Transcript Antipsychotics

Psychotropics in Psychiatric
Patient - Psychotic disorders:
Pharmacology and Clinical
Applications of Antipsychotics
Pongsatorn Meesawatsom
B. Pharm., M.Sc. (Pharmacology)
Faculty of Pharmacy
Srinakarinwirote University
Characteristics of schizophrenia
Prevalence 0.5–1.0% of population
Onset
 Positive features in late adolescence or early adulthood
 Aspects of cognitive deficits detectable earlier in life
Comorbidity
 Depression: ∼30–50%
 Substance abuse: ∼50%
 Suicide: ∼5–10%
Schizophrenia:
A Disease with Various Aspects
Positive Symptoms
Delusions
Hallucinations
Disorganized speech
Catatonia
Cognitive Deficits
Attention
Memory
Executive functions
(e.g., abstraction)
Social/Occupational
Dysfunction
Work
Interpersonal
relationships
Self-care
Negative Symptoms
Affective flattening
Alogia
Avolition
Anhedonia
Social withdrawal
Mood Symptoms
Depression
Anxiety
Aggression
Hostility
Hopelessness
Suicidality
Inter-relationship between disease factors and drug-induced adverse factors in
the burden of schizophrenia
Other effects
•Anticholinergic
•Prolactin elevation
•QTc prolongation
Adverse effect of
antipsychotic drugs
Risk of hyperglycemia/
diabetes
Sedation
Extrapyramidal
symptoms
Weight gain
Drug-induced factors
Tardive
dyskinesia
Dysphoria
Disease factors
Suicidality
Positive
symptoms
Cognitive
symptoms
Negative
symptoms
Depression/Anxiety
Diverse symptoms
of schizophrenia
Int Clin Psychopharmacol 2005, 20:183–198.
Treatment Goal of Schizophrenia
Stabilization Phase
Treatment
Acute Phase Treatment
 Rapid symptom control


Initiation of
therapeutically effective
dose
No need for initial dose
titration for tolerability
 Patient relationship
 Insight on medication


Minimal drug-drug
interaction
Proven efficacy and
safety
Maintenance
Phase Treatment
 Relapse/recurrence
prevention
 Adherence
 Functional recovery



