Cardiovascular and metabolic side effects of antipsychotics

ANTIPSYCHOTIC INDUCED CARDIOVASCULAR AND METABOLIC SIDE EFFECTS

CURRENT UNDERSTANDING

Dr. Pawan Sharma

[email protected]

1

• INTRODUCTION• HISTORICAL PERSPECTIVE• EPIDEMIOLOGY • PATHOPHYSIOLOGY• MANAGEMENT

PREVENTION PHARMACOTHERAPY MONITORING

• CONCLUSIONS • FUTURE DIRECTIONS

2




3

INTRODUCTION

1952

• Use of chlorpromazine in schizophrenia

• Revolutionized the management in psychiatry

1958

• Haloperidol developed

• Many similar kind of drugs developed world wide

1972

• Clozapine trials performed but withdrawn in 1975 due to hematological side effects

• 1989: FDA approved with blood count monitoring

1990s• Olanzapine, Zotepine, Sertindole, Risperidone and Quetiapine

came in market

2000s

• Ziprasidone, Aripiprazole, Asenapine, Iloperidone,

• Blonanserin (2008) and Lurasidone approved by US FDA (2010)

4

Neurotherapeutics (2009) 6, 78-85

INTRODUCTION

FGA

High affinity and antagonistic effect on

dopamine receptors (D2) (extra pyramidal

symptoms)

SGA

Antagonistic effects on both serotonin and dopamine receptors

Histamine, muscarinic, adrenergic

5

INTRODUCTION

FIRST GENERATION SECOND GENERATION

Chlorpromazine Clozapine Lurasidone

Thioridazine Olanzapine Aripiprazole

Perphenazine Risperidone Blonanserin

Trifluoperazine Quetiapine

Fluphenazine Ziprasidone

Pimozide Amisulpride

Haloperidol Asenapine

Droperidol Iloperidone

Flupenthixol Paliperidone

Zuclopenthixol Zotepine

Clopenthixol Sertindole

6

HISTORICAL PERSPECTIVE-METABOLIC AND CARDIOVASCULAR SIDE EFFECTS

• The metabolic and cardio vascular side effects of conventional antipsychotics had been recognized just after few years of introduction

• Studies show Phenothiazine derivatives to be associated with cardio vascular and metabolic side effects

– Impaired glucose tolerance and diabetes

Arneson, 1964

7

HISTORICAL PERSPECTIVE-METABOLIC SIDE EFFECTS

• The glucose tolerance studied in groups of patients during long-term treatment (more than three months) showed aberrations in glucose tolerance test

– 40% patients Chlorpromazine

– 35% patients Perphenazine

– 15% patients Clopenthixol

Amdisen A, 1964

• A prospective study of schizophrenic patients on injectable depot neuroleptic drugs as maintenance therapy showed a clinically significant weight gain in 55% of patients

Johnson, 1979

8


• It is common for the patients receiving Phenothiazine to gain 10-15 pounds of weight in the course of 1-2 year of treatment

• Many patients discontinue the medication due to this side effect

Jerrold, 1987

• In a meta-analysis , over a period of 10 weeks treatment

– Conventional agents, mean weight change ranged from a reduction of 0.39 kg with Molindone to an increase of 3.19 kg with Thioridazine

– Newer antipsychotic agents, mean increases were as follows: clozapine-4.45 kg olanzapine- 4.15 kg; Sertindole- 2.92 kg; risperidone-2.10 kg; and Ziprasidone- 0.04 kg.

