schizophrenia is most common psychiatric condition characterized by disturbance in thinking, emotion and volition with presence of clear consciousness.

1. •
•Schizophrenia
(F20-F29)

2. • Schizophrenia literally means “Fragmented Mind”. Skhizo= Split and
phren= Mind
• This term was coined by swiss psychiatrist Eugen Bleuler.
• Schizophrenia is one of the most complex, chronic and challenging
of psychiatric disorders that affects how a person thinks, feels,
behaves. It is characterized by disturbance in thinking, emotions,
volitions and faculties in the presence of clear consciousness which
lead to social wirhdrawl.
• It represents a heterogeneous syndrome of disorganized thoughts,
delusions, hallucinations, and impaired psychosocial functioning.

3. ETIOLOGY
• While many factors have been associated with developing
schizophrenia—including genetics, early environment, neurobiology,
and psychological and social processes—the exact cause of the
disease is unknown…..
Biological theories- Biochemical theories, Neurostuructural theories,
Genetic Theories, Perinatal Risk Factor
Psychodynamic Theories- Developmental Theories, Family Theories
Vulnarability stress model
Social Factors

4. • Genetic Theory: • A strong genetic link exists for the development of
schizophrenia. Occurs in 1% of general population, however this
increases to 10% if a 1st degree relative has a history of
schizophrenia. Risk of developing schizophrenia further increases
to 40% when both parents have a history of schizophrenia.
Monozygotic twins have demonstrated a 48% risk of developing
schizophrenia if one twin has the disease. Studies are going to
locate specific genes to the development of schizophrenia.

5. • Dopamine Theory: • The dopamine hyperactivity in the brain is responsible for
psychotic symptoms present in schizophrenia. While dopamine hyperactivity is
present in mesolimbic pathway, other areas of the brain such as the prefrontal,
frontal and temporal cortices have decrease activity during acute psychosis.
Other neurotransmitters thought to be involved in schizophrenia include 5-HT,
glutamate. The role of glutamate is also being evaluated because one of its major
functions is to regulate dopamine activity. Glutamate deficiency has been found to
cause similar effects to that of dopamine hyperactivity.
• Neurodevelopmental Theory: • Schizophrenia occurs as a result of an in
uterodisturbance during pregnancy. Potential causes of this disturbance include upper
respiratory infection, obstetric complication and neonatal hypoxia.
• Psychosocial Theories: • These theories propose that situation such as stress, poor
interpersonal skills, conflicting family, communication and various socio-economic
influences are linked to development of schizophrenia.
• Neurotransmitter Abnormalities • Abnormalities in the dopaminergic system –
Hypodopaminergic activity in the mesocortical system, leading to negative
symptoms – Hyperdopaminergic activity in the mesolimbic system, leading to

6. • . Viral Infections and Immune Disorders : • Schizophrenia may be
triggered by environmental events, such as viral infections ( Maternal
Influenza) or immune disorders. For instance, babies whose mothers get
the flu while they are pregnant are at higher risk of developing
schizophrenia later in life. People who are hospitalized for severe
infections are also at higher risk.
• Genetics (Heredity) : • The risk of developing schizophrenia is increases
to approximately 10% if a first-degree relative has the illness and to 3% if
a second-degree relative has the illness. If both parents have
schizophrenia, the risk of producing a schizophrenic offspring increases to
approx 40%.

7. EPIDEMIOLOGY
• The prevalence of schizophrenia ranges from 0.6% to 1.9%, with an
average of approximately 1% • Schizophrenia most commonly has its
onset in late adolescence or early adulthood and rarely occurs before
adolescence or after the age of 40 years. The peak ages of onset are
20–38 years for males and 26–32 years for females. • Slightly more
men are diagnosed with schizophrenia than women (on the order of
1.4:1) and women tend to be diagnosed later in life than men