Increased tolerance to
occasional missed doses
Proven relapse
prevention effect
Improved PSP
Factors affecting antipsychotic response
Receptor pharmacology
(binding capacity)
Pharmacokinetics
Patient variables
Pharmacogenetics
(CYP450)
Comorbid condition/
polypharmacy
The Dopamine hypothesis of psychosis
Overactivity of dopamine neurons in the
mesolimbic dopamine pathway may mediate the
positive symptoms
Dopamine hypocactivity in mesocortical
dopamine pathway may mediate the negative and
cognitive symptoms
 Dorsolateral prefrontal cortex – negative, cognitive
symptoms
 Ventromedial prefrontal cortex – negative, affective
symptoms
Brain dopaminergic tracts
2
3
1
4
5 CTZ
6 Lateral hypothalamus
Simplify Neurocircuitry of Dopamine in Schizophrenia
Mesolimbic pathway
Hyperdopaminergia
DA
D2
Mesocortical pathway
Hypodopaminergia
DA
Limbic
Positive symptoms
D1
PFCx
Negative symptoms
Cognitive symptoms
Affective symptoms
Antipsychotic Drugs: Development Timeline
 Minimal efficacy with regard to positive
symptoms in 20-30% of patients
 Much weaker effect on negative
symptoms than positive symptoms
 Significant parkinsonian symptoms and
anticholinergic effects (poor
compliance and potentially disabling)
 Tardive dyskinesia in a minimum of
20% of patients who receive chronic
neuroleptic treatment.
 At least as effective as typical
neuroleptics with regard to positive
symptoms
 More effective than typical agents with
regard to negative symptoms
 Much lower incidence of parkinsonian
symptoms and anticholinergic effects
than typical agents
 TD does occur but at much lower
incidence
 Elevated risk of metabolic side effects
Therapeutic effects from
D2 receptor blockade
Amelioration of the positive signs,
symptoms of psychosis, manic symptoms,
aggressive behaviors
Antiemetic effect
Modified J Clin Psychiatry 1999;60(suppl 10):5–14.
Adverse effects from
D2 receptor blockade
Extrapyramidal symptom (EPS)
Acute; akathisia, acute dystonia, parkinsonism
Late; tardive dyskinesia
Endocrine effects: prolactin elevation
Weight gain due to increase feeding
Modified J Clin Psychiatry 1999;60(suppl 10):5–14.
Binding affinities of chlorpromazine and
haloperidol for various receptor
J Psychiatr Pract 2005;11:258–61.
Higher potency
Higher EPS
Lower anticholinergic effect
Haloperidol
Fluphenazine
Trifluoperazine
Thioxanthine
Perphenazine
Pimozide
Lower potency
Low EPS
Higher anticholinergic effect
Chlorpromazine
Thioridazine
Mesoridazine
Rational explanations for SDA
therapeutic effects
Therapeutic effects
 D2-receptor blockade in the mesolimbic pathway to reduce
positive symptoms
 Enhanced dopamine release and 5-HT2A receptor blockade
in the mesocortical pathway to reduce negative symptoms
Side-effect profile
 5-HT2A antagonism in the nigrostriatal pathway reduces
EPS and tardive dyskinesia
 5-HT2A antagonism in the tuberoinfundibular pathway
reduces hyperprolactinemia
Role of 5-HT in Nigrostriatal Dopaminergic Synapse
Raphe
Sunstantia nigra
pars
compacta
Nigrostriatal tract
5-HT
5-HT2A
DA
D1
D2
Caudate/putamen
Normal function
Role of 5-HT in Nigrostriatal Dopaminergic Synapse
Raphe
Sunstantia nigra
pars
compacta
Nigrostriatal tract
5-HT
5-HT2A
DA
Haloperidol
D1
D2
Caudate/putamen
EPS
Role of 5-HT in Nigrostriatal Dopaminergic Synapse
Raphe
Sunstantia nigra
pars
compacta
Nigrostriatal tract
5-HT
5-HT2A
DA
D1
SDA
D2
Caudate/putamen
Less EPS
Receptor affinities of selected atypical
antipsychotics
Receptor
D2
5-HT1A
5-HT2A
5-HT2C
1
2
H1
M1
HAL CLOZ OLAN
0.7
126
11
2600
875 >7100
45
16
4
1500
16
23
6
360
440
>1500
7
8
6
1.9
RIS
4
210
0.5
25
19
0.7
230
3
7
20
1.9 >10,000
QUET
160
>830
295
1500
ZIP
5
3
0.4
1
ARI
0.45
4.4
3.4
15
7
10
57
87
–
–
11
47
61
120 >1,000 >10,000
All values are reported as Ki (nM).
Modified from Clin Ther 2004;26:649-66
(partial)
(partial)
Effects of blockade of neuroreceptors
Receptors
Effects of blockade
D2
Anipsychotic, antimanic, antiaggressive,
EPS/akathisia, tardive dyskinesia, increase
prolactin, weight gain
5-HT1A
Anxiolytic, antidepressant, anti-EPS/akathisia
5-HT2A
Anti-EPS/akathisia, possible antipsychotics,
improve REM sleep
5-HT2C
Possible increased appetite/weight
Modified from J Clin Psychiatry 2008;69[suppl4]:26-36.
Effects of blockade of neuroreceptors
Receptors
1
Effects of blockade
Postural hypotension, dizziness, syncope, nasal