Allison et al, 1999

9


• In 2003 FDA required all manufacturers of atypical antipsychotics to include a warning about the risk of hyperglycemia and diabetes

• The end of the conventional antipsychotic era and the beginning of the atypical antipsychotic era of 1990s coincided with the onset of an epidemic of type II diabetes

Stahl et al, 2009

10

HISTORICAL PERSPECTIVE-CARDIOVASCULAR SIDE EFFECTS

• The first report of sudden arrhythmic death—Thioridazine, 1963

• Isolated case reports of increased blood pressure and sudden cardiac death reported with use of haloperidol

Gerle B, 1964

• As early as 1968, American Heart Association had advised routine ECG and Chest X-ray 6 monthly for the patients on Phenothiazines

• Major and possibly fatal arrhythmias can occur in young adults without antecedent heart disease who are receiving therapeutic dosages of Thioridazine

Libscomb PA, 1980

11

HISTORICAL PERSPECTIVE-CARDIOVASCULAR SIDE EFFECTS

• In 1991, Mehtonen et al. examined all medico legal autopsies in Finland over a 3-year period (N= 24158).

– 49 sudden unexpected deaths among apparently healthy adults taking psychotropic medication.

– Forty-six of these 49 deaths involved a phenothiazine, primarily

Thioridazine (28 of the 46 cases)

• 12 unexplained sudden deaths and 23 cases of syncope occurred among 1,446 patients during Sertindole premarketing trials in 1996

Glassman and Bigger, 2001

12




13

Total life expectancy among psychiatric patients and general population in Denmark, Finland

and Sweden 1987–2006 at 15 years of age.

Wahlbeck et al, 201114

Cardiovascular disease is primary cause of death in persons with mental illness*

*

Pe

rce

nta

ge o

f d

eat

hs

50

40

20

10

0

30

Heart disease Cancer Cerebrovascular Chronic respiratory

Diabetes Influenza/pneumoniaAccidents Suicide

MO OK RI TX UT VA

Colton & Manderscheid, 200615

MO: MissouriOK: OklahomaRI: Rhode IslandTX: TexasUT: UtahVA: Virginia

15

Prevalence of diabetes in schizophrenia compared to general population

8.6% diabetes; n=415

De Hert et al 2006

15

Age group (years)

General population Patients

15–25 25–35 35–45 45–55 55–65

0

5

10

20

25

30

0.42.0

0.9 1.1

6.1

25.0

5.8

Pre

vale

nce

of

dia

bet

es

(%)

3.2 2.4

12.7

1616

PREVALENCE OF CARDIOVASCULAR RISK FACTORS

Schizophrenia Bipolar Illness

Risk Factors Prevalence(%) Relative Risk Prevalence(%) Relative Risk

Smoking 50-80 2-3 54-68 2-3

Dyslipidemia 25-69 <5 23-38 <3

Diabetes 10-15 2-3 8-17 1.5-3

Hypertension 19-58 2-3 35-61 2-3

Obesity 45-55 1.5-2 21-49 1-2

Metabolic Syndrome

37-63 2-3 30-49 2-3

Holt R, 2012 17

Study Type Sample size

Characteristics

Ryan et al., 2003

Compared drug-naive 1st episode schizophrenia patients with matched healthy controls

Case 26Control 26

Increase in fasting glucose level, impaired glucose tolerance, deranged fasting plasma insulin, insulin resistance

Spelman et al., 2007

Compared between first- episode Drug naïve schizophrenia patients, their first degree relatives and matched controls

Case 38+44 control 38

Impaired glucose tolerance, deranged fasting plasma insulin, insulin resistance

Venkatasba-manian et al., 2007

Compared antipsychotic-naïve schizophrenia patients with matched Controls

Case 44 Control 44

Deranged fasting plasma insulin, insulin resistance

METABOLIC ABNORMALITIES AND SCHIZOPHRENIA

The drug naïve patients of Schizophrenia have deranged metabolic parameters

18

ANTIPSYCHOTICS AND DIABETES

• Percentage of Patients With Schizophrenia Receiving Atypical and Typical Neuroleptic Medication with Diabetes Mellitus

Sernyak et al,200219

ANTIPSYCHOTICS AND DIABETES

• Meta analysis consisting 11 RCTs

• SGA Vs. FGASGA RR(95% CI) Number of studies

Risperidone 1.16(0.99-1.35) 6

Quetiapine 1.28(1.14-1.45) 3

Olanzapine 1.28(1.12-1.45) 8

Clozapine 1.39(1.24-1.55) 7

The relative risk of diabetes in patients with schizophrenia prescribed one of the second-generation vs. first-generation antipsychotics was 1.32 (95% CI 1.15–1.51)

