This post was sponsored by Otsuka and Lundbeck.

Transitioning treatment from oral to injectable

Craig Chepke, MD,
DFAPA

Craig Chepke, MD, DFAPA

Craig Chepke is a paid consultant of Otsuka America Pharmaceutical, Inc and received an honorarium for participation in this program.

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Schizophrenia and bipolar I disorder are both chronic mental disorders. Patients are often treated with antipsychotic medication over long periods of time, and due to the negative consequences associated with symptoms, medication adherence is critical for treating symptoms and preventing relapses.1,2

A long-acting injectable, or LAI, is an injected medication that gradually releases into the bloodstream. Despite their effectiveness, LAIs are highly underutilized.1,2 The National Council of Mental Wellbeing suggests introducing LAIs early in the appropriate patients’ treatment plans as a preventive strategy;3 however, there are important factors to consider before transitioning to an LAI.

Who May Be Appropriate for LAI Treatment?

According to the National Council, patients who are currently on an oral antipsychotic can benefit from transitioning to an LAI, especially if they have difficulty adhering to oral medications; are not responding well to the oral antipsychotic; are concerned about the social stigma of taking pills; are transitioning between settings, such as inpatient discharge; need consistent and predictable dosing; want fewer medications daily; or simply prefer an LAI.3

I often prescribe LAIs to patients with schizophrenia or bipolar I disorder who want to take one less pill when managing their illness. Although they had been stable on oral antipsychotics, these patients may appreciate the treatment schedule of an LAI.

Initiating conversations about LAIs with patients early in the treatment process helps inform the patient of their treatment options.3

In a survey administered by Otsuka and Lundbeck, 42 expert researchers and prescribers reported that the most important topics to discuss with patients before transitioning to an LAI were how the LAI works; the patient’s previous response to specific antipsychotics and notable side effects; expectations for tolerability and efficacy; potential side effects; dosing intervals; the site of injection; and patients’ out-of-pocket expenses.2

Transitioning From Oral Aripiprazole to ABILIFY ASIMTUFII® (aripiprazole)4

ABILIFY ASIMTUFII is an atypical antipsychotic injection indicated for the treatment of schizophrenia in adults and the maintenance monotherapy treatment of bipolar I disorder in adults. This LAI is administered once every 2 months and can be given to patients who already tolerate oral aripiprazole or are taking another oral antipsychotic.4 Please see the IMPORTANT SAFETY INFORMATION, including the BOXED WARNING regarding Increased Mortality in Elderly Patients with Dementia-Related Psychosis.

In my experience, I have found that my patients who transition to ABILIFY ASIMTUFII have enjoyed the cadence of every-2-month visits to my clinic.

If a patient is stable on oral aripiprazole, an injection of ABILIFY ASIMTUFII 960 mg can be administered right away. The patient should continue taking the oral antipsychotic medication for the next 14 days, and then the next injection is 56 days after the first.4

If a patient is new to aripiprazole, it is important to establish tolerability to this medication before initiating treatment with ABILIFY ASIMTUFII. This can take up to 2 weeks. Once the patient is stable on oral aripiprazole, the first injection can be administered. The patient should continue taking their oral antipsychotic for the next 14 days. As noted previously, the second injection will be given 56 days after the dose.4

Patients may be given their injection up to 2 weeks before or after the scheduled time point. If an appointment is missed, the patient has 6 weeks after the scheduled dose before they must restart the oral overlap.4

If a patient experiences adverse reactions with the 960 mg dosage of ABILIFY ASIMTUFII, the dose can be reduced to 720 mg every 2 months.4

Dosage adjustments for patients who are CYP2D6 poor metabolizers and/or in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors for more than 14 days are described in the FULL PRESCRIBING INFORMATION.4

Overall, patients with schizophrenia or bipolar I disorder may benefit from transitioning from oral antipsychotics to an LAI, such as ABILIFY ASIMTUFII. In my experience, LAIs can be an appropriate option for patients.

 

IMPORTANT SAFETY INFORMATION and INDICATIONS for ABILIFY ASIMTUFII® (aripiprazole) and ABILIFY MAINTENA® (aripiprazole)

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death (1.6 to 1.7 times) compared to placebo-treated patients. ABILIFY ASIMTUFII and ABILIFY MAINTENA are not approved for the treatment of patients with dementia-related psychosis.

Contraindication: Known hypersensitivity reaction to aripiprazole. Reactions have ranged from pruritus/urticaria to anaphylaxis.

Cerebrovascular Adverse Events, Including Stroke: Increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, have been reported in clinical trials of elderly patients with dementia-related psychosis treated with oral aripiprazole.

Neuroleptic Malignant Syndrome (NMS): NMS is a potentially fatal symptom complex reported in association with administration of antipsychotic drugs including aripiprazole. Clinical signs of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage NMS with immediate discontinuation of aripiprazole, intensive symptomatic treatment, and monitoring.

Tardive Dyskinesia (TD): Risk of TD, and the potential to become irreversible, are believed to increase with duration of treatment and total cumulative dose of antipsychotic drugs. TD can develop after a relatively brief treatment period, even at low doses, or after discontinuation of treatment. Prescribing should be consistent with the need to minimize TD. If antipsychotic treatment is withdrawn, TD may remit, partially or completely.

Metabolic Changes: Atypical antipsychotic drugs have caused metabolic changes including:

  • Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics including aripiprazole. Patients with diabetes mellitus should be regularly monitored for worsening of glucose control; those with risk factors for diabetes (e.g., obesity, family history of diabetes), should undergo baseline and periodic fasting blood glucose testing. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of the suspect drug.
  • Dyslipidemia: Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics.
  • Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.

Pathological Gambling and Other Compulsive Behaviors: Intense urges, particularly for gambling, and the inability to control these urges have been reported while taking aripiprazole. Other compulsive urges have been reported less frequently. Prescribers should ask patients or their caregivers about the development of new or intense compulsive urges. Consider dose reduction or stopping aripiprazole if such urges develop.

Orthostatic Hypotension or Syncope: ABILIFY ASIMTUFII and ABILIFY MAINTENA may cause orthostatic hypotension and should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions which would predispose them to hypotension. Monitoring of orthostatic vital signs should be considered in patients who are vulnerable to hypotension.

Falls: Antipsychotics may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls causing fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating treatment and recurrently during therapy.

Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia, neutropenia, and agranulocytosis have been reported with antipsychotics. Monitor complete blood count in patients with pre-existing low white blood cell count (WBC)/absolute neutrophil count or history of drug-induced leukopenia/neutropenia. Discontinue ABILIFY ASIMTUFII or ABILIFY MAINTENA at the first sign of a clinically significant decline in WBC and in severely neutropenic patients.

Seizures: ABILIFY ASIMTUFII and ABILIFY MAINTENA should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold.

Potential for Cognitive and Motor Impairment: ABILIFY ASIMTUFII and ABILIFY MAINTENA may impair judgment, thinking, or motor skills. Patients should be cautioned about performing activities that require mental alertness such as operating hazardous machinery or operating a motor vehicle, until they are reasonably certain that therapy with ABILIFY ASIMTUFII or ABILIFY MAINTENA does not affect them adversely.

Body Temperature Regulation: Use ABILIFY ASIMTUFII or ABILIFY MAINTENA with caution in patients who may experience conditions that increase body temperature (e.g., strenuous exercise, extreme heat, dehydration, or concomitant use with anticholinergics).

Dysphagia: Esophageal dysmotility and aspiration have been associated with aripiprazole. Use caution in patients at risk for aspiration.

Alcohol: Advise patients to avoid alcohol while taking ABILIFY ASIMTUFII or ABILIFY MAINTENA.

Concomitant Medications: Dosage reductions are recommended in patients who are CYP2D6 poor metabolizers and/or in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors for greater than 14 days. Avoid concomitant use of CYP3A4 inducers with ABILIFY ASIMTUFII and ABILIFY MAINTENA for greater than 14 days. Dosage adjustments are not recommended for patients with concomitant use of CYP3A4 inhibitors, CYP2D6 inhibitors or CYP3A4 inducers for less than 14 days.

Most Commonly Observed Adverse Reactions: The most commonly observed adverse reactions with ABILIFY MAINTENA in patients with schizophrenia (incidence of ≥5% and at least twice that for placebo) were increased weight, akathisia, injection site pain, and sedation.

Injection Site Reactions:

  • ABILIFY MAINTENA: In a short-term, clinical trial with ABILIFY MAINTENA in patients with schizophrenia treated with gluteally administered ABILIFY MAINTENA, the percent of patients reporting any injection site-related adverse reaction was 5.4% and 0.6% for placebo. In an open-label study of ABILIFY MAINTENA administered in the deltoid or gluteal muscle, injection site pain was observed at approximately equal rates.
  • ABILIFY ASIMTUFII: In an open-label study in patients with schizophrenia or bipolar I disorder, the percent of patients reporting any injection site-related adverse reactions was 19% for ABILIFY ASIMTUFII and 9.0% for ABILIFY MAINTENA. In both treatment groups, the majority of the injection site pain events coincided with the first injection and were reported with decreasing frequency upon subsequent injections. Patient-reported rating of pain was similar in both treatment groups at the last injection.

Dystonia: Symptoms of dystonia may occur in susceptible individuals during the first days of treatment and at low doses.

Pregnancy: Neonates exposed to antipsychotic drugs, including aripiprazole, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms. There are risks to the mother associated with untreated schizophrenia or bipolar I disorder and with exposure to antipsychotics, including ABILIFY ASIMTUFII and ABILIFY MAINTENA, during pregnancy.

Lactation: Aripiprazole is present in human breast milk. Monitor the breastfed infant for dehydration and lack of appropriate weight gain. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ABILIFY ASIMTUFII or ABILIFY MAINTENA and any potential adverse effects on the breastfed infant from ABILIFY ASIMTUFII or ABILIFY MAINTENA or from the underlying maternal condition.

To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1‑800‑438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

INDICATIONS

ABILIFY ASIMTUFII® (aripiprazole) is an atypical antipsychotic indicated for treatment of schizophrenia in adults and maintenance monotherapy treatment of bipolar I disorder in adults.

ABILIFY MAINTENA® (aripiprazole) is an atypical antipsychotic indicated for treatment of schizophrenia in adults and maintenance monotherapy treatment of bipolar I disorder in adults.

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING, for ABILIFY ASIMTUFII and ABILIFY MAINTENA.

References: 1. Pacchiarotti I, Tiihonen J, Kotzalidis GD, et al. Long-acting injectable antipsychotics (LAIs) for maintenance treatment of bipolar and schizoaffective disorders: a systematic review. Eur Neuropsychopharmacol. 2019;29(4):457-470. 2. Sajatovic M, Ross R, Legacy SN, et al. Initiating/maintaining long-acting injectable antipsychotics in schizophrenia/schizoaffective or bipolar disorder — expert consensus survey part 2. Neuropsychiatr Dis Treat. 2018;14:1475-1492. 3. National Council for Mental Wellbeing. Guide to Long-acting medications. June 2025. Available at: https://www.thenationalcouncil.org/resources/guide-to-long-acting-medications/. Accessed June 2025. 4. ABILIFY ASIMTUFII® (aripiprazole) Prescribing Information.