This post was sponsored by Otsuka and Lundbeck.

Advancing bipolar I disorder management: the impact of long-acting injectables

Eric Thomason, MSN, PMHNP-BC, MBA

Eric Thomason, MSN, PMHNP-BC, MBA

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

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Bipolar I disorder is a severe mental illness that causes extreme shifts in a person’s mood, energy, activity levels, and concentration. It is characterized by recurrent manic and/or depressive episodes that require medical care. Due to the chronic nature of the disorder and the negative consequences of symptoms, bipolar I disorder usually requires long-term treatment.1

Many providers prescribe oral antipsychotics to treat patients and help them establish and maintain stability;2 however, circumstances are always changing and it’s easy for a patient to forget or miss a daily dose. What treatment options are available with a longer dosing interval?

Long-Acting Injectables

A long-acting injectable, or LAI, is an injected medication that gradually releases into the bloodstream. Despite their effectiveness, LAIs are highly underutilized as a maintenance treatment option for individuals with bipolar I disorder.2,3 However, this practice is changing.3

According to the American Psychiatric Association, the main goals for treating patients with bipolar I disorder are to prevent relapse and recurrence, reduce subthreshold symptoms, reduce the cycling frequency of mania, hypomania, and depression, and improve functioning.4

To accomplish these goals, the National Council for Mental Wellbeing recommends the earlier use of LAIs in treating appropriate patients.3 Patients with bipolar I disorder may not immediately address their symptoms, which may lead to relapse. Therefore, consistent treatment is crucial for delaying recurrences or hospitalization.2–5

According to the National Council for Mental Wellbeing, clinicians may
consider LAIs for patients who3

  • Have difficulty adhering to oral medications
  • Are not responding well to an oral antipsychotic
  • Are concerned about the social stigma of taking pills
  • Are transitioning between settings, such as inpatient discharge
  • Want fewer daily medications
  • Need consistent and predictable dosing

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

Considerations Before Switching to an LAI

Initiating conversations about LAIs with patients early in the treatment process is critical.3

In a survey administered by Otsuka and Lundbeck, 42 expert researchers and prescribers found that the most important topics to discuss with patients before switching 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 out-of-pocket expenses.2

These experts also rated LAI efficacy and ease of adherence as the most motivating factors for patients in choosing an LAI over oral medications.2

LAIs may be an effective maintenance treatment option for patients with bipolar I disorder.1

On the other hand, drawbacks to an LAI treatment include adverse reactions to the medication or acute pain at the site of injection.1,5 In addition, for patients who work full-time or live in rural areas, it may be difficult to drive to a clinic for treatment.3 Finally, if a patient has had negative experiences with injectable medications in the past, it may be challenging for the patient and provider to have an open conversation about LAIs.3 Informed discussions that highlight the benefits of, and address any concerns about LAIs are crucial for helping patients understand these antipsychotics as a positive, practical treatment option and feel empowered to make their own decisions.3

 

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. Hirschfeld RMA, Bowden CL, Gitlin MJ, et al. Practice Guideline for the Treatment of Patients With Bipolar Disorder. 2nd ed. APA, 2010: APA Publishing website. Accessed April 2024. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/bipolar.pdf  5. Lin CH, Chan HY, Hsu CC, Chen FC. Time to rehospitalization in patients with bipolar mania discharged on long-acting injectable or oral antipsychotics. J Affect Disord. 2021;279:292-298.