The long-acting injectable space has expanded considerably in the past few years, and one of the more useful additions is Uzedy, a subcutaneous formulation of risperidone approved by the FDA in 2023 for the treatment of schizophrenia in adults. It is unusual among LAIs in two ways: it is given subcutaneously (under the skin) rather than intramuscularly, and it requires neither a loading dose nor a period of oral overlap to reach therapeutic levels.
Uzedy is a subcutaneous long-acting injectable form of risperidone, dosed once monthly or every two months, with no loading dose and no required oral overlap.
What it is
Uzedy uses a copolymer-based extended-release technology developed by MedinCell and commercialised by Teva. After subcutaneous injection in the abdomen or upper arm, the polymer matrix slowly releases risperidone over weeks, producing therapeutic blood levels within hours and steady-state levels within the first dosing interval.
Unlike older risperidone LAIs such as Risperdal Consta (which requires three weeks of oral overlap) and Perseris (a different subcutaneous formulation), Uzedy was designed specifically to avoid both an oral overlap and a loading injection.
Dosing
Per FDA labelling, Uzedy is available in several strengths and supports two dosing intervals:
- Monthly: 50 mg, 75 mg, 100 mg, 125 mg, or 150 mg every 4 weeks
- Every 2 months: 100 mg, 150 mg, 200 mg, 250 mg, or 300 mg every 8 weeks
The dose is generally chosen based on the patient's previous oral risperidone dose. Common conversions are roughly:
- 2 mg/day oral risperidone → 50 mg monthly or 100 mg every 2 months
- 3 mg/day → 75 mg monthly or 150 mg every 2 months
- 4 mg/day → 100 mg monthly or 200 mg every 2 months
- 5 mg/day → 125 mg monthly or 250 mg every 2 months
Final dosing is decided by the prescriber, taking into account tolerability and clinical response.
The "no oral overlap" advantage
For Risperdal Consta, patients have historically needed to continue oral risperidone for the first three weeks after their first injection because the depot does not release meaningful drug for that long. Uzedy skips this requirement: a single subcutaneous injection produces useful risperidone levels within hours of administration. For people who came to LAIs in the first place because they cannot reliably take pills, this difference matters.
Subcutaneous versus intramuscular
Uzedy is injected into subcutaneous tissue (under the skin) in the abdomen or upper arm, using a small needle. Patients who have had painful gluteal or deltoid intramuscular injections often find subcutaneous administration more comfortable. Common injection-site experiences include mild pain, redness, or a small lump at the injection site, generally resolving over days. See our injection-site care guide for what to expect.
Effectiveness
The pivotal RISE trial (results submitted to the FDA and published in subsequent peer-reviewed reports) showed that Uzedy significantly reduced the risk of relapse compared with placebo in adults with stable schizophrenia. Risperidone as a class is among the most thoroughly studied antipsychotics, and the LAI form generally shows a lower hospitalisation rate than oral risperidone in real-world cohorts — consistent with the broader LAI literature including Schneider-Thoma et al. (Lancet, 2022).
Side effects
Side effects mirror oral risperidone closely:
- Hyperprolactinemia — risperidone is one of the most prolactin-elevating antipsychotics; sexual side effects, breast changes, menstrual changes are common
- Weight gain — moderate, generally less than olanzapine but more than aripiprazole
- Sedation
- Extrapyramidal symptoms — particularly at higher doses
- Akathisia
- Injection-site reactions — usually mild
- Orthostatic hypotension
You develop a high fever with muscle rigidity (possible neuroleptic malignant syndrome), persistent involuntary movements (possible tardive dyskinesia), or a severe rash or signs of allergic reaction.
Who Uzedy fits well
- People who responded well to oral risperidone
- People who want a monthly or two-month interval without the start-up complexity of older LAIs
- People who prefer subcutaneous over intramuscular injections
- People whose previous LAI failed because of missed oral overlap doses
Who might choose differently
- People with significant prolactin-related symptoms on oral risperidone — switching to a different antipsychotic class is often more useful
- People with metabolic or cardiovascular concerns who would prefer a lighter antipsychotic like aripiprazole
- People with very treatment-resistant illness who may need clozapine
Practical considerations
- The two-month option requires that the patient be tolerating risperidone well — switching to a long interval is a commitment
- Missed dose guidance is provided in the FDA label and depends on how late the dose is
- Cost varies; manufacturer assistance programs are available for eligible patients
What to ask your prescriber
- Why Uzedy specifically, rather than Risperdal Consta or Invega Sustenna?
- Should we start with monthly or every two months?
- How will we monitor prolactin and metabolic labs?
- What's the plan if I miss an appointment?
This article is for educational purposes only and is not medical advice. Information is summarised from publicly available FDA labelling and peer-reviewed sources. Always consult your prescribing clinician before starting, stopping, or changing any medication.