Chap 16: Treatment of Psychosis and Mania Short Term Antipsychotic Treatment

- For disorders with transient symptoms

- Only administered during and shortly after periods
First-Generation Antipsychotics of symptom exacerbation
- Low potency D2 antagonists - Discontinued after resolution of psychotic symptoms
o Chlorpromazine o Bipolar disorder
- Medium-to-High Potency D2 antagonists ▪ Treatment may extend for several
months after resolution of mania
o Haloperidol and psychosis because
o Fluphenazine antipsychotics help prevent mania
o Trifluoperazine relapse
o Thiothixene Delirium, Dementia, and Parkinson Disease Psychosis
- Treated with low-dose medications, but may have to
o Perphenazine be repeated at frequent intervals
o Loxapine - Anticholinergic drugs may exacerbate symptoms --
AVOID
- Drug of choice:
Second-Generation Antipsychotics
o High-dose typical antipsychotics (i.e.,
- 5HT2A and D2 antagonists Haloperidol)
o Asenapine o Atypical antipsychotics with limited
o Clozapine antimuscarinic properties (i.e., risperidone)
- DOSAGES:
o Iloperidone
o Usually ¼ of schizophrenia dosage
o Lurasidone o Acute psychosis:
o Olanzapine ▪ Significant antipsychotic effects
o Paliperidone seen 60 – 120 minutes after drug
administration
o Quetiapine o ODT and liquid concentrate forms available
o Risperidone o Olanzapine and Ziprasidone
o Serindole ▪ IM administration
o Ziprasidone ▪ Treatment of agitated or
uncooperative patients
- D2 Partial Agonist o Inhaled Loxapine 10mg
o Aripiprazole ▪ t ½ = 7.6h
o Brexpiprazole ▪ Only in centers where airway
o Cariprazine management is possible
o Pimavanserin
- D2 and D3 Antagonist ▪ Treatment of PDP
o Amisulpride ▪ T ½ = 57H
▪ Clinical effects seen for 2-6 weeks
5HT2A Inverse Agonist without D2 Binding Mania
- All atypical antipsychotics are indicated for acute
- Pimavanserin mania
o Except: Clozapine, Iloperidone,
Mood Stabilizers Brexpiprazole, Luradisone
- Doses are titrated rapidly to near maximum over the
(Acute mania and/or bipolar maintenance)
first 24-72h of treatment
- Lithium - Typical antipsychotics – not preferred for acute
- Valproate (Divalproex) mania due to possibility of EPS
- Carbamazepine - Clinical response occurs within occurs 7 days
o Decreased agitation and irritability,
- Lamotrigine
increased sleep, reduced or absent
hallucinations and delusions)
- Management:
o Atypical Antipsychotic + Mood Stabilizer
▪ May need to be continued for
months after resolution of
symptoms
 o Oral aripiprazole or Olanzapine
▪ Monotherapy for bipolar D/O
maintenance treatment
▪ Olanzapine – Not preferred due to
adverse metabolic effects (weight
gain, hyperlipidemia,
hyperglycemia)
o Long-Acting Injectable (LIA) Risperidone
▪ Monotherapy for patients with
Bipolar I D/O
- ADVERSE EFFECTS:
o Antipsychotic + Mood stabilizer
▪ Improves control of manic
symptoms and reduces risk of
relapse
▪ Main ADVR: Weight gain
o Olanzapine & Clozapine
▪ More likely to cause weight gain
▪ Should be avoided unless patients
are refractory to preferred
treatments
o Gradual drug tapering should be attempted
after 6 months of treatment, as symptoms
permit – to lessen weight gain
Major Depression
- Require lower-than-average doses of antipsychotics
+ antidepressant
- Atypical antipsychotics for adjunctive therapy
- Antipsychotics with antidepressant activity:
o Amisulpride
o Loxapine
o Lurasidone
o Quetiapine
- Mechanisms of Action include:
o 5HT2C Antagonism (Olanzapine &
Quetiapine) → facilitates DA & NE release
o DA D3 partial agonism (Aripiprazole,
Brexpiprazole, Craiprazine) → stimulates
reward centers
- DOSAGE:
o Quetiapine 300mg/d
▪ Treatment of bipolar disorder
o Lurasidone 20-120mg/d
▪ Treatment of bipolar disorder
▪ Taken with an evening meal of at
least 350 kcal
Schizophrenia
- Acute therapy requires doses higher than the
maintenance dose
- Clozapine
o Effective for refractory schizophrenia
- Atypical Antipsychotics – preferred to typical due to
better side-effect profile
o Typical – causes excessive D2 blockade,
causing EPS, slow mentation, and
anhedonia
o Chlorpromazine
▪ Low-dose typical antipsychotic
▪ Not used due to high affinity for H1,
M1, and α1 receptors → causes
sedation, anticholinergic
properties and orthostasis)
▪ Possible QT prolongation
- MANAGEMENT:
o Avoid antipsychotics with greater metabolic
liabilities (i.e., weight gain)
o Preferred drugs → weight and metabolically
benign atypical agents
▪ Ziprasidone (available as IM)
▪ Aripiprazole
▪ Iloperidone
▪ Brexpiprazole
▪ Cariprazine
▪ Lurasidone
o Schizophrenic patients have higher risk of
developing metabolic syndrome and its
complications
▪ Determine baseline of serum
glucose, lipids, weight, BP, and
personal and family histories of
metabolic and CV disease
o In elderly patients:
▪ Reduce antipsychotic dose by 50%
to avoid drug-induced
parkinsonism
Long-Term Antipsychotic Treatment
- Indicated for chronic diseases (delusional D/O,
Schizophrenia, schizoaffective D/O, PDP)
- Poor adherence increases relapse risk
o Due to adverse effects, cognitive
dysfunction, substance use, and limited
illness insight
- Immediate goal: Decrease in acute symptoms
- Principal determinants of initial antipsychotic
therapy:
o Avoidance of adverse effects
o Exploitation of medication properties
Antipsychotic Agents
- Choice of long-term schizophrenia therapy is based
on:
o Avoidance of adverse effects
o Prior history of patient response
o Need for long-acting injectable formulation
due to adherence issues
- Main ADVR with atypical antipsychotics:
o Weight gain, dyslipidemia, glucose-insulin
homeostasis dysfunction
o Clozapine & Olanzapine – have the highest
metabolic risk; should be used only as a last
resort
▪ Olanzapine used first before