Clinical features and Management of Schizophrenia

1. Presenter: Dr Kaushik Nandi
Clinical Features
and
Management
of

2. OVERVIEW
• Introduction
• Clinical features
• DSM 5 vs ICD 10
• Assessment and evaluation
• Treatment modalities
• Adherence to treatment
• Phases of illness
• Side-effects of medication
• Special Populations
• References

3. INTRODUCTION
• Benedict Augustin Morel in 1850s used Demence precoce to
describe a young boy who suddenly had symptoms of mental
deterioration
• Emil Kraepelin described Dementia precox as characterised
by early onset of symptoms followed by progressive course
culminating in dementia
• “Schizophrenia” was first used by Eugene Bleuler in 1911

4. • Bleuler laid emphasis on symptom presentation and described
fundamental or primary symptoms now called as Bleuler’s 4
As
1. Ambivalence: Marked inability to decide for or against
2. Autistic behavior: Withdrawal into self
3. Affect disturbances: such as inappropriate affect, blunted
affect.
4. Association disturbances: Loosening of associations;
thought disorder

5. • Bleuler considered the loss of association between thought
processes, emotion, and behavior to be the hallmark of the
illness.
• He also considered hallucinations, delusions, social
withdrawal, and diminished drive as secondary
manifestations of the illness that depended on the adaptive
capacity of the individual and environmental circumstances.

6. • Kurt Schneider in his classification of thought disorders
attempted to make the diagnosis of schizophrenia more
reliable by identifying a group of symptoms (known as First
rank symptoms) of schizophrenia that were the most
characteristic of the illness.
• The presence of one of these symptoms, in the absence of
intoxication, brain injury, or clear affective illness, was taken
as sufficient for making the diagnosis of schizophrenia.

7. First-Rank Symptoms of Kurt Schneider:
1. Audible thoughts: Auditory hallucinations of a person’s voice
being spoken aloud
2. Voices arguing or discussing: Auditory hallucinations of two
or more voices arguing or discussing, usually about the
person experiencing the hallucination
3. Voices commenting on patient’s actions: Auditory
hallucinations commenting on a person’s behaviors

8. 4. Thought withdrawal: Sensation of thoughts being actively
removed from a person’s mind
5. Thought insertion: Thoughts inserted into a person’s mind by
some external agent
6. Thought broadcasting: The sense that a person’s thoughts are
experienced as real phenomena by others— the thoughts are
made audible, or may be experienced by others through
telepathy

9. 7. Made feelings: Feelings that are not a person’s own are
imposed on that person by an external agent
8. Made impulses or drives: An impulse or action is imposed on
a person by some external agent
9. Made volitional acts: A person’s actions are from and are
controlled by an external agent; the person is a passive
participant in the action

10. 10. Somatic passivity: Passive recipient of bodily sensations
imposed from outside forces.
11. Delusional perception: A perception that has a unique and
idiosyncratic meaning for a person, which leads to an
immediate delusional interpretation

11. • Some schizophrenic patients never exhibit first-rank symptoms
or only experience them in some psychotic episodes.
• They may also be present in other conditions like:
1. Mania
2. Delusional disorder
3. Personality disorders
4. Substance use disorders
5. Organic brain disorder

12. • As per Schneider, there were less important criteria for the
diagnosis of schizophrenia other than FRS and he termed them
as second rank symptoms.
• Those are:
1. Other hallucinations
2. Delusional notions
3. Perplexity
4. Depressed or elated mood,
5. Experiences of flattened feelings.

13. • Other abnormal modes of expression eg., disorder of speech
and other motor manifestations were known as third rank
symptoms.

15. CLINICAL FEATURES
• Diagnosis of Schizophrenia can be made by following the
diagnostic criteria of any of the two manuals:
1. ICD-10 (International Classification of Disease, WHO)
2. DSM-5 (Diagnostic and Statistical Manual, APA)

16. ICD-10
• Schizophrenia (F20): The schizophrenic disorders are
characterized in general by fundamental and characteristic
distortions of thinking and perception, and by inappropriate or
blunted affect.
• For practical purposes it is useful to divide the symptoms into
groups that have special importance for the diagnosis and often
occur together.

17. a) Thought echo, thought insertion or withdrawal, and thought
broadcasting;
b) Delusions of control, influence, or passivity, clearly referred
to body or limb movements or specific thoughts, actions, or
sensations; delusional perception;
c) Hallucinatory voices giving a running commentary on the
patient's behaviour, or discussing the patient among
themselves, or other types of hallucinatory voices coming
from some part of the body;

18. d) Persistent delusions of other kinds that are culturally
inappropriate and completely impossible, such as religious or
political identity, or superhuman powers and abilities (e.g.
being able to control the weather, or being in communication
with aliens from another world);
e) Persistent hallucinations in any modality, when accompanied
either by fleeting or half-formed delusions without clear
affective content, or by persistent over-valued ideas, or when
occurring every day for weeks or months on end;

19. f) breaks or interpolations in the train of thought, resulting in
incoherence or irrelevant speech, or neologisms;
g) catatonic behaviour, such as excitement, posturing, or waxy
flexibility, negativism, mutism, and stupor;
h) "negative" symptoms such as marked apathy, paucity of
speech, and blunting or incongruity of emotional responses,
usually resulting in social withdrawal and lowering of social
performance; it must be clear that these are not due to
depression or to neuroleptic medication;

20. i) a significant and consistent change in the overall quality of
some aspects of personal behaviour, manifest as loss of
interest, aimlessness, idleness, a self-absorbed attitude, and
social withdrawal.

21. Diagnostic guidelines
A minimum of one very clear symptom (and usually two
or more if less clear-cut) belonging to any one of the groups listed
as (a) to (d) above,
or
Symptoms from at least two of the groups referred to as
(e) to (h), should have been clearly present
for most of the time during a period of 1 month or more.

22. • Viewed retrospectively, it may be clear that a prodromal phase
in which symptoms and behaviour, such as loss of interest in
work, social activities, and personal appearance and hygiene,
together with generalized anxiety and mild degrees of
depression and preoccupation, preceded the onset of psychotic
symptoms by weeks or even months.
• Because of the difficulty in timing onset, the 1-month duration
criterion applies only to the specific symptoms listed above
and not to any prodromal nonpsychotic phase.

23. Pattern of course
• F20.x0 Continuous
• F20.x1 Episodic with progressive deficit
• F20.x2 Episodic with stable deficit
• F20.x3 Episodic remittent
• F20.x4 Incomplete remission
• F20.x5 Complete remission
• F20.x8 Other
• F20.x9 Course uncertain, period of observation too short

24. DSM-5
Diagnostic Criteria: (295.90)
A. Two (or more) of the following, each present for a significant
portion of time during 1 -month period (or less if successfully
treated). At least one of these must be (1 ), (2), or (3):
1. Delusions.
2. Hallucinations.
3. Disorganized speech (e.g., frequent derailment or incoherence).
4. Grossly disorganized or catatonic behavior.
5. Negative symptoms (i.e., diminished emotional expression or
avolition).

25. B. For a significant portion of the time since the onset of the
disturbance, level of functioning in one or more major areas,
such as work, interpersonal relations, or self-care, is markedly
below the level achieved prior to the onset.
C. Continuous signs of the disturbance persist for at least 6
months. This 6-month period must include at least 1 month of
symptoms (or less if successfully treated) that meet Criterion A
(i.e., active-phase symptoms) and may include periods of
prodromal or residual symptoms.

26. D. Schizoaffective disorder and depressive or bipolar disorder
with psychotic features have been ruled out
E. The disturbance is not attributable to the physiological effects
of a substance (e.g., a drug of abuse, a medication) or another
medical condition.

27. Course specifiers:
Only to be used after a 1-year duration of the disorder
• First episode, currently in acute episode
• First episode, currently in partial remission
• First episode, currently in full remission
• Multiple episodes, currently in acute episode
• Multiple episodes, currently in partial remission
• Multiple episodes, currently in full remission
• Continuous
• Unspecified

28. Differences between DSM 5 and ICD10

29. • Schizophrenia spectrum and
other psychotic disorders
• Schizophrenia, schizotypal
and delusional disorders
ICD 10DSM 5

30. • Schizotypal disorder
• Brief psychotic disorder
• Delusional disorder
• Schizophreniform disorder
• Schizophrenia
• Schizoaffective disorder
• Psychotic disorders induced by another
condition (Substance induced/ medical
condition)
• Catatonia
• Other specified and unspecified
schizophrenia spectrum and other
psychotic disorders
• Schizophrenia F20
• Schizotypal disorder F21
• Persistent delusional disorder F22
• Acute and transient psychotic disorder
F23
• Induced delusional disorder F24
• Schizoaffective disorder F25
• Other non-organic psychotic disorder
F28
• Unspecified non-organic psychotic
disorder F29
ICD 10DSM 5

31. Differences – Schizophrenia
• First rank symptoms
excluded
• Includes First Rank Symptoms
• Thought echo, insertion or
withdrawal, broadcasting,
delusions of control, influence or
passivity, delusional perception,
hallucinatory voices (commenting
or discussing the patient with
each other), persistent delusions.
ICD 10DSM 5

32. Differences – Schizophrenia
• Duration of illness is 6
months
• Impairment in level of
functioning is one of the
criteria
• Duration of illness is 1
month or more
• No mention of functioning
ICD 10DSM 5

33. Differences – Schizophrenia
• Subtypes excluded
• Subtype present
• F20.0: paranoid schizophrenia
• F20.1: hebephrenic schizophrenia
• F20.2: catatonic schizophrenia
• F20.3: undifferentiated schizophrenia
• F20.4: post-schizophrenia depression
• F20.5: residual schizophrenia
• F20.6: simple schizophrenia
• F20.8: other schizophrenia
• F20.9: schizophrenia, unspecified
ICD 10DSM 5

34. Differences – Schizophrenia
– Course specifier
• Catatonia
• Severity
• Catatonic schizophrenia is
a subtype
• No course specifier for
severity
ICD 10DSM 5

35. Assessment and Evaluation

36. Patient with Psychotic features
Consider differential diagnoses like
• Organic Mental Conditions
• Acute and transient psychotic disorder
• Persistent Delusional disorder
• Schizoaffective disorder
• Severe depression with psychotic symptoms
• Mania with psychotic symptoms
• Drug induced psychosis
Establish the
diagnosis of
Schizophrenia

37. Assessment
• Severity of illness
• Risk of harm to self and others
• Comorbid substance use/dependence
• Level of functioning
• Detailed Physical examination
• Record- blood pressure, weight and wherever indicated body
mass index and waist circumference
• Mental Status Examination

38. • Investigations- haemogram, liver function test, renal function
test, fasting blood glucose level, electrocardiogram (focus on
QTc)
• Treatment history- response to previous medication trials,
compliance, side effects, etc.
• Patient’s and caregivers beliefs about the cause of illness and
beliefs about the treatment
• Assessment for social support, stigma, coping skills
• Assessment of caregiver burden, coping and distress

39. Decide about treatment setting
Indications for inpatient care:
• Presence of suicidal behaviour which puts the life of the
patient at risk
• Presence of severe agitation or violence which puts the life of
others at risk
• Refusal to eat which puts the life of patient at risk
• Severe malnutrition

40. Liaison with other specialists depending on the need of
the patient
• Patient unable to care for self to the extent that she/he requires
constant supervision or support
• Catatonia
• Presence of general medical or comorbid psychiatric
conditions which make management unsafe and ineffective in
the outpatient setting

42. Options for management
Pharmacological Non-Pharmacological
• Antipsychotic medications
• Adjunctive medications
• Somatic treatments
• Psychosocial interventions
• Lifestyle and dietary
modifications

43. Options for management
• Antipsychotic medications
– First-generation antipsychotic medications
(Oral/parenteral/depot or long acting- preparations)
– Second-generation antipsychotic medications
(Oral/parenteral/depot or long acting- preparations)
• Somatic treatments
– Electroconvulsive therapy (ECT)

44. • Adjunctive medications
– Anticholinergics, antidepressants, benzodiazepines,
hypnotic - sedatives, anticonvulsants, lithium carbonate
• Psychosocial interventions
– Family intervention, cognitive behavioural therapy, social
skills training, individual & group therapy, vocational
rehabilitation, early-intervention programmes, community
mental-health teams
• Other measures
– Lifestyle and dietary modifications

45. Factors that influence selection of
antipsychotics
• Past treatment response
• Cost of treatment,
affordability
• Psychiatric comorbidity
• Medical comorbidity
• Side effects
• Patient or family preference
• Preferred route of
administration
• Concomitant medications
• Non-adherence
• Treatment resistance

46. Recommended therapeutic dose ranges for
various antipsychotics
First Generation
Antipsychotics (FGAs)
Usual daily dose
(in mg/day)
Maximum
daily dose
Chlorpromazine 300-800 800
Haloperidol 5-20 20
Penfluridol 20-60 mg/week 250 mg/week
Perphenazine 12-64 64
Trifluoperazine 15-30 30
Grover, et al.: CPG for Schizophrenia

47. Second Generation
Antipsychotics (SGAs)
Usual daily dose
(in mg/day)
Maximum
daily dose
Amisulpride 50-800 1200
Aripiprazole 10-30 30
Clozapine 150-600 900
Olanzapine 10-30 30
Paliperidone 3-12 12
Quetiapine 300-800 800
Risperidone 2-8 16
Grover, et al.: CPG for Schizophrenia

48. Antipsychotic depot preparations available in India
Name of antipsychotic Usual 2-4 weekly dose in mg
Zuclopenthixol decanoate 200
Paliperidone palmitate 234 initially, followed by 117 monthly
Fluphenazine decanoate 12.5-50
Haloperidol decanoate 50
Risperidone depot 25-50
Olanzapine pamoate 210-405
Grover, et al.: CPG for Schizophrenia

49. Treatment Response
• RESPONSE:
A score of 2 or 1 in the CGI-change (Clinical Global
Impression Scale) or > 20 points on FACT SCZ (functional
assessment for comprehensive treatment for schizophrenia )
or
> 20 % decrease in BPRS or PANSS
[Suzki et al,2012]

50. • PARTIAL RESPONSE:
A score of 3 in the CGI-change or 10 - 20 points
increase on FACT SCZ (functional assessment for
comprehensive treatment for schizophrenia )
or
GAF or >10% decrease in BPRS or PANSS
[Suzki et al,2012]

51. Defining Remission
• REMISSION:
Reduction of symptoms to a level that does not
interfere with patient’s psychosocial functions, quantified by
using 8 symptoms of PANSS which may reach upto
maximum level of 3 ( mild).
[Suzki et al,2012]

52. Evaluation of patient with non-response to
antipsychotic medications
Patient given an adequate
antipsychotic trial (adequate
dose for atleast 6 weeks
duration)
Adequate Response:
Continue with the same dose
of antipsychotic medication
and keep on monitoring the
side effects
Non-response to treatment
Evaluation
• Re-evaluate the diagnosis
• Medication compliance

53. True Non-response
• Change the antipsychotic
medication
Pseudo Non-response due to poor
compliance
• Evaluate the causes, address the same
and ensure compliance
• In case of poor compliance due to
intolerable side effects –consider
change of antipsychotic (oral/depot)
Failure of 2 adequate
trials of antipsychotic,
one of which is SGA
• Consider clozapine
Adequate Response
• Continue with the same dose of
antipsychotic medication and keep
on monitoring the side effects

54. Inadequate Response to clozapine
• Consider combining clozapine with ECT or another
antipsychotic medication
• More intensive psychosocial intervention
Failure of 2 adequate trials
of antipsychotic, one of
which is SGA
• Consider clozapine
Grover, et al.: CPG for Schizophrenia

55. ADJUNCTIVE MEDICATIONS
• Although antipsychotic agents are the mainstay of treatment of
schizophrenia, management may involve use of adjunctive
treatments like with antidepressants, mood stabilizers or
benzodiazepines.
• However, these can be used with proper rationale and for
shortest possible duration.
• Lithium and other mood stabilizers can be prescribed in
agitated, overactive patients or those with affective symptoms

56. • Benzodiazepines can be useful in managing agitation and
sleep disturbance.
• Antidepressants may be of use in post-psychotic depression
and may be avoided when the patient has florid psychotic
symptoms.
• In general prophylactic use of anticholinergics is not
recommended. It is better to start these drugs when the patient
actually develops extrapyramidal side effects.

57. ECT in Schizophrenia
Possible indications:
• Catatonic symptoms
• Need for rapid control of symptoms
• Presence of suicidal behaviour which puts the life of the
patient at risk
• Presence of severe agitation or violence which puts the life of
others at risk
• Affective symptoms

58. Possible indications (contd.):
• Refusal to eat which puts the life of patient at risk
• History of good response in the past
• Patients not responding to adequate trial of an antipsychotic
medication
• Augmentation of partial response to antipsychotic medication
• Clozapine resistant schizophrenia
• Not able to tolerate antipsychotic medications
• Pregnant patients

59. Basic components of Psychoeducation
• Assessing the knowledge of the patient and caregivers about
aetiology, treatment and prognosis
• Introducing the diagnosis of schizophrenia into discussion
• Discussing about various symptom dimensions
• Providing information about aetiology
• Providing information about treatment in terms of available
options, their efficacy/effectiveness, side effects, duration of
use

60. • Discussing about importance of medication and treatment
compliance
• Providing information about possible course and long term
outcome
• Discussing about problems of substance abuse, marriage and
other issues
• Discussing about Communication patterns, problem solving,
disability benefits

61. • Discussing about relapse and how to identify the early signs of
relapse
• Dealing with day-to-day stress
• Handling expressed emotions and improving communication
• Enhancing adaptive coping to deal with persistent/residual
symptoms

62. Life style and Dietary modifications
• All the patients are to be advised for a change in the life style
and diet to reduce the risk of metabolic side effects and
cardiovascular morbidity and mortality.
• These include physical exercises, dietary modifications and
abstinence from smoking etc.

63. TREATMENT ADHERENCE
• Adherence is defined as “the extent to which the patients’
behaviour, in terms of regular clinic visit, taking medications,
following diets, executing lifestyle changes, coincide with the
clinical prescription”.
• Non-adherence in this context thus denotes failure to enter a
treatment programme, premature termination of treatment, or
incomplete implementation of instructions, including those
that pertain to medication administration.

64. • Evidence suggests that about half of the patients with
schizophrenia do not comply with the treatment
recommendations, about one-third miss their appointments
with the clinicians and 20-60% of patients drop out from
treatment.

65. Factors associated with poor medication
compliance
• Demographic risk factors: Younger age, male gender,
unemployment, lower socioeconomic status
• Patient related factors: Knowledge about illness and
treatment, perceived need for treatment (insight), motivation,
beliefs about treatment risks and benefits, past
experiences/“transference”, past history of adherence,
self-stigma

66. • Social risk factors: Living independently, poor social support,
poor financial support
• Clinical risk factors: Poorer premorbid functioning, earlier
age of onset, prior history of non-adherence
• Symptom-related risk factors: Lack of insight, paranoia,
grandiose delusions, conceptual disorganization, impaired
cognition, substance abuse, comorbidities, depression,
refractoriness, spontaneous remissions

67. • Treatment-related risk factors: Medication side effects, poor
treatment alliance, complex dosing, negative experience of
medication, route of administration, length of treatment, cost
of treatment, number of medications
• Service-related risk factors: High cost of medication, poor
accessibility of treatment services

68. • Family/caregivers-related risk factors: Lack of supervision,
negative attitudes towards treatment, lack of knowledge about
medicines, nature of relationship with patient, perceived need
for treatment, involvement in treatment, stigma, financial
constraints
• Clinician/provider related factors: Therapeutic alliance,
frequency and nature of contact with clinicians, accessibility to
clinicians and services, reimbursement, psychoeducation and
psychosocial treatment, complexity of administration

69. • Some of the common clinician related factors which may be
relevant in Indian context include poor communication
between the clinician and the patient/caregiver, poor
therapeutic alliance and non-collaborative decision-making.
• Hence, clinicians need to focus on better communication and
improve therapeutic alliance with patient and the family to
improve overall outcome.
• Medication compliance can be improved by using depot
preparations and use of mouth dissolving formulations under
supervision.

70. Phases of Illness
• Management of schizophrenia can be broadly divided into
three phases:
1. acute phase,
2. continuation or stabilization phase,
3. maintenance or stable phase.
• Some patients may present very early in a prodromal phase
and appropriate strategies for detection and management for
this phase might be required.

71. Prodromal stage
• It is now well known that onset of frank psychosis is often
preceded by psychological and behavioral abnormalities
involving cognition, emotion, perception, communication,
motivation and sleep.
• These symptoms may precede the psychosis by weeks to
years.
• Evidence also suggests that many patients with prodrome,
have higher chance of conversion to frank schizophrenia.

72. • Therefore, now more and more emphasis is laid on early
detection and intervention.
• In terms of management of prodrome it is suggested that
treatment ought to be based on the needs of the patient.
• There is some evidence to suggest that use of antipsychotics in
prodromal phase can delay the conversion to psychosis and
antidepressants may be useful in symptomatic improvement in
a sub-group of patients.

73. • However, at present evidence for use of antipsychotics in
prodromal phase is not convincing to recommend its use in all
patients.
• Use of pharmacotherapy need to be weighed against the side
effects of antipsychotics and sensitization of dopamine
receptors in brain, which can possibly lead to super-sensitivity
psychosis or rapid-onset psychosis following stoppage of
antipsychotic medication.

74. Management in the Acute phase
• Comprehensive assessment (psychiatric/medical/psychosocial)
• Deciding on goals of treatment
• Choice of treatment setting
• Antipsychotic treatment
• Use of adjunctive medications when indicated
• Use of ECT when indicated
• Planning for further treatment

75. Management in the Continuation and
Maintenance phase
• Determining goals
• Further assessment
• Antipsychotic treatment
• Psychosocial interventions
• Monitoring for response, side effects and treatment adherence
• Early intervention for relapses

76. Duration of treatment
• Duration of treatment depends on a number of factors and will
need to be individualized.
• The suggested guidelines are as follows:
– First-episode patients ought to receive 1-2 years of
maintenance treatment
– Patients with several episodes or exacerbations are to
receive maintenance treatment for 5 years or longer after
the last episode
– Patients with history of aggression or suicide attempts
should receive treatment for longer period or lifelong.

77. Indications for life long/long term use of
antipsychotic medications
• History of multiple relapses while on treatment
• History of relapses when the medications are tapered off
• History of suicidal attempts
• Presence of residual psychotic symptoms
• Family history of psychosis with poor outcome
• Comorbid substance dependence

79. SIDE EFFECTS AND THIER
MANAGEMENT
• Antipsychotics are associated with many side effects, which
require intervention.
• Some of the common side effects that can be very distressing
to the patients include extrapyramidal side effects,
cardiovascular side effects, sexual dysfunction and metabolic
side effects.
• The cardiovascular side effects can be life threatening too.

80. Extrapyramidal side effects:
• Extrapyramidal side effects (EPS) are often noted in patients
receiving FGAs, especially high potency antipsychotic
medications. However, EPS is also seen with SGAs.
• The acute EPS include Acute dystonia, Pseudo-
parkinsonism and Akathisia.
• Acute EPS is usually seen during the first few days or weeks
of starting treatment, is dose dependent and subsides with
stoppage of offending agent.

81. • Chronic EPS is usually seen after prolonged use (months to
years) of antipsychotics.
• It is important to note that chronic EPS is not dependent on the
dose of antipsychotics and persists even after stopping the
offending agent.
• In case a patient is experiencing Parkinsonism during the
initial phase of treatment, the first step of management
involves lowering the dose of the antipsychotic medication.

82. • If reduction in dose is associated with unacceptable efficacy
than change of antipsychotic medication may be considered.
• When change of antipsychotic medication is considered, a
medication with lower EPS potential need to be opted.
• In patients who respond to an antipsychotic and continue to
experience Parkinsonism, a short course of anticholinergic
medications may be considered.

83. • Acute dystonia is also seen during the initial phase of
treatment, i.e., after receiving first few doses of antipsychotics.
Acute dystonias respond dramatically to administration of
parenteral anticholinergic medications.
• First step in management of acute akathisia involves
reduction in dose or changing the antipsychotic to a
medication with lower EPS potential. Some patients may
require the use of medications like beta-blockers and
benzodiazepines like clonazepam or lorazepam for
management of akathisia.

84. Neuroleptic Malignant Syndrome (NMS):
• It is an acute psychiatric emergency, which has been reported
to occur more often with FGAs.
• However, data in the form of case reports and case series also
suggest association of almost all SGAs with development of
NMS.
• Various factors like young age, male gender, use of high
potency antipsychotic, dehydration, etc. increase the risk of
NMS

85. • Management involves stopping the antipsychotic medication,
supportive measures and use of Bromocriptine, Amantadine or
Dantrolene.
• Use of Lorazepam may also be helpful and those patients with
NMS, who do not respond to these treatments, may benefit
with ECT.

86. Sedation:
• Many antipsychotics are known to cause sedation by virtue of
their anti-histaminergic, anti-adrenergic, and anti-
dopaminergic action.
• The risk of sedation is high with Chlorpromazine, Clozapine
and Quetiapine.
• Initial strategy should be to wait and watch and if this is not
beneficial, if possible dose reduction must be considered.

87. Anticholinergic and antiadrenergic side
effects:
• These side effects manifest as dry mouth, blurred vision,
constipation, urinary retention, thermoregulatory effects,
impaired learning and memory and slowed cognition.
• Some patient may develop confusion, delirium, somnolence
and hallucinations due to severe anticholinergic side effects.
• Anticholinergic side effects are more commonly seen with
Clozapine and Chlorpromazine.

88. • It is reported that the anticholinergic side effects are usually
dose-dependent and reduce with reduction in the dose of
antipsychotic or concomitantly used anticholinergic agent.

89. Cardiovascular side effects:
• The commonly encountered side effects include QTc
prolongation, orthostatic hypotension and tachycardia.
• QTc interval of more than 500 milliseconds is associated with
elevated risk of ventricular arrhythmias, known as “torsades
de pointes”, which may lead to ventricular fibrillation and
sudden cardiac death.
• Among the older antipsychotics, thioridazine, pimozide and
high dose of intravenous haloperidol are reported to be
associated with increased risk of QTc prolongation.

90. • Among the SGAs, ziprasidone is reported to have higher risk
of QTc prolongation; however, this has not been shown to be
associated with sudden cardiac deaths.
• In case, there is QTc prolongation, change of antipsychotic is
to be considered.

91. • Hypotension associated with various antipsychotics is
attributed to antiadrenergic activity.
• It is commonly seen with Clozapine, Risperidone,
Quetiapine.
• Among the FGAs, hypotension is often seen with
chlorpromazine.
• Hypotension can be prevented by starting with lower doses
and slow upward titration of medication.

92. Hyperprolactinemia and Sexual dysfunction:
• In general, rates of sexual dysfunction are reported to be
higher with FGAs and risperidone.
• One of the common causes for sexual dysfunction with FGAs
and risperidone is increase in prolactin levels, which leads to
disruption of hypothalamo-pituitary-gonadal axis.
• Females have been reported to be more sensitive to
hyperprolactinemia related sexual dysfunction.

93. Monitoring for metabolic side effects:
• Higher prevalence of metabolic syndrome suggests that
clinicians need to monitor the patients for emergence of
metabolic side effects and manage the same to reduce the
cardiovascular morbidity and mortality.
• Antipsychotics have also been shown to increase the risk of
development of diabetes mellitus.
• Clozapine and olanzapine have been reported to be associated
with highest risk for development of weight gain, lipid
abnormalities and elevation in blood glucose levels

94. • In general it is suggested that patients need to be monitored for
metabolic disturbances at baseline, at 4-6 weeks and 12 weeks
after starting antipsychotic and then after every 3 months or at
least annually.
• In general if a patient gains more than 7% of the baseline
weight or develops hyperglycemia, hyperlipidemia,
hypertension or any other significant cardiovascular or
metabolic side effect, then a change in antipsychotic is to be
considered.

95. • If switching of antipsychotic is not possible then medications
like metformin or topiramate may be considered, along with
more intensive dietary and life style modifications.
• A close liaison need to be maintained with endocrinologist and
cardiologist to provide best quality care to patients.

96. SPECIAL POPULATIONS

97. Pregnancy
• No clear evidence that any antipsychotic is a major teratogen
• Consider using/continuing drug mother has previously
responded to rather than switching prior to/during pregnancy
• Avoid depot preparations and anticholinergic medications.
• Most experience with Chlorpromazine, Trifluoperazine,
Haloperidol, Olanzapine

98. • Experience growing with Risperidone, Quetiapine and
Aripiprazole
• Screen for adverse metabolic effects
• Arrange for the woman to give birth in a unit with access to
neonatal intensive care facilities.
• Antipsychotic discontinuation symptoms can occur in the
neonate (e.g. crying, agitation, increased suckling).

99. Breastfeeding
• All psychotropics are excreted in breast milk, to varying
degrees.
• Neonates and infants do not have the same capacity for drug
clearance as adults.
• Wherever possible:
– use the lowest effective dose
– avoid polypharmacy
– time dosing to avoid feeding at peak plasma/milk levels or express milk
to give later

100. • Recommended Antipsychotic: Olanzapine
• Others may be used like Risperidone, Quetiapine and
Aripiprazole

101. Renal impairment
No agent clearly preferred to another, however:
• Avoid Sulpiride and Amisulpride
• Avoid highly anticholinergic agents because they may cause
urinary retention
• First-generation antipsychotic – suggest Haloperidol 2–6 mg
a day
• Second-generation antipsychotic – suggest Olanzapine 5 mg a
day

102. Hepatic impairment
• Use lower starting doses and Avoid medicines with a long-
half life or those that need to be metabolised to render them
active (pro-drugs).
• Avoid drugs that are very sedative because of the risk of
precipitating hepatic encephalopathy.
• Monitor LFTs weekly, at least initially.

103. • Haloperidol: low dose
or
• Sulpiride/amisulpride: no dosage reduction required if renal
function is normal
• Paliperidone: if depot required

104. Elderly
• Use drugs only when absolutely necessary.
• Start with a low dose and increase slowly but do not
undertreat. Some drugs still require the full adult dose.
• Try not to treat the side-effects of one drug with another drug.
• Daily doses: Aripiprazole: 5–15 mg, Olanzapine: 5–10 mg,
Quetiapine: 75–125 mg, Risperidone: 1.0–2.5 mg,
Haloperidol: 1.0–3.5 mg

105. References
• Sadock BJ, Sadock VA. Kaplan and Sadock’s Synopsis of Psychiatry. 10th
ed. New York: Lippincott and Williams; 2007.
• Tasman A, Kay J, Lieberman JA, First MB, Riba MB. Psychiatry. 4th ed.
West Sussex: John Wiley & Sons Ltd; 2015.
• American Psychiatric Association, Diagnostic and Statistical Manual of
Mental Disorders. 5th ed. Washington DC: New School Library; 2013.
• World Health Organization. ICD-10 : International statistical classification
of diseases and related health problems : tenth revision, 2nd ed. World
Health Organization; 2004.

106. • T. Suzuki et al. Defining treatment-resistant schizophrenia and response to
antipsychotics: A review and recommendation. Psychiatry Research 197
(2012) 1–6
• Grover S, Chakrabarti S, Kulhara P, Avasthi A. Clinical Practice Guidelines
for Management of Schizophrenia. Indian J Psychiatry 2017;59:19-33.
• Kurt Schneider ( 1887–1967 ): First- and Second- Rank Symptoms , Not
Pathognomonic of Schizophrenia, Explained by Psychotic Mood Disorders,
chapter 8
• Abel KM, Taylor D, Duncan D, McConnell H, Kerwin R. The Maudsley
Prescribing Guidelines. 12th ed. London, Wiley Blackwell, 2015.