introduction

 Antipsychotic drugs (also called neuroleptics or major

tranquilizers) are used primarily to treat schizophrenia
(a biologic illness),
 but they are also effective in other psychotic states,
including manic states with psychotic symptoms such
as grandiosity, paranoia, and hallucinations, and
delusions.
Antipsychotic drugs
 Antipsychotic drugs are not curative and do not
eliminate the chronic thought disorder, but they often
decrease the intensity of hallucinations and delusions
and permit the person with schizophrenia to function
in a supportive environment.
History of antipsychotic drugs
 Antipsychotic drugs have been used in Western
medicine for more than 50 years.
 Chlorpromazine (1952) and Reserpine were the first
drugs found to be useful in schizophrenia.
 Major novel antipsychotics are selective serotonin
reuptake inhibitor and it has been introduced in 1980s.
Classification of antipsychotic
drugs
 PHARMACOLOGICAL CLASSIFICATION –
 FIRST-GENERATION ANTIPSYCHOTIC (low potency)

 Chlorpromazine
 Prochlorperazine
 Thioridazine –

 FIRST-GENERATION ANTIPSYCHOTIC (high potency)

 Fluphenazine
 Haloperidol
 Pimozide
 Thiothixene –
Classification of antipsychotic
drugs
 SECOND GENERATION ANTIPSYCHOTIC
 Aripiprazole
 Asenapine
 Clozapine
 Iloperidone
 Lurasidone
 Olanzapine
 Quetiapine
 Paliperidone
 Risperidone
 Ziprasidone
First-generation antipsychotics
 The first-generation antipsychotic drugs (also called
conventional, typical, or traditional antipsychotics) are
competitive inhibitors at a variety of receptors, but
their antipsychotic effects reflect competitive blocking
of D2 dopamine receptors.
 First-generation antipsychotics are more likely to be
associated with movement disorders, particularly for
drugs that bind tightly to dopaminergic
neuroreceptors, such as haloperidol. Pharmacotherapy
of metal illness
Second-generation antipsychotic
drugs
 The second generation antipsychotic drugs (also
referred to as “atypical” antipsychotics) have fewer
extrapyramidal symptoms (EPS) than the first-
generation agents, but are associated with a higher risk
of metabolic side effects, such as diabetes,
hypercholesterolemia, and weight gain.
 The second-generation drugs appear to owe their
unique activity to blockade of both serotonin and
dopamine receptors. Pharmacotherapy of metal illness
New antipsychotics
Typical antipsychotic Atypical
PIPOTHIAZINE antipsychotic
MOLINDONE Pimavanserin
MESORIDAZINE PEROSPIRONE
CYAMEMAZINE LURASIDONE
ILOPERIDONE
ASENAPINE
ZOTEPINE
Pimavanserin
 Atypical antipsychotic
 Antagonism/inverse agonism at 5HT2A receptors
 Pimavanserin is also an antagonist/inverse agonist at
5HT2C receptors (activity is very low compared to that
at 5HT2A receptors)
Pimavanserin
 Usual Dosage Range
 34 mg once daily

 How to Dose
 34 mg/day taken once daily; no titration required
Pimavanserin
 How Drug Causes Side Effects
 Mechanism of peripheral edema,
 confusional state, and nausea unknown

 Notable Side Effects

 Peripheral edema
 Confusional state
 Nausea
Pimavanserin
 Potential Advantages
 Does not worsen motor symptoms of Parkinson’s disease
 Not associated with the metabolic side effects of quetiapine
and clozapine, including weight gain, dyslipidemia, and
diabetes mellitus
 Not associated with the sedation
 Does not require dose reduction of antiparkinsonian
dopaminergic therapy given concomitantly

 Potential Disadvantages
 Expensive
PIPOTHIAZINE
 dopamine receptor antagonist (D-RAn)
 Blocks dopamine 2 receptors, reducing positive
symptoms of psychosis.
 Conventional antipsychotic (neuroleptic,
phenothiazine, dopamine 2 antagonist
 Only available in long-acting parenteral formulation)
PIPOTHIAZINE
 How Drug Causes Side Effects
 By blocking dopamine 2 receptors
 -motor side effects
 -elevations in prolactin
 -worsening of negative and cognitive symptoms
 Notable Side Effects
 Excitement, insomnia, restlessness
 Rare tardive dyskinesia (risk increases with duration of
treatment and with dose)
 Galactorrhea, amenorrhea
PIPOTHIAZINE
 Usual Dosage Range
 50–100 mg once a month
 Dosage Forms
 Injection 50 mg/mL
 How to Dose
 Initial 25 mg; can be increased by 25–50 mg; maximum
200 mg once a month
 Drug should be administerd intramuscularly in the
gluteal region
 Only available as long-acting intramuscular formulation
and not as oral formulation
PIPOTHIAZINE
 SPECIAL POPULATIONS
 Renal Impairment,
 Hepatic Impairment,
 Cardiac Impairment- Use with caution
 Elderly-Dose should be reduced
 Recommended starting dose 5–10 mg
 Children and Adolescents
 Not recommended for use in children
PEROSPIRONE
 Atypical antipsychotic
 dopamine and serotonin receptor antagonist (DS-
RAn)
 Blocks dopamine 2 receptors, reducing positive
symptoms of psychosis
 Blocks serotonin 2A receptors, causing enhancement
of dopamine release in certain brain regions and thus
reducing motor side effects and possibly improving
cognitive and affective symptoms
PEROSPIRONE
 Interactions at 5HT1A receptors may contribute to effi
cacy for cognitive and affective symptoms in some
patients

 Potential of weight gain, diabetes, and dyslipidemia

associated with perospirone has not been
systematically studied, but patients should be
monitored the same as for other atypical
antipsychotics.
PEROSPIRONE
 Notable Side Effects
 Extrapyramidal symptoms, akathisia
 Insomnia

 Usual Dosage Range

 8–48 mg/day in 3 divided doses
PALIPERIDONE
 Atypical antipsychotic (second generation
antipsychotics; also a mood stabilizer)
 dopamine, serotonin receptor antagonist (DS-RAn)
PALIPERIDONE
 Usual Dosage Range
 6 mg/day (oral)
 Initial dose 6 mg/day taken in the morning
 Can increase by 3 mg/day every 5 days; maximum dose
generally 12 mg/day
 LAI paliperidone
 39–234 mg/month
 273–819 mg/3 months
PALIPERIDONE
 Potential Advantages
 Some cases of psychosis and bipolar disorder
refractory to treatment with other antipsychotics
 Patients requiring rapid onset of antipsychotic action
without dosage titration
PALIPERIDONE
 Potential Disadvantages
 Patients for whom elevated prolactin may not be
desired (e.g., possibly pregnant patients; pubescent
girls with amenorrhea;
 postmenopausal women with low estrogen who do not
take estrogen replacement therapy)
MOLINDONE
 Conventional antipsychotic (neuroleptic, dopamine 2
antagonist)
 Blocks dopamine 2 receptors, reducing positive
symptoms of psychosis
MOLINDONE
 Usual Dosage Range
 40–100 mg/day in divided doses
 How to Dose
 Initial 50–75 mg/day; increase to100 mg/day after 3–4
days;
 Maximum 225 mg/day
 Liquid 20 mg/mL
 Pharmacokinetics
 Half-life approximately 1.5 hours
MOLINDONE
 Potential Advantages
 Some patients benefi t from molindone’s sedative
properties
 Potential Disadvantages
 Patients with tardive dyskinesia
Other Warnings/
Precautions
 If signs of neuroleptic malignant syndrome develop,
treatment should be immediately discontinued
 Liquid molindone contains sodium metabisulfi te,
which may cause allergic reactions in some people,
especially in asthmatic people
 Use cautiously in patients with alcohol withdrawal or
convulsive disorders because of possible lowering of
seizure threshold
MESORIDAZINE
 Conventional antipsychotic (neuroleptic,
phenothiazine, dopamine 2 antagonist)
 Blocks dopamine 2 receptors, reducing positive
symptoms of psychosis
MESORIDAZINE
 Notable Side Effects
 Neuroleptic-induced defi cit syndrome
 Akathisia
 Priapism
 Extrapyramidal symptoms, parkinsonism, tardive
dyskinesia
 Galactorrhea, amenorrhea
 Pigmentary retinopathy at high doses
MESORIDAZINE
 Usual Dosage Range
 Oral: 100–400 mg/day
 Injection: 25–200 mg/day

 Dosage Forms
 Tablet 10 mg, 25 mg, 50 mg, 100 mg
 Ampul 25 mg/mL, 1 mL
 Concentrate 25 mg/mL

