Stimulants and Schizophrenia
Stimulants should not be used in patients with schizophrenia, as they are contraindicated due to their known psychotomimetic effects that can trigger or worsen psychotic symptoms. 1
Clear Contraindication
The American Academy of Child and Adolescent Psychiatry explicitly states that stimulants are a known psychotomimetic for individuals with schizophrenia, and should not be used in patients with an Axis I diagnosis of schizophrenia, psychosis NOS, or manic episodes with psychosis. 1 This represents a true contraindication in clinical practice, even though FDA package inserts paradoxically fail to mention psychosis as a contraindication. 1
Mechanism of Harm
Stimulants exacerbate symptoms of behavior disturbance and thought disorder in patients with pre-existing psychotic disorders. 2 The FDA drug label for amphetamines warns that administration of stimulants may worsen psychosis in these patients. 2
Evidence from Challenge Studies
Methylphenidate consistently worsens psychotic symptoms or predicts relapse in patients with schizophrenia. 3 Challenge studies demonstrate that:
- 50-70% of patients with schizophrenia and pre-existing acute psychotic symptoms experience a brief increase in psychosis ratings after a single stimulant dose, regardless of antipsychotic medication use. 4
- Even patients with schizophrenia without acute psychotic symptoms respond with worsening psychosis 30% of the time. 4
- Compliance with antipsychotic medication will not prevent relapse or worsening of psychotic symptoms if stimulants are used. 4
Lack of Therapeutic Benefit
Despite theoretical interest in treating negative symptoms, no proven efficacy exists for stimulants or atomoxetine on negative symptoms of schizophrenia. 3 Meta-analysis failed to confirm any effect of stimulants in any symptom domain, including negative symptoms. 3 While atomoxetine showed some improvement in problem-solving and amphetamines trended toward improvement in executive functions, these modest cognitive benefits do not justify the substantial risk of psychotic exacerbation. 3
Real-World Harms
Stimulant use disorders in patients with schizophrenia are associated with severe clinical deterioration: 5
- More frequent relapses and hospitalizations 6
- Increased violent behaviors 6
- Higher rates of homelessness 6, 5
- Frequent emergency department presentations (52%) 5
- Admissions with injury or self-harm (44%) 5
- Infectious disease diagnoses (22%) 5
Clinical Bottom Line
There is no clinical scenario where prescribing stimulants to a patient with schizophrenia is appropriate. The risk of triggering or worsening psychosis far outweighs any potential benefit. 1 If a patient with schizophrenia presents with comorbid ADHD symptoms, alternative non-stimulant treatments should be pursued, and the primary focus must remain on optimizing antipsychotic therapy as recommended by the American Psychiatric Association. 1