Side Effects of Geodon (Ziprasidone)
Geodon (ziprasidone) commonly causes somnolence, extrapyramidal symptoms, headache, dizziness, and nausea, with the most clinically significant concern being QTc interval prolongation that requires cardiac monitoring in at-risk patients. 1
Most Common Side Effects
Oral Ziprasidone
The most frequently reported adverse effects in clinical trials include:
- Somnolence (20-21%) - most common side effect across all indications 1, 2
- Extrapyramidal symptoms (13-14%) - includes dystonia, tremor, hypertonia, dyskinesia, and akathisia 1, 2
- Headache (13%) - though this may not differ significantly from placebo 1, 2
- Dizziness (including lightheadedness) - occurs in approximately 8% of patients 1
- Nausea (10%) - particularly with intramuscular administration 1
- Respiratory tract infections - more common in schizophrenia trials 1
Intramuscular Ziprasidone
For IM administration, the most common adverse effects are:
- Somnolence (20%) 1
- Headache (13%) 1
- Nausea (12%) 1
- Insomnia - paradoxically can occur despite sedation 3
- Hypertension - noted in flexible-dose trials 3
Cardiovascular Effects: The Critical Safety Concern
QTc interval prolongation is ziprasidone's most significant safety issue, requiring specific screening and monitoring protocols. 1, 4
QTc Prolongation Details
- Average QTc prolongation of approximately 20 milliseconds at peak serum concentrations 4
- Range of prolongation: 5-22 milliseconds 5
- Only 0.06% of patients (2 out of ~3,300) had QTc >500 msec in manufacturer data 4
- Risk is comparable to haloperidol IM 3
Absolute Contraindications
Ziprasidone must be avoided in patients with: 6, 5
- History of long QT syndrome
- Recent acute myocardial infarction
- Baseline QT prolongation
- Concurrent use of other QT-prolonging medications
- Risk factors for torsades de pointes
Required Monitoring
- Obtain baseline ECG if any cardiac risk factors are present 5
- Avoid in patients with severe heart failure or certain cardiac arrhythmias 6
Metabolic Profile: A Key Advantage
Unlike most atypical antipsychotics, ziprasidone is weight-neutral and does not cause adverse metabolic changes. 7, 8
- No clinically significant weight gain 7, 8
- No adverse effects on cholesterol or triglycerides 7
- No impairment of glycemic control 7
- Patients may experience moderate improvement in metabolic parameters when switching from other antipsychotics to ziprasidone 7
- This makes ziprasidone particularly suitable for patients with metabolic concerns 9
The American Diabetes Association notes that ziprasidone (along with aripiprazole) tends to have fewer metabolic effects compared to olanzapine, clozapine, quetiapine, and risperidone 10
Movement Disorders and Neurological Effects
Extrapyramidal Symptoms (EPS)
- Incidence: 14% vs. 8% for placebo in schizophrenia trials 1
- Risk difference of 6% attributable to ziprasidone itself 2
- Significantly lower burden than haloperidol 3
- Includes: dystonia, tremor, hypertonia, dyskinesia, hypokinesia, akathisia 1
Dystonia Risk
Acute dystonia can occur, particularly in males and younger patients, typically within the first few days of treatment. 1
Symptoms include:
- Spasm of neck muscles
- Tightness of throat
- Swallowing difficulty
- Difficulty breathing
- Tongue protrusion
Rare but Serious Neurological Events
Postmarketing reports include: 1
- Neuroleptic malignant syndrome - rare but potentially fatal
- Tardive dyskinesia - risk exists with all antipsychotics
- Serotonin syndrome - when combined with other serotonergic agents
- Facial droop
Other Significant Side Effects
Endocrine Effects
- Minimal persistent effects on prolactin levels - advantage over risperidone 7
- Transient hyperprolactinemia may occur 8
- Postmarketing reports of galactorrhea 1
Autonomic Effects
- Orthostatic hypotension - can occur, particularly with dose escalation 1, 8
- Not anticholinergic - advantage over many other antipsychotics 7
- Postural hypotension and syncope reported postmarketing 1
Gastrointestinal Effects
- Nausea (10%) 1
- Dyspepsia (risk difference 4%) 2
- Constipation 1
- Vomiting - more common in bipolar disorder trials 1
- Postmarketing: swollen tongue 1
Dermatologic Reactions
- Rash was the most common reason for discontinuation (1% of patients) 1
- Postmarketing reports include: 1
- Allergic dermatitis
- Angioedema
- Orofacial edema
- Urticaria
- DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms)
Genitourinary Effects
Postmarketing reports include: 1
- Priapism - medical emergency requiring immediate attention
- Urinary incontinence
- Enuresis
Dose-Related Side Effects
Several adverse effects show clear dose-response relationships, requiring careful titration. 1
Dose-dependent effects include:
- Asthenia
- Postural hypotension
- Anorexia
- Dry mouth
- Increased salivation
- Arthralgia
- Anxiety
- Dizziness
- Dystonia
- Hypertonia
- Somnolence
- Tremor
- Rhinitis
- Rash
- Abnormal vision
Discontinuation Rates
- 4.1% of patients discontinued oral ziprasidone due to adverse effects in short-term trials vs. 2.2% on placebo 1
- 6.5% discontinued in bipolar disorder trials vs. 3.7% on placebo 1
- Most common reasons for discontinuation: rash, akathisia, anxiety, depression, dizziness, dystonia, vomiting 1
Critical Clinical Pitfalls to Avoid
Food Requirement
Ziprasidone absorption is substantially reduced without food - this cannot be compensated by increasing the dose. 7
- Must be administered with a 500 kcal meal for adequate absorption 7
- Failure to ensure food intake is a common cause of apparent treatment failure 7
Inadequate Dosing
- Target dose range: 120-160 mg/day for optimal symptom control 7
- Lower doses (40-80 mg/day) may be ineffective 7
- Allow 4-6 weeks at therapeutic doses before concluding ineffectiveness 5