8. CLASSIFICATION OF SCHIZOPHRENIA
• F20- SCHIZOPHRENIA
• F20.0- PARANOID SCHIZOPHRENIA
• F20.1- HEBEPHRENIC SCHIZOPHRENIA
• F20.2- CATATONIC SCHIZOPHRENIA
• F20.3- UNDIFFERENCIATED SCHIZOPHRENIA
• F 20.4- POST SCHIZOPHRENIC DEPRESSION
• F20.5-RESIDUAL SCHIZOPHRENIA
• F 20.6- SIMPLE SCHIZOPHRENIA
• F21- SCHIZOTYPAL DISORDER

9. TYPES
• Paranoid schizophrenia • Common form of schizophrenia •
Prominent hallucinations and/or delusions* • May develop at a
later age than other types of schizophrenia • Speech and emotions
may be unaffected • At risk for suicidal or violent behavior under
influence of delusions • Hebephrenic / Disorganized schizophrenia •
Behaviour is disorganised and without purpose* • Thoughts are
disorganised, difficult to understand by others
• Catatonic schizophrenia – Cata- Disturbed. Marked disturbance
in motor behaviour.
Catatonic Excitement
Retarded Catatonia / Catatonic Stupor

10. SIGN AND SYMPTOMS
Positive Symptoms –
 DELUSION : False beliefs that are not based in reality
 HALLUCINATION : Involving seeing or hearing things that don't exist •
 DISORGANIZED SPEECH & THINKING : Effective communication can be impaired
and answers to questions may be partially or completely unrelated
 CATATONIA : Purposeless abnormal motor activity or aggressive behavior Cognitive
Symptoms
• POOR EXECUTIVE FUNCTIONING : Unability to understand information to make
decisions
 POOR WORKING MEMORY : Unability to use information immediately after learning
EXCITEMENT OR AGITATION
HOSTILITY
SUSPECIOUSNESS

11. • Negative Symptoms –
 FLAT EFFECT : Reduced expression of emotions via facial
expression or voice tone
 ALOGIA : Reduced speech
AVOLITION : Inability to begin & sustain activities
 ANHEDONIA : Inability to experience pleasure •
ASOCIALITY : Withdrawal from social contacts , Reluctance to
perform everyday tasks
ATTENTIONAL IMPAIREMENT

12. CLINICAL FEATURES – BLEULER’S 4 A
• AFFECTIVE DISTURBANCE- Inability to show appropriate emotional
response
• AUTISTIC THINKING- Individual is unable to relate to the
environment. Preoccupation with self and little concern for external
reality
• AMBIVALANCE- It refers to contradictory or opposing emotions,
attitudes, ideas, or desire for same person, thing or situation
simultaneously opposite feeling
• Associative Looseness- Inability to think logically.

13. SFRS- SCHNEIDER’S FIRST RANK
SYMPTOMS OF SCHIZOPHRENIA
• THOUGHT WITHDRAWAL
• THOUGHT INSERTION
• THOUGHT BROADCASTING
• MADE VOLITION
• MADE FEELING

14. PATHOPHYSIOLOGY
• . Dopamine Hypothesis • Numerous Positron Emission Tomography
(PET) studies have shown dopaminergic hyperactivity in the nucleus
accumbens and dopaminergic hypofunction in the fronto temporal
regions. • PET studies using D2-specific ligands provide data
suggesting increased densities of D2 receptors in the nucleus
accumbens. • PET studies assessing D1 function suggest that
subpopulations of schizophrenics may have decreased densities of D1
receptors in the prefrontal cortex. • Thus positive symptoms are
thought to result from overactivity in the mesolimbic
dopaminergic pathway activating D2 receptors whereas negative
symptoms may result from a decreased activity in the
mesocortical dopaminergic pathway where D1 receptors
predominate.