Smith et al, 200820

METABOLIC SYNDROME

• Cluster of physiological abnormalities characterized by insulin resistance leading to increased risk of DM type II and cardiovascular risk

• WHO defines:

– Diabetes or impaired fasting glycaemia or impaired glucose tolerance or insulin resistance

– Plus 2 or more of the following

• Obesity: BMI 30 or waist-to-hip ratio 0·9 (male) or 0·85 (female)

• Dyslipidaemia: triglycerides 150 mg/dl or HDL cholesterol<50 (male) or 40 (female) mg/dl

• Hypertension: blood pressure 140/90 mm Hg

• Microalbuminuria: albumin excretion> 20 g/min

21

METABOLIC SYNDROME

ATP III ATP III A IDF

3 out of 5 3 out of 5 Waist plus any 2 criteria

Waist(cm) Male >102, Female>88

Male >102, Female>88

Male ≥94, Female≥80

BP ≥130/85 ≥130/85 ≥130/85

HDL(mg/dl) Male <40Female <50

Male <40Female <50

Male <40Female <50

Triglycerides(mg/dl) ≥150 ≥150 ≥150

Glucose(mg/dl) ≥110 ≥100 ≥100

Hert et al, 200922

METABOLIC SYNDROMEStudy N Ethnicity Criteria Prevalence

(%) patients

prevalence (%)-population

Brunero et al., 2009

73 schizophrenic patients on Clozapine

Australia IDF 69 21

Huang et al., 2009

650 schizophrenia or schizoaffective in hospital care

Taiwan ATP III 34.9 15

Mattoo et al, 2010

90 psychiatric patient in-patient care

Indian IDF 37.8 25

Sugawara et al, 2010

1186 schizophrenia or schizoaffective in hospital

Japan ATP III 27.5 14.1

Yazici et al,2011

319 Schizophrenia patients on medication

Turkey ATP III/IDF

34.2/41.7 10.2

Pallava et al, 2012

50 schizophrenic patients on medication

Indian IDF 50 25-36

Chadda et al, 201323

METABOLIC SYNDROME

• Study exploring metabolic syndrome status in patients of CATIE (Clinical Antipsychotic Trial of Intervention Effectiveness)

• N=660

• Compared between base line and 3 months of treatment

– Olanzapine and Quetiapine: largest mean increase of waist circumference (0.7 inch) followed by Risperidone (0.4 inch) no change in Ziprasidone group

– Olanzapine group had increased fasting triglyceride (+21.5mg/dl) compared to Ziprasidone (-32.1 mg/dl)

– No significant finding in blood pressureMeyer et al, 2008

24

METABOLIC SYNDROME

Meta analysis comparing different SGAs

• Weight gain :

– Rapid gain slight decrease plateau

Weight gain SGA

Maximum elevation Olanzapine , Clozapine

Intermediate elevation Quetiapine, Risperidone, and Sertindole

Low elevation Aripiprazole and Amisulpride

Least elevation Ziprasidone

Kluge R, 201025

METABOLIC SYNDROME

• Olanzapine caused the most elevation in cholesterol, clearly more than Aripiprazole, Risperidone, and Ziprasidone

• No differences were found in comparison between Amisulpride, Clozapine and Quetiapine

• Quetiapine showed more cholesterol increase than Risperidone and was close to that observed with olanzapine

• Similarly olanzapine and clozapine had maximum change in the glucose utilization

Kluge, R 2010

26

METABOLIC SYNDROME

• Comparison of Atypicals for First Episode (CAFE) study

• N=400,

• 16 to 40 years either Schizophrenia, Schizophreniform or Schizoaffective disorder

• Duration 1 month to 5 years

• BMI ≥ 1 unit in Olanzapine group as compared to otherPatel et al, 2009

Dosage(mg /day)

12 weeks (≥7kg)

52weeks(≥7kg)

Metabolic syndrome (n=52 at 52 weeks)

Olanzapine 2.5-20 59.8% 80% 22 (42.3%)

Quetiapine 100-800 29.2% 50% 18(34.6%)

Risperidone 0.5-4 32.5% 57.6% 11(21.15%)

27

CARDIOVASCULAR SIDE EFFECTS

• Study comparing 10 year risk of Coronary Heart Disease between the subjects who participated in CATIE trial and controls from National Health and Nutrition Examination Survey (NHANES)-III

• N=689

• Age, sex , gender matched controls

CATIE NHANES-III

Diabetes 13 % 3 %

Hypertension 27 % 17 %

Lower HDL 43.7 mg/dl 49.3 mg/dl

Total cholesterol levels did not differ between groups

Ten-year CHD risk was significantly elevated in male (9.4% vs. 7.0%) and female (6.3% vs. 4.2%) CATIE patients compared to controls ( p =0.0001)

Goff et al, 200528


• Study comparing the effect of Ziprasidone, Risperidone, olanzapine, Quetiapine, Thioridazine, and Haloperidol on the QT interval

• All previous medications stopped for 7 days , Placebo for 5 days and base line ECG performed

• Randomly assigned to receive one of the six drugs

• Blood levels were obtained, and repeat ECGs were recorded at the time of maximum drug blood level

• Maximum prolongation was seen with Thioridazine group followed by Ziprasidone ,Quetiapine and Risperidone (unlike published literature)

Glassman et al, 200129


• Clozapine: Cardiomyopathy and Myocarditis

• Range from subclinical presentation to fulminant pulmonary edema and cardiogenic shock

• 15 cases (0.187%) of clozapine-related myocarditis out of 8000 clozapine-treated patients in Australian patients

Kilian et al, 1999

• 9 of 94 patients initiated on clozapine over 3 years appeared to have experienced a suspected myocarditis (incidence of 9.6%)

Reinders et al,2004

• Tends to appear at any time during treatment but more frequently from 4 days to 22 weeks after initiation

30

HYPERPROLACTINEMIA

• Roughly equated to the potency of an antipsychotic to block D2 receptors

• More common with FGA than SGA except Risperidone and Paliperidone

• Short-term– Include menstrual disturbances– Galactorrhea, sexual dysfunction, infertility in women – Sexual dysfunction and Gynaecomastia in men

• Long term:– Estrogen deficiency in women – Testosterone deficiency in men resulting in decreased

bone mineral density Bostwick et al, 2009

31

Study Sample Type of study Drugs received Significant findings

Smith et al 2002 67 Any one of the FGAfor 2 years

Flupenthixol, haloperidol(injand oral), Pimozide,chlorpromazine

34% male and 75% female had level more than upper limit

Kim et al 2002 20 female On Risperidone shifted to olanzapine due to prolactin related side effect

Risperidoneolanzapine

Decrease in mean prolactin level after shift to olanzapine

Weiden et al 2003

108 FGA104 olanzapineRisperidone58

Combined analysis of3 open labeled study

All shifted to Ziprasidone

6 weeks later decreased in 2 groups but no change in olanzapine group

Kane et al 2002 Aripiprazole -204Haloperidol 104Placebo 106

4 weeks randomized double blind placebocontrolled

Weaned from previousantipsychotics and started either Aripiprazole or HPL

Mean level decreased in Aripiprazole group from baseline But increased in HPL groupNo change in placebo

First-generation antipsychotics, Risperidone, Paliperidone >Ziprasidone > olanzapine > Quetiapine, clozapine> Aripiprazole

32

To summarize

• There is definite risk of antipsychotics for

– Weight gain

– Diabetes

– CHD

– Metabolic Syndrome

– QTc prolongation and Sudden cardiac death

– Hyperprolactinemia

• The relative risk of metabolic abnormalities is more with second generation antipsychotics as compared to first generation