congestion
2
Antidepressive effect, increase alertness,
increase blood pressure
H1
Anxiolytic, sedation, weight gain, potentiate CNS
depressant drug
Modified from J Clin Psychiatry 2008;69[suppl4]:26-36.
Effects of blockade of neuroreceptors
Receptors
Effects of blockade
M1
Memory dysfunction, delirium, confusion, sedation,
(central)
REM sleep disturbance , anti-EPS
M2, M3
Blurred vision, attack or exacerbation of narrow-angle
(peripheral) glaucoma, dry mouth, sinus tachycardia, constipation
urinary retention, interfere pancreatic insulin release
Modified from J Clin Psychiatry 2008;69[suppl4]:26-36.
Impact of receptor binding
affinity on clinical
responses of antipsychotics
Receptor affinities of selected atypical
antipsychotics: Potential risk
Receptor
HAL
CLOZ
OLAN
RIS
QUET
ZIP
0.7
126
11
4
160
5
0.45 (partial)
5-HT1A
2600
875
>7100
210
>830
3
4.4 (partial)
5-HT2A
45
16
4
0.5
295
0.4
3.4
5-HT2C
1500
16
23
25
1500
1
15
1
6
7
19
0.7
7
10
57
2
360
8
230
3
87
–
–
H1
440
6
7
20
11
47
61
M1
>1500
1.9
1.9
>10,000
120
>1,000
>10,000
D2
ARI
All values are reported as Ki (nM).
EPS risk and
hyperprolactinemia
Orthostatic
hypotension
Sedation, weight gain
Anticholinergics
Modified from Clin Ther 2004;26:649-66
Receptor affinities of selected atypical
antipsychotics: Potential Benefit
Receptor
HAL
CLOZ
OLAN
RIS
QUET
ZIP
0.7
126
11
4
160
5
0.45 (partial)
5-HT1A
2600
875
>7100
210
>830
3
4.4 (partial)
5-HT2A
45
16
4
0.5
295
0.4
3.4
5-HT2C
1500
16
23
25
1500
1
15
1
6
7
19
0.7
7
10
57
2
360
8
230
3
87
–
–
H1
440
6
7
20
11
47
61
M1
>1500
1.9
1.9
>10,000
120
>1,000
>10,000
D2
ARI
All values are reported as Ki (nM).
PD psychosis
BPSD, autism
Sedative action
Alleviate EPS risk
Modified from Clin Ther 2004;26:649-66
Sleep quality
improvement
Aripiprazole Activity at Cloned Human D2
Receptors
Dopamine
Maximum DA Response (%)*
100
100 nM Dopamine
+ Aripiprazole
Full
Receptor Activity
50
Aripiprazole
Partial
Receptor Activity
100 nM Dopamine
+ Haloperidol
(Modulated)
0
No
Receptor Activity
10-10
10-9
10-8
10-7
10-6
Drug Concentration
10-5
(Blocked)
Haloperidol
*Receptor activity measured as inhibition of forskolin-induced cAMP accumulation in CHO cells transfected with human D2L DNA.
Adapted from Burris et al. J Pharmacol Exp Ther. 2002;302:381.
Paliperidone vs Risperidone
 Paliperidone is
active metabolite
of risperidone via
metabolism by
CYP2D6.
 High affinity for
D2, 5-HT2A, 1 and
2 receptors
 Very low affinity
for M1 as same as
as risperidone
Expert Opin Drug Saf. 2007 ;6(6):651-62.
Pharmacokinetics differences of risperidone
and paliperidone
Risperidone
Tmax
Paliperidone
1-2 hr (risperidone)
1-2 Hr (IR form)
3 hr (paliperidone in CYP2D6 EM)
24 hr (ER form)
17 hr (paliperidone in CYP2D6 PM)
T1/2
3 hr
23 hr (IR and ER
form)
Elimination
CYP2D6 to paliperidone (major)
pathway
CYP3A4 (minor)
CYP3A4 to (minor)
inactive metabolite
and >80% found in
urine and
60%unchanged
Adverse Effect Profile
of Antipsychotics
Shift in Risk Perception
of Antipsychotics
Past Areas of
Concern
Current Medical Realities
Diabetes
Weight Gain
Weight
Gain
Sedation
Tardive
Dyskinesia
Insulin
Resistance
CHD
Prolactin
Hyperlipidemia
Prolactin
TD
Hyperlipidemia
Insulin
Resistance
Sedation
Coronary Heart
Disease
D2 Blocking-related
Side Effects
Late
onset
Acute
onset
Spectrum of EPS
Acute dystonia
Relationship between clinical effectiveness, EPS
and D2 receptor occupancy
80%
Threshold for EPS
Threshold for
antipsychotic
efficacy
Medication used to treat EPS
Am J Health-Sys Pharm 1997;54:2461-77.
Association of medication, target dose, and likelihood of
treatment-emergent EPS
J Psychiatric Pract 2007;13:13–24.
Tardive dyskinesia (TD)
TD is a latent extrapyramidal effect
generally not occurring for months or
years, occur in 20% patient treated with
antipsychotic.
It is characterized by abnormal movements
that can occur in any part of the body,
including faces, tongue, shoulders, hips,
extremities, fingers, and toes
Prominent Feature of TD
 Lingual-facial hyperkinesias
 Neck and trunk movements
 Chewing movements
 Spasmodic torticollis
 Smacking and licking of the
lips
 Retrocollis
 Sucking movements
 Axial hyperkinesia (hip-rocking)
 Tongue movements within the
oral cavity
 Tongue protrusion
 Tongue tremor with mouth
open
 Myokemic movements (wormlike movement on the surface