15. PATHOPHYSIOLOGY CONTINUE….
Glutamate Hypothesis • NMDA receptor hypofunction is thought to reduce the
level of activity in mesocortical dopaminergic neurons. This would result in a decrease
in dopamine release in the prefrontal cortex and thus give rise to negative symptoms
of schizophrenia. • On the other hand, NMDA receptor hypofunction is thought to
enhance activity in the mesolimbic dopaminergic pathway, perhaps because in this
pathway the important NMDA receptors are those located on GABAergic interneurons.
• Thus NMDA receptor hypofunction would result in reduced GABAergic inhibition
(disinhibition) of mesolimbic dopaminergic neurons and thus give rise to enhanced
dopamine release in limbic areas such as the nucleus accumbens.
5-HT Hypothesis • Serotoninergic receptors are present on dopaminergic axons and
it is known that stimulation of these receptors will decrease DA release in prefrontal
cortex. • Patients with schizophrenia with abnormal brain scans have higher whole
blood 5-HT concentrations and these concentrations are correlated with increased
ventricular size. • Atypical antipsychotics with potent 5-HT2 receptor antagonist effects
reverse worsening of symptomatology induced by 5-HT agonists in patients with

16. COMPLICATION
• 1. DEPRESSION : Depression afflicts approximately half of schizophrenic patients. Sadly, it is not always
recognized or treated. It can significantly add to the suffering of the person. Additionally, comorbid
depression increases the risk of suicide in schizophrenic.
• 2. ANXIETY : Many individuals with schizophrenia also have an anxiety disorder, such as social anxiety
disorder, PTSD, generalized anxiety disorder, OCD or panic disorder. In fact, research suggests between
30% and 85% of people with schizophrenia have had an anxiety disorder at some point in time.
• 3. SUICIDE : Suicide is one of the primary causes of death for individuals with schizophrenia. There are
several factors which contribute to suicide risk in schizophrenia which include psychotic symptoms, such
as voices telling the person to kill himself, substance abuse, recent diagnosis of schizophrenia and
comorbid depression.
• 4. SUBSTANCE ABUSE & SMOKING : Substance abuse is a form of self-medication for many people
with psychiatric disorders. Unfortunately, when patients use substances such as alcohol or street drugs it
can make their symptoms worse. They are also less likely to continue taking their medications when they
abuse substances.
• 5. VIOLENCE : While the media often depicts schizophrenic patients as violent, they are not necessarily
more prone to violence than the general population. That being said, some factors can increase the risk of
violent behavior in individuals with schizophrenia, such as delusions or command hallucinations, a history
or violent acts or using alcohol or drugs.
• 6. SELF-INJURY : Self-injury, especially bizarre types of self-mutilation, is not uncommon with
schizophrenia. Hallucinations and delusions can cause them to harm themselves in ways which can be

17. DIAGNOSTIC CRITERIA FOR
SCHIZOPHRENIA :
• It includes the criteria in the Diagnostic and Statistical Manual of Mental
Disorders (DSM-IV), published by the American Psychiatric Association.
• • MEDICAL HISTORY : A thorough medical history is the first step in the
diagnosis of schizophrenia. This may be done to find other problems that
could be causing symptoms and to check for any related complications.
• • BLOOD TESTS & IMAGING : A Complete Blood Count (CBC) test is
helpful to monitor general health and rule out other conditions that may have
been responsible for the symptoms. A blood test can provide accurate
information about the involvement of recreational drugs.
• In some cases, certain imaging techniques such as Magnetic Resonance
Imaging (MRI) or Computed Tomography (CT) scan may aid in the diagnosis

18. PSYCHIATRIC EVALUATION :
• A doctor or mental health professional checks mental status by
observing appearance, demeanor and asking about thoughts, moods
and awareness.
• A person may be diagnosed if they have at least 2 of the
following symptoms usually over a month : • Delusions •
Hallucinations • Disorganised behaviour • Disorganised speech and
thought processes • Catatonic behaviour, presenting as strong daze
or hyperactivity • Negative symptoms, impaired normal function

19. PROGNOSIS
• • There is no known cure for Schizophrenia. Fortunately, there are
effective treatments that can reduce symptoms, decrease the
likelihood that new episodes of psychosis will occur, shorten the
duration of psychotic episodes, and in general, offer the majority of
people the possibility of living more productive and satisfying lives. •
With the proper medications and supportive counseling, the ability of
schizophrenic persons to live and function relatively well in society is
excellent.