33

• INTRODUCTION• HISTORICAL PERSPECTIVE • EPIDEMIOLOGY • PATHOPHYSIOLOGY• MANAGEMENT



34

PATHOPHYSIOLOGY

Metabolic

Weight Gain, esp. abdominal obesity

Impaired Glucose Metabolism

• Hyperglycemia

• Type 2 DM

Dyslipidemia

• Hyper cholesterolmia

• Hypertriglyceridemia

• Low HDL

Cardiovascular

Arterial Hypertension

Disorder of Heart and Blood Vessels , Atherosclerosis

Sudden cardiac death, Myocarditis

35

FACTORS AFFECTING SIDE EFFECTS

• Long term treatment

• Polypharmacy

• High dosage

• Type of medications

• History of prior treatment

• Episode of illness

• Cannabis use

• Smoking

• BMI

• Negative Symptoms

• ethnicity

• Family History of obesity

• Parental BMI

• Genetic Factors

FAMILIAL PERSONAL

TREATMENTILLNESS

Hasnain et al, 200836

FACTORS AFFECTING SIDE EFFECTS

Diabetes

Dyslipidemia

Metabolic Syndrome

Vascular Inflammation and Hyper -coagulation

Increased Mortality and

Morbidity

37

PATHOPHYSIOLOGY

Increased appetite leading to increased weight and increases BMI

Direct production of atherogenic dyslipidemia

Insulin resistance

Hyperinsulinemia

Beta cell failure

Pre diabetes

Diabetes

Cardio vascular events

38

PATHOPHYSIOLOGY• Blockade of H1 receptors and activation of hypothalamic AMP

kinase leads to increased appetite

• 5HT2C receptor is involved in the feeding behavior

• Peripheral factors unrelated to appetite, such as increased cellular lipogenesis because of enhanced activity of fatty acid synthase and stearoyl-CoA desaturase

• Hypothetical role of receptor X: adipose tissue, liver and skeletal muscle – and possibly the brain – which would lead to insulin resistance

• Hypothetical role of M3 muscarinic cholinergic receptors: more propensity for developing Diabetic ketoacidosis

Stahl et al, 2009

39

PATHOPHYSIOLOGY

• Genome wide association studies (GWAS) to search for genetic variation affecting the susceptibility to metabolic side effects

• Schizophrenia patients from CATIE trial

• Different SNPs and intragenic markers were found to be significant in the change of metabolic parameters

• SNP in MEIS2 gene mediated the effects of Risperidone on waist circumference

Adkins et al, 2011

40

PATHOPHYSIOLOGY

• To study the susceptibility of antipsychotic induced metabolic changes, 76 mice were treated with haloperidol, olanzapine or clozapine for 7 days

• Functional analysis was conducted on the putative targets of altered microRNA

• Metabolic pathways were enriched in olanzapine and clozapine treatments, possibly associated with their weight gain side effects

• Suggests a role for microRNA in the mechanism of action and the metabolic side effects of the atypical antipsychotic drugs

Santarelli et al, 2013

41

• INTRODUCTION• HISTORCAL PERSPECTIVE• EPIDEMIOLOGY • PATHOPHYSIOLOGY• MANAGEMENT



42

MANAGEMENT FOR WEIGHT GAIN AND METABOLIC ABNORMALITIES

The 2010 PORT guidelines:

• Early behavioral intervention

• Pharmacotherapy

switching from one agent to another

addition of another medication before the initiation of antipsychotic treatment

addition of another medication during the antipsychotic treatment

Buchanan et al. 2010

43

EARLY BEHAVIOURAL INTERVENTION

• 61 treatment naive psychotic patients

• Randomly assigned to Olanzapine, Risperidone or Haloperidol

• Further randomized to either early behavioral intervention (EBI) or routine care intervention (RCI)

• EBI: 8 flexible intervention modules that incorporated behavioural interventions, nutrition, and exercise) (10-14 sessions over 3 M)

• RCI: patients were informed about potential weight gain and advised to increase their exercise and limit food intake

