symptoms are
decreased, but this is
not an effective long-
term solution, because it
leads to feminization of
the men
(Mueser and McGurk,
2004).

5. Sign and
Symptoms
Positive Negative Cognitive
Behaviour changes that are
added by disorder and which
are not found in healthy
person
Ability that are lacking or
missing in schizophrenic
individuals but are present in
normal people
Disorganized thoughts,
difficulty concentrating and/or
following instructions,
difficulty completing tasks,
memory problems• Hallucination
Visual
Olfactory (Smell)
Auditory (Most common)
Gastatory (Taste)
Tectile (Feel)
• Delusion
Delusion of Control
Delusion of Reference
Delusion of Persecution
Delusion of Grandeur
• Disorganized Thinking
 Lack of Emotional response
Lack facial Expression
Neither Sadness nor
Happiness
 Social withdrawal
Being isolating socially
 Lack of initiative or drive
Lacking self care &
motivation
 Apathy
Lack of interest

6. Subtypes of schizophrenia
Catatonic
Schizophrenia
Simple
Schizophrenia
Hebephrenic
Schizophrenia
Paranoid
Schizophrenia
• Main subtype
• Positive
symptoms are
prominent
Hallucination Delusion
Commenting
Commanding
Bodily
sensation
Persecution
Reference
Grandiosity
Catatonic stupor is
one of the most
dramatic psychiatric
presentations
Stupor- Patient is
mute and immobile
Signs-
Posturing
Waxy flexibility
Negativism
Automatic Obedience
Excitement
Inappropriate/
incongruous effect
Incoherent,
disjointed rambling
speech
Aimless behavior
Hallucination and
delusion are absent
or not prominent
Predominance of
negative symptoms -
Absence of positive
symptoms
Social withdrawal
Loss of motivation
Aimlessness
Apathy
Poverty of speech

7. Pathophysiology of Schizophrenia
Abnormal brain anatomy
Large Ventricles (Sowell et al 2000)
Decrease in size of corpus Collasum (Jack E Downhill Jr. et al 2000)
Decrease in size of Thalamus (Ian Methew et. al 2014)

8. Dopamine hypothesis
Proposed by Carlson (Nobel Prize in 2000)
Mesolimbic Dopaminergic pathway Mesocortical Dopaminergic pathway
Hyperactivity of D2 receptor
Positive symptoms
Hypoactivity of D1 receptor
Negative symptoms

9. Genetic
Abnormality in more than one gene (Polygenic)
Stahl et al 2008
More than 20 susceptible genes
GRM 3 (Carlomaj et al 2016)
22q11.2 deletion

10. Current approaches for the treatment of Schizophrenia
Pharmacological Treatment Non- Pharmacological Treatment
First generation/
Typical/Older
Second generation/
Atypical/Newer
 Chlorpromazine
 Haloperidol
 Risperidone
 Olanzapine
 Clozapine
 Quetiapine
 Lurasidone
Non-selective
dopamine antagonist
Common side effects-
Extrapyramidal side-
effect
Metabolic side- effects
(Diabetes, weight gain,
increase lipids
 Psychoeducation
 Cognitive behavior therapy (CBT)
 Family therapy/ family intervention
 Art therapy
 Social skill therapy
 Cognitive Remediation therapy
Antipsychotic Agents

11. Aripiprazole Lauraxil (AristadaTM)
Prodrug of Aripiprazole
Extended released injectable atypical antipsychotic
Long acting
Approved by FDA for the treatment
of schizophrenia ( june 2017)
Approved dose- 441mg per month
662mg per month
882mg per month
Absorption and distribution
Reach steady state after
the 4th monthly injection
Metabolism and elimination
Prodrug- undergo enzyme mediated hydrolysis
water mediated hydrolysis
Aripiperazole
Eliminated hepatically by CYP3A4 & CYP2D6
T1/2 - 29.2 days to 34.9 days

12. Primary change in PANSS
Reduces dopaminergic neurotransmission
through D2 partial agonism, not D2 antagonism.
Mechanism of action (Flavio Guzman et al 2018)
Aripirazole binds to number of CNS receptors
partial D2 agonist
partial 5-HT1A agonist
5-HT2A antagonist

13. Vitamin- D
(Ana Dias Amaral et al
2014)
Vitamin D (VD) is a
steroid hormone
Synthesized in the skin upon
exposure to UVB radiation
Some dietary source
also provide it
VDR and
1 α hydroxylase
in Brain
1,25(OH)2 D3
synthesis in CNS
It can be considered as
neuroactive steroid with
autocrine and paracrine action
D2 D3
Ergocalciferol Cholecalciferol
Critical regulator of calcium metabolism also play
role in gene expression and immune function

14. In Schizophrenic patient the level of 25(OH)D3 inversely proportional to psychosis risk
VD
promote-
Neurone growth
factor (NGF)
Neurotrophin-3
(NT-3)
Glial cell line
derived
neurotrophic
factor (GDNF)
If VD is absent NGF, & NT-3
NGF have neurotrophic activity on cholinergic neurons of basal forebrain
Which projection to Hippocampus
Whereas GDNF act on dopaminergic neurons
GDNF also control dopaminergic apoptosis in substantia nigra
Dose- 400 iu to 1000 iu

16. CBT combines cognitive and behavioral therapies treating mood and anxiety disorders
(Chambless & Ollendick, 2001)
The basic premise of CBT is that emotions are difficult to change directly, so CBT targets
emotions by changing thoughts and behaviors that are contributing to the distressing
emotions (DeRubeis & Crits-Christoph, 1998)
Cognitive Behavioral Therapy (CBT)

17. Psychoeducation
 Any programme involving interaction between an information provider and service
users or their carers, which has the primary aim of offering information about the
condition; and
 The provision of support and management strategies to service users and carers.
To be considered as well defined, the educational
strategy should be tailored to the need of
individuals or carers.

18. ‘Family’ includes people who have a significant emotional connection to the service
user, such as parents, siblings and partners.
Family Intervention
• The goals of family-based services are-
to increase understanding of the disorder,
reduce levels of expressed emotion,
reduce feelings of isolation, stress, and burden of
family members,
foster development of coping skills, and
develop an ongoing collaborative relationship
between family and clinicians.

19. To help families cope with their relatives
Collaboration with relatives who care for the person with schizophrenia
Reducing the emotional stress and burden on relatives and within the family unit.
Reducing expressions of anger and guilt by the family
Aims of family intervention

20. Art Therapy
Art as an Expression of feelings
 Feeling alone
 Isolated
 Tired
 Depressed
 Anxiety
No hands –
Feeling unable to
come out the situation Swirling in the head
Art therapy is the way by which a person can
express their emotions, feeling and condition

21. References:-
1. Chien WT, Yip ALK. Current approaches to treatments for schizophrenia spectrum disorders, part I: an
overview and medical treatments. Neuropsychiatr Dis Treat. 2013;9:1311–1332.
2. Mosher LR, Keith SJ. Psychosocial treatment: individual, group, family, and community support
approaches. Schizophr Bull. 1986(1): 10–41.
3. Picchioni MM, Murray RM(2007): Schizophrenia. BM.J, 335: 91-95.

22. Thank
You