1. University of Nizwa
College of Pharmacy and Nursing
School of Pharmacy
PHARMACOTHERAPY - I
PHCY 310
Lecture -12 Psychiatric Disorders “Schizophrenia” Dr. Sabin Thomas, M. Pharm. Ph. D. Assistant Professor in Pharmacy Practice School of Pharmacy University of Nizwa

2. Course Outcome
Upon completion of this lecture the students will be able to
Describe pathophysiology, diagnosis, and therapeutic choices including non-pharmacologic and pharmacologic treatments for schizophrenia,
Explain the different phases of treatment in schizophrenia.

3. Pathophysiology
Schizophrenia is usually a lifelong psychiatric disability.
Psychosis may result from hyper- or hypoactivity of dopaminergic processes in specific brain regions.
This may include the presence of a dopamine (DA) receptor defect.
Clinical presentation
Symptoms of the acute episode may include the following: being out of touch with reality; hallucinations (especially hearing voices); delusions (fixed false beliefs); ideas of influence (actions controlled by external influences); disconnected thought processes (loose associations); ambivalence (contradictory thoughts); flat, inappropriate, or labile affect; autism (withdrawn and inwardly directed thinking); uncooperativeness, hostility, and verbal or physical aggression; impaired self-care skills; and disturbed sleep and appetite.

4. Psychosis is brain disorder in which there is loss of
contact with reality, affecting the ability to think, feel,
perceive and act.
Investigations
1- History
- Withdrawal from usual activities with friends and family
- Rapid fluctuations in mood (emotional lability)
- Unreasonable suspiciousness
- Unusual or bizarre behaviour
- Hallucinations
- Difficulties in thinking or expressing thoughts
2- Clinical rating scales to monitor the psychotic event
- Clinical Global Impression Scales for Severity (CGI-S)
- Clinical Global Impression Scales for Change (CGI-C)
- Global Assessment of Functioning (GAF)

5. Therapeutic Choices
Nonpharmacologic Choices
- Medication adherence
- Family psychoeducation
- Assessment of postpsychotic depression and suicidality
Pharmacologic Choices
There are two major classes of antipsychotics:
First-generation (typical) antipsychotics (FGAs): e.g., fluphenazine, trifluoperazine, chlorpromazine, haloperidol, and pimozide.
Second-generation (atypical) antipsychotics (SGAs): e.g., aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and paliperidone.
Paliperidone is the active metabolite of risperidone, and
it is not metabolized by the liver. Therefore it has less drug-drug interactions compared to other antipsychotics.

6. INITIAL THERAPY
The goals during the first 7 days are decreased agitation, hostility, anxiety, and aggression and normalization of sleep and eating patterns.
In general, titrate over the first few days to an average effective dose.
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.
IM antipsychotic administration (e.g., ziprasidone 10 to 20 mg, olanzapine 2.5 to 10 mg, or haloperidol 2 to 5 mg) can be used to calm agitated patients.
Intramuscular (IM) lorazepam, 2 mg, as needed in combination with the maintenance antipsychotic may actually be more effective in controlling agitation than using additional doses of the antipsychotic.

7. STABILIZATION THERAPY
During weeks 2 and 3, the goals should be to improve socialization, selfcare habits, and mood.
Improvement in formal thought disorder may require an additional 6 to 8 weeks.
Most patients require a dose of 300 to 1,000 mg of CPZ equivalents (of FGAs) daily or SGAs in usual labeled doses.
Dose titration may continue every 1 to 2 weeks as long as the patient has no side effects.
If symptom improvement is not satisfactory after 8 to 12 weeks, a different strategy should be tried.

8. MAINTENANCE THERAPY
Medication should be continued for at least 12 months after remission of the first psychotic episode.
Continuous treatment is necessary in most patients at the lowest effective dose.
Antipsychotics (especially FGAs and clozapine) should be tapered slowly before discontinuation to avoid rebound cholinergic withdrawal symptoms.