20. MANAGEMENT HOSPITALIZATION
• • PSYCHOSOCIAL INTERVENTIONS
• •Group Therapy
• Behaviour Therapy
• Individual therapy : Psychotherapy may help to normalize thought patterns. Also, learning to cope
with stress and identify early warning signs of relapse can help people to manage their illness.
• • Social skills training : This focuses on improving communication, social interactions and improving
the ability to participate in daily activities.
• • Family therapy : This provides support and education to patient families.
• • Vocational rehabilitation and supported employment : This focuses on helping people with
schizophrenia prepare for, find and keep jobs

21. • ELECTROCONVULSIVE THERAPY adults with schizophrenia who do not respond
to drug therapy, electroconvulsive therapy (ECT) may be considered. ECT may be
helpful for someone who also has depression. • The indications for ECT in
schizophrenia are : • Catatonic stupor & uncontrolled catatonic excitement • Acute
exacerbations not controlled with drugs • Risk of suicide, homicide or danger of
physical assault
• COGNITIVE BEHAVIOURAL THERAPY - CBT aims to help to identify the thinking
patterns that are causing to have unwanted feelings & behavior and learn to replace
this thinking with more realistic and useful thoughts. • Most people require between
8 and 20 sessions of CBT over the space of 6 to 12 months. CBT sessions usually
last for about an hou

22. CLINICAL MANAGEMENT
• The APA guidelines treatment recommendations for patient with
schizophrenia divide the treatment into 3 phases :
• 1. Acute Phase (Initial Presentation) 4 to 8 weeks : Defined by
acute psychotic episode
• 2. Stabilization Phase (Early symptom remission) as long as 3
months : Constitutes a time – limited transition to continuing treatment
• 3. Stable Phase (Maintenance treatment) : Involves stable
treatment
*APA guideline refers to the American Psychiatric Association

23. • ANTIPSYCHOTIC / NEUROLEPTIC / ATARACTIC/ MAJOR
TRANQUILLIZER Typical or Classical or 1st generation antipsychotics: A.
Phenoziazins: 1. With aliphatic amine side chain : Chlorpromazine,
Triflupromazine 2. With Piperidine side chain : Thioridazine 3. With
Piperazine side chain : Trifluoperazine, Fluphenazine B. Butyrophenones :
Haloperidol, Trifluperidol, Penfluridol C. Thiohaxanes : Flupenthixol,
Thiothixene D. Other heterocyclics : Pimozide, Loxapine 28
• Atypical or Novel or 2nd generation antipschycotics : • Clozapine •
Olanzapine • Quetiapine • Aripiprazole • Risperidone • Amisulpride •
Ziprasidone

24. • First Generation Antipsychotic
• SGA – Second Generation Antipsychotic
• ECT – Electro Convulsive Therapy
• • Stage 1 of the treatment algorithm applies only to those patients
experiencing their first episode of schizophrenia.
• • Stage 2 recommends either FGAs or SGAs, with the exception of
clozapine. Because of safety concerns and the need for white blood cell
(WBC) monitoring, it is recommended that patients be tried on one newer
SGA and one other SGA or FGA as monotherapy before proceeding to a trial
of clozapine. * Clozapine has superior efficacy in decreasing suicidal
behavior, and it should also be considered as a higher treatment option in the
suicidal patient (Stage 3). Clozapine can also be considered earlier in

25. • Stage 4 of the treatment algorithm includes clozapine and augmentation with either a
FGA, SGA, or electroconvulsive therapy (ECT). Combination treatment at this stage is
supported by limited controlled and equivocal evidence. • In general, patients who
experience poor improvement with clozapine do not respond well with other
antipsychotic monotherapies (Stage 5).
• • Stage 6 combination pharmacotherapy interventions should be implemented with time
limited, careful evaluation of a patient’s symptom response and discontinuation of the
combination if improvement does not occur. • If partial or poor adherence contributes to
inadequate clinical improvement, then long-acting or depot injectable antipsychotics
should be considered. • Risperidone microspheres is the only available long-acting
injectable SGA, and long-acting FGAs include fluphenazine decanoate and haloperidol
decanoate

