Can depot antipsychotic (long-acting injectable antipsychotic medication) be commenced for a patient with first-episode psychosis?

From the Guidelines

Depot antipsychotics can be considered for first episode psychosis, particularly when there are concerns about medication adherence or the patient prefers less frequent dosing, as suggested by the American Psychiatric Association practice guideline for the treatment of patients with schizophrenia 1. When managing first episode psychosis, initial treatment typically involves oral antipsychotics to establish tolerability and efficacy.

• Oral antipsychotics like risperidone (2-6 mg/day), olanzapine (5-20 mg/day), or aripiprazole (10-30 mg/day) are commonly used for at least several weeks.
• If a patient demonstrates poor medication adherence, has a preference for less frequent dosing, or shows good response to an oral antipsychotic with an available depot formulation, long-acting injectable options can be considered. Some key points to consider when using depot antipsychotics for first episode psychosis include:
• Establishing tolerability with the oral equivalent medication for at least a week before starting a depot.
• Common depot options include paliperidone palmitate (monthly or 3-monthly injections), risperidone microspheres (biweekly), aripiprazole monohydrate (monthly), or aripiprazole lauroxil (monthly to bimonthly).
• The advantage of depot formulations is that they ensure consistent medication levels, eliminate daily adherence issues, and allow healthcare providers to clearly identify non-adherence versus medication failure. However, depot antipsychotics also have disadvantages, including less dosing flexibility, potential injection site reactions, and psychological barriers for some patients who may feel coerced or stigmatized by injectable treatment, as noted in clinical guideline recommendations for antipsychotic long-acting injections 1. Given the most recent and highest quality evidence from the American Psychiatric Association practice guideline for the treatment of patients with schizophrenia 1, the use of depot antipsychotics in first episode psychosis is supported, especially in cases where adherence is a concern or the patient prefers this formulation, to reduce morbidity, mortality, and improve quality of life.

From the FDA Drug Label

These patients must be previously stabilized on antipsychotic medication before considering a conversion to haloperidol decanoate, USP Furthermore, it is recommended that patients being considered for haloperidol decanoate, USP therapy have been treated with, and tolerate well, short-acting haloperidol, USP in order to reduce the possibility of an unexpected adverse sensitivity to haloperidol, USP

The FDA drug label does not support commencing depot antipsychotic for first episode psychosis as it recommends that patients should be previously stabilized on antipsychotic medication before considering a conversion to haloperidol decanoate, USP 2.

From the Research

Depot Antipsychotic for First Episode Psychosis

• The use of depot antipsychotics for first episode psychosis is not directly addressed in the provided studies, but the effectiveness of antipsychotic treatment in general is supported by several studies 3, 4, 5.
• A study comparing the long-term effectiveness of risperidone and haloperidol in first-episode psychosis patients found that relatively low doses of antipsychotic drugs lead to significant symptom amelioration in the majority of patients 3.
• Another study compared the clinical effectiveness of six antipsychotics (olanzapine, risperidone, haloperidol, aripiprazole, ziprasidone, and quetiapine) in the treatment of first episode of psychosis and found that olanzapine, risperidone, and aripiprazole presented advantages for the first-line treatment of first episode of psychosis in terms of effectiveness 4.
• The evaluation and treatment of first-episode psychosis is crucial, and antipsychotic medication is strongly supported as both acute and maintenance treatment for patients with a first episode of psychosis 5.
• However, the optimal duration of maintenance treatment and the use of depot antipsychotics specifically for first episode psychosis are not addressed in the provided studies.

Initiating Antipsychotic Treatment

• A study investigated whether initiating antipsychotic treatment in the clinical high risk of psychosis phase was superior to initiating antipsychotic treatment in the first episode of psychosis phase, and found that initiating antipsychotic treatment in the first episode of psychosis phase predicted remission 6.
• This suggests that antipsychotic treatment, including potentially depot antipsychotics, may be more effective when initiated at the first episode of psychosis phase rather than earlier 6.