laboratory tests in psychiatry

Laboratory Tests in psychiatry

Presented by Dr.Monirul Islam

Resident,MD(Phase-B) Dept.of psychiatry

BSMMU

A medical laboratory is a place where tests are done on clinical specimens and samples in order to get information about the health of a patient as pertaining to the diagnosis, treatment, and prevention of disease

Laboratory Services include testing of materials, tissues or fluids obtained from a patient or clinical studies to determine the cause and nature of disease

Medical Laboratories

Clinical Pathology Clinical Microbiology Clinical Biochemistry

Haematology

Histopathology

Cytology

Routine Pathology

Bacteriology

Mycobacteriology

Virology Mycology

Parasitology

Immunology

Serology

Biochemical analysis

Hormonal assays

What are Laboratory Services all about?

Laboratory Services play a critical role in the detection, diagnosis and treatment of disease. Samples are collected and examination and analysis of body fluids, tissue and cells are carried out. Main services are:

To Perform diagnostic tests To Identify organisms To Count and classify blood cells to identify

infection or disease To Perform immunological tests to check for

antibodies To Type and cross-match blood samples for

transfusions To Analyze DNA

Health Screening

• Programs to detect

important (and treatable)

disease in apparently

healthy individuals

Types of Screening

• Population

• Risk group

• Opportunistic

Principles for Screening Programs

1. There should be a recognizable early or latent stage

2. There should be an accepted treatment for the condition

3. The screening test is valid, reliable

4. The test must be acceptable to population to be screened

5. Cost of screening and case finding should be economically balanced in relation to medical care as a whole

Attributes of Test

Sensitivity

Specificity

Safety

Cost-effectiveness

Check-Up for a 50-Yr Woman

• BP measurement

• Fasting blood glucose

• Fasting lipid profile

• Pap’s smear

• Mammography

• FOBT

– Colonoscopy: F/H of colon Ca

• Vision & hearing

Ref: Harrison's

Internal Medicine

Check-Up for a 50-Yr Man

• BP measurement

• Fasting blood glucose

• Fasting lipid profile

• DRE/PSA

• FOBT

– Colonoscopy: F/H of colon Ca

• Vision & hearing

Ref: Harrison's Internal

Medicine

Benefits

• A primary goal of screening is the early

detection of a risk factor or disease at a

stage when it can be corrected or cured

• More effective treatment

– Improved quality of life

– Prolongation of survival

Adverse Consequences of Screening

• Not all are evidence-based

• Generates a number of false positive results

– Require further expensive & risky

investigations

– Anxiety in patient & family

– Dilemmas in the clinician

BASIC SCREENING TESTSCBCECGLiver function testRenal function testThyroid function testElectrolytesBlood sugarAim: ruling out organicity Ref: Kaplan & Sadock's Synopsis of

Psychiatry

Principles of endocrine tests

Timing of measurement: Release of many hormones is rhythmical(pulsatile, circadian, monthly)random test may be invalid, sequential/dynamic test may be required.

Choice of dynamic tests: -If deficiency suspected: stimulation test -If excess suspected: suppression test -Avoid interpreting one result in isolationImaging,Biopsy: may be needed

Thyroid Function TestsIndications:-MDD,BMD -Hypothyroidism -Hyperthyroidism -Lithium-induced hypothyroidism TFTs : First-line: S.TSH,T3,T4 Second-line: TSH receptor

antibody Isotope scanningSensitivity : T4>T3

Interpretation of TFTs TSH T4 T3 Interpretation

U.D. (Undetectable)

Raised Raised Primary thyrotoxicosis

U.D. Normal Raised Primary T3-toxicosis

U.D. Normal Normal Subclinical thyrotoxicosis

U.D. Raised Low,normal or raised

Sick euthyroidism

Elevated >20 mu/L

Low Low Primary hypothyroidism

Mildly5-20 mu/L

Normal Normal Subclinical hypothyroidism

20-500 mu/L

Normal Normal Artefact

Non-specific laboratory abnormalities in thyroid dysfunction

Thyrotoxicosis: • Alanine aminotransferase, γ-glutamyl transferase

(GGT), and alkaline phosphatase from liver and bone • bilirubin • Mild hypercalcaemia • Glycosuria

Hypothyroidism: • Creatine kinase, aspartate aminotransferase, LDH • Hypercholesterolaemia • Anaemia

– Normochromic normocytic or macrocytic • Hyponatraemia

Dexamethasone-suppression test

• Indication: Supporting Dx of MDD.• Procedure: pt is given 1mg of D.methasone

by mouth at 11pm & plasma cortisol is measured at 8am,4pm,11pm.

• Result: -Nonsuppression:cortisol>5mg/dl -Suppression: HPA-axis is normal• Nonsuppression is associated with stress.• Limitation: False +ve & -ve, Low sensitivity

Dexamethasone-suppression test

Importance: 1.+ve DST,Good response to ECT or TCA 2.To differentiate MDD from minor

dysphoria 3.Predicting outcome of treatment 4.Predicting relapse:Persistent

nonsuppression 5.Differenting delusional from

nondelusional MDD 6.High abnormal cortisol >10µg/dl are

more significant than mildly elevated level

Hyperprolactinaemia• Causes: A.Physiological:-stress –pregnancy -

exercise -Lactation –sleep -coitus B.Drug-induced: Dopamine antagonists -antipsychotics -antiematics:Domperidone Dopamine-depleting drugs -methyldopa

C.Pathological:Prolactinoma,PCOS,primary hypothyroidism,renal failure

Hyperprolactinaemia• C/F: Male:sex.dysfunction,infertility,breast

growth,bone mineral density. Female:Amenorrhoea,galactorrhoea• Monitoring: -ask prolactin-related

symptoms - prolactin level:at prescribing at 3 months yearly• Avoid prolacting-elevating drugs: -pt under 25yrs –pt with osteoporosis -pt with H/O breast cancer

Hyperprolactinaemia Prolactin concentration interpretation: Take blood sample at least one hour

after waking or eating Minimise stress during venepuncture

(stress elevates plasma prolactin) Normal : Women :0–25 ng/ml

Men :0–20 ng/mlRe-test: if prolactin concentration 25–100

ng/ml ( 530–2120 mIU/l)Referral :to rule out prolactinoma if

prolactin concentration>150 ng/ml (>3180 mIU/l)

Hyperprolactinaemia

Established antipsychotics not usually associated with hyperprolactinaemia

• Aripiprazole• Clozapine• Olanzapine• Quetiapine• Ziprasidone

HyperprolactinaemiaTreatment: Switch to a non prolactin-elevating

drug is the first choice An alternative is to add aripiprazole

to existing treatment For patients who need to remain on a

prolactin-elevating antipsychotic,dopamine agonists may be effective Amantadine, carbergoline and bromocriptine,but each has the potential to worsen psychosis.

Psychiatric Disorders No laboratory tests in psychiatry can confirm or

rule out diagnoses Psychiatrists depend more on the history, clinical

examination and MSE to make a diagnosis • Investigations: 1.Routine: -FBC, U&Es, LFTs, TFTs,RFTs, RBS,CXR, ECG 2.Special: (if indicated by history or physical

signs) -Urine toxicology -Antinuclear antibody(SLE) -Syphilis serology -CT/MRI, EEG, LP -HIV testing

DM & AntipsychoticsSchizophrenia: Associated with

Insulin resistance & Diabetes mellitus.

Mechanism: -Not clear -5HT antagonism -increase plasma lipids -Wt gain -Leptin resistance

A1C ≥6.5%OR

Fasting plasma glucose (FPG)≥126 mg/dL (7.0 mmol/L)

OR

2-h plasma glucose ≥200 mg/dL(11.1 mmol/L) during an OGTT

OR

A random plasma glucose ≥200 mg/dL (11.1 mmol/L)

Criteria for the Diagnosis of Diabetes

ADA. I. Classification and Diagnosis. Diabetes Care 2012;35(suppl 1):S12. Table 2.

Criteria for Testing for Diabetes in Asymptomatic Adult Individuals (1)

•Physical inactivity• First-degree relative with diabetes• High-risk race/ethnicity (e.g., African

American, Latino, Native American, Asian American, Pacific Islander)• Women who delivered a baby weighing >9 lb

or were diagnosed with GDM• Hypertension (≥140/90 mmHg or on therapy

for hypertension)*At-risk BMI may be lower in some ethnic groups.

Testing should be considered in all adults who are overweight (BMI ≥25 kg/m2*) and who have one or more additional risk factors:


• HDL cholesterol level<35 mg/dL (0.90 mmol/L) and/or a triglyceride level >250 mg/dL (2.82 mmol/L)• Women with polycystic ovarian syndrome (PCOS)• A1C ≥5.7%, IGT, or IFG on previous testing• Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans)• History of CVD

*At-risk BMI may be lower in some ethnic groups.

1. In the absence of risk factors testing for diabetes should begin at age 45 years

2. If results are normal, testing should be repeated at least at 3-year intervals, with consideration of more frequent testing depending on initial results (e.g., those with prediabetes should be tested yearly), and risk status

ADA. Testing in Asymptomatic Patients. Diabetes Care 2012;35(suppl 1):S14. Table 4.


Categories of increased risk fordiabetes (prediabetes)

A1C: 5.7%-6.4%

Impaired Fasting Glucose(IFG) FPG: 5.6-6.9 mmol/L (100-125mg/dl)

Impaired Glucose Tolerance (IGT) 2-h value in OGTT: 7.8-11.0 mmol/L (140-199mg/dl)

Monitoring:Pt receiving antipsychotics

TIME IDEAL TEST MINIMUM TEST

Base lineOGTT or FPGHBA1C if fasting not possible(+RBS)

Urine glucoseRBS

Continuation All Drugs:OGTT or FPG or HBA1C every 12months (+RBS)

Olanzapine,Clozapine: OGTT or FPG after 1 month,then every 4-6 months

Urinary glucose or RPG every 12 months + symptoms monitoring

Risk of DM with antipsychotics

Degree of risk Antipsychotics

High Clozapine,Olanapine

Moderate Quetiapine,Risperidone,Phenothiazines

Low High potency FGAs: Haloperidole

Minimal Aripiprazole,Amisulpride,AsenapineZiprasidone

DyslipidaemiaCAUSES OF SECONDARY HYPERLIPIDAEMIA Secondary hypercholesterolaemia - Hypothyroidism -Pregnancy -Drugs (antipsychotics, corticosteroids) -Nephrotic syndrome -Anorexia nervosa Secondary hypertriglyceridaemia -Diabetes mellitus (type 2) -Abdominal obesity -Excess alcohol -Drugs (β-blockers, retinoids, corticosteroids)

Antipsychotics & Dyslipidaemia

FGAs: -Phenothiazines: TG, LDL,HDL

-Haloperidole: minimal effects

SGAs: -Mild: Aripiprazole,Ziprasidone

May even reverse -

Moderate:Risperidone,Quetiapine -Severe: Olanzapine,Clozapine

Monitoring

Antipsychotics drugs

Suggested monitoring

Clozapine and Olanzapine

Fasting lipid at baseline,then every 3 months for a year,then annually.

Other antipsychotics Fasting lipid at baseline,then at 3 months, then annually.

HyponatraemiaCauses of hyponatraemia Treatment

Water intoxication Monitor serum sodium( as day progress)Fluid restrictionCareful use of IVsaline:RhabdomyolysisConsider treatment with clozapineRefer if Na<125 mmol/L

SIADH: Associated with all antipsychotics

Monitor serum sodiumFluid restrictionSwitch to different antipsychoticsRefer if Na<125 mmol/L

Severe hyperlipidaemia and/or hyperglycaemia

PseudohyponatraemiaTreat the cause

Antidepressant-induced hyponatraemia

• Most antidepressants have been associated with hyponatraemia

• Onset:is usually within 30 days of starting treatment

• not dose-related • The mechanism:probably the

syndrome of inappropriate secretion of antidiuretic hormone (SIADH); serotonin is thought to be involved in the regulation of ADH release

Antidepressant-induced hyponatraemia

MONITORING: • pt taking antidepressants:observe signs of

hyponatraemia Serum sodium should be determined :at

baseline 2 & 4 wks

• and then 3-monthly those at high risk The high-risk factors are as follows: - extreme old age (>80 years) - history of hyponatraemia - co-therapy with drugs associated with

hyponatraemia - reduced renal function (GFR <50 ml/min) - medical co-morbidity common in elderly patients so monitoring is

essential

Anorexia nervosaEndocrine: -LH,FSH,T3,RBS -GH,CortisolHaematological: -Normocytic normochromic

anaemia -Thrombocytopenia -Leucopenia with

rel.LymphocytosisMetabolic: -Hypercholesterolaemia -HypophosphataemiaOthers: -Electrolytes imbalance

Sexual dysfunction

• Should be arranged according to cause ED: -FBS -Testosterone -SHBG -LH/FSH

-Prolactin -Thyroid Function -PSA

-S. Lipid profile

Lab Test: FSAD• Depends on relevent symptoms• If low desire suspected along with

arousal: S.Testosterone, SHBG• If menopausal (vaginal dryness) state – S. Estrogen

• If comorbid with marked oligomenorrhoea– S. Prolactin

• Thyriod Status if clinical history suggest

NMS

NMS is rare,even fatal outcome of antipsychotics

Incidence:0.2% of pt taking antipsychotics

Onset: often first 10 days of treatmentLab findings: - Creatinine

phosphokinase - WBC - Alter LFT

Pre-anaesthetic check prior to ECT

ECT work-up:-CBC -ECG -Liver function test -Renal function test -Electrolytes -Blood sugar -Vital signs:pulse,BP,tem,RR -Check no medication or seizure threshold

Rapid tranquillisation

The clinical practice of RT is used to de-escalate acutely disturbed

behaviour

The aims of RT are : 1. To reduce suffering for the patient 2. To reduce risk of harm to others 3. To do no harm

RT:monitoring After any parenteral drug administration,

monitor as follows: Pulse Blood pressure Temperature Respiratory rate Time: Every 5–10 min for 1 hour, and then half-

hourly until patient is ambulatory. If pt is asleep or unconscious :use pulse

oximetry ECG and haematological monitoring:strongly

recommended when parenteral antipsychotics are given

Hypokalaemia, stress and agitation place the patient at risk of cardiac arrhythmia

ECG monitoring :for all patients who receive haloperidol.

Substances of Abuse That Can Be Tested in Urine

Substance Length of Time Detected in Urine

Alcohol 7-12 hours

Amphetamine 2 days

Barbiturate 1 day (short-acting) 3 weeks (long-acting)

Benzodiazepine 3 days

Cannabis 3 days to 4 weeks (depending on use)

Cocaine 6-8 hours (metabolites 2-4 days)

Codeine 2 days

Heroin 36-72 hours

Methadone 3 days

Morphine 2-3 days

Plasma level monitoring of psychotropics

Is there a clinically useful assay method available? Is the drug at ‘steady state’? Is the timing of the sample correct? Is there a target range of plasma levels? Is there a clear reason for plasma level

determination? Only the following reasons are valid: – to confirm compliance – if toxicity is suspected – if drug interaction is suspected – if clinical response is difficult to assess directly – if the drug has a narrow therapeutic index and

toxicity concerns are considerable.

Interpreting sample results

Drug Target range Sample timing Time to steady state

Aripiprazole

150–210 µg/L Trough 15–16 days

Clozapine

350–500 µg/L Trough 2–3days

Lithium 0.6–1.0 mmol/L(may be >1.0 mmol/L in mania)

12 hours post-dose

5-7 days

Olanzapine

20–40 µg/L 12 hours post-dose

1 week

Tricyclics Nortriptyline :50–150 µg/LAmitriptyline: 100–200 µg/L

Trough 2–3 days

Valproate 50–100 mg/L Trough 2–3 days

TCAIndication for plasma

monitoring: 1.To check compliance 2.Toxic side effect at low dose 3.Lack of therapeutic response

4.Doses>200mg 5Coexisting medical

illness(e.g.Epilepsy) 6.Possibility of drug interaction

Clozapine Many adverse effects are dose-dependent & more

common at beginning of treatment Target dose: Average dose is around 450mg/day Response seen in the range 150–900 mg/day Plasma levels : Response is in range 350–420 µg/L Mandatory blood monitoring and registration - Register with the relevant monitoring service. -Perform baseline blood tests (WCC and

differentialcount) before starting clozapine. -first 18 weeks=Weekly -remainder of the year=2 weekly -After that= monthly Stop cloapine: WBC<3000 OR Neutrophil<1500 per

mm3

Clozapine Additional monitoring: -Wt -Lipid profile -LFTs -Plasma glucose -BMI -Waist

Timing: at 1,3,6 and 12 months.

Clozapine:MyocarditisTime/condition Monitor

Baseline Pulse,tem,RR,CRP,Troponin,Echo

Daily Pulse,tem,RR

Days 7,14,28 CRP,Troponin

If CRP>100mg/L,Troponin>twice upper limit

Stop cloapine,repeat Echo

If fever+tachycardia+CRP OR Troponin

CRP and Troponin daily

LithiumPre-Lithium work-up: 1.Physical examination: BP,

Wt 2.RFT: eGFR,Creatinine or

CCr 3.TFT 4.CBC 5.ECG 6.Pregnancy test-if indicated

LithiumOn treatment monitoring: 1.Plasma lithium: -First after 7 days -Then weekly=3weeks -Once every 6 week -Then 2-3 months. 2.e-GFR & TFTs : every 6 months 3.BMIPlasma level: Acute mania: 0.8-1 mmol/L Prophylactic: 0.5-0.8 mmol/L Toxicity: >1.5 mmol/LNarrow therapeutic index: Lithium toxicity

Lithium Toxicity1.Mild to moderate intoxication (lithium level = 1.5 to 2.0 mEq/

GI Vomiting,Abdominal pain

Neurologic Ataxia,Dizziness,Slurred speechNystagmus,Lethargy or excitementMuscle weakness

2,Moderate to severe intoxication (lithium level = 2.0 to 2.5 mEq/L)

GI AnorexiaPersistent nausea and vomiting

Neurologic Blurred vision,Muscle fasciculationsClonic limb movementstendonreflexes,Convulsions,Delirium,SyncopeStupor,Coma,Circulatory failure

3.Severe lithium intoxication (lithium level >2.5 mEq/L)

Generalized convulsions , Oliguria renal failure, Death

Management of Lithium Toxicity

Lithium must be stoped at onceHigh intake of fluid,maintenance of

electrolyte balanceExamination :vital signs,neuro. Exam, MSELab:Lithium level,serum

electrolytes,RFTs,ECG Acute ingestion:gastric lavage,activated

charcoalOsmotic or forced alkaline diuresis should be

used . NEVER thiazide or loop diuretics Lithium level >3.0 mEq/L: haemodialysis Repeat dialysis :every 6 to 10 hours, until

the lithium level is within nontoxic range

Instructions to Pt Taking Lithium

DosingTake lithium exactly as directed by your doctore.Do not stop taking without speaking to your doctor.If you miss a dose, take it as soon as is possible. If it is within 4 hours of the next dose, skip the missed dose. Never double up doses.

Blood TestsComply with the schedule of recommended regular blood tests.you should have taken your last lithium dose 12 hours earlier.

Use of Other MedicationsDo not start any prescription without telling your doctor

Diet and Fluid IntakeAvoid sudden changes in your diet or fluid intake. If you do go on a diet, inform your doctor.Caffeine and alcohol act as diuretics and can lower your lithium concentrations.it is recommended that you drink about 2 or 3 quarts of fluid daily, and use normal amounts of salt.

Recognizing Potential ProblemsIf you engage in vigorous exercise or have an illness that causes sweating, vomiting, or diarrhea, consult your doctor.Pt is educated about early signs of lithium toxicity

Lithium & eGFR• Indication for referral to specialist in pt

taking Lithium: 1.eGFR is decreased by >4 ml/min

annually 2.Progressive rise in creatinine in 3 or

more serial test 3.Proteinuria 4.Haematuria 5.Symptoms of CRF(Anaemia,tiredness) 6.e-GFR <30 ml/min

Valproate:MonitoringIndications Mania, hypomania, bipolar depression and

prophylaxis of bipolar affective disorder.Note that sodium valproate is licensed only for epilepsy and semi-sodium valproate only for acute mania

Pre-valproate work up

FBC and LFTs. Baseline measure of weight

Prescribing Loading doses can be used and are generally well tolerated. CR sodium valproate can be given once daily. All other formulations must be administered at least twice dailyPlasma levels can be used to assure adequate dosing and treatment compliance. Blood should be taken immediately before the next dose

Monitoring As a minimum, FBC and LFTs after 6 monthsWeight (or BMI) should also be monitored

Stopping Reduce slowly over at least 1 month

Lab Monitoring:Carbamazepine Test Frequency

Complete blood count (CBC) Before treatment and every 2 weeks for the first 2 months of treatment; thereafter, once every 3 months

Platelet count and reticulocyte count

Before treatment and yearly

Serum electrolytes Before treatment and yearly

Electrocardiogram Before treatment and yearly

SGOT,SGPT,LDH Before treatment and every month for the first 2 months of treatment; thereafter, every 3 months

Pregnancy test for women of childbearing age

Before treatment and as frequently as monthly in noncompliant patients

Other Laboratory TestsTest Major

Psychiatric Indications

Comments

Adrenocorticotropic hormone (ACTH)

Organic workup

Increased in steroid abuse; may be increased in seizures, Cushing's disease, and in response to stressDecreased in Addison's disease

Alanine aminotransferase (ALT)

Organic workup

Increased in hepatitis, cirrhosis, liver metastasesDecreased in pyridoxine (vitamin B6) deficiency

Antinuclear antibodies

Organic workup

Found SLE and drug-induced lupus (e.g., secondary to phenothiazines, anticonvulsants)



Comments

Calcium (Ca) Organic workupMood disordersPsychosisEating disorders

Increased in hyperparathyroidism,delirium, depression, psychosisDecreased in hypoparathyroidism, long-term laxative use

Catecholamines urinary and plasma

Panic attacksAnxiety disorders

Elevated in pheochromocytoma

Ceruloplasmin, copper, serum

Organic workup Low in Wilson's disease



Comments

Cortisol Organic workupMood disorders

Excessive level may indicate Cushing's disease associated with anxiety, depression

Estrogen Mood disorder Decreased in menopausal depression and premenstrual syndrome

Glutamyl transaminase, serum

Alcohol abuseOrganic workup

Increased in alcohol abuse, cirrhosis, liver disease

Folate (folic acid), serumVitamin B12, serum

Alcohol abuseDementia

associated with dementia, deliriumalcohol dependence, use of phenytoin, oral contraceptives



Comments

Holter monitor Panic disorder Evaluation of panic-disorder patients with palpitations and other cardiac symptoms

Nocturnal penile tumescence

Erectile disorder

Helpful in differentiation between organic and functional causes of impotence

Testosterone, serum

ImpotenceHypoactive sexual desire disorder

Increased in anabolic steroid abuseMay be decreased in impotenceDecrease may be seen in hypoactive sexual desire disorder

Take Home MessageNo laboratory tests in psychiatry can

confirm or rule out diagnosesHealth screening should be done in all

psychiatric pt to exclude organicityTFTs are used to rul out hypothyroidism

which can appear as MDDDST:help confirm diagnostic impression

of MDDAlways check for Metabolic syndrome

patient taking psychotropicsLab tests should be arranged according

to cause in sexual dysfunction

Take Home Message• Urine test is an important test for

substance abuser• Be sure that pt is fit biochemically

for giving anaesthesia in ECT• Drug level monitoring help in

optimising treatment & assure adherence

• Treat the patient,not the level• ECG and haematological monitoring:

strongly recommended when parenteral antipsychotics are given

Take Home Message

• Clozapine is associated with myocarditis and cardiomyopathy

• ANC is mandatory blood monitoring for clozapine

• Be aware about psychotropics induced electrolytes imbalance

• RFTs,TFTs are most important Pre-Lithium work-up

• Lithium toxicity is a medical emergency often having fatal outcome

laboratory tests in psychiatry

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