Most Common Reasons for Antipsychotic Discontinuation in Schizophrenia
Side effects are the most common reason for antipsychotic medication noncompliance in patients with schizophrenia, which significantly increases the risk of relapse and greater morbidity. 1
Primary Reasons for Discontinuation
Side Effects
Side effects represent the leading cause of antipsychotic discontinuation in schizophrenia patients, particularly:
Akathisia - A sense of severe restlessness frequently manifested as pacing or physical agitation. It is often misinterpreted as psychotic agitation or anxiety and is a common reason for medication noncompliance 1
Extrapyramidal Symptoms (EPS) - Including:
- Dystonia (sudden spastic contraction of muscle groups)
- Parkinsonism (bradykinesia, tremors, rigidity)
- These symptoms are particularly problematic with high-potency first-generation antipsychotics 1
Sedation - Excessive drowsiness that interferes with daily functioning 2
Metabolic effects - Weight gain and metabolic disturbances, particularly with medications like olanzapine 3
Patient Perception of Symptom Improvement
The second major reason for discontinuation is patients' belief that they no longer need medication because they feel better. This is particularly common in first-episode schizophrenia patients 4. A pooled analysis found that:
- Discontinuation due to poor response was more predominantly linked to patient perception than to physicians' conclusions (80% vs. 20%) 5
- Patient perception of poor response appeared to occur particularly early in treatment 5
Discontinuation Rates and Patterns
Overall discontinuation rates are extremely high, with studies showing 74-84% of patients discontinuing their index antipsychotic during follow-up periods 6, 3
In a large study of 1493 patients with schizophrenia, discontinuation rates were:
- 64% for olanzapine
- 75% for perphenazine
- 82% for quetiapine
- 74% for risperidone
- 79% for ziprasidone 3
Risk Factors for Earlier Discontinuation
Several factors are associated with higher risk of antipsychotic discontinuation:
- Younger age
- Non-white race
- Homelessness
- Substance use disorder
- Recent inpatient mental health hospitalization
- Prescription of multiple antipsychotics 6
- Longer duration of untreated psychosis
- Lower compliance at baseline
- Higher self-belief of coping without medication 4
Clinical Implications
Side effect management is crucial for improving adherence. Proactive monitoring and management of side effects, particularly akathisia and other EPS, can significantly improve medication adherence 1
For patients at high risk of extrapyramidal symptoms, consider:
- Using prophylactic antiparkinsonian agents, especially in those with history of dystonic reactions
- Regular assessment for dyskinesias (every 3-6 months)
- Using the Abnormal Involuntary Movement Scale to monitor for movement disorders 1
Clozapine has shown lower risk for all-cause discontinuation compared to oral olanzapine in multivariate analyses 7
Long-acting injectable (LAI) antipsychotics (both first and second generation) show significantly lower risks for patient-decided discontinuation than oral olanzapine 7
Therapeutic alliance and psychoeducation are essential to address the patient perception component of discontinuation, particularly helping patients understand the need to continue medication even when feeling better 4, 5
By addressing both side effects and patient perceptions about medication necessity, clinicians can improve adherence and ultimately reduce relapse rates in patients with schizophrenia.