1. SCHIZOPHRENIA- CURRENT
TRENDS IN ITS TREATMENT

2. CONTENTS
• Introduction
• Causes
• Symptoms
- Positive symptoms
- Negative symptoms
• Drug treatment
• Mechanism of action
• Adverse effects
• Current trends in the treatment
of schizophrenia.

3. Schizophrenia
• Schizophrenia is a
complex mental
disorder that makes it
difficult to-
• Tell the differences between
real and unreal experiences
• Think logically
• Have normal emotional
responses
• Behave normally in social
situations

4. CAUSES
• No one knows the exact cause of
schizophrenia, but multiple possible
factors have been discovered.
• It is a complex illness, possibly due to the
dysfunction of the mesolimbic or
mesocortical dopaminergic neurons.
• It has a strong genetic component.

6. SYMPTOMS
• Delusions (strongly held
beliefs that are not based on
reality)
• Hallucinations (Hearing or
seeing things that are not
there)
• Disorganised speech
• Disorganised behaviour
• Irritable or tense feeling
• Lack of emotion

7. POSITIVE SYMPTOMS
• Delusions
• Hallucinations
• Disorganized
thinking
• Agitation

8. NEGATIVE SYMPTOMS
• Affective flattening
(person’s range of
emotional expression
is clearly diminished)
• Alogia (A poverty of
speech)
• Avolition (Inability to
initiate and persist in
gaol directed
activities)

9. TYPES OF SCHIZOPHRENIA
• There are five types of schizophrenia:
1.Paranoid- Person feels extremely suspicious,
persecuted.
2.Disorganised- person is often incoherent but
may not have delusions.
3.Catatonic- Person is withdrawn, mute,
negative and often assumes very unusual
postures.

10. 4.Residual- person is no longer delusion or
hallucinating, but has no motivation or interest
in life.
5.Undifferentiated- does not fit in one of the
above categories because the patient suffers
from symptoms of multiple types.

11. DRUG TREATMENT
Drugs
Typical neuroleptic Typical neuroleptic Atypical neuroleptic
(low potency) (High potency) •Aripiprazole
•Chlorpromazine •Fluphenazine •Clozapine
•Prochlopromazine •Haloperidol •Olanzapine
•Thioridazine •Thiothixene •Resperidone

12. MECHANISM OF ACTION
• Dopamine receptor
blocking activity in the
brain.
• Serotonin receptor
blocking activity in the
brain.

13. ADVERSE EFFECTS
• COMMON SIDE EFFECTS
-Lethargy & drowsiness
-Anticholinergic effects (dry mouth, blurred
vision, constipation & retention of urine)
-Postural Hypotension (Dizziness on standing up)

14. •MOVEMENT DISORDERS
-Acute dystonia (muscle spasms)
-Parkinsonism (tremors, stiff posture,
immobile & expressionless face)
-Akathisia (restless fidgeting and pacing)
-Tardive dyskinesia (repetitive involuntary
muscle movements, lip-smacking and
protrusion of tongue)

15. CURRENT TRENDS IN THE
TREATMENT OF SCHIZOPHRENIA
• Antipsychotic effects of
novel compounds
• Partial dopamine agonists
• Acetylcholinesterase
inhibitors in schizophreni
• COX-2 inhibitors as an
adjunctive treatment for
schizophrenia
• Human stem cells in the
treatment of
schizophrenia

16. ANTIPSYCHOTIC EFFECTS OF NOVEL
COMPOUNDS
• The two new receptors which have been implicated in the
pathophysiology of schizophrenia are 5HT2 and neurotensin-1
receptors.
• Eplivanserine is a 5HT2 receptor antagonist. Antagonism of this
receptor appears to regulate dopaminergic activity, and this
compound appears to reverse amphetamine induced inhibition of A-
10 dopaminergic cells.
• SR46349B is a neurotensin-1 receptor antagonist that appears to
diminish the spontaneous activity of dopaminergic neurons.
• Both these drugs were effective in treating the negative and
depressive symptoms as well.

17. PARTIAL DOPAMINE AGONISTS
• The dopaminergic hypothesis of schizophrenia indicates that in this
condition there is a both hyperdopaminergic state in the cortical
mesolimbic tract (causing positive symptoms) and a
hypodopaminergic state in the mesocortical tract (causing negative
symptoms).
• The full agonist allows full neurotransmitter activity at the synaptic
site .
• An antagonist, when bound to the receptor allows no receptor
activity. In contrast, a partial agonist will allow some
neurotransmitter activity when bound to the receptor.
• Ariprazole is a dopamine partial agonist that has recently been
approved in the United States. It is 10 times more potent than other
drugs.

18. ACETYLCHOLINESTERASE
INHIBITORS IN SCHIZOPHRENIA
• Neurotransmitters implicated in the pathogenesis of schizophrenia
have included dopamine, serotonin, glutamine and acetylcholine.
• Cognitive impairment in schizophrenia may at least partially due to
diminished acetylcholine activity in the cortex.
• Donepezil is an acetylcholinesterase inhibitor that appears to
enhance cognitive functioning in patients with schizophrenia.

19. COX-2 INHIBITORS AS AN ADJUNCTIVE
TREATMENT FOR SCHIZOPHRENIA
• Recently, increased attention has been paid to the interface
between the immune system and the treatment of schizophrenia.
• When the mentally ill group was afflicted with an infection, half
showed improvements in their psychotic symptoms.
• It is believed that there may be an imbalance between the type1 and
type2 immune systems in patients with psychosis.
• Schizophrenic patients who are treatment-resistant appear to have
an increase in interleukin-6 level, which is a part of type1 system.
• COX-2 inhibitor Celecoxib is an inhibitor of prostaglandin E2 and IL-
6 which was found to restore the imbalance between the type1 and
type2 immune systems.

20. HUMAN STEM CELLS IN THE
TREATMENT OF SCHIZOPHRENIA
• The National Institutes of Health states that stem cell “have the
remarkable potential to develop into many different cells types in the
body during early life and growth”.
• The stem cells can be coaxed to become brain cells such as
neurons. Because they have the DISC1 mutation, they stand to play
an important role in the screening of drugs for treatments of major
mental illnesses such as schizophrenia.
• Inspite of holding the key to an effective treatment, the stem cell
research may not work for the disorder as they are still not exactly
sure what goes wrong in the schizophrenic brain.

21. REFERENCES
• Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-
generation versus first-generation antipsychotic drugs for
schizophrenia: a meta-analysis. Lancet. 2009;373:31-41. Epub
2008 Dec 6. [PubMed]
• Psych Central, National Mental Health Association,
National Institute for Mental Health, National Alliance for the
Mentally Ill, Internet Mental Health.
• Kostic D, Manos G, Stock E, et al. Long-term effects of
aripiprazole on the negative symptoms of schizophrenia. J Eur
Coll Neuropsychopharmacol. 2003;13(supp 4):S328.
• Marder SR, McQuade RD, Stock E, et al. Aripiprazole in the
treatment of schizophrenia: safety and tolerability in short-term,
placebo-controlled trials. Schizophr Res. 2003;61:123-126.