Samir

(Schizophrenia)

 Introduction: the most debilitating psychiatric illnesses, chronic characterized by episodes of

psychosis and abnormal behavior lasting > 6 months.

 Psychosis is defined as a distorted perception of reality in which patients experience delusions,

hallucinations, and disordered thinking

 Delusions are false beliefs about oneself or others, that persist despite the facts and hallucinations

 Genetic factors likely contribute to the development of schizophrenia

 Symptoms:

 Positive :

1) Delusions: grandiose, paranoid

2) Strange behavior/disorganization.

3) Hallucinations: Typically auditory (40–80%)

Samir

 Negative :

1) Social withdrawal.

2) Flat affect: Patient talks in a monotone voice and does not show any emotion.

3) Thought blocking: Patient starts talking about a topic but stops in midsentence and is unable to

continue with what he was saying.

4) Lack of motivation

5) Poverty of speech

 Diagnosis: requires that two or more of the three symptoms present that for at least 1 month:

 Hallucinations

 Delusions

 Negative symptoms

 Symptoms cause significant impairment in daily living.

Samir

 Symptoms are not due to any other medical condition or substance abuse

 The cause: Hyperactivity of dopaminergic at the mesolimbic pathway, serotonergic at the

cortex.
Samir

 The treatment:

 First-Generation: Chlorpromazine, trifluoperazine, fluphenazine (high potency)and

haloperidol

 Mechanism: blocking postsynaptic D2 receptors. The low-potency drugs (chlorpromazine,

thioridazine) also have an affnity for muscarinic ACh receptors, α-adrenergic receptors,

and histaminergic receptors and High-potency drugs (haloperidol) have greater affinity for

D2 receptors.

 Uses: treatment of acute psychosis, schizophrenia and bipolar disorder. Haloperidol can be
used in Tourette syndrome (to control tics) and Huntington disease (to combat chore form
movements associated with advanced disease).
 side effects :
1) Extrapyramidal symptoms, due to dopamine blockade of the nigrostriatal pathway
2) Acute dystonia (hours): Muscle spasm/stiffness; treat with diphenhydramine
Samir

 Second-Generation (Atypical) :Clozapine, ,olanzapine,quetiapine, ziprasidone, risperidone,

aripiprazole.

 mechanisms the serotonergic, dopaminergic (with affnity for D2), and noradrenergic systems.

Each medication has a different neuroreceptor profle,

 uses: effective with negative and chronic symptoms of schizophrenia (eg, avolition, alogia,

flattened affect risk of tardive dyskinesia, neuroleptic malignant syndrome, and

extrapyramidal signs is lower

 Uses: schizophrenia, psychosis, bipolar disorder syndrome, and for antidepressant

augmentation (aripiprazole, quetiapine).

Samir

 Side effects:

 Cardiotoxicity and Neuroleptic malignant syndrome: Fever, rigidity, mental status

changes, and autonomic instability. Discontinue the drug and treat with dantrolene and
dopamine agonists.
 Extrapyramidal signs:

1) Akathisia (days): Restlessness; treat with β-blockers (propanolol).

2) Bradykinesia/parkinsonism (weeks): Treat with benztropine.

3) Tardive dyskinesia (months-years): Stereotypic oral-facial movements; irreversible.

4) Agranulocytosis (clozapine): Requires weekly WBC monitoring for the frist 6

months.

5) Seizures and Weight gain (clozapine, olanzapine).

6) Insulin intolerance, leading to type 2 diabetes (for some second-generation agents, this

side effect may be unrelated to weight gain).

Samir

7) Hyperlipidemia.

8) Electrocardiogram abnormalities (prolongation of QT and PR intervals may occur

with ziprasidone).

9) Increase in prolactin levels (gynecomastia, galactorrhea, and amenorrhea especially

with risperidone).

10) Ziprasidone and aripiprazole have fewer metabolic side effects than do the other

second generation antipsychotics.

11) Hyperprolactinemia, due to dopamine blockade in the tuberoinfundibular

pathway (dopamine inhibits prolactin release).

 Anticholinergic side effects (low-dose antipsychotics):

a) Irreversible retinal pigmentation (thioridazine).

b) Corneal and lens deposits (chlorpromazine).

Samir

 Management and prognosis:

 psychosocial interventions ( family, individual, and behavioral therapy).

 Haloperidol decanoate is an example of a long-acting injectable medication that can be useful

for non compliant or poorly compliant psychotic patients

Samir

 The adventage of atypical antipsychotics increased the utility of these agents for the treatment

of patients with psychotic symptoms because they lack the side effects associated with earlier

antipsychotics (Parkinsonism and tardive dyskinesia).

 A continued treatment over several years is required that is associated with frequent treatment

noncompliance and recurrent psychotic episodes.

 Earlier onset of schizophrenia may impair normal brain development and has been shown to

indicate a poor prognosis.

 Better prognosis is highly associated with community support

 Positive symptoms generally respond better than negative symptoms to typical

antipsychotics.

 Negative symptoms generally respond better to atypical antipsychotics.

 Clozapine:for resistant cases.