Clinical features and Management of Schizophrenia

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 Ambivalence : Marked inability to decide for or against Autistic behavior : Withdrawal into self Affect disturbances : such as inappropriate affect, blunted affect. 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: Audible thoughts : Auditory hallucinations of a person’s voice being spoken aloud Voices arguing or discussing : Auditory hallucinations of two or more voices arguing or discussing, usually about the person experiencing the hallucination Voices commenting on patient’s actions : Auditory hallucinations commenting on a person’s behaviors

8. Thought withdrawal : Sensation of thoughts being actively removed from a person’s mind Thought insertion : Thoughts inserted into a person’s mind by some external agent 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. Made feelings : Feelings that are not a person’s own are imposed on that person by an external agent Made impulses or drives : An impulse or action is imposed on a person by some external agent 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. Somatic passivity : Passive recipient of bodily sensations imposed from outside forces . 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: Mania Delusional disorder Personality disorders Substance use disorders 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: Other hallucinations Delusional notions Perplexity Depressed or elated mood, Experiences of flattened feelings.

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

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

15. 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.

16. Thought echo , thought insertion or withdrawal, and thought broadcasting ; Delusions of control, influence, or passivity, clearly referred to body or limb movements or specific thoughts, actions, or sensations; delusional perception ; 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;

17. 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 ); 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;

18. breaks or interpolations in the train of thought, resulting in incoherence or irrelevant speech , or neologisms ; catatonic behaviour , such as excitement, posturing, or waxy flexibility, negativism, mutism , and stupor ; "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;

19. 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.

20. 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 .

21. 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.

22. 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

23. 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 ).

24. 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 .

25. 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.

26. 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

27. Differences between DSM 5 and ICD10

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

29. 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 10 DSM 5

30. 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 10 DSM 5

31. 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 10 DSM 5

32. 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 10 DSM 5

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

34. Assessment and Evaluation

35. 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

36. 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

37. 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

38. 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

39. 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

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

41. 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)

42. 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

43. 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

44. 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

45. 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

46. 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

47. 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]

48. 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]

49. 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]

50. 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

51. 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

52. 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

53. 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

54. 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.

55. 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

56. 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

57. 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

58. 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

59. 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

60. 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.

61. 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.

62. 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.

63. 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

64. 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

65. 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

66. 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

67. 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.

68. Phases of Illness Management of schizophrenia can be broadly divided into three phases: acute phase, continuation or stabilization phase, 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.

69. 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.

70. 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.

71. 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.

72. 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

73. 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

74. 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 .

75. 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

76. 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.

77. 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 .

78. 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 .

79. 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.

80. 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 .

81. 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

82. 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.

83. 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.

84. 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 .

85. 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.

86. 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.

87. 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.

88. 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 .

89. 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.

90. 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

91. 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.

92. 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.

93. SPECIAL POPULATIONS

94. 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

95. 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).

96. 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

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

98. 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

99. 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 .

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

101. 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

102. References Sadock BJ, Sadock VA. Kaplan and Sadock’s Synopsis of Psychiatry. 10 th ed. New York: Lippincott and Williams; 2007. Tasman A, Kay J, Lieberman JA, First MB, Riba MB. Psychiatry. 4 th ed. West Sussex: John Wiley & Sons Ltd; 2015 . American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. 5 th 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 .

103. 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. 12 th ed. London, Wiley Blackwell, 2015.