Schizophrenia

Schizophrenia is a chronic severe mental disorder characterized by disturbances in thought, perception, emotions, drive, behaviour, and withdrawal from reality. Patients experience episodes of psychosis with varying combinations of positive, negative, and cognitive symptoms. The illness commonly follows a relapsing and remitting course, resulting in significant impairment in social, occupational, and interpersonal functioning. Symptoms vary considerably between individuals and may change over time. Early diagnosis and long-term treatment are essential to improve functional outcomes and reduce relapse.

Epidemiology

• Lifetime prevalence is approximately 1% worldwide.

• The usual age of onset is:

  • Males: late adolescence to early twenties.

  • Females: late twenties to early thirties.

• Earlier onset is more common in males.

• Schizophrenia is one of the leading causes of psychiatric disability worldwide.

Risk factors

Genetic factors

• Family history of schizophrenia.

• First-degree relatives have a substantially increased risk.

• Polygenic inheritance.

Neurodevelopmental factors

• Prenatal infections.

• Obstetric complications.

• Low birth weight.

• Maternal malnutrition.

Neurobiological factors

• Dopaminergic dysfunction.

• Glutamatergic dysfunction.

• Structural brain abnormalities.

Environmental factors

• Urban upbringing.

• Childhood trauma.

• Psychosocial stress.

• Cannabis use.

• Substance misuse.

Pathophysiology

Schizophrenia results from abnormalities involving multiple neurotransmitter systems and neural circuits.

Major mechanisms include:

• Increased mesolimbic dopamine activity producing positive symptoms.

• Reduced prefrontal dopamine activity contributing to negative and cognitive symptoms.

• Glutamate receptor dysfunction.

• Neurodevelopmental abnormalities.

• Impaired synaptic connectivity.

• Deficits in cognitive processing.

Clinical presentation

Patients may present during the prodromal, active psychotic, or residual phases of illness. Clinical manifestations include disturbances of thought, perception, emotion, behaviour, cognition, and social functioning.

Symptoms

Positive symptoms

• Delusions.

• Hallucinations (most commonly auditory).

• Disorganized speech.

• Disorganized thought processes.

• Disorganized or bizarre behaviour.

• Agitation.

Negative symptoms

• Reduced emotional expression.

• Flattened affect.

• Social withdrawal.

• Poverty of speech.

• Lack of motivation (avolition).

• Anhedonia.

Cognitive symptoms

• Poor attention.

• Memory impairment.

• Executive dysfunction.

• Poor insight.

Clinical signs

• Flattened or inappropriate affect.

• Poor eye contact.

• Social withdrawal.

• Reduced spontaneous speech.

• Psychomotor agitation or retardation.

• Delusional thinking.

• Hallucinatory behaviour.

• Disorganized behaviour.

• Impaired judgment.

• Functional impairment in occupational, educational, or social activities.

Differential diagnosis

• Schizoaffective disorder.

• Bipolar disorder with psychotic features.

• Major depressive disorder with psychotic features.

• Substance-induced psychotic disorder.

• Delirium.

• Dementia.

• Temporal lobe epilepsy.

• Brain tumours.

• Autoimmune encephalitis.

Diagnostic criteria

Diagnosis is based on the DSM-5 criteria.

The following criteria should be met:

• Presence of two or more of the following symptoms during a 1-month period, with at least one symptom being delusions, hallucinations, or disorganized speech:

  • Delusions.

  • Hallucinations.

  • Disorganized speech.

  • Grossly disorganized or catatonic behaviour.

  • Negative symptoms.

• Significant impairment in occupational, social, academic, or interpersonal functioning compared with the premorbid level.

• Continuous disturbance for at least 6 months, including at least 1 month of active-phase symptoms.

• Symptoms are not attributable to substance use or another medical condition.

Investigations

Baseline investigations

• Full blood picture (FBP).

• Serum electrolytes.

• Renal function tests (RFT).

• Liver function tests (LFT).

• Blood glucose.

• Lipid profile.

• Thyroid function tests.

• HIV testing where indicated.

• Syphilis screening where indicated.

• Urine toxicology screen.

Additional investigations

• Electrocardiogram (ECG) before initiating antipsychotic therapy when indicated.

• CT or MRI brain for first-episode psychosis or where neurological abnormalities are suspected.

• Weight, body mass index (BMI), and waist circumference.