of the tongue)
 Blinking
 Grotesque grimaces and
spastic facial distortions
 Torsion movements of the trunk
 Choreoathetoid movements of
the extremities
Neuroleptic malignant syndrome
 NMS is an uncommon but serious and potentially fatal
complication of therapy
 It is a syndrome of EPS, hyperthermia, altered
consciousness, and autonomic changes (tachycardia,
unstable BP, incontinence)
 Management
 Discontinuation of the antipsychotic agents
 Supportive therapy
 Bromocriptine may be benificial
 The onset is sudden and recovery may take 5-10 days
after discontinuation of the agent
Simplified Pathophysiology of
Neuroleptic Malignant Syndrome (NMS)
Am J Psychiatry 2007;164:870-876.
Spectrum-based concept of NMS
J Am Acad Child Adolesc Psychiatry 1992;31:1161–4.
Proposed Treatment Algorithm for NMS
Spectrum-Related Symptoms
Am J Psychiatry 2007;164:870-876.
Hyperprolactinemia: possible signs and
symptoms
Osteoporosis
J Clin Psychopharmacol 2007;27:639–661.
Mean Plasma Prolactin Level Changes Over 24 Hours in 18 Patients After Taking
Clozapine, Olanzapine, or Risperidone and in Five of the Same Patients After Not
Taking the Drugs
Am J Psychiatry 2002; 159:133–135
Effects of Antipsychotics on Prolactin Levels
J Clin Psychopharmacol 2007;27:639–661.
Sedation
Receptor blocking properties that affect
arousal and sleep stages
Blocking of H1  sedation
Blocking of M1  sedation, REM sleep
interference
Blocking of 1, 2, 5-HT2A promote
cholinergic pedunculopontine (PPT) and
laterodorsal tegmental nuclei (LDT) firing 
REM sleep improvement
Receptor affinities of selected atypical
antipsychotics
Receptor
D1
D2
D3
D4
5-HT1A
5-HT2A
5-HT2C
1
2
H1
M1
HAL CLOZ
210
85
0.7
126
2
473
3
35
2600
875
45
16
1500
16
6
360
440
>1500
RIS OLAN
460
31
4
11
10
49
9
27
210 >7100
0.5
4
25
23
7
0.7
8
3
6
20
1.9 >10,000
19
230
7
1.9
QUET
455
160
340
1600
>830
295
1500
ZIP
525
5
7
32
3
0.4
1
ARI
265
0.45
0.8
44
4.4
3.4
15
7
10
57
87
–
–
11
47
61
120 >1,000 >10,000
All values are reported as Ki (nM).
Clin Ther 2004;26:649-66
(partial)
(partial)
SGAs and sedation
J Clin Psychiatry 2008;69 Suppl 1:18-31.
Obesity and
metabolic
syndromes
Clinical issues of weight gain and
antipsychotics
Not everyone gains weight
Difficult to predict who will have weight
gain
Multifactorial etiology
Not dose related ADR.
Start in first few weeks
Reach plateau between 3 months to 1 year
Mean weight gain during treatment with
antipsychotic drugs.
CNS Drugs 2005; 19 (Suppl. 1): 1–93.
Mechanisms of antipsychotic-induced weight
gain and metabolic abnormalities
Interfere feeding behavior by blocking many
neuroreceptor
 Feeding center
 Lateral hypothalamus (DA  D2)
 Ventromedial hypothalamus (5-HT 5-HT2A, 5-HT2C)
 Satiety center
 Paraventricular nuclei (NE  1, , Histamine  H1)
Interfere pancreatic insulin release
 Pancreas (ACh  M3 )
Atropine
Olanzapine
Ziprasidone
Risperidone
Diabetes 2005; 54:1552–1558.
Clozapine
Haloperidol
Receptor affinities of selected atypical
antipsychotics
Receptor
D1
D2
D3
D4
5-HT1A
5-HT2A
5-HT2C
1
2
H1
M1
HAL CLOZ
210
85
0.7
126
2
473
3
35
2600
875
45
16
1500
16
6
360
440
>1500
RIS OLAN
460
31
4
11
10
49
9
27
210 >7100
0.5
4
25
23
7
0.7
8
3
6
20
1.9 >10,000
19
230
7
1.9
QUET
455
160
340
1600
>830
295
1500
ZIP
525
5
7
32
3
0.4
1
ARI
265
0.45
0.8
44
4.4
3.4
15
7
10
57
87
–
–
11
47
61
120 >1,000 >10,000
All values are reported as Ki (nM).
Clin Ther 2004;26:649-66
(partial)
(partial)
Olanzapine-Associated Weight Gain
Plateaus After First 39 Weeks of Treatment
LOCF; Median = 2.5 Years
Mean Weight Change (kg)
up to 3 years
8
6
4
2
0
-2
-4
OLZ (N=573)
-6
HAL (N=103)
-8
0
20
40
60
80
100
Patients Observed for 39 Weeks or More; Week
Double-blind and open-label olanzapine.
120
140
160
Kinon BJ, et al. J Clin Psychiatry 2001;62:92-100
Weight gain by
olanzapine is
not dose
dependent (5-20
mg dose range).
Why Less weight gain in quetiapine,
ziprasidone and aripiprazole?
Quetiapine
 Norquetiapine inhibit
norepinephrine reuptake
transporter
 Aripiprazole
 Low affinity H1, 5-HT2C
 Partial D2 agonist
Ziprasidone
 Moderate affinity for 1
 Low affinity H1
 Full 5-HT1A agonist
 Inhibit 5-HT/NA reuptake
transporter
SGAs and metabolic abnormalities
Clin Psy 2007;68(Suppl 7):27-33.
Monitoring protocol for patients on SDAs
Baseline 4 weeks
8 weeks
12 weeks
Personal/
family history