Jimenez et al,2006

44

EARLY BEHAVIOURAL INTERVENTION

J Clin Psychiatry. 2006 Aug;67(8):1253-60 Jimenez et al,200645

SWITCHING OF ANTIPSYCHOTICSSTUDY SAMPLE

SIZE SHIFT RESULTS PSYCHOPAT

HOLOGY

Newcomer et al. 2008Multicentric double blind RCT

173 Random assignment of switch from olanzapine to Aripiprazole or stay on olanzapine

Improvement in metabolic parameters and weight In the Aripiprazole group

Not discussed

Stroup et al. 2011

89

98

olanzapine, Quetiapine or risperidoneto Aripiprazole

Remained on the same

Significant weight reductions andan improvement of metabolic parameters in the Aripiprazole Group

Not discussed

• The switch to Ziprasidone might have some advantages compared to staying on Risperidone/olanzapine, but the evidence is limited

• Switch to Aripiprazole is a promising approach for treating antipsychotic induced weight gain 46

SWITCHING OF ANTIPSYCHOTICS

47Buckley et al, 2008

ADDITION OF ANOTHER MEDICATION

• Amantadine:

– Case reports

– Risk of flaring psychosis

• H2 receptor antagonist

– Nizatidine :

Double-blind RCT. Patients on olanzapine (5 – 20 mg/day) significantly less weight gain after 4 weeks add-on treatment with doses of 300 mg bd

Result not significant after 24 weeks Cavazzoni et al. 2003

48


Metformin:Study Method Participants Intervention Result

Bapista et al,2006

Randomized double blinding, 14 weeks

Schizophreniaand schizoaffective n=40

Olanzapine plus metformin or placebo(Metformin=850 to 1750)

In meta-analysis, weight reduction was 5.02% with metforminThe adverse events reportedwith metformin were similar to placebo groups

Bapista et al, 2007

Do 12 weeks

Schizophrenia and Bipolar n=80

DoMetformin 850 to 2550

Wu et al, 2008 Do, 12 weeks

Schizophrenia n=40

DoMetformin 750

Wu et al, 2008 Do, 14 weeks

Schizophrenian=64

Do Metformin 750

Praharaj et al, 201149


Topiramate:• N=72 randomized to receive Olanzapine+placebo or

Olanzapine+Topiramate(100mg/day)

• Results: In the topiramate group there was found to be reduction of mean weight of 1.27±2.28 kg , decrease in glucose cholesterol and triglyceride level

Narula et al. 2010

• Topiramate with clozapine : no weight loss in a double-blind, placebo-controlled RCT in which weight gain was not the primary outcome parameter

Muscatello et al. 2011

• Some case reports but no controlled trials

– Modafinil

– Orlistat

– Rosaglitazone

50

OTHER GUIDELINES

Risk Factors ADA-APA Guidelines(2004) Mount Sinai Guidelines(2004)

Weight gain

If patient gains 5% of initial weight,

consider cross-titration of medication.

Closer monitoring, adjunctive

treatment for weight loss, or

change in medication. If on a

medication with greater risk of

weight gain, consider

switching.

Referral to weight management program.

Diabetes or glucose

intolerance

Consider change to lower risk

medication. Refer to diabetes

education program and clinician with

experience treating diabetes.

Referral to a primary care

physician or internist.

Dyslipidemia

Consider change to lower risk

medication. May consider specialist

referral.

Dietary advice to reduce fat

intake.

Pharmacologic intervention

with a lipid-lowering agent.

51

MONITORINGRisk factors ADA-APA

Guidelines(2004)

Mount

Sinai Guidelines

(2004)

NICE guidelines

(2010)

Personal and family history of risk factors

Baseline then annually

Baseline Baseline

Ethnicity Not addressed Baseline Baseline

Smoking status Not addressed Baseline Baseline

Weight, height (BMI) Baseline 4, 8 and 12 weeks then quarterly

Baseline and every 6 months

Every weekly or every clinic visit

Waist circumference Baseline then annually

Baseline and every 6 months

Not addressed

Blood Pressure Baseline 12 weeks then annually

Not addressed Baseline, 12 weeks, annual

52

MONITORINGRisk Factors

ADA-APA

Guidelines(2004)

Mount

Sinai Guidelines(2004)

NICE guidelines

(2010)/Maudsley 2012

Fasting Plasma Glucose

Baseline, at 12 weeks, then annually

Baseline, If risk factors for diabetes, at 4 months, then annually. If gaining weight, every 4 months.