• Blood pressure monitoring.

Management

Management requires a multidisciplinary approach aimed at controlling acute psychosis, preventing relapse, improving functional recovery, minimizing adverse effects, and supporting long-term community reintegration.

Initial management includes:

• Assess risk to self and others.

• Exclude medical or substance-related causes of psychosis.

• Manage acute behavioural disturbance where present.

• Initiate antipsychotic therapy.

• Provide psychoeducation and involve family members in care planning.

Non-pharmacological treatment

• Family counselling and psychoeducation.

• Cognitive Behavioural Therapy (CBT) for stabilized patients.

• Supportive group therapy.

• Occupational therapy.

• Work assessment.

• Rehabilitation programmes.

• Assertive community treatment where available.

• Bridging programmes before return to the community.

• Social and vocational rehabilitation.

• Medication adherence counselling.

Pharmacological treatment

Acute psychotic episodes

Manage acute agitation according to the guideline for Aggressive and Disruptive Behaviours.

Maintenance treatment

Use only one antipsychotic at a time.

• Haloperidol – 3–4.5 mg – PO – every 12 hours.

OR

• Chlorpromazine – 100–600 mg – PO – every 24 hours in divided doses.

OR

• Olanzapine – 5–10 mg – PO – once daily; titrate to a maximum dose of 20 mg per 24 hours.

OR

• Risperidone – 1 mg – PO – every 12 hours initially; increase by 1 mg every 2–3 days to 2–3 mg every 12 hours (maximum dose: 16 mg/day).

Long-acting injectable (Depot) antipsychotics

For patients with poor adherence to oral medication or where depot treatment is preferred:

• Fluphenazine decanoate – 6.25–50 mg – IM – every 2–4 weeks.

OR

• Zuclopenthixol decanoate – 100–600 mg – IM – every 2–4 weeks.

OR

• Flupenthixol decanoate – 20–40 mg – IM – every 4 weeks.

Adjunct treatment

Antiparkinsonian medication should be used only when extrapyramidal side effects (excluding tardive dyskinesia) occur or when higher doses of antipsychotics likely to cause extrapyramidal symptoms are required.

• Promethazine – 25–50 mg – PO – every 24 hours until symptoms resolve.

OR

• Benzhexol – 5 mg – PO – every 24 hours to every 12 hours; administer the last daily dose before 1400 hours to reduce the risk of insomnia.

Management according to underlying condition

First episode psychosis

• Use the lowest effective antipsychotic dose.

• Provide intensive psychoeducation.

• Closely monitor treatment response and adverse effects.

Poor medication adherence

• Consider long-acting injectable antipsychotic therapy.

• Reinforce adherence counselling.

• Engage family and community support services.

Coexisting substance use

• Integrate treatment for substance use disorders with schizophrenia management.

Behavioural disturbance

• Manage according to the Aggressive and Disruptive Behaviours guideline.

Referral

Refer patients to the next level of care in the following situations:

• First psychotic episode.

• High suicidal risk.

• Risk of harm to others.

• Children and adolescents.

• Older adults.

• Pregnant or breastfeeding women.

• Failure to respond to treatment.

• Intolerance to antipsychotic medication.

• Coexisting significant medical conditions.

• Coexisting mental disorders requiring specialist management.

Urgent referral is indicated when there is severe behavioural disturbance, inability to ensure patient safety, suspected organic psychosis, or severe medication-related adverse effects.

Complications

• Suicide.

• Self-neglect.

• Violence or aggression.

• Substance misuse.

• Homelessness.

• Social isolation.

• Occupational disability.

• Cognitive impairment.

• Metabolic syndrome.

• Extrapyramidal side effects.

• Tardive dyskinesia.

• Neuroleptic malignant syndrome.

Prognosis

The prognosis varies considerably among individuals. Better outcomes are associated with early diagnosis, prompt treatment, good medication adherence, family support, and shorter duration of untreated psychosis. Poor prognostic factors include early onset, prominent negative symptoms, recurrent relapses, substance misuse, and poor treatment adherence.

Prevention

Although primary prevention is limited, secondary prevention focuses on:

• Early recognition and treatment of first-episode psychosis.

• Continuous maintenance therapy.

• Relapse prevention strategies.

• Avoidance of alcohol and illicit substances.

• Family education and support.

• Regular psychiatric follow-up.

• Early recognition of relapse warning signs.