Weight
(BMI)

Waist
circumference

() ()
Blood
pressure

() ()

Fasting
plasma
glucose

() ()
Fasting lipid
profile

()
Quarterly
Annually





Every
5 years
()
() ()

()
()

()

()

()

()
()

() ()
Diabetes Care 2004; 27(2): 596-601.
Other Adverse effects
QTC interval prolongation
Thioridazine, ziprasidone
Agranulocytosis
Clozapine
Epileptogenic
Clozapine
Retinitis pigmentosa
Thioridazine > 800 mg/day
Incidence of categorical increases in QTc (Bazett
correction)
There is a consensus that a QTc interval of >500ms, or an absolute in-crease of 60ms compared with drug-free
baseline, puts a patient at significant risk of torsade depointes, ventricular fibrillation and sudden death
Clozapine safety issues
Clozapine is one of the atypical agents
that is EPS/TD free, as same as quetiapine
However, clozapine is still reserved as
last-line therapy because of its increased
incidence of agranulocytosis,
myocarditis/cardiomyopathy, and convulsion
and the need for frequent monitoring
Clozapine safety issues
Seizure risk
 1-2% and increase to 3-5% if dose is greater than 600
mg/day.
Agranulocytosis
 1% in general
 95% cases in first 6 m,
peak in 4-18 week 
CBC weekly
Management of clozapine-induced
agranulocytosis
US
 New patients: weekly blood
counts
UK
 New patients: weekly blood
counts
 Twice weekly monitoring: WBC
 Weekly monitoring: WBC 3000-
3000-3500 and ANC >1500
3500 and/or ANC1500-2000
 Temporary discontinuation: WBC
2000-3000 and/or ANC 10001500
 Permanent discontinuation: WBC
<2000 and/or ANC <1000
 > 6 months: monitor once every
two weeks
 Discontinue: WBC <3000 and/or
ANC ≤1500
 Weeks 19-52: at least every 2
weeks
 > 52 weeks: monitor at least
monthly thereafter
Contribution of CYP450 in atypical
antipsychotic drug metabolism
Drug
CYP450
1A2
Aripiprazole
2C9/2C19
2D6
3A4