26. TYPICAL ANTIPSYCHOTIC
• • All anti psychotics (except clozapine-like atypical) have potent dopamine D2 receptor
blocking action. • Antipsychotic action of typical neuroleptic is believed to produced by
competitive blockade of postsynaptic D2 receptors in mesolimbic system. • Initially D2
presynaptic receptors are also blocked, which increases, synthesis and release of
dopamine, so its metabolites like HVA and DOPAC level is increase in blood and urine. •
But on prolonged use, there is a feedback inhibition of DA release, due to increased DA
concentration in synaptic cleft, which result in decrease turnover and release. • Atypical
neuroleptics drug also block D2 receptor in nigrostriatal pathway and explain the unwanted
exrapyramidal side effects (EPS).
• Blockage of D2 receptor in CTZ is responsible for antiemetic effects. • Neuroleptics
consistently increase prolactin release by blocking the inhibitory action of DA on pituitary
lactotropes. This may result in galactorrhoea and gynaecomastia • Typical antipsychotic
drugs Have varying degree of other receptor blocking activity : Clorpromazine : α1 = 5-HT2 >
D2 = D4 > D1 > M1 Thioridazine : α1 > D2 > M1 = 5-HT2 > D1 Haloperidole : D2 > α1 > D4 >
5-HT2 > D1 Primozide : D2 > 5-HT2 > D4 • These drugs produce hypotension due to high α
blocking property. • Chlorpromazine potent a local anaesthetic as procaine but is not used for

27. ATYPICAL ANTIPSYCHOTIC
• • These newer atypical antipsychotic medications are general preffered because they pose a
lower risk of serious adverse effects than do typical antipsychotics. • These drugs have a
moderate to high D2 antagonism and high 5-HT2A antagonism. Clozapine have low D2
antagonism and high 5-HT2A antagonism. • Exception of aripiprazole, all atypical antipsychotics
have higher 5-HT2A antagonism than D2 receptor antagonism. • Blockade of 5-HT2A receptor
leads to release of dopamine in prefrontal cortex responsible for decrease in negative
symptoms while modest D2 receptor blockade in limbic system responsible for decrease in
positive symptoms. 35
• 36. 36 • At least 60% to 65% occupation of D2 receptors antagonism is necessary to decrease
positive antipsychotic symptoms, whereas 77% or more blockade is associated with
extrapyramidal side effects. • One of the most common adverse effects of newer antipsychotics
is weight gain. • Other adverse effects include sedation and diabetes. • Atypical antipsychotic
drugs have varying degree of other receptors blocking activity : • Clozapine : D4 = α1 ˃ 5-HT2 =
M ˃ D2 = D1 = α2 • Quetiepine : 5-HT2 = D2 = α1 = α2 • Risperidone : 5-HT2 ˃˃ α1 ˃ H1 ≥ D2
˃ α2 ˃˃ D1 • Olanzepine • Aripiprazole
• 37. Drug D2 binding 5-HT2A binding Sedation EPS Anti- cholinergic Prolactin Low dose
High dose Typical antipsychotics 70-90% ++++ +++ +++ +++ Clozapine 38-47% 38-47%
100% ++++ + +++ + Riserpidone 60-79% 77% 70% (low) 100% (high) + ++ + ++++ Olanzapine
71-80% 83-88% 100% ++ + ++ + Quetiapin 0-20% 30% 45-90% + + + + Aripiprazole + + + + +

28. ADVERSE EFFECTS
• 1. SEDATION • Although sedation is most commonly associated with
chlorpromazine and clozapine, it is primarily related to dosage with other
antipsychotics.
• 2. AUTONOMIC SIDE EFFECTS • Some antipsychotic drugs are associated
with changes to the QT interval measured on the elecrocardiogram (ECG)
and, if given in high doses, may increase the risk of sudden cardiac death
due to α adrenergic blockage. • Anticholinergic side effects such as dry
mouth, constipation, blurred vision are particularly associated with piperidine
phenothiazines. • Postural hypotension, palpitation, inhibition of ejaculation
and photosensitivity are associated with the aliphatic phenothiazines.

29. EPS
• NEUROLEPTIC INDUCED PARKINSONISM
• ACUTE DYSTONIA
• AKATHESIA
• TARDIVE DYSKINESIA
• NEUROLEPTIC MALIGNANT SYNDROME
• AUTONOMIC SIDE EFFECT
• SEIZURE
• SEDATION
• OTHER EFFECT

30. EXTRAPYRAMIDAL SIDE EFFECTS
• • Side effects such as akathisia, dystonia, parkinsonian effects and tardive dyskinesia are associated with
typical antipsychotic drugs and occur frequently, particularly with piperazine phenothiazines such as
trifluoperazine, fluphenazine and butyrophenones such as haloperidol. Akathisia • It is defined as the inability
to sit and being functionally motor restless. It is characterized by restlessness, convulsions, feeling of
discomfort uncontrollable & without any anxiety. The use of non-selective β blocker can provide relief.
Dystonia • It is a state of abnormal tonicity, sometimes described as a severe “muscle spasm”, characterized
spasm of muscles of tongue, face neck and back; Pharangeal laranreal dystonia is life threatening.
Treatment can be made by using benzodiazepine and anticholinergic drug.
• Puedoparkinsonism - It results due to blockadge of D2 receptor in nigrostratial pathway. • With typical
manifestations rigidity, tremor, hypokinesia, , mask-like facial expression, micrographia, slowed speech,
postural imbalance and decreased arms wing; between 1-4 weeks of therapy and persists unless dose is
reduced. • Treatment involve restoration of cholinergic doapaminergic balance by using centrally acting
antimuscarinic drugs like trihexyphenidyl, procyclidin, biperiden and dopamine agonist. Tardive Dyskinesia • It
is a syndrome characterized by abnormal involuntary movements occurring late in onset in relation to
initiation of antipsychotic therapy. • The classic description is the buccal-lingual-masticatory (BLM) syndrome,
or orofacial movements causing involuntary facial tics or random uncontrolled muscle movements of the
hands, feet, limbs trunk.

31. NEUROLEPTIC MALIGNANT SYNDROME (NMS) • The NMS is a rare but serious complication
of antipsychotic drug treatment. The primary symptoms are rigidity, fever, diaphoresis, confusion
and fluctuating consciousness. • Confirmation can be sought through detection of elevated levels
of creatinine kinase. • The onset is particularly associated with high-potency typical drugs such
as haloperidol, recent and rapid changes to dose and abrupt withdrawal of anticholinergic drugs.
• Treatment usually requires admission to a medical ward and withdrawal of all antipsychotic
drugs. Intravenous dantrolene may benefit as skeletal muscle relaxant. The Dopamine agonist
Bromocriptine in large doses has been found useful to reduce rigidity and fever.

32. • HORMONAL EFFECTS AND SEXUAL DYSFUNCTION • Blockade
of D2 receptor in pituitary gland results into the effect on prolactin.
This may result in galactorrhoea, missed menstrual periods, loss of
libido in female and gynaecomasia in male. • Some studies have
suggested very high levels of sexual dysfunction with some
antipsychotic drugs such as risperidone and amisulpride. • These drug
also inhibit FSH and LH release results in amenorrhoea and inhibition
of ovulation.
• 6. MISCELLANEOUS • Weight gain • Jaundice • Photosensitivity

33. • CLOZAPINE • The first of the new generation, clozapine is the only drug that has been
shown to be effective where other antipsychotics have failed. • Clozapine was developed
as an antipsychotic drug during the 1960s. • It is the drug of choice for treatment
resistant schizophrenia. • It has only weak D2 blocking activity. • Selectivity of receptor
are: 5-HT2>H1=M1>α1=D4>D2=D1 ADVERSE EFFECTS • Produce no or few
extrapyramidal symptoms. • Major side effect is agranulocytosis. • Other side effects are
sedation, unstable BP, tachycardia, urinary incontinence, weight gain and precipitation of
diabetes. 43
USE • It decreases hallucination and helps to prevent suicide in people who are likely
to try to harm themselves. • It helps to think more clearly and positively and take part in
everyday life. PHARMACOKINETIC • Metabolized in liver by CYP34A with average half-life
12 hours. • Bioavailability is 60 to 70%

34. THANK YOU