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Psikotik
Acute and transient psychotic disorders
Acute onset is defined as a change from a state without
psychotic features to a clearly abnormal psychotic state,
within a period of 2 weeks or less.
 The order of priority used here is:
an acute onset (within 2 weeks) as the defining feature of the
whole group;
the presence of typical syndromes;
the presence of associated acute stress
the absence of organic causation, such as states of concussion,
delirium, or dementia.
 typical syndromes
the rapidly changing and variable state, called here
"polymorphic", that has been given prominence in acute
psychotic states in several countries, and second, the
presence of typical schizophrenic symptoms
 Associated acute stress
Typical events would be bereavement, unexpected loss of
partner or job, marriage, or the psychological trauma of
combat, terrorism, and torture.
 Complete recovery usually occurs within 2 to 3 months,
often within a few weeks or even days, and only a small
proportion of patients with these disorders develop
persistent and disabling states
Prognosis
 Schizophrenia
Schizophrenia is a severe, persistent, debilitating, and poorly
understood psychiatric disorder that probably comprises
several separate illnesses.
Schizophrenia is a clinical diagnosis
People with schizophrenia have lower rates of employment,
marriage, and independent living than other people do.
Hallmark symptoms of schizophrenia are psychotic ones,
such as auditory hallucinations (voices) and delusions (fixed
false beliefs). Impaired cognition or a disturbance in
information processing is a less vivid symptom that is highly
disruptive.

http://emedicine.medscape.com/article/288259 - updated 8th April 2013

Etiology
The causes of schizophrenia are not known.
Most likely, there are at least 2 sets of risk factors, genetic
and perinatal.
Genetics
The risk of schizophrenia is elevated in biologic relatives of persons with
schizophrenia but not in adopted relatives.
The risk of schizophrenia in first-degree relatives of persons with
schizophrenia is 10%. If both parents have schizophrenia, the risk of
schizophrenia in their child is 40%.
Some people with schizophrenia have no family history of the disorder.
These cases may be the result of new mutations.
 The COMT gene codes for the postsynaptic intracellular enzyme,
COMT, which is involved in the methylation and degradation of the
catecholamine neurotransmitters dopamine, epinephrine, and
norepinephrine.
The RELN gene codes for the protein reelin, which plays a role in brain
development and GABAergic activity. In an international study using a
genome-wide association scan, a common variant in this gene increased
the risk of schizophrenia, but only in women.
The NOS1AP gene codes for the enzyme nitric oxide synthetase, which
is found in high concentration in inhibitory neurons in the brain
researchers have identified a single-nucleotide polymorphism
associated with higher levels of expression of this gene in postmortem
brain samples from individuals with schizophrenia
 Perinatal factors
Women who are malnourished or who have certain viral illnesses during
their pregnancy may be at greater risk of giving birth to children who
later develop schizophrenia.
Ex : children born to Dutch mothers who were malnourished during
World War II have a high rate of schizophrenia.
Obstetric complications may be associated with a higher incidence of
schizophrenia. Children born in the winter months may be at greater risk
for developing schizophrenia.
pathophysiology
Both anatomic and neurotransmitter system abnormalities
have been implicated in the pathophysiology of
schizophrenia.
Anatomic abnormalities
Neuroimaging studies in patients with schizophrenia show abnormalities
such as enlargement of the ventricles, decreased brain volume in medial
temporal areas, and changes in the hippocampus.
In the Edinburgh High-Risk Study, brain imaging showed reductions in
whole-brain volume and in left and right prefrontal and temporal lobe
volumes in 17 of 146 people who were at high genetic risk for
schizophrenia.
The changes in prefrontal lobes were associated with increasing severity
of psychotic symptoms.
 Neurotransmitter system abnormalities
Abnormalities of the dopaminergic system are thought to exist in
schizophrenia
little direct evidence to support this belief.
Hypodopaminergic activity in the mesocortical system, leading to
negative symptoms, and hyperdopaminergic activity in the mesolimbic
system, leading to positive symptoms, may coexist.
Clozapine, perhaps the most effective antipsychotic agent, is a particularly
weak dopamine D2 antagonist.
Drugs that diminish the firing rates of mesolimbic dopamine D2 neurons
are antipsychotic, and drugs that stimulate these neurons (eg,
amphetamines) exacerbate psychotic symptoms.
 Inflammation and immune function
Immune system function is disturbed in schizophrenia.
Overactivation of the immune system (eg, from prenatal infection or
postnatal stress) may result in overexpression of inflammatory cytokines
and subsequent alteration of brain structure and function.
For example, schizophrenic patients have elevated levels of
proinflammatory cytokines that activate the kynurenine pathway, by
which tryptophan is metabolized into kynurenic and quinolinic acids;
these acids regulate NMDA receptor activity and may also be involved in
dopamine regulation.
Insulin resistance and metabolic disturbances, which are common in the
schizophrenic population, have also been linked to inflammation.
Epidemiology
Prevalence estimates from countries considered least developed
were significantly lower than those from countries classed as
emerging or developed.
People with schizophrenia have a 5% lifetime risk of suicide
Mortality is also increased because of medical illnesses, which
result from a combination of unhealthy lifestyles, side effects of
medication, decreased health care, and perhaps even some
fundamental vulnerability to medical comorbidities.
The onset of schizophrenia is later in women than in men, and the
clinical manifestations are less severe. This may be because of the
antidopaminergic influence of estrogen.
Classification
Schizophrenia can be divided into the following types on the
basis of the symptom pattern:
Paranoid schizophrenia This is characterized by delusions and
auditory hallucinations but relatively normal intellectual
functioning and affect. Delusions of persecution or grandeur are
common
Disorganized schizophrenia This involves both speech and
behavior, as well as flattened or inappropriate emotions
Catatonic schizophrenia This is characterized by disturbances
of movement that may render the person incapable of caring for
himself or herself
Undifferentiated schizophrenia
 Residual schizophrenia is the term used to describe the
illness of a person who has a history of at least 1 episode of
schizophrenia but who currently has rather mild symptoms.
Patients with residual schizophrenia may progress to
complete remission or continue in this state for years
without experiencing any further psychotic episodes.
Clinical presentation (history)
Information about the medical and psychiatric history of the
family, details about pregnancy and early childhood, history
of travel, and history of medications and substance abuse are
all important.
The patient usually had an unexceptional childhood
family members may describe the person with schizophrenia as
a physically clumsy and emotionally aloof child.
The child may have been anxious and preferred to play by
himself or herself.
The child may have been late to learn to walk and may have
been a bedwetter.
 A noticeable change in personality and a decrease in
academic, social, and interpersonal functioning often begin
during mid-to-late adolescence.
The first psychotic episode usually occurs between the late
teenage years and the mid-30s.
 The symptoms of schizophrenia may be divided into the following 4
domains:
Positive symptoms These include psychotic symptoms, such as
hallucinations, which are usually auditory; delusions; and disorganized
speech and behavior
Negative symptoms These include a decrease in emotional range,
poverty of speech, loss of interests and drive; the person with schizophrenia
has tremendous inertia
Cognitive symptoms These include neurocognitive deficits (eg, deficits
in working memory and attention and in executive functions, such as the
ability to organize and abstract); patients also find it difficult to understand
nuances and subtleties of interpersonal cues and relationships
Mood symptoms Schizophrenia patients often seem cheerful or sad in a
way that does not make sense to others; they often are depressed
Clinical presentation (physical
examination)
Findings on a general physical examination are usually not
contributory.
This examination is necessary to rule out other illnesses.
Mental Status Examination
the following observations may be made in the severely ill person:
The patient may be dressed oddly (eg, may be wearing heavy jackets in
the summer)
The patient may pay insufficient attention to personal hygiene
The patient may be unduly suspicious of the examiner or be socially
awkward
 The patient may express a variety of odd beliefs or delusions
The patient often has a flat affect (ie, little range of expressed emotion)
The patient may admit to hallucinations or respond to auditory or visual
stimuli that are not apparent to the examiner
The patient may show thought blocking, in which long pauses occur
before he or she answers a question
The patients speech may be difficult to follow because of the looseness of
his or her associations; the sequence of thoughts follows a logic that is
clear to the patient but not to the interviewer
Conversation and initiation of speech may be limited
The patient has difficulty with abstract thinking, demonstrated by inability
to understand common proverbs or idiosyncratic interpretation of them
 The speech may be circumstantial (ie, the patient takes a long time and
uses many words in answering a question) or tangential (ie, the patient
speaks at length but never actually answers the question)
The patient often shows poor attention
The patients thoughts may be disorganized, stereotyped or perseverative
The patient may make odd movements (which may or may not be related
to neuroleptic medication)
The patient may have little insight into his or her problems (the term for
this is anosognosia)
Patients may have thoughts about hurting or harming themselves or
others or may hear voices telling them to commit some kind of violence;
note that suicide is not uncommon in people with schizophrenia, but
violence towards others is uncommon
Orientation is usually intact (ie, patients know who and where they are
and what time it is)
 Persons with schizophrenia may display strange and poorly
understood behaviors.
These include :
drinking water to the point of intoxication,
staring at themselves in the mirror,
performing stereotyped activities,
hoarding useless objects
and mutilating themselves.
Their wake-sleep cycle may be disturbed.
They often experience difficulty dealing with change.
Criteria diagnostic
According to the American Psychiatric Associations
Diagnostic and Statistical Manual of Mental Disorders,Text Revision
(DSM-IV-TR),
to meet the criteria for diagnosis of schizophrenia, in most
cases the patient must have experienced at least 2 of the
following symptoms :
Delusions
Hallucinations
Disorganized speech
Disorganized or catatonic behavior
Negative symptoms
 Only 1 symptom is required under the following
circumstances:
The delusions are bizarre
Auditory hallucinations occur in which the voices comment in
an ongoing manner on the persons behavior
Two or more voices are talking with each other
The patient must experience at least 1 month of symptoms
(or less if successfully treated) during a 6-month period, with
social or occupational deterioration problems occurring over
a significant amount of time.
These problems must not be attributable to another
condition.
Workup
Approach Considerations
Schizophrenia is not associated with any characteristic
laboratory results.
The following blood tests should be performed on all patients,
both at the beginning of the illness and periodically afterwards:
Complete blood count (CBC)
Liver, thyroid, and renal function tests
Electrolyte, glucose, vitamin B12, serum methylmalonic acid, folate, and
calcium levels
 Neuropsychological testing may be considered; determination
of the patients cognitive weaknesses and strengths can be
helpful in treatment planning. Common findings in patients
with schizophrenia are as follows:
Poor executive functioning (ie, poor planning, organizing, or initiation of
activities)
Impaired memory
Difficulty in abstraction and recognizing social cues
Easy distractibility
Differential diagnosis
other problems to be considered
in the differential diagnosis of
schizophrenia include the
following:
Other psychiatric illnesses
Anatomic lesions
Metabolic illnesses
Endocrine disorders
Infectious illnesses
Miscellaneous disorders
Vitamin deficiency
Alcohol-Related Psychosis
Bipolar Affective Disorder
Brief Psychotic Disorder
Cocaine-Related Psychiatric
Disorders
Delusional Disorder
Depression
Mental Disorders Secondary to
General Medical Conditions
Schizoaffective Disorder
Schizophreniform Disorder
Shared Psychotic Disorder
Therapy
Essential update: FDA approves once-monthly
aripiprazole for maintenance therapy in schizophrenia
The US Food and Drug Administration (FDA) approved a once-
monthly, long-acting agentaripiprazole
in late February 2013, for the maintenance treatment of adults with
schizophrenia. Aripiprazole, an intramuscular (IM) depot
formulation, was approved after a phase 3, double-blind, placebo-
controlled trial of the drug yielded positive results.
The study found that adult outpatients who received monthly IM
injections of aripiprazole had a significantly greater delay in time to
relapse and a significantly lower rate of relapse than did their
counterparts who received placebo
 The Schizophrenia Patient Outcomes Research Team (PORT)
of the University of Maryland recommends that any
antipsychotic medication, with the exceptions of
clozapine and olanzapine, can be used as first-line
treatment for patients with schizophrenia who are
experiencing their first episode of acute positive symptoms
adverse side-effect profile of clozapine and the significant
metabolic risks associated with olanzapine,
PORT notes that early treatment with antipsychotic drugs is
associated with significant symptom reduction and that first-
and second-generation antipsychotics may have equivalent
significant short-term efficacy.
 PORT recommends starting antipsychotic treatment for the
former at doses lower than those recommended for the
latter.
An exception is quetiapine, which may not be effective in
lower doses
 There is no clear antipsychotic drug of choice for
schizophrenia.
Clozapine is the most effective medication but is not
recommended as first-line therapy. It has a high burden of
side effects and requires regular blood work.
If the patient has not responded to a medication, physicians
can switch medications or add another one. Using 2 or even
3 different antipsychotic agents together is common,
 Clozapine
Clozapine is the oldest atypical antipsychotic agent and probably the
most effective.
associated with about a 1% risk of agranulocytosis, patients must
undergo white blood cell (WBC) count monitoring every week for
the first 6 months, then every 2 weeks for 6 months, and finally every
4 weeks, as long as the absolute neutrophil count (ANC) is normal
If the ANC drops, a strict protocol of monitoring and possibly
medication cessation must then be followed.
associated with anticholinergic adverse effects, sedation, and
drooling. Constipation and cardiac side effects (cardiomyopathy and
myocarditis) can be life-threatening.
 Loxapine inhaled
Loxapine inhaled (Adasuve) is the first noninjectable therapy to
treat acute agitation associated with schizophrenia and bipolar I
disorder.
 The following are adverse effects typically associated with
conventional antipsychotic agents and with risperidone, a
novel antipsychotic agent, at dosages higher than 6 mg/day:
Akathisia
Dystonia
Hyperprolactinemia
Neuroleptic malignant syndrome(NMS)
Parkinsonism
Tardive dyskinesia (TD)
 Anticholinergic effects
Anticholinergic side effects occur with most antipsychotics
(though risperidone, aripiprazole, and ziprasidone are relatively
free of them). Such effects include the following:
Dry mouth
Exacerbation of glaucoma
Confusion
Decreased memory
Agitation
Visual hallucinations
Constipation
 Antipsychotic agents are the mainstay of medical treatment
of schizophrenia.
These medications diminish the positive symptoms of
schizophrenia and prevent relapses.
The second-generation (novel or atypical) antipsychotic
drugs may be more effective in treating negative symptoms
and cognitive impairment.
All medications should be given at lower dosages in children
and elderly patients and used with great caution in women
who are pregnant or breastfeeding.
 1st generation of anti psychotic therapy
strong dopamine D2 antagonists.
have a high rate of extrapyramidal side effects, including rigidity,
bradykinesia, tremor, and akathisia.
first-generation antipsychotics have large cost advantages over
second-generation antipsychotics.
Chlorpromazine (Thorazine)
Fluphenazine hydrochloride (Prolixin)
Haloperidol (Haldol, Haldol Decanoate, Haloperidol LA, Peridol)
Perphenazine (Trilafon)
Thiothixene (Navane)
Trifluoperazine (Stelazine)
Loxapine inhaled (Adasuve)
 2nd generation of anti psychotic therapy
Second-generation antipsychotics are also known as atypical
antipsychotics.
exception of aripiprazole, are dopamine D2 antagonists.
associated with lower rates of extrapyramidal side effects and
TD than the first-generation antipsychotics are; however, they
have higher rates of metabolic side effects and weight gain.

 Aripiprazole (Abilify)
Asenapine (Saphris)
Clozapine (Clozaril)
Iloperidone (Fanapt)
Lurasidone (Latuda)
Olanzapine (Zyprexa)
Paliperidone (Invega)
Quetiapine (Seroquel)
Risperidone (Risperdal , Risperdal Consta, Risperdal M-Tab)
Ziprasidone (Geodon)
Psychosocial Interventions
The best-studied psychosocial treatments are
social skills training,
cognitive behavioral therapy,
cognitive remediation,
and social cognition training.
the goals of treatment for a person with schizophrenia are as
follows:
To have few or stable symptoms
Not to be hospitalized
To manage his or her own funds and medications
To be either working or in school at least half-time
 Some studies have found that family therapy or family
interventions may prevent relapse, reduce hospital admission,
and improve medication compliance
Most patients with schizophrenia smoke.
This may be a result of previous conventional antipsychotic
treatment, as nicotine may ameliorate some of the adverse
effects of these drugs.
Smoking may also be related to the boredom associated with
hospitalizations, the peer pressure from other patients to
smoke, or the anomie associated with unemployment.
Complications
Depression
Substance abuse
Anxiety
Violance
Prognosis
Full recovery is unusual
Early onset of illness, family history of schizophrenia, structural brain
abnormalities, and prominent cognitive symptoms are associated with a
poor prognosis.
The prognosis is better for people living in low-income and middle-
income countries.
Positive symptoms respond fairly well to antipsychotic medication, but
the other symptoms are quite persistent.
People with schizophrenia have a 5% lifetime risk of suicide.
Because of vocational difficulties, many patients with schizophrenia also
have to cope with the burdens of poverty.
Other factors that contribute to an increased mortality in people with
schizophrenia include lifestyle issues such as cigarette smoking, poor
nutrition, and lack of exercise, and perhaps poorer medical care and
complications of medications
Patient Education
teaching the patient to understand the importance of
medication compliance and abstinence from alcohol and
other drugs of abuse is important.
Working with the patient so that patient and family can learn
to recognize early signs of a decompensation (eg, insomnia or
increased irritability) is helpful.
Social skills training is helpful, but the effects are not long-
lived.
Physical illnesses in schizophrenia are common. The
importance of a healthy lifestyle and regular health care
should be stressed.