Ziprasidone is an antipsychotic medication classified as a second-generation, or atypical, antipsychotic. It is used in mental health care to help manage symptoms of psychosis and mood disturbance, and it can play a role in stabilizing thoughts, perceptions, and behavior for certain conditions. In clinical practice, ziprasidone may be prescribed for schizophrenia and for manic or mixed episodes of bipolar disorder, and it is sometimes used to treat acute agitation in hospital settings. Like all medicines, it works best when it is taken as prescribed and as part of a broader treatment plan that includes therapy and social support.
How ziprasidone works
Ziprasidone acts on several brain receptor systems that influence mood, thinking, and perception. The medication primarily blocks dopamine D2 receptors and serotonin 5-HT2A receptors, which can help reduce psychotic symptoms and help regulate mood. It also has activity at other serotonin receptors (including 5-HT1A partial agonist activity) and may affect norepinephrine pathways to some degree. Because it targets multiple neurotransmitter systems, ziprasidone can help alleviate a range of symptoms—such as delusions, disorganized thinking, mood swings, agitation, and irritability—without producing as much weight gain as some other antipsychotics. However, its precise mechanism is complex and not fully understood, and individual response can vary widely.
Common uses and conditions treated
- Schizophrenia in adults (and in some cases, older adolescents under medical supervision)
- Bipolar I disorder, including manic or mixed episodes, in adults
- Acute agitation associated with schizophrenia or bipolar mania (treated with an injectable form in clinical settings)
Ziprasidone is not approved for major depressive disorder on its own, though it may be used as part of combination therapy in some circumstances under a clinician’s guidance. The choice to use ziprasidone and the specific indications depend on a patient’s history, symptom profile, and how they respond to other treatments. If you have questions about whether ziprasidone is appropriate for a particular condition, discuss them with your clinician or psychiatrist.
Typical dosages and administration
Oral dosing (tablets or capsules)
The usual starting dose is 40 mg taken twice daily with meals. Taking ziprasidone with food is important because meals of sufficient caloric content enhance absorption and the medicine works best when absorbed consistently. Depending on response and tolerability, the dose may be adjusted by your clinician, commonly up to 80 mg twice daily. In some cases, the daily total may be increased further within labeled guidelines, but your doctor will determine the safest and most effective dose for you.
Intramuscular dosing for agitation
For acute agitation, ziprasidone can be given as an intramuscular (IM) injection. A single dose is typically 10–20 mg, with the option to repeat after about 2 hours if necessary, for a maximum of 40 mg in 24 hours. The IM form is intended for short-term management in a controlled setting and is not a substitute for ongoing oral therapy.
Side effects and monitoring
Every medication carries potential benefits and risks. Ziprasidone is associated with a range of possible side effects, most of which are mild to moderate and often temporary. Less common but more serious risks require medical attention.
- Common: sleepiness or drowsiness, dizziness, nausea, stomach upset, constipation, dry mouth, restlessness or mild anxiety, and slight weight changes.
- Less common but important: tremor or slowed movements (extrapyramidal symptoms) and akathisia (a sense of inner restlessness).
- Important safety concern: QT interval prolongation on an electrocardiogram (ECG), which can affect heart rhythm. This risk is higher if ziprasidone is used with other QT-prolonging medicines or in people with certain heart conditions or electrolyte abnormalities.
- Serious but rare: Neuroleptic malignant syndrome (NMS) and tardive dyskinesia (TD) with long-term use.
Monitoring is a key part of treatment with ziprasidone. Your clinician may recommend:
- Baseline and periodic EKGs (particularly if you have heart disease or are taking other heart-affecting drugs)
- Electrolyte tests (potassium, magnesium) and blood pressure measurements
- Regular weight checks and metabolic monitoring (glucose and lipid levels) because antipsychotics can affect metabolic health
- Watchfulness for movement disorders, sedation, or signs of mood changes
Any concerning symptoms—such as fainting, rapid heartbeat, severe dizziness, chest pain, weakness, or seizure-like activity—require prompt medical evaluation. If you notice persistent muscle stiffness, fever, confusion, or uncoordination, seek urgent care.
Drug interactions
- QT-prolonging drugs: Ziprasidone can increase the risk of cardiac rhythm problems when used with other medications that also prolong the QT interval. Examples include certain antiarrhythmics, some antibiotics (like certain macrolides), and some antifungal drugs. Always tell your clinician about all medicines you take, including over-the-counter drugs and supplements.
- Other antipsychotics and sedatives: Co-administration with other central nervous system depressants can increase drowsiness or dizziness.
- CYP3A4 inhibitors or inducers: Ziprasidone is processed in part by the CYP3A4 enzyme. Strong inhibitors or inducers of this enzyme can alter ziprasidone levels, potentially requiring dose adjustments. Examples include ketoconazole (inhibitor) and certain anticonvulsants or smoking (inducer).
- Alcohol: Consuming alcohol with ziprasidone can exacerbate sedation and impair thinking or reaction times.
Before starting ziprasidone, and whenever your prescription changes, review all medicines and supplements you take with your clinician to minimize interaction risks.
Important considerations for patients
- Absorption with meals: Take oral ziprasidone with a meal or shortly after eating, ideally with a meal containing at least about 500 calories. Irregular or no meal intake can reduce drug absorption and effectiveness.
- Driving and activities requiring alertness: Ziprasidone can cause sleepiness or dizziness in some people. Be cautious when driving or operating machinery until you know how it affects you.
- Alcohol and safety: Limit or avoid alcohol to reduce additive sedative effects and potential heart-related risks.
- Pregnancy and breastfeeding: Discuss risks and benefits with your clinician if you are pregnant, planning to become pregnant, or breastfeeding. Ziprasidone is categorized with specific pregnancy considerations, and alternatives may be discussed.
- Elderly patients: The risk of adverse effects, including movement disorders and sedation, may be higher in older adults. Dose adjustments and careful monitoring are common in this group.
- Dementia-related psychosis: As with many antipsychotics, ziprasidone carries a higher risk of mortality in elderly people with dementia-related psychosis and should be used with caution or avoided when possible.
- Adherence and monitoring: Keep regular follow-up appointments, report new symptoms promptly, and avoid stopping the medication abruptly without professional advice, as this can cause withdrawal or relapse of symptoms.
Safety in special populations and general considerations
- Liver function: Ziprasidone is primarily metabolized by the liver, so liver disease can affect drug levels. Your clinician may adjust dosing or choose an alternative medication if liver function is significantly impaired.
- Kidney function: In many cases, kidney impairment does not require a major dose change, but your clinician will assess overall health to decide on the safest approach.
- Long-term use: Because ziprasidone is a psychoactive medication, ongoing assessment of benefits, risks, and metabolic health is important. Discuss any concerns about weight, blood sugar, or lipid changes with your healthcare provider.
- Medication safety: Always store medications as directed and keep them out of reach of children. Do not share prescriptions with others.
Further reading and resources
For more information about ziprasidone, including patient-focused summaries and professional labeling, you may consult reputable medical resources. For example:
