What are the treatment guidelines for schizophrenia?

Treatment Guidelines for Schizophrenia

Antipsychotic medication should be offered to individuals who have experienced a week or more of psychotic symptoms with associated distress or functional impairment, with treatment decisions made collaboratively with patients based on side-effect profiles and efficacy. 1

General Principles

• Treatment should involve shared decision making with patients and carers whenever possible, informing them about available treatment options, potential risks and benefits 1
• Treatment should be individualized based on current symptoms, patient preferences regarding side effects, efficacy, and route of administration 1
• Early assessment of treatment effectiveness and a proactive approach to treatment adjustments are essential for optimal outcomes 1

Initial Treatment Approach

First Episode Psychosis

• Antipsychotic treatment should be initiated for individuals with at least one week of psychotic symptoms causing distress or functional impairment 1
• Earlier initiation is appropriate when symptoms cause severe distress or pose safety concerns 1
• Consider delaying treatment when symptoms are clearly related to substance use or medical conditions and don't pose safety concerns 1

Medication Selection

• The initial choice of antipsychotic should be made collaboratively with the patient based on side-effect and efficacy profiles 1
• First-generation and second-generation antipsychotics should not be considered distinct categories for guiding treatment choices 1
• Common first-line options include aripiprazole, risperidone/paliperidone, or olanzapine 2

Treatment Algorithm for Positive Symptoms

First Antipsychotic Trial

• Give the first antipsychotic at therapeutic dose for at least 4 weeks, assuming good adherence 1
• If significant positive symptoms persist after 4 weeks, consider switching to an alternative antipsychotic with a different pharmacodynamic profile 1

Second Antipsychotic Trial

• If first-line treatment was a D2 partial agonist, consider switching to amisulpride, risperidone, paliperidone, or olanzapine (with metformin to mitigate weight gain) 1
• Use gradual cross-titration informed by the half-life and receptor profile of each medication when switching antipsychotics 1

Treatment-Resistant Schizophrenia

• If positive symptoms remain significant following two adequate antipsychotic trials (at least 4 weeks each at therapeutic doses with good adherence), reassess diagnosis and consider contributing factors 1
• If schizophrenia diagnosis is confirmed, a trial of clozapine should be initiated 1
• Metformin should be offered concomitantly with clozapine to attenuate potential weight gain 1
• Clozapine dose should be titrated to achieve a plasma level of at least 350 ng/mL, increasing up to 550 ng/mL if needed 1
• For persistent symptoms despite adequate clozapine trial, consider augmentation with amisulpride, aripiprazole, or electroconvulsive therapy 1

Management of Negative Symptoms

• Address secondary causes of negative symptoms (positive symptoms, depression, substance misuse, social isolation, medical illness, medication side effects) 1
• Offer psychosocial interventions to address psychological factors and encourage social engagement 1
• If positive symptoms are well controlled, consider gradual reduction of antipsychotic dose while remaining within therapeutic range 1
• For medication switches, consider cariprazine or aripiprazole 1
• Low-dose amisulpride (50 mg twice daily) may be beneficial for predominant negative symptoms when positive symptoms are controlled 1
• Antidepressant augmentation may have modest benefits for negative symptoms 1

Management of Depressive Symptoms

• Rule out secondary causes of depressive symptoms 3
• Consider antidepressant augmentation if depressive symptoms persist despite antipsychotic optimization 3
• Offer psychosocial interventions and encourage social engagement 3

Cognitive Symptoms Management

• Review and minimize anticholinergic burden of medications 1
• Consider gradual reduction of antipsychotic dose if positive symptoms are well controlled 1
• Consider switching to an antipsychotic with more benign metabolic profile 1
• Cognitive remediation may be beneficial 1

Monitoring and Side Effect Management

Baseline and Follow-up Monitoring

• Before starting antipsychotics, obtain: BMI, waist circumference, blood pressure, HbA1c, glucose, lipids, prolactin, liver function tests, electrolytes, complete blood count, and ECG 1
• Check fasting glucose 4 weeks after initiation 1
• Monitor BMI, waist circumference, and blood pressure weekly for 6 weeks after starting or switching antipsychotics 1
• Repeat all measures after 3 months and annually thereafter 1

Cardiometabolic Side Effects

• Offer lifestyle advice (healthy diet, physical activity, tobacco cessation) to all patients 1
• Consider metformin when starting antipsychotics with poor cardiometabolic profiles (olanzapine, clozapine) 1
• Start metformin at 500 mg daily, increasing by 500 mg every 2 weeks up to 1g twice daily as tolerated 1

Movement Disorders

• For akathisia, consider dose reduction, switching antipsychotics, or adding propranolol (10-30 mg two to three times daily) 1
• For acute dystonia, treat with anticholinergic medication 1
• For tardive dyskinesia, consider VMAT2 inhibitors 1

Long-term Treatment

• Patients who have responded to an antipsychotic medication should continue treatment with the same medication 1
• Consider long-acting injectable antipsychotics for patients with history of poor adherence or if patients prefer this formulation 1

Special Considerations

• For persistent suicidal risk despite treatment, clozapine is recommended 1
• For persistent aggressive behavior despite treatment, clozapine should be considered 1
• Substance use comorbidities require a non-judgmental supportive approach and collaboration with specialist services 1

Psychosocial Interventions

• Cognitive-behavioral therapy for psychosis (CBTp) is recommended 1
• Psychoeducation should be provided to all patients 1
• Supported employment services improve functional outcomes 1
• Family interventions are beneficial for patients with ongoing family contact 1
• Assertive community treatment is recommended for patients with history of poor engagement with services 1