SCHIZOPHRENIA

• What is Schizophrenia?• Types • Causes • Pathophysiology• Symptoms • Diagnosis• Treatment• Prevention• Case study• Conclusion• References

Table of Content

What is Schizophrenia?

Paranoid.

Disorganized

Catatonic

Undifferentiated

Residual

Etiology • Exact cause- unknown.• Some hypotheses suggested:

Pathophysiology

1) Dopamine Studies

2) Serotonin studies

3) GABA studies

4) Norepineprine studiesPharmacological evidence of NE involvement in schizophrenia is weak.

Symptoms According to Type of Schizophrenia

Paranoid schizophrenia : Hallucinations. Delusions.

Disorganized schizophrenia : Speech difficulties and abnormalities. Unable to think clearly. Unusual behaviour.

Catatonic schizophrenia : Movement disorders.

Undifferentiated schizophrenia : Mixture of symptoms.

Residual schizophrenia : Mild decrease or loss of normal function.

Management

Chart 1: Management of Schizophrenia (http://www.e-mfp.org/)

Treatment

• Pharmacological TreatmentsPharmacological Treatments– Antipsychotics

• First-generation (typical) / APs– Haloperidol– Perphenazine– Sulpiride

• Second-generation (atypical) /AAPs– Amisulpiride (AMS)– Olanzapine (OLZ)– Clozapine

• Pharmacological TreatmentsPharmacological Treatments– Antipsychotics

• First-generation (typical) / APs– Haloperidol– Perphenazine– Sulpiride

• Second-generation (atypical) /AAPs– Amisulpiride (AMS)– Olanzapine (OLZ)– Clozapine

Chart 2: Medication of Schizophrenia (http://www.e-mfp.org/)

Antipsychotics (APs)Antipsychotics (APs)Antipsychotics (APs)Antipsychotics (APs)

Atypical Antipsychotics (AAPs)Atypical Antipsychotics (AAPs)Atypical Antipsychotics (AAPs)Atypical Antipsychotics (AAPs)

Clozapine *Clozapine *Clozapine *Clozapine *

Clozapine + AP/ electroconvulsive therapy (ECT)Clozapine + AP/ electroconvulsive therapy (ECT)Clozapine + AP/ electroconvulsive therapy (ECT)Clozapine + AP/ electroconvulsive therapy (ECT)

Combination therapy: Combination therapy: • Combination of APs• APs + ECT• APS + mood stabilizer

Combination therapy: Combination therapy: • Combination of APs• APs + ECT• APS + mood stabilizer

*refer to psychiatristsFigure1: Electroconvulsive therapy

• AntiPsychotics1) Haloperidol

• Mechanism of actionMechanism of action– Dopamine antagonist– Site of action: Dopamine D2 receptors– Mediated by G proteins – Inhibit adenylyl cyclase – no cyclic AMP

• DoseDose– ≤ 20mg/day (oral)– 2mg/ml ; 2-3X/day (IV)

• PharmacokineticPharmacokinetic– t1/2: 18 ± 6 hr– Mean absoprtion: 0.4 ± 0.2 hr (70%)

• AntiPsychotics1) Haloperidol

• Mechanism of actionMechanism of action– Dopamine antagonist– Site of action: Dopamine D2 receptors– Mediated by G proteins – Inhibit adenylyl cyclase – no cyclic AMP

• DoseDose– ≤ 20mg/day (oral)– 2mg/ml ; 2-3X/day (IV)

• PharmacokineticPharmacokinetic– t1/2: 18 ± 6 hr– Mean absoprtion: 0.4 ± 0.2 hr (70%)

Figure 2: Haloperidol tablet

Figure 3: Haloperidol IV

2. Perphenazine (Trilafon)

• Mechanism of actionMechanism of action- Dopamine antagonist- Binds to the dopamine D1 and dopamine D2 receptors and inhibits their

activity- Produce anti-emetic effect (blockage of D2 NT receptors in the

chemoreceptor trigger zone and vomiting centre)- Binds the alpha-andrenergic receptor (activate phosphatidylinositol-calcium

second messenger system)

• DoseDose- ≤ 8mg/day (oral)- 5mg/ml (IV)

• PharmacokineticsPharmacokinetics- t1/2: 9-12hr- Mean absorption: 1-3 hr

Figure 3: Perphenazine tablet

3) Sulpiride

• Mechanism of actionMechanism of action– More selective dopamine antagonist– Primarily act on D2 receptor– Lack effects on NE, ACh, 5-HT, histamine & GABA receptors

• DoseDose– ≤ 400mg/day (oral)– 100mg/ml (IV)

• PharmacokineticPharmacokinetic– t1/2: 7 hr– Absorption: 2 hr (35%)

3) Sulpiride

• Mechanism of actionMechanism of action– More selective dopamine antagonist– Primarily act on D2 receptor– Lack effects on NE, ACh, 5-HT, histamine & GABA receptors

• DoseDose– ≤ 400mg/day (oral)– 100mg/ml (IV)

• PharmacokineticPharmacokinetic– t1/2: 7 hr– Absorption: 2 hr (35%)

Figure 4: Sulpiride tablet

• Atypical AntiPsychotics1. Amisulpride (AMS)• Mechanism of actionMechanism of action

– Selectively bind to dopamine D2 and D3 receptors – Low doses : block presynaptic D2/D3-dopamine autoreceptors

(enhancing dopaminergic transmission)– Higher doses: block postsynaptic receptors (inhibiting dopaminergic

hyperactivity– Effective on negative symptoms of acute schizophrenia

• DoseDose– 800mg/day (oral)– 50mg/kg (IV)

• PharmacokineticsPharmacokinetics– t1/2: 12 hr– Absorption: 28%

• Atypical AntiPsychotics1. Amisulpride (AMS)• Mechanism of actionMechanism of action

– Selectively bind to dopamine D2 and D3 receptors – Low doses : block presynaptic D2/D3-dopamine autoreceptors

(enhancing dopaminergic transmission)– Higher doses: block postsynaptic receptors (inhibiting dopaminergic

hyperactivity– Effective on negative symptoms of acute schizophrenia

• DoseDose– 800mg/day (oral)– 50mg/kg (IV)

• PharmacokineticsPharmacokinetics– t1/2: 12 hr– Absorption: 28%

Figure 5: Amisulpiride tablet

2) Olanzapine (OLZ)

• Mechanism of actionMechanism of action– Affinity for 5-HT2A/2C, DA, muscarinic M1-M5, histamine H1 &

adrenergic α1 receptors– Antagonize the effect of levodopa & dopamine agonists

• DoseDose– ≤ 20mg/day (oral)– 10mg/ml (IV)

• PharmacokineticsPharmacokinetics– t1/2: 33 hr– Absorption: 45%

Figure 6: Olanzapine tablet

3) Clozapine

• Mechanism of actionMechanism of action– Combination of antagonistic effect on:

• D2 receptors in the mesolimbic pathway (relieves positive symptoms) • 5-HT2A receptors in the frontal cortex (alleviates negative symptoms)

• DoseDose– ≤ 50mg/day (oral)– 4-16mg/kg (IV)

• PharmacokineticsPharmacokinetics– t1/2: 14hr– Rapidly absorbed (50%)

Figure 7: Clozapine tablet

Action of Antipsychotic Drugs

Figure 8: Action of Antipsychotics

Blocks D2 postsynaptic receptors in the DA pathways of brain

Antipsychotic Drugs

DA released has less effect

Psychotic: excess release of DA in mesolimbic pathway

Reduced dopaminergic neurotransmission

Adverse Effects of Antipsychotics:

• Delirium• Neurotoxicity• Sedation• Hypotension• Blurry vision• Unable to control body movement• Dizziness• Drowsiness• Tachycardia• Menstrual problem• Skin rashes• Stiffness in the body• Continual inadherence

• Akathisia• Agitation• Arousal• Insomnia• Dystonic reaction• Tardive dyskinesia• Hyperprolactinemia• Sexual Dysfunction• Agranulocytosis• Cardiac arrythmias• Seizures• Metabolic syndrome (weight gain)

Contraindication of Antipsychotic Drugs:1. History of drug hypersensitivity2. Severe depression3. Blood dyscrasias4. Brain damage

That require close observation:1. History of impaired liver function2. Cardiovascular disease3. Hypertension4. Glaucoma5. Diabetes6. Parkinson’s disease7. Peptic ulcer disease8. Seizure disorder9. Pregnancy10.Along with drug induce psychosis:

– Cocaine– Amphetamines– L-dopa

Contraindication of Antipsychotic Drugs:1. History of drug hypersensitivity2. Severe depression3. Blood dyscrasias4. Brain damage

That require close observation:1. History of impaired liver function2. Cardiovascular disease3. Hypertension4. Glaucoma5. Diabetes6. Parkinson’s disease7. Peptic ulcer disease8. Seizure disorder9. Pregnancy10.Along with drug induce psychosis:

– Cocaine– Amphetamines– L-dopa

• Non-pharmacological TreatmentNon-pharmacological Treatment– Psychosocial treatment

• Family education: whole family learn how to cope with illness• Illness management skills: increase adherence to medication• Rehabiliation: promote better communication and coping skills• Social skill training: enhance quality of life and promote recovery• Therapy: guidance from therapists on how to manage symptoms

(delusion and hallucination)

• Non-pharmacological TreatmentNon-pharmacological Treatment– Psychosocial treatment

• Family education: whole family learn how to cope with illness• Illness management skills: increase adherence to medication• Rehabiliation: promote better communication and coping skills• Social skill training: enhance quality of life and promote recovery• Therapy: guidance from therapists on how to manage symptoms

(delusion and hallucination)

Prevention

• Primary PreventionPrimary Prevention– Modify potential exposure– Preventing risks factors of schizophrenia

• Secondary PreventionSecondary Prevention– Modify the course of an illness by early intervention– Detecting and treating early psychosis

• Tertiary PreventionTertiary Prevention– Reduce the burden of established disorder– Optimizing treatment and rehabilitation

• Primary PreventionPrimary Prevention– Modify potential exposure– Preventing risks factors of schizophrenia

• Secondary PreventionSecondary Prevention– Modify the course of an illness by early intervention– Detecting and treating early psychosis

• Tertiary PreventionTertiary Prevention– Reduce the burden of established disorder– Optimizing treatment and rehabilitation

CASE STUDY Background

- 5 ½ year old girl

- Strange behavior and speech

- Not eating/dressing herself

- Alternate crying and laughing without reason

- Increased level of hyperactivity

- Not sleeping and talking to herself until late hours

- Not talking and responding to anyone-x

Diagnosis

- Provisional diagnosis of VEOS

- Medical and neurological work-up

Result

- Normal cranial MRI

- Normal sleep EEG

- Negative metabolic disorder

- Normal blood test

Treatment

Conclusions