Why would a patient on olanzapine depot want to stop it?

Why Patients Want to Stop Olanzapine Depot

Patients most commonly want to discontinue olanzapine depot due to adverse effects—particularly weight gain, sedation, and injection site reactions—followed by perceived lack of efficacy against positive or negative symptoms. 1

Primary Reasons for Discontinuation

Adverse Effects Drive Most Discontinuation Requests

Weight gain is the most significant tolerability concern with olanzapine depot. 2, 3 The FDA label documents that:

• Adolescents show particularly dramatic weight increases, with 49.7% gaining >10 kg (22 lbs) within 6 months 2
• Adult patients experience mean weight gains of 2.6 kg at 6 weeks, with discontinuation due to weight gain occurring in 2.2% of patients 2
• Weight gain occurs significantly more frequently with olanzapine compared to risperidone 3

Sedation and somnolence are among the most common adverse effects, reported frequently enough to impact daily functioning and quality of life 4, 3. Additional troublesome effects include:

• Dizziness and orthostatic hypotension (affecting ≥20% of patients) 2
• Anticholinergic effects including dry mouth and constipation 3
• Metabolic concerns including hyperglycemia and diabetes risk 5, 2

Injection site-related adverse events occur in 5.3% of patients, with pain being most common (2.9% of all patients) 6. While generally mild and lasting a median of 3 days, these reactions can accumulate over time and contribute to treatment refusal 6.

Perceived Lack of Efficacy

The second major category of discontinuation involves insufficient improvement or worsening of symptoms. 1 Specifically:

• Insufficient improvement or worsening of positive symptoms (hallucinations, delusions) 1
• Insufficient improvement or worsening of negative symptoms (flat affect, social withdrawal) 1
• Lack of perceived overall improvement from the patient's perspective 1

Extrapyramidal Symptoms and Movement Disorders

Tardive dyskinesia represents a potentially irreversible reason for discontinuation. 2 The FDA label emphasizes:

• Risk increases with duration of treatment and cumulative dose 2
• The syndrome can develop after relatively brief treatment periods 2
• Elderly women face the highest risk 2
• If signs of tardive dyskinesia appear, drug discontinuation should be considered 2

Acute extrapyramidal symptoms (EPS) including akathisia, tremor, and dystonia can prompt discontinuation requests, though olanzapine causes significantly fewer EPS compared to haloperidol and risperidone 3, 5.

Cardiovascular and Serious Safety Concerns

Orthostatic hypotension with associated syncope, bradycardia, and falls particularly affects elderly patients and those with cardiovascular disease 2. The FDA label documents:

• Approximately one-third of patients experience significant orthostatic blood pressure decreases 2
• Syncope occurred in 0.6% of oral olanzapine-treated patients 2
• Three volunteers experienced hypotension, bradycardia, and sinus pauses up to 6 seconds 2

Post-injection delirium/sedation syndrome is unique to the depot formulation and can be frightening for patients 7, 6. Patients who experience this syndrome are more likely to report injection site-related adverse events 6.

Special Population Concerns

Elderly Patients

Older adults face heightened risks that commonly lead to discontinuation requests, including 5:

• Falls, stroke, and increased mortality risk (FDA black box warning for dementia-related psychosis) 5
• Cognitive impairment and functional decline 5
• Greater sensitivity to anticholinergic and sedative effects 5

Patients with Dementia

Olanzapine use for behavioral symptoms in dementia is off-label, lacks supporting evidence, and carries serious risks including falls, stroke, and death 5. This often prompts families and clinicians to pursue discontinuation 5.

Concordance Between Patient and Clinician Perspectives

Research demonstrates high concordance between patient and clinician ratings regarding reasons for discontinuation 1. Both groups identify:

• Medication efficacy (especially for positive symptoms) as the primary determinant of continuation 1
• Adverse events as a major driver of discontinuation 1
• The importance of functional improvement in the decision to continue treatment 1

Clinical Implications for Discontinuation

When patients request discontinuation, gradual withdrawal over >1 month is essential to minimize withdrawal effects 5. Abrupt discontinuation risks:

• Dyskinesias, parkinsonian symptoms, and dystonias 5
• Neuroleptic malignant syndrome 5
• Symptom rebound and relapse 5

Re-escalation of dosing may be necessary if withdrawal symptoms cause patient distress 5. Nonpharmacological psychosocial interventions should be implemented concurrently to support discontinuation and manage behavioral symptoms 5.