What is the treatment for schizophrenia (Tx)?

Treatment of Schizophrenia

Antipsychotic medication is the cornerstone of schizophrenia treatment and should be initiated early when psychotic symptoms cause distress or functional impairment, with selection based on the patient's individual side effect profile preferences and efficacy considerations. 1, 2

Pharmacological Treatment Algorithm

First-line Treatment

• Antipsychotic treatment should be offered to individuals who have experienced a week or more of psychotic symptoms with associated distress or functional impairment 1
• Initial antipsychotic should be given at a therapeutic dose for at least 4 weeks to properly assess efficacy, assuming good adherence 1, 2
• Treatment decisions should incorporate patient preferences regarding side effects, efficacy, and route of administration 1
• Common first-line options with good efficacy include risperidone, olanzapine, amisulpride, and aripiprazole 3

Management of Inadequate Response

• If significant positive symptoms persist after 4 weeks of treatment at an appropriate dose, switch to an alternative antipsychotic with a different pharmacodynamic profile 1, 2
• For patients whose first-line treatment was a D2 partial agonist, consider second-line treatment with amisulpride, risperidone, paliperidone, or olanzapine 1
• After two failed antipsychotic trials of adequate dose and duration, clozapine should be considered 1, 2

Treatment-Resistant Schizophrenia

• Clozapine is specifically recommended for treatment-resistant schizophrenia and when suicide risk remains substantial despite other treatments 1, 3
• Clozapine has superior efficacy for treatment-resistant schizophrenia compared to other antipsychotics 3, 4

Side Effect Management

Extrapyramidal Side Effects

• For acute dystonia, treat with an anticholinergic medication 1
• For parkinsonism, consider lowering the dose, switching antipsychotics, or adding an anticholinergic 1
• For akathisia, consider dose reduction, medication switch, adding a benzodiazepine, or a beta-blocker like propranolol (10-30 mg two to three times daily) 1
• For tardive dyskinesia, consider VMAT2 inhibitors for moderate to severe cases 1

Metabolic Side Effects

• Lifestyle advice (healthy diet, promotion of physical activity, and tobacco cessation) should be offered to all patients 1
• Consider metformin for metabolic side effects, particularly with clozapine or olanzapine 1, 2
• Monitor weight, blood glucose, and lipid profiles regularly 2

Hyperprolactinemia

• For symptomatic hyperprolactinemia, consider switching to a D2 partial agonist or adding low-dose aripiprazole 1
• Counsel patients on risks of untreated hyperprolactinemia, including reduced bone mineral density and increased risk of breast cancer in women 1

Psychosocial Interventions

• Antipsychotic medication should be combined with psychosocial interventions for optimal outcomes 1, 2
• Recommended psychosocial interventions include:
  • Coordinated specialty care for first-episode psychosis 1, 2
  • Cognitive-behavioral therapy for psychosis (CBTp) 1, 2
  • Psychoeducation for patients and families 1, 2
  • Supported employment services 1
  • Assertive community treatment for those with history of poor engagement 1

Special Considerations

Medication Adherence

• Consider long-acting injectable antipsychotics if patients prefer such treatment or have a history of poor or uncertain adherence 1
• Patient psychoeducation is essential for treatment adherence 2

Substance Use Comorbidities

• Use a non-judgmental supportive approach and consider co-working with specialist substance use disorder services 1
• For tobacco use, consider varenicline, bupropion, or nicotine replacement therapy 1
• For alcohol use disorders, consider naltrexone 1

Antipsychotic Polypharmacy

• Antipsychotic polypharmacy should generally be avoided and only considered after a failed clozapine trial 1, 2
• Augmentation of clozapine or aripiprazole augmentation may be considered in specific cases 1

Common Pitfalls to Avoid

• Inadequate duration of antipsychotic trials (should be at least 4 weeks at therapeutic dose) 1, 2
• Neglecting physical health monitoring and interventions 2
• Overlooking clozapine as an option for treatment-resistant cases 1, 3
• Using doses above the therapeutic range, which has little evidence to support it 3
• Categorically distinguishing between first-generation and second-generation antipsychotics, as there is substantial variation within both classes 5, 6