The document discusses the pharmacotherapy of schizophrenia. It begins by outlining the objectives of recognizing symptoms, explaining pathophysiology, identifying treatment goals, and comparing antipsychotic medications. It then covers the introduction, etiology, types, pathophysiology, signs and symptoms, and management of schizophrenia including current practices. Management involves psychosocial interventions, medications, and ECT. Treatment is divided into acute, stabilization, and maintenance phases. The document provides recommendations for antipsychotic selection and monitoring side effects. It acknowledges controversies around first-generation versus second-generation antipsychotics and long-acting injections.

1. PHARMACOTHERAPY OF SCHIZOPHRENIA
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2. CONTENT
 Introduction
 Etiology
 Pathophysiology
 Signs and symptoms
 Management
 Current Clinical Practices At WSUCSH
 Recommendations
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3. Objectives
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 Recognize signs and symptoms of schizophrenia
 Explain potential pathophysiologic mechanisms
that are thought to underlie schizophrenia.
 Identify treatment goals for a patient with
schizophrenia.
 Recommend appropriate antipsychotic
medications based on patient-specific data.
 Compare side effect profiles of individual
antipsychotics.

4. INTRODUCTION
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 Schizophrenia literally means “Fragmented Mind”.
 Schizophrenia is one of the most complex, chronic
and challenging of psychiatric disorders that affects
how a person thinks, feels, behaves.
 It represents a heterogeneous syndrome of
disorganized thoughts, delusions, hallucinations,
and impaired psychosocial functioning.
 The prevalence of schizophrenia ranges from 0.6%
to 1.9%, with an average of approximately
1%.(Reeves et al., 2011)

5. Cont...
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 Prevalence is equal in men and women, but
symptoms appear earlier in men with first
hospitalization typically occurring at 15 to 24 years
compared to 25 to 34 years in women. (Saha et al.,
2005)
 In Ethiopia the overall Prevalence were 0.4% and
0.3%, for schizophrenia 0.5% and 0.4% for
schizoaffective disorders, respectively.(Kassa and
Abajobir, 2018)

6. ETIOLOGY
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 The exact cause of the disease is unknown.
 Genetics, environment, psychological and social
processes.

7. TYPES
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 Paranoid schizophrenia
 Common form of schizophrenia
 Prominent hallucinations and/or delusions
 Speech and emotions may be unaffected
 At risk for suicidal or violent behavior under
influence of delusions
 May develop at a later age than other types of
schizophrenia.

8. Cont.…
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 Hebephrenic / Disorganized schizophrenia
 Behavior is disorganized and without purpose
 Thoughts are disorganized, difficult to understand by
others.
 Delusions and hallucinations are fleeting
 Usually develops between 15-25
 Catatonic schizophrenia
 Rarer than other types
 At risk for malnutrition, exhaustion or self-injury
 Unusual movements, often switching between extremes of
overactivity and stillness
 Unable to talk (Catatonia)

9. Cont.…
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 Undifferentiated schizophrenia
 Some characteristics of paranoid, hebephrenic or
catatonic schizophrenia, but does not obviously fit
one of these types.
 Residual schizophrenia
 Past History of psychosis but only having negative
symptoms

10. PATHOPHYSIOLOGY
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11. Cont.…
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12. Cont.…
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 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.
 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.

13. SIGNS & SYMPTOMS
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14. Cont.…
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 The Diagnostic and Statistical Manual for Mental
Disorders (DSM-5) identifies five symptoms for
diagnosis
 At least two of the following symptoms must be
present for at least 1 month, and at least one of
the symptoms should be
 delusions, hallucinations, or disorganized speech.
 Continuous signs of disturbance must be present
for at least 6 months.