 How to Dose
 Oral: initial 50 mg 3 times a day; increase dose cautiously as
needed
 Injection: initial 25 mg; repeat after 30–60 minutes if needed
 Take liquid formulation in water, orange juice, or grapefruit juice
MESORIDAZINE
 Potential Advantages
 • Only for patients who respond to this agent
 and not other antipsychotics
 Potential Disadvantages
 • Vulnerable populations such as children or
 elderly
 • Patients on other drugs
LURASIDONE
 A typical antipsychotic (serotonin-dopamine
antagonist; second generation antipsychotic; also a
potential mood stabilizer)
 Usual Dosage Range
 40–80 mg/day for schizophrenia
 Some patients with schizophrenia may benefi t from
doses up to 160 mg/day
 20–60 mg/day for bipolar depression
 Some patients with bipolar depression may benefi t
from doses up to 120 mg/day
LURASIDONE
 Potential Advantages
 Patients requiring rapid onset of antipsychotic action
without dosage titration
 Patients who wish to take an antipsychotic once a day
 Patients experiencing weight gain from other
antipsychotics or who wish to avoid weight gain
 Potential Disadvantages
 Patients who cannot take a medication consistently
with food
ILOPERIDONE
 dopamine and serotonin receptor antagonist (DS-
RAn)
 Atypical antipsychotic (serotonindopamine
antagonist; second-generation antipsychotic; also a
mood stabilizer)
ILOPERIDONE
 Notable Side Effects
 Orthostatic hypotension
 May increase risk for diabetes and dyslipidemia
 Usual Dosage Range
 12–24 mg/day in 2 divided doses
ILOPERIDONE
 Potential Advantages
 Some cases of psychosis and bipolar disorder
refractory to treatment with other antipsychotics
 Patients wishing to avoid EPS
 Potential Disadvantages
 Patients requiring rapid onset of antipsychotic action
without dosage titration
 Patients noncompliant with twice daily dosing
 Cognitive symptoms
CYAMEMAZINE
 Conventional antipsychotic (neuroleptic,
phenothiazine, dopamine 2 antagonist, serotonin
dopamine antagonist)
 Anxiety associated with psychosis
 Although classifi ed as a conventional antipsychotic,
cyamemazine is a potent serotonin 2A antagonist
CYAMEMAZINE
 Specifically, antagonist actions at 5HT2C receptors
may contribute to notable anxiolytic effects in many
patients
 Usual Dosage Range
 50–300 mg at bedtime for treatment of psychosis
 25–100 mg for anxiety; duration of treatment 4 weeks
 Children (ages 6 and older): 1–4 mg/kg per day
 Injection: 25–100 mg/day
CYAMEMAZINE
 Potential Advantages
 For anxiety in patients with psychotic illnesses
 For anxiety in patients with nonpsychotic illnesses
 For severe depression
 Potential Disadvantages
 Patients with tardive dyskinesia
 Children
 Elderly
ASENAPINE
 Atypical antipsychotic (serotonindopamine
antagonist; second generation antipsychotics; also a
mood stabilizer)
 Serotonin 2C, serotonin 7, and alpha 2 antagonist
properties may contribute to antidepressant actions
ASENAPINE
 Notable Side Effects
 Sedation, dizziness
 Extrapyramidal symptoms, akathisia
 May increase risk for diabetes and dyslipidemia
ASENAPINE
 Usual Dosage Range
 10–20 mg/day in 2 divided doses for schizophrenia
 10–20 mg/day in 2 divided doses for bipolar mania
 Must be administered sublingually; patients may not
eat or drink for 10 minutes following administration
 Children and Adolescents
 Approved to treat acute manic/mixed episodes of
bipolar I disorder in childrenages 10 and older
 Children and adolescents using asenapine may need to
be monitored more often than adults
ZOTEPINE
 Atypical antipsychotic (serotonin-dopamine
antagonist)
 Usual Dosage Range
 75–300 mg/day in 3 divided doses
 Children and Adolescents
 Not recommended for use in children under age 18
ZOTEPINE
 Zotepine inhibits norepinephrine reuptake, which may
have implications for treatment of depression, as well
as for cognitive symptoms of schizophrenia
ZOTEPINE
 Potential Advantages
 Norepinephrine reuptake blocking actions have
theoretical benefi ts for cognition (attention) and for
depression
 Potential Disadvantages
 Patients not compliant with 3 times daily dosing
 Patients requiring rapid onset of antipsychotic action
 Patients with uncontrolled seizures