Clozapine


Olanzapine

 //-
Paliperidone

Quetiapine
Risperidone
Ziprasidone



(1/3 with
aldehyde oxidase)
Enzyme
CYP1A2
Substrate
Clozapine, olanzapine
CYP2C19
Inhibitor
Inducer
Fluvoxamine,
ciprofloxacin
Carbamazepine,
smoking
Fluoxetine, fluvoxamine
Carbamazepine,
phenytoin
CYP2D6
Aripiprazole,
clozapine,
olanzapine,
risperidone,
conventional
antipsychotics
Bupropion, fluoxetine,
paroxetine, duloxetine
CYP3A4
Aripiprazole,
clozapine,,
quetiapine,
ziprasidone
Azole antifungal
Carbamazepine,
Most of macrolide except
phenytoin,
azitromycin
rifampin,
ARVs; indinavir, nelfinavir,
phenobarbita
ritonavir
l
Dose-response curve for
seizure risk with clozapine
Dose-response curve for
extrapyramidal adverse
effects with risperidone
J Psychiatric Pract 2005;11:116-122.
Acute treatment of psychotic
patients
Injectable, conventional agents are typically used
such as haloperidol 5-10 mg IM or zuclopenthixol
acetate 50150mg
It may be given every hour until
 Acute symptoms are controlled
 Side effects occur
 Patient falls asleep
Once control has been obtained, the patient can
be converted to oral therapy
Selection of antipsychotic agents
Based on the patient’s history and safety
profile of the available agents
Newly diagnosed patients, the APA suggest
initiating therapy with atypical agent (SGAs)
because of these agents’improve safety profile
Monitoring of first episode
 Less disturbed sleep patterns and decreased anger and
anxiety should be observed within the first day or two of
treatment, with gradual improvement in other symptoms
in the first week and near-maximal effects in six to eight
weeks
 Lack of improvement in the first one to four weeks should
prompt an increase in the dose, followed by a change to
another drug, usually clozapine or another secondgeneration drug after an additional four to six weeks, if
the response remains inadequate
N Eng J Med 2003;349:1738-49.
Monitoring of early adverse effects
It appears within days to weeks of starting
the antipsychotic dose
It maybe transient and time limited (it will
be disappear after the first month of
treatment)
J Clin Psy 2007;68(Suppl 7):34-43.
Initial dose and titration
schedule for a firstepisode
J Clin Psy 2007;68(Suppl 7):3443.
Strategies for managing side effects in
stable patients
J Clin Psy 2007;68(Suppl 7):34-43.
Medical Issues in Schizophrenia
Factor
Prevalence in
Schizophrenia
Prevalence in
General Population
Smoking
75%
25%
Obesity
50%
33%
13-14%
7%
HIV
3%
0.3%
Hepatitis C
20%
1.8%
Diabetes Mellitus
Other:
-inactivity, poor nutrition
-substance use
Meyer JM and Nasrallah H eds. Medical Illness and Schizophrenia. APPI 2003
Regenold WT, et al. Increased prevalence of type 2 diabetes mellitus among psychiatric inpatients with bipolar I affective and
schizoaffective disorders independent of psychotropic drug use. Journal of Affective Disorders. 2002 Jun;70(1):19-26
Medical conditions that may influence
antipsychotic treatment dicisions
Antipsychotics switching
Avoid if possible
Consider in
Not responing patient with adequate trial
Not able to tolerate
Non-compliance (switch to depot preparation)
Significant long term risk with current medication
 Obesity, TD, persistent cognitive deficit, CVS problems,
DDI
Patient/family member request
Switching techniques for antipsychotics
CNS Drugs 2005; 19 (1): 27-42
Dopaminergic considerations
Cross switching of 2 high potency D2
antagonist may increase EPS risk.
J Clin Psy 2007;68(Suppl 7):109.
Dopaminergic considerations
Prolong exposure of high potency D2 antagonist
results in D2 supersensitivity
Switching D2 antagonist from higher potency to
lower potency or D2 partial agonist
 May lead to switch-emergent dopamine psychosis.
 Improvement in prolactin-related side effects such as
galactorrhea, amenorrhea and sexual dysfunction and EPS
Muscarinic considerations
There is a potential that patient who have
been maintained on anticholinergic
antipsychotics to develop cholinergic
supersensitivity.
Nausea, vomiting and insomnia may occur
when anticholinergic drugs is withdrawn or
switched to less potent anticholinergic
drugs.
Muscarinic considerations
If patient is being changed because of EPS in
which an anticholinergic agents was initiated, the
patient can remain on the anticholinergic agent
until the cross taper and titrated is completed
Exception in the case of clozapine being added
as the new therapy, the anticholinergic drugs
should be discontinued when the cross taper and
titration begins
Estimated side effects after switching
J Clin Psy 2008;69(Suppl 1):4-17.
Conclusions
Antipsychotics are not uniform drug class which
different in their pharmacological profile, efficacy
and ADRs.
Adherence of treatment should be enhanced by
various strategies e.g.
 Counseling
 Awareness of DDI
 ADR monitoring and management