15. MANAGEMENT
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 General approach
 Psychosocial Interventions
 Cognitive Behavioral Therapy
 Pharmacological
 Electroconvulsive Therapy

16. Cont.…
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 Clinical Management
 Acute Phase (Initial Presentation) 4 to 8 weeks :
Defined by acute psychotic episode
 Stabilization Phase (Early symptom remission) as
long as 3 months.
 Stable Phase (Maintenance treatment) : Involves
stable treatment

17. Cont.…
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 Pharmacotherapeutic algorithm for schizophrenia.
 Stage 1A
 Applies to those patients experiencing their first
acute episode of schizophrenia.
 Studies suggest that the use of SGAs during the first
acute episode results in greater treatment retention
and are more effective in preventing a second
psychotic episode compared to FGAs. (Hasan et al.,
2013)
 In addition, SGAs carry a reduced risk of EPS.

18. Cont.…
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 Because first-episode patients demonstrate
greater sensitivity to adverse effects, antipsychotic
dosing should be initiated at the lower end of the
dose range.(Kane et al.)
 Among the SGAs,aripiprazole, olanzapine,
quetiapine, risperidone, and ziprasidone have
evidence of efficacy in first-episode
patients.(Goldman et al., 2017)

19. Cont.…
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 Stage 1B
 addresses pharmacotherapy of a patient who was
previously treated with an antipsychotic, and
treatment is being restarted because the patient
stopped taking the medication.
 If during the initial antipsychotic trial
 the patient Experienced a robust improvement in
symptoms, good tolerability, and the patient is
positive about taking this antipsychotic again,
then that medication can be restarted.

20. Cont.…
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 Stage 2
 Addresses pharmacotherapy in a patient who had
inadequate clinical improvement with the
antipsychotic used in stage 1A or 1B.
 Stage 2 recommends antipsychotic monotherapy
with an FGA or SGA not used in stage 1 or
stage1B.(Bajor et al., 2011)
 Because of safety concerns and the need for white
blood cell (WBC) monitoring, clozapine is not
generally recommended at stage 2.(Bajor et al.,
2011)

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 However, clozapine has superior efficacy in
decreasing suicidal behavior, and it should be
considered at stage 2 for the suicidal
patient.(Remington et al., 2017)
 Clozapine can also be considered at stage 2 in
patients with a history of violence or comorbid
substance abuse.(Bajor et al., 2011)
 Long-acting injectable antipsychotics(LAIAs)
should be considered as an optionat stage 2.

22. Cont.…
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 Stage 3
 Poor symptom improvement with two different
antipsychotic trials at appropriate dose and
duration.
 the recommended treatment is clozapine.
 stage 4
 Only minimal evidence exists for any treatment
option for those patients who do not have
adequate symptom improvement with clozapine.

23. Initial Treatment in an Acute
Psychotic Episode
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 The goals during the first 7 days of treatment should be
decreased agitation, hostility, anxiety, tension, and
aggression, and normalization of sleep and eating
patterns.
 The usual recommendation is to initiate therapy and to
titrate the dose over the first few days to an average
effective dose.
 Intramuscular (IM) antipsychotic administration (eg,
aripiprazole 5.25-9.75 mg IM, haloperidol 2-5 mg IM,
olanzapine 2.5-10 mg IM, or ziprasidone 10-20 mg IM) can
be used to assist in calming a severely agitated patient.

24. Cont.…
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 If the patient is receiving an antipsychotic within
the usual therapeutic range, the use of lorazepam
2 mg IM as needed in combination with the
maintenance antipsychotic is a rational alternative
for treatment of aggression.

25. Stabilization Therapy
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 Symptom improvement may occur over 6 to 12
weeks
 During the first 2 to 3 weeks, goals should
include increased socialization and improvement
in self-care habits and mood.
 In general, if a patient has shown no improvement
after 2 weeks of treatment at therapeutic doses
 only a partial decrease in positive symptoms
within 8 to 12 weeks at adequate doses, then the
next algorithm stage should be considered.

26. Maintenance Treatment
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 Maintenance drug therapy prevents relapse, as
shown in numerous double-blind studies, and
avoiding relapse is a major goal of treatment.
 The average relapse rate after 1 year is 18% to
32% with active drug (including some
nonadherent patients) versus 60% to 80% for
placebo.(Bajor et al., 2011)
 After treatment of the first psychotic episode in a
patient with schizophrenia, medication should be
continued for at least 18 months after
remission.(Remington et al., 2017)

27. Treatment Adherence
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 Antipsychotic nonadherence is estimated to occur
in at least 40% to 50% of patients with
schizophrenia.
 For patients who have
 Relapsed several times because of nonadherence
 have a history of dangerous behavior, or risk a
significant loss of social or vocational gains when
relapsed
 treatment with long-acting injection (LAI) should
be encouraged.

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29. Side effect
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30. Cont.…
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31. Adjunct Treatments
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 Pharmacologic therapies other than
antipsychotics is often necessary for the treatment
of motor side effects, anxiety, depression, mood
elevation.
 Anticholinergic medications (eg, benztropine, 1–2
mg twice daily; trihexyphenidyl, 1–3 mg thrice
daily; and diphenhydramine, 25–50 mg twice
daily) are used to treat EPS.
 β-Blockers (eg, propranolol 30–120 mg/day) are
sometimes effective for patients who develop
akathisia.

32. CONTROVERSY
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 With the introduction of SGAs in the 1990s, the use of
FGAs has progressively decreased, and FGAs have less than
10% market share of the antipsychotics used for
schizophrenia.
 This decline occurred because of the touted better side
effect profile and other possible benefits of SGAs in
nonpsychotic domains of the illness.
 However, a large landmark study (the Clinical
Antipsychotics Trials of Intervention Effectiveness [CATIE
trial]; The study revealed that the FGA was equal to the
SGAs for the primary endpoint of time to discontinuation
of medication. (Lieberman et al., 2005)

33. Cont.…
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 SGAs have historically been much more expensive than the
FGAs
 When selecting an antipsychotic, the risk-to-benefit profile
becomes fundamental and the varying side effect profiles
must be considered.
 Early studies did not consistently demonstrate an
advantage of long-acting injectable antipsychotics (LAIAs)
over oral agents.
 In contrast,recent studies, designed to reflect real-world
practices, have more consistently demonstrated an
advantage in reduced hospitalizations and relapse
prevention in patients with schizophrenia.(Citrome, 2013)

34. Cont.…
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 Combining an FGA with an SGA and combining different
SGAs have been suggested as intervention strategies for
treatment-resistant patients.
 there is limited rationale to explain how combinations of
antipsychotics would produce enhanced efficacy, but
increased side effects, particularly increased EPS,
metabolic effects, and hyperprolactinemia, are possible
results.
 The evidence to support antipsychotic combinations is
scant at best, and recent treatment guidelinesstate that
there is insufficient evidence to support this
practice.(Remington et al., 2017)

35. Current Clinical Practices At
WSUCSH
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 Emergency phase
 First line Haloperidol, 5-10mg I.M./I.V. over 30-60 minutes. Daily dose
may go as high as 40mg.
 Stabilization phase
 First line Haloperidol, 1-15mg/day P.O.
 Alternative Chlorpromazine, 75-300mg/P.O., in divided doses.
 Maintenance (chronic therapy)
 First line Haloperidol, 1-15mg/day P.O.
 Alternatives Chlorpromazine, 75-300mg/day P.O. QD. in divided doses.
 OR Fluphenazine decanoate, 12.5-100mg IM every 3-4 weeks
 Adjunct treatment
 Trihexyphenidyl, oral, initial 1 mg/day; increase as necessary to usual
range: 5-15mg/day in 3-4 divided doses

36. Recommendations
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 For Multi-disciplinary Team
 Monitor appropriate laboratory measures to prevent or minimize
adverse effects, including metabolic abnormalities
 For clinical pharmacist team
 Educate patient and caregiver (with patient consent) about the illness,
medication treatments, possible side effects, and goals of treatment.
 Discuss medication adherence and healthy lifestyle goals, including
substance and cigarette use.
 Select or optimize the dose of an antipsychotic based on the side effect
profile that is most appropriate and acceptable to the patient.

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