Schizophrenia

1. Clinical Overview

Definition

A severe, chronic psychotic disorder characterized by distortions in thinking, perception, emotions, language, sense of self, and behavior.

Key Concepts

• Psychosis: Loss of contact with reality.
• Positive Symptoms: "Added" experiences (Voices, Delusions).
• Negative Symptoms: "Lost" functions (Apathy, Withdrawal).

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2. Epidemiology

• Prevalence: 1% lifetime risk (Universal across cultures).
• Age of Onset: Males 18-25, Females 25-35 (bimodal peak).
• Gender: M=F, but Males have earlier onset and worse prognosis.
• Genetic: Strong link. Monozygotic twin concordance 48%. Parent with schizophrenia = 13% risk.
• Environmental Triggers: Urban birth, Migration, Cannabis use (heavy use in adolescence increases risk 6x).

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3. Diagnostic Criteria (ICD-10 / Schneider)

Schneider's First Rank Symptoms (PATHOGNOMONIC)

If present, diagnosis is highly likely (in absence of organic disease).

1. Audible Thoughts (Thought Echo): Hearing own thoughts spoken aloud.
2. Voices Arguing/Commenting: Third person auditory hallucinations ("He is stupid"

• "She is ugly").

3. Thought Alienation:
   • Insertion: Thoughts put into mind.
   • Withdrawal: Thoughts taken out.
   • Broadcasting: Thoughts transmitted to others.
4. Delusional Perception: Normal perception given abnormal meaning (e.g., "The traffic light turned red so I am the King").
5. Somatic Passivity: Sensations imposed by external agency.
6. Made Volition/Affect: Actions/Emotions controlled by others ("Robot").

ICD-10 Requirement

• Symptoms present for > 1 month. (If less than 1 month = Acute Transient Psychotic Disorder).

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4. Clinical Features

Positive Symptoms (Dopamine Excess in Mesolimbic Pathway)

• Delusions: Fixed false belief held despite evidence (Persecutory, Grandiose, Nihilistic).
• Hallucinations: Auditory (most common), Visual, Tactile, Olfactory (Rare - think Temporal Lobe Epilepsy).
• Disorganized Speech: Word salad, Knight's move thinking (derailment).

Negative Symptoms (Dopamine Deficit in Mesocortical Pathway)

• The 5 A's:
  1. Apathy (Lack of motivation).
  2. Anhedonia (No pleasure).
  3. Affective flattening (No emotion).
  4. Alogia (Poverty of speech).
  5. Asociality (Social withdrawal).
• Note: Negative symptoms are harder to treat and predict poor outcome.

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5. Differential Diagnosis

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6. Management: Pharmacotherapy (Antipsychotics)

Mechanism

• All block Dopamine D2 receptors.

Atypical (Second Generation) - First Line

• Risperidone, Olanzapine, Quetiapine, Aripiprazole.
• Pros: Less EPSE (Extrapyramidal Side Effects).
• Cons: Metabolic Syndrome (Weight gain, Diabetes, Lipids). Olanzapine is worst offender. Aripiprazole is weight neutral.

Typical (First Generation)

• Haloperidol, Chlorpromazine.
• Pros: Cheap, available as Depot.
• Cons: High EPSE risk.

Clozapine (The "Gold Standard" for Refractory)

• Used if 2 other antipsychotics have failed (one must be atypical).
• Efficacy: Works when nothing else does. Reduces suicide.
• Risks:
  • Agranulocytosis (1%): Neutrophils drop -> Fatal Sepsis. Mandatory Monitoring (FBC weekly for 18 weeks, then fortnightly). "Red Traffic Light" system.
  • Myocarditis.
  • Hypersalivation (Wet pillow).
  • Seizures.

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7. Side Effects: Extrapyramidal (EPSE)

Caused by D2 blockade in Nigrostriatal pathway.

1. Acute Dystonia (hours): Muscle spasm (Oculogyric crisis, Torticollis). Treat: Procyclidine (Anticholinergic).
2. Akathisia (days): Inner restlessness. Can't sit still. Suicide risk. Treat: Propranolol.
3. Parkinsonism (weeks): Tremor, rigidity, bradykinesia. Treat: Procyclidine.
4. Tardive Dyskinesia (years): Chewing, grimacing movements. Irreversible. Prevention is key.

Neuroleptic Malignant Syndrome (NMS)

• Emergency.
• Signs: Fever, Muscle Rigidity ("Lead pipe"), Autonomic instability, Confusion, Raised CK.
• Treatment: Stop drug, IV Fluids, Dantrolene/Bromocriptine.

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8. Management: Psychosocial

• CBT for Psychosis (CBTp): Challenge delusions without confrontation.
• Family Therapy: Reduces "High Expressed Emotion" (Hostility/Criticism) which triggers relapse.
• Early Intervention in Psychosis (EIP): Specialist team for first 3 years.
• Supported Employment.

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9. Prognosis: The Rule of Thirds

1. 1/3: Complete recovery (one episode only).
2. 1/3: Recurrent episodes with recovery in between.
3. 1/3: Chronic residual symptoms and decline.

Good Prognostic Factors:

• Acute onset.
• Older age at onset.
• Female.
• Positive symptoms dominate.
• Good pre-morbid function.

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10. Treatment Resistance & The CATIE Trial

Definition

Failure to respond to 2 antipsychotics (at least one atypical) at therapeutic dose for 6 weeks.

The CATIE Trial (2005)

• Compared Olanzapine, Quetiapine, Risperidone, Perphenazine (Typical).
• Finding: High discontinuation rates (74%) across ALL drugs due to inefficacy or side effects.
• Winner: Olanzapine slightly better efficacy but massive weight gain.
• Conclusion: Switch to Clozapine earlier.

Clozapine Titration

• Must start slow (12.5mg) to avoid hypotension/seizures.
• Target dose 300-450mg.
• Smoking cessation INCREASES Clozapine levels (Smoke creates enzymes that metabolize it). Watch out when patients enter non-smoking wards!

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11. Long-Acting Injections (Depots)

Indications

• Poor compliance (very common).
• Patient preference.

Options

• Atypical Depots: Paliperidone Palmitate (Monthly), Aripiprazole Maintena (Monthly), Risperidone Consta ( 2-weekly).
• Typical Depots: Zuclopenthixol (Clopixol), Flupentixol (Depixol).
  • Expert Tip: Clopixol has a separate "Acuphase" formulation for rapid sedation (lasts 3 days) - do NOT confuse with Depot (lasts weeks).

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12. Catatonia

Features

• Stupor: No psychomotor activity.
• Waxy Flexibility: Limbs stay in position placed by examiner.
• Mutism.
• Negativism: Resisting instructions.
• Echolalia/Echopraxia: Mimicking speech/movements.

Management

• Benzodiazepines: High dose Lorazepam.
• ECT: If refractory.
• Antipsychotics: Can worsen catatonia - use caution.

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13. Post-Schizophrenic Depression

Overview

• A depressive episode occurring after the resolution of psychotic symptoms.
• Risk: Very high suicide risk (Patient gains insight into their condition/losses).
• Differentiation: distinguish from "Negative Symptoms" (Apathy) or Antipsychotic Side Effects (Sedation/Akinesia).

Management

• Add Antidepressant (SSRI).
• Psychology support.

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14. Clinical Case Study: The "Monster Resource" Viva

Presentation

A 22-year-old male student is brought by housemates. He has covered his windows with foil "to block the MI5 rays". He hears two voices discussing his thoughts. He hasn't washed in 2 weeks.

Clinical Decision Points (Viva Style)

Q1: Identify the First Rank Symptoms. A:

1. Delusion of Persecution (MI5).
2. Third Person Auditory Hallucination (Voices discussing him).

Q2: He has never taken drugs. Diagnosis? A: First Episode Psychosis (likely Schizophrenia if > 1 month).

Q3: Management Plan? A:

• Referral: Early Intervention in Psychosis (EIP) team.
• Medication: Oral Atypical (e.g., Aripiprazole or Risperidone).
• Assessment: MRI Brain (rule out organic) + Toxicology.

Q4: He starts Haloperidol (refused others). 2 days later his eyes roll up and neck twists. What is this? A: Acute Dystonic Reaction (Oculogyric crisis).

• Treatment: IM Procyclidine.

Q5: 6 months later he is well but gains 20kg on Olanzapine. What to do? A: Switch to Aripiprazole (Weight neutral). Lifestyle advice. Metformin?

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15. References (High-Yield List)

1. NICE CG178 (2014). Psychosis and schizophrenia in adults: prevention and management.
2. Leucht S et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013.
3. Kane JM et al. Clozapine for the treatment-resistant schizophrenic. Arch Gen Psychiatry. 1988.
4. Schneider K. Clinical Psychopathology. 1959. (First Rank Symptoms).
5. Tiihonen J et al. 11-year follow-up of mortality in patients with schizophrenia. Lancet. 2009.
6. Howes OD et al. The dopamine hypothesis of schizophrenia: version III--the final common pathway. Schizophr Bull. 2009.
7. McGorry PD et al. Early intervention in psychosis. Br J Psychiatry. 2008.
8. Meltzer HY. Suicide and schizophrenia: clozapine and the InterSePT study. J Clin Psychiatry. 2002.
9. Lieberman JA et al (CATIE). Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005.
10. McGlashan TH. Early detection and intervention of schizophrenia: rationale and research. Br J Psychiatry. 1998.

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16. Examination Focus (Monster Mode)

Common Exam Questions

1. "First Rank Symptoms list?" → Audible Thoughts, Voices Arguing, Passivity, Delusional Perception.
2. "Clozapine Indication?" → Treatment Resistant (2 failed trials).
3. "Clozapine most dangerous side effect?" → Agranulocytosis (Sepsis).
4. "Acute Dystonia treatment?" → Procyclidine.
5. "NMS tetrad?" → Fever, Rigidity, Confusion, Autonomic instability.

"Do Not Miss" Red Flags

1. Command Hallucinations: "Kill yourself" or "Kill him". Immediate admission.
2. Clozapine missed doses: If missed > 48 hours, must re-titrate from start (risk of seizure/cardiac arrest).
3. Fever on Antipsychotics: Think NMS or Agranulocytosis.

Examiners' Pearls

• Delusion definition: "Fixed false belief out of keeping with patient's cultural background".
• Tactile hallucinosis: Suggests Cocaine ("Cocaine bugs") or Alcohol withdrawal. Not Schizophrenia.
• Post-Schizophrenic Depression: Very common after resolution of psychosis. High suicide risk period.

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Medical Reviewer: Dr. P. Psych, Consultant Psychiatrist (Jan 2026) Last Updated: 2026-01-04