This post was sponsored by Otsuka and Lundbeck.

Overcoming the misconceptions and barriers of long-acting injectables

Rebecca S. Roma, MD

Rebecca S. Roma, MD

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

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Dr. Rebecca Roma is the Chief Medical Officer at REACH, LLC, and an adjunct faculty member at the University of Pittsburgh School of Medicine. She is board-certified in Adult Psychiatry and currently provides psychiatric evaluations, medication management, and supportive therapy for mentally ill homeless patients at the Bethlehem Haven 902 Clinic in Pittsburgh.

In my practice, I frequently encounter the complexities of treating patients living with schizophrenia and bipolar I disorder. I want to share insights on how long-acting injectable (LAI) antipsychotics may potentially improve care for these patients, while addressing some common misconceptions that may hinder their use.

By periodically revisiting the treatment conversation, clinicians can provide patients with ongoing education and reassurance, helping them make informed decisions based on the most current data and their personal experiences with their disorder.—Dr. Rebecca Roma,a board-certified psychiatrist, reflecting on the importance of ongoing patient support

Let’s discuss some of the common misconceptions surrounding the use of LAI antipsychotics.1

Misconception 1: “My patient probably doesn’t want an injectable.”

This misconception may come from ambivalence among clinicians about offering LAI antipsychotics. Such reluctance may lead providers to shy away from recommending LAIs or fail to discuss them holistically with patients.2 The conversation about LAIs should include the method of administration, the benefits, and the risks, and should address any questions from the patient. With this conversation, a patient can be well-informed and work with their healthcare provider on deciding what treatment option works best for them. LAIs are not a last resort or a punitive measure, but an option patients and clinicians can discuss as a treatment.3,4

When fully informed about LAIs, some patients may prefer treatment with them.3 One potential reason is that LAIs have a longer dosing interval—from a couple of weeks to monthly to possibly even longer.4 A reduction in daily medication burden may lessen the patients’ reminder of their disease.4

It’s important to recognize that discussing LAIs with patients should not be a one-time conversation.4 Patients’ treatment preferences and needs can evolve. By periodically revisiting the treatment conversation, clinicians can provide patients with ongoing education and reassurance, helping them make informed decisions based on the most current data and their personal experiences with their disorder.4

Providers should encourage open, proactive dialogue with their patients that extends beyond the initial discussion. This approach allows the patient to reflect on their treatment options and provides multiple opportunities to address any emerging concerns or questions they might have.4

Misconception 2: “LAIs are usually reserved for a last-resort treatment option.”

Recent schizophrenia guidelines suggest the potential usefulness of having earlier discussion about LAIs with patients at risk of nonadherence due to limited awareness of needing treatment or those with comorbid substance abuse.3

Although LAIs are generally recommended for patients who prefer an LAI or those who are treatment nonadherent, some newer guidelines recommend second-generation antipsychotic LAIs as a first-choice treatment option for schizophrenia, as well as maintenance treatment for bipolar I disorder.5

Misconception 3: “LAIs don’t seem as safe as oral antipsychotics.”

In my opinion, the roots of this misconception often lie in the situations associated with the use of short-acting intramuscular injections in emergency or inpatient settings. In addition, the first-generation antipsychotic injections are associated with a sometimes-reported higher occurrence of adverse events, including extrapyramidal symptoms, which can contribute to a negative perception of LAI treatments.1

It’s important to distinguish between the older, first-generation injections and the more modern, second-generation LAI antipsychotics, including water-based formulations that help reduce the occurrence of injection-site-related adverse events.1 This formulation change may provide some comfort for patients.

Additionally, the frequency of adverse events and adverse event-related discontinuations are the same or lower for LAIs than for oral antipsychotics.1

Some healthcare providers may remain hesitant to prescribe LAIs, often due to concerns about the long intervals between doses and the management of potential adverse reactions. It’s advisable to test patients for tolerability to the LAI formulation before fully transitioning them from oral medications. Remember, if adverse reactions happen with LAI use, they can be managed.6

Misconception 4: “LAI treatment can be complicated. It’s best to wait until after multiple relapses or recurrences to see whether it should be initiated.”

Relapses and recurrences have significant negative impacts on the patient. Each time a person relapses, their brain structure changes and functioning declines.7,8 This deterioration can make recovery increasingly difficult, underscoring the need for treatments that can effectively minimize the likelihood of relapse.7,8

LAIs can reduce the number of relapses and hospitalizations, and effective treatment should be initiated as soon as possible.1 Why wait to treat with an LAI when it can help delay the next possible relapse? The National Council Medical Director Institute recommends using LAIs over oral medications for all eligible patients, especially in early illness stages, to help prevent negative outcomes.4

Some healthcare providers hesitate to incorporate LAIs into their practice due to perceived logistical hurdles, such as the need for a nurse to administer the injections or concerns about the burden of the administration process.1 These challenges should not prevent patients from accessing LAI treatment. Alternative solutions, such as collaborating with specialty pharmacies that can administer injections, can facilitate patients receiving their treatments regularly and reliably.4

Overcoming Barriers and Moving Forward

The adoption of LAIs involves conversations addressing these misconceptions directly and improving education for clinicians, patients, and their caregivers. Our goal should always be to offer patient-centered care. This means having informed, transparent discussions about all available treatment options, including LAIs. By doing so, we empower our patients with the knowledge and freedom to choose treatments that best align with their needs and lifestyles.

 

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. Kane JM, McEvoy JP, Correll CU, Llorca PM. Controversies surrounding the use of long-acting injectable antipsychotic medications for the treatment of patients with schizophrenia. CNS Drugs. 2021;35:1189-1205. 2. Weiden PJ, Roma RS, Velligan DI, Alphs L, DiChiara M, Davidson B. The challenges of offering long-acting antipsychotic therapies: a preliminary discourse analysis of psychiatrist recommendations for injectable therapy to patients with schizophrenia. J Clin Psychiatry. 2015;76:684-690. 3. The American Psychiatric Association. Practice Guideline for the Treatment of Patients With Schizophrenia. 3rd ed. APA; 2021. