SCHIZOPHRENIA

● Schizophrenia is one of the most complex and challenging of psychiatric disorders. It

represents a heterogeneous syndrome of disorganized and bizarre thoughts, delusions,
disorganized thinking and speech,hallucinations, inappropriate affect, impaired psychosocial
functioning, abnormal motor behavior, and negative symptoms.
● Schizophrenia is usually a lifelong psychiatric disability

EPIDEOMOLOGY

● Onset of schizophrenia usually occurs during late adolescence or early adulthood.

● Studies indicate that males are affected earlier than females by about 3 to 5 years. Males
commonly exhibit schizophrenia between the ages of 15 and 25, whereas the illness affects
females between the ages of 15 and 30, and a smaller group between ages 45 and 50.

ETIOPATHOGENESIS (neurobiology)

Schizophrenia causation theories include genetic predisposition, obstetric complications, increased

neuronal pruning, immune system abnormalities, neurodevelopmental disorders, neurodegenerative
theories, dopamine receptor defect, and regional brain abnormalities including hyper- or
hypo-activity of dopaminergic processes in specific brain regions.

ETIOLOGY PATHOGENESIS
Genetic and Environmental ● Studies have clearly established a familial predisposition for schizophrenia.
Risk Factors ● Siblings of a proband with schizophrenia have a sevenfold to tenfold
increased risk of the disorder; children born to a parent with schizophrenia
have a 13-fold to 15-fold increased risk.6
● The risk is highest (40%–50%) in a monozygotic (identical) twin of a person
with schizophrenia
● Environmental factors such as prenatal difficulties (i.e., malnutrition in the
first trimester of pregnancy or influenza in the second trimester), perinatal
complications, and various nonspecific stressors may also influence the
development of schizophrenia
● Recent work has shown that polymorphism in the VAL/MET alleles of the
catecholamine-o methyl transferase gene may explain some of the frontal
lobe functional deficits in patients with schizophrenia
● Risk for schizophrenia is, to some extent, genetically transmitted and is
probably determined by multiple genes

Neuroanatomy ● Computed tomography and magnetic resonance imaging brain studies of

individuals with schizophrenia have shown enlarged ventricles, particularly
the lateral and third ventricles
 ● Other consistently reported findings include morphologic abnormalities
involving the temporal, frontal, and parietal lobes, and the subcortical
structures
● Findings include decreased neuronal volume and density, decreased
synaptic connections, decreases in synaptophysin (a membrane protein of
synaptic vesicles), and loss of microtubule-associated protein and
synaptosomal protein in certain regions of the cortex.
● Medial temporal structures are important for the processing of sensory
information, and abnormalities in this area may explain distortions in the
interpretation of external reality that are characteristic of schizophrenia
(i.e., delusions and hallucinations) The prefrontal cortex is also largely
responsible for the regulation of working memory, which involves
maintaining information in temporary memory
● Functional imaging studies have demonstrated alterations in either
cerebral perfusion or glucose metabolism in frontal, temporal, and basal
ganglia areas of the brain. Hence, these abnormalities in prefrontal areas
could explain the deficits in working memory and attention that are often
present in schizophrenia (i.e., cognitive impairment).

Neurochemistry ● Nearly all drugs that decrease dopamine activity decrease the positive
symptoms of schizophrenia
● Although other classes of dopamine receptors have been identified (e.g.,
D1, D3, D4), this close relationship to clinical potency exists only for the D2
receptor subtype
● Dopaminergic innervation from the ventral striatum decreases the limbic
system’s inhibitory activity (perhaps through γ -aminobutyric acid [GABA]
interneurons); thus, dopaminergic stimulation increases arousal
● Excess dopaminergic activity in the mesolimbic system has been associated
with the positive symptomatology of schizophrenia.
● The “hypofrontality theory” suggests that reduced or dysfunctional
dopaminergic neurotransmission within the prefrontal cortex or
mesocortical area of schizophrenic patients may be responsible for
negative symptoms
● It has also been proposed that a chronically low level of striatal dopamine
release causes negative symptoms (caused by low levels of dopamine in
the prefrontal cortex), This theory explains why dopamineblocking drugs
improve positive symptoms, but not negative symptoms
● Serotonin also seems to play a role in schizophrenia. Serotonin receptors
are abundant in mesocortical areas, and agonism at these receptor sites
may have an inhibitory effect on dopaminergic receptors or dopamine
release, possibly contributing to negative schizophrenia symptoms
● Another area of focus is the involvement of excitatory amino acids and the
glutamate transmitter system in the pathogenesis of schizophrenia.20
Decreased activation of N-methyl-daspartic acid (NMDA) or glutamate
receptors may increase cortical dopamine release and produce a syndrome
resembling schizophrenia.
 ● It has also been proposed that an imbalance between NMDA, GABA, and
dopamine activity may cause the symptoms of schizophrenia

THEORIES AND MODELS OF SCHIZOPHRNIA

Although the cause of schizophrenia remains unknown, there are many theories and models.

Models THEORIES
Vulnerability model ● The vulnerability model postulates that the persistent characteristic of
schizophrenia is not the schizophrenic episode itself but the vulnerability to
the development of such episodes of the disorder. The episodes of the illness
are time limited but the vulnerability remains, awaiting the trigger of some
stress.
● Manipulation and avoidance of stress can abort a potential schizophrenic
episode

Developmental ● The developmental model postulates that there are critical periods in the
model development of neuronal cells which, if adversely affected, may result in
schizophrenia.
● Two such critical periods are postulated to occur when migrant neural cells
do not reach their goal in fetal development and when supernumerary
neural cells slough off at adolescence.

Ecological model ● The ecological model postulates that external factors involving social,
cultural and physical forces in the environment, such as population density,
individual space, socio-economic status and racial status, influence the
development of the disorder.

Other factors ● Numerous other factors have been implicated in the development and cause
of schizophrenia. These include migration, socio-economic factors, perinatal
insult, infections, season of birth, viruses, toxins and family environment.
 ● In reality, all of these factors may influence both the development and
progression of schizophrenia.

SIGNS AND SYMPTOMS

A) Acute psychotic illness :

symptoms which commonly occur in the acute phase of a psychotic illness include the
following:
• awkward social behaviour, appearing preoccupied, perplexed and withdrawn, or showing
unexpected changes in behaviour
• initial vagueness in speech which can progress to disorders of the stream of thought or
poverty of thought
• abnormality of mood such as anxiety, depression, irritability or euphoria
• auditory hallucinations, the most common of which are referred to as ‘voices’; such voices
can give commands to patients or may discuss the person in the third person, or comment
on their actions
• delusions, of which those relating to control of thoughts
• lack of insight into the illness
These symptoms are commonly called positive symptoms.

B) Chronic schizophrenia:
● Between 60% and 80% of patients who suffer from an acute psychotic illness will
suffer further illness and become chronically affected
● As schizophrenia progresses, there may be periods of relapse with acute symptoms
but the underlying trend is towards symptoms of lack of drive, social withdrawal and
emotional apathy. Such symptoms are sometimes called negative symptoms and
respond poorly to most antipsychotic drugs.

POSITIVE SYMPTOMS NEGATIVE SYMPTOMS COGNITIVE DYSFUNCTION

● Suspiciousness ● Affective flattening ● Impaired attention

● Unusual thought content ● Alogia ● Impaired working
(delusions) ● Anhedonia memory
● Hallucinations ● Avolition ● Impaired executive
● Conceptual function ● Loss of emotional function
disorganization connectedness
● Disorganized speech (loose ● Lack of socialization
Alogia associations, tangential, ● Psychomotor
Loss of emotional retardation
connectedness blocking)
● Combativeness, agitation, and
hostility

DIAGNOSIS

A) DSM-IV-TR Criteria for Schizophrenia

Characteristic Symptoms At least two (or more) of the following, each present for a
significant portion of time during a 1-month period (or less if
successfully treated). At least one of these should include
1–3:
1. Delusions
2. Hallucinations
3. Disorganized speech (e.g., frequent derailment or
incoherence)
4. Grossly disorganized or catatonic behavior

Social or Occupational For a significant portion of the time since the onset of the
Dysfunction disturbance, one or more major areas of functioning such as
work, interpersonal relationships, or self-care is markedly
below the level achieved before the onset (or when the
onset is in childhood or adolescence, failure to achieve
expected level of interpersonal, academic, or occupational
achievement)

Duration Continuous signs of the disturbance persist for at least 6

months. This 6-month period must include at least 1 month
of symptoms (or less if successfully treated) that meet
criterion A (i.e., active-phase symptoms) and may include
prodromal or residual symptoms.
During these prodromal or residual periods, signs of the
disturbance may be manifested by negative symptoms or by
two or more symptoms listed in criterion A present in an
attenuated form (e.g., odd beliefs, unusual perceptual
disturbances).

Schizoaffective Disorder Schizoaffective disorder and mood disorder with psychotic

and Mood Disorder features have been ruled out because either
Exclusion (a) no major depressive, manic, or mixed episodes have
occurred concurrently with the active phase symptoms or
 (b) if mood episodes have occurred during active phase
symptoms, their total duration has been brief relative to the
duration of the active and residual periods

Substance or General
Medical Condition The disturbance is not caused by direct physiological effects
Exclusion of a substance (e.g., drug of abuse or medication) or a
general medical condition

Relationship to a Pervasive If there is a history of autistic disorder or another pervasive

Development Disorder development disorder, the additional diagnosis of
schizophrenia is made only if prominent delusions or
hallucinations also are present for at least a month (or less if
successfully treated)

B) Schizophrenia rating scales

C) Other tests
● Psychiatric history
 ● Mental status examination
● Mood and affect
● CT and MRI scan of the brain

TREATMENT

A) GOALS OF THERAPY
● The goal is to alleviate target symptoms, avoid side effects,
● improve psychosocial functioning and productivity,
● achieve compliance with the prescribed regimen,
● and involve the patient in treatment planning

B) NONPHARMACOLOGICAL THERAPY
● Psychosocial rehabilitation programs oriented toward improving patients’ adaptive
functioning are the mainstay of nondrug treatment for schizophrenia. These
programs may include basic living skills, social skills training, basic education, work
programs, and supported housing.
● Programs that involve families in the care and life of the patient have also been
shown to decrease rehospitalization and to improve functioning in the community
● Programs that involve families in the care and life of the patient have also been
shown to decrease rehospitalization and to improve functioning in the community

C) Therapeutic interventions

D) Treatment algorithm for initial therapy in an acute psychotic episode

● The goals during the first 7 days are decreased agitation, hostility, anxiety, and
aggression and normalization of sleep and eating. For first episode psychosis, the
dose range is about 50% of that of chronically ill patients.
● Titrate over the first few days to an average effective dose. Titrate iloperidone and
clozapine more slowly due to risk of hypotension. After 1 week at a stable dose, a
modest dosage increase may be considered. If there is no improvement within 3 to 4
weeks at therapeutic doses, then an alternative antipsychotic should be considered
(ie, move to the next treatment stage)
 ● Intramuscular (IM) antipsychotic administration (eg, aripiprazole 5.25–9.75 mg,
ziprasidone 10–20 mg, olanzapine 2.5–10 mg, or haloperidol 2–5 mg) can be used to
calm agitated patients. However, this approach does not improve the extent of
response, time to remission, or length of hospitalization.
● IM lorazepam, 2 mg, as needed added to the maintenance antipsychotic may be
more effective for agitation than additional doses of antipsychotic. Combining IM
lorazepam with olanzapine or clozapine is not recommended because of the risk of
hypotension, CNS depression, and respiratory depression.

E) STABILIZATION THERAPY
During the stabilization phase, acute symptoms gradually decrease in severity as the
patient begins to stabilize. The goals of treatment during the stabilization phase of the illness
are to reduce the likelihood of symptom exacerbation and to develop a plan for long-term
treatment
● Improvement is usually a slow but steady process over 6 to 12 weeks or longer.
During the first 2 to 3 weeks, goals should include increased socialization and
improvement in self-care habits and mood.
● Improvement in formal thought disorder should follow and may take an additional 6
to 8 weeks to respond. Patients who are early in the course of their illness may
experience a more rapid resolution of symptoms than individuals who are more
chronically ill.
● In general, if a patient has not received a robust decrease in positive and negative
symptoms within 8 to 12 weeks at adequate doses, then an alternate monotherapy
antipsychotic in the algorithm should be considered.
● In a more chronically ill patient, symptoms may continue to improve for 3 to 6
months. During acute stabilization, usual labeled doses of SGAs are recommended
with FGAs, a range of 300 to 1,000 mg of chlorpromazine equivalents daily is
recommended
● An optimum dose of the chosen drug should be estimated in the initial treatment
plan. If the patient begins to show adequate response before or at this dosage, then
the patient should remain at this dosage as long as symptoms continue to improve.
● However, if necessary, dose titration may continue within the therapeutic range
every week or two as long as the patient has no side effects.
● Before changing medications in a poorly responding patient, the following should be
considered:
Were the initial target symptoms indicative of schizophrenia or did they
represent manifestations of a different diagnosis ?
Is the patient adherent with pharmacotherapy?
Are the persistent symptoms poorly responsive to antipsychotics (e.g., impaired
insight or judgment, or fixed delusions)?
● Medications are effective at decreasing many of the symptoms of schizophrenia (and
are thus referred to as palliative), but they are not curative, and all symptoms may
not abate
● It is important to screen patients for co-occurring mental disorders, and their
presence may become more apparent during the stabilization or maintenance
phases of schizophrenia treatment. Examples include substance abuse disorders,
depression, obsessive-compulsive disorder, and panic disorder
 ● . Pharmacological and nonpharmacological interventions specific for the
co-occurring disorder should be implemented in combination with evidence-based
treatment for schizophrenia

F) MAINTENANCE THERAPY
• Continue medication for at least 12 months after remission of the first psychotic episode.
Lifetime pharmacotherapy is necessary in most schizophrenic patients.
• Antipsychotics (especially FGAs and clozapine) should be tapered slowly before
discontinuation to avoid rebound cholinergic symptoms.
• In general, when switching from one antipsychotic to another, the first should be tapered
and discontinued over 1 to 2 weeks while the second antipsychotic is initiated and tapered
upward.

G) Management of extrapyramidal side effects of antipsychotics

Extrapyramidal effects Description Management

Dystonia ● Dystonia is defined as a state of abnormal ● Treatment includes IM or IV

tonicity, sometimes described
simplistically as a severe “muscle spasm
● they are prolonged tonic contractions,
with a rapid onset, usually within 24 to 96
hours of dosage initiation or dosage
increase
● Types of dystonic reactions include
trismus, glossospasm, tongue protrusion,
pharyngeal-laryngeal dystonia,
blepharospasm, oculogyric crisis,
torticollis, and retrocollis.
● Dystonic reactions occur primarily with
FGAs.
anticholinergics (Table 69–4) or
benzodiazepines.
● Benztropine mesylate, 2 mg, or
diphenhydramine, 50 mg, may be
given IM or IV, or diazepam, 5 to 10
mg slow IV push
● Relief usually occurs within 15 to
20 minutes of IM injection or 5
minutes of IV administration.
● Dystonias can be minimized by
using lower initial doses of FGAs
and by using SGAs instead of FGAs.

Akathisia ● Akathisia is defined as the inability to sit ● Reduction in antipsychotic dose

still and as being functionally motor
restless.
● The most accurate diagnosis is made by
combining subjective complaints with
objective symptoms (pacing, shifting,
shuffling, or tapping feet).
● Akathisia occurs in 20% to 40% of
patients treated with high-potency FGAs
may be the best intervention.
● Alternatively, switch to an SGA,
although akathisia occasionally
occurs with the SGAs. Quetiapine
and clozapine appear to have the
lowest risk.
● Benzodiazepines may be used, but
not in patients with a history of
substance abuse.
● Propranolol (up to 160 mg/day),
nadolol (up to 80 mg/day), and
metoprolol (up to 100 mg/day) are
reported to be effective.
Pseudoparkinsonism ● Patients with pseudoparkinsonism may ● • Benztropine dosing is 1 to 2 mg
have any of four cardinal symptoms: twice daily up to a maximum of 8
a) Akinesia, bradykinesia, or decreased mg daily.
motor activity, including mask-like ● Trihexyphenidyl, diphenhydramine,
facial expression, micrographia, and biperiden usually require
slowed speech, and decreased arm three-times-daily dosing
swing ✓
b) Tremor
c) Rigidity—stiffness; cogwheel rigidity
is seen as the patient’s limbs yield in
jerky,
d) Postural abnormalities—stooped,
unstable posture and slow, shuffling,
or festinating gait
● Risk factors—FGAs (especially in high
dose), increasing age, and possibly female
gender

Tardive dyskinesia ● Tardive Dyskinesia (TD) is characterized ● Dosage reduction or

by abnormal involuntary movements discontinuation may reduce
occurring with chronic antipsychotic symptoms
therapy. ● Prevention of TD—
● The classic presentation is (1) use SGAs as first-line agents;
buccolingual-masticatory (BLM) or (2) use the DISCUS or other scales
orofacial movements. Symptoms may to assess for early signs of TD at
become severe enough to interfere with least quarterly; and
chewing, wearing dentures, speech, (3) discontinue antipsychotics or
respiration, or swallowing. switch to SGAs at the earliest
● Facial movements include frequent symptoms of TD, if possible.
blinking, brow arching, grimacing, upward
deviation of the eyes, and lip smacking
● Risk factors for TD—duration of
antipsychotic therapy, higher dose, ,
increasing age, occurrence of acute
extrapyramidal symptoms, poor
antipsychotic response, and diagnosis of
organic mental disorder, diabetes
mellitus, mood disorders, and possibly
female gender

Sedation and mood ● Sedation must be recognized as an ● Administration of most or the

antipsychotic side effect and not as an
indication of therapeutic effect.
● It occurs more frequently with
antipsychotics with antihistaminic
properties. Chlorpromazine, thioridazine,
mesoridazine, clozapine, olanzapine, and
entire daily dose at bedtime can
decrease daytime sedation and
may eliminate the need for
hypnotics
 quetiapine are most frequently
implicated

Seizures ● There is an increased risk of drug-induced ● When an isolated seizure occurs, a

seizures in all patients treated with
antipsychotics. However, this risk is
greater if the following predisposing
factors are present: preexisting seizure
disorder, history of drug-induced seizure,
abnormal electroencephalogram (EEG),
or head trauma
● The highest risk for antipsychotic-induced
seizures is with the use of chlorpromazine
or clozapine.
dosage decrease is first
recommended; anticonvulsant
therapy is not recommended.
● If a change in antipsychotic therapy
is required because of a
drug-induced seizure, risperidone,
molindone, haloperidol, pimozide,
and fluphenazine are associated
with the lowest potential

Thermoregualtion ● Hyperpyrexia can lead to heat stroke. ● Maintain environmental conditions

● Hypothermia is also a risk, particularly in
elderly patients.
● These problems are more common with
the use of low-potency FGAs and can
occur with the more anticholinergic SGAs.

Neuroleptic malignant ● Neuroleptic malignant syndrome occurs ● • Discontinue antipsychotics, and

syndrome in patients taking FGAs. It has been
reported with the SGAs, including
clozapine, but is less frequent than with
the FGAs.
provide supportive care.
● Bromocriptine reduces rigidity,
fever, or CK levels
● Amantadine has been used
successfully
● Dantrolene has been used with
favorable effects on temperature,
heart rate, respiratory rate

THERAPEUTIC DRUG MONITORING

● The Positive Symptom Rating Scale and the Brief Negative Symptom Assessment are brief
enough to be useful in the outpatient setting. Patient-rated self-assessments can also be
useful, as they engage the patient in treatment and can open the door for patient education
and addressing misconceptions.
● The brief psychiatric rating scale (BPRS) and the Positive and Negative Symptom Scale
(PANSS) were developed for use in clinical trials as research tools to quantify symptoms and
improvement seen with antipsychotic treatment
● Systematically monitor for side effects. Monitor body weight monthly for 3 months, then
quarterly. Monitor body mass index, waist circumference, blood pressure, fasting plasma
glucose, and fasting lipid profile at the end of 3 months, then annually.
 LONG-ACTING OR DEPOT INJECTABLE ANTIPSYCHOTICS

● Depot or long-acting antipsychotics are recommended for patients who are unreliable in
taking oral medication on a daily basis, and thus are not usually used as first-line therapy
● Conversion from oral therapy to a long-acting injectable is most successful in patients who
have been stabilized on oral therapy.
a) Risperidone Consta is started at 25 mg. Usual dosing range is 25 to 50 mg deep
IM every 2 weeks
b) Paliperidone palmitate is started at 234 mg and 156 mg 1 week later given in the
gluteal or deltoid muscle
c) fluphenazine decanoate, the simplest conversion is the Stimmel method—1.2
times the oral daily dose for stabilized patients, rounding up to the nearest 12.5
mg interval, administered IM in weekly doses for the first 4 to 6 weeks
 d) haloperidol decanoate, a factor of 10 to 15 times the oral daily dose is
commonly recommended, rounding up to the nearest 50-mg interval,
administered IM oncemonthly with oral haloperidol overlap for 1 month
e) Administer haloperidol and fluphenazine decanoate by a deep, “Z-track” IM
method. Inject long-acting risperidone deep IM in the gluteus maximus;
Z-tracking is not necessary

Advantages of LAI

Disadvantages of LAI

DIFFERENT TYPES OF SCHIZIPHRENIA

The DSM-4 classified the following types of schizophrenia as :

 1) PARANOID TYPE :

previously characterized a person with paranoid schizophrenia as meeting

the following criteria:

● a preoccupation with one or more delusions or frequent auditory

hallucinations
● certain symptoms — disorganized speech, disorganized or catatonic
behavior, and a lack of or inappropriate emotional response — are
not prominent
● late teens to early 20s onset

2) DISORGANIZED TYPE:
Late teens onset

3) CATATONIC TYPE

Catatonia is a crucial component of catatonic schizophrenia. Catatonia is a

type of syndrome that causes a person to have abnormal physical
movements, behaviors, and withdrawal.

A person may appear excited or withdrawn. They may also display other
symptoms, such as :

● mutism, which is being unable to speak

● echolalia, or repeating other people’s words
 ● echopraxia, which refers to mimicking other people’s actions
● depression, mania, or psychosis
● onset in early 20s

A person must have at least two symptoms of catatonia to receive a

diagnosis of catatonic schizophrenia.

4) Undifferentiated type / Hebephrenic :

5) Residual type :

(also write acute and chronic schizo from signs and symptoms )