Baseline, 12 weeks and annually

Lipid profile

Baseline, at 12

weeks, then every 5

years if normal lipid

profile

Baseline, every 2 years

for normal LDL, every 6

months if LDL >

130mg/dl

Baseline,12 weeks and

annually

EKGBaseline and

annually

Baseline. Subsequent

EKG if symptoms

present.

Baseline, 12 weeks and

annually

Signs/Symptoms

of DiabetesBaseline

Baseline and at regular

intervals

Baseline and 12 weeks and

annually

53

MONITORINGRisk factors ADA-APA

Guidelines(2004)

Mount

Sinai Guidelines(2004)

NICE guidelines

(2010)/Maudsley 2012

Hemoglobin A1C Not addressed

Recommended

alternative when

measurement of

plasma glucose level is

not feasible

Baseline, 12 weeks and

annually

Target:

• BP: <140/90

• BMI<25 kg/m2

• Fasting Glucose<6.0 mmol/l, Non fasting <7.8mmol/l

• Glycosylated Hb: If no h/o DM <6%, If H/O 6.5-7.5(individualized)

• Total Cholesterol <5.0mmol/l or 4 mmol/l If established DM or CVD

• LDL <3 mmol/l or <2.0mmol/l if established DM or CVD 30% reduction after starting of Statins 54

HYPERPROLACTINEMIA

Guidelines :

– Use lowest effective dosage

– Use of prolactin sparing antipsychotics

– Add another antipsychotic that normalizes prolactin like Aripiprazole

– Obtain a baseline prolactin level if any symptoms of raised prolactin present

– If still the symptoms explained by raised prolactin use of Bromocriptine or Cabergoline (risk of increasing psychotic symptoms )

Bostwick et al, 2009

55

NEGLECT IN RECORDING BASIC PARAMETERS IN PATIENTS ON ANTIPSYCHOTICS

Clinical records of 1966 eligible patients under the care of clinical teams in 21 mental health services across the UK (2005)

Barnes et al, 2007

It was recommended these parameters to be reviewed once a year, from the guidelines

56

NEGLECT IN RECORDING BASIC PARAMETERS IN PATIENTS ON ANTIPSYCHOTICS

• Although blood pressure and obesity are relatively simple and easy to measure, the screening rates over the year for these variables were no better than those for tests requiring blood samples

• Increased rate of screening were seen for

– Patients on clozapine

– Advancing age

– Comorbid diagnosis of diabetes, dyslipidemia or hypertension

Barnes et al, 2007

57

• INTRODUCTION• HISTORCAL PERSPECTIVE• EPIDEMIOLOGY • PATHOPHYSIOLOGY• MANAGEMENT



58

CONCLUSION• The metabolic and cardiovascular side effects of antipsychotics were

identified around a decade after its use started

• The potential of antipsychotic drugs to induce or trigger metabolic and cardiovascular dysregulation is firmly established but individual agents differ markedly in their propensities

• Despite the ease of measurement of the parameters for monitoring the side effects they largely remain unmonitored

• Regular monitoring and life style intervention a must for the patients receiving antipsychotics with high propensity of metabolic and cardiovascular side effects

• If still the side effects occur, multidisciplinary approach and addition of another medication can be done 59

FUTURE DIRECTIONS

• The search of antipsychotic free of all the metabolic and cardiovascular side effects is warranted

• Further research on the molecular mechanism of side effects could give better idea for newer drug development

• Regarding the switching of antipsychotics the larger studies taking the symptomatology into account would provide better insight

• Another area of research could be the genetic studies so that a earlier prediction could be made for the susceptibility to develop side effects

60

THANK YOU

61

Health & Medicine

Cardiovascular and metabolic side effects of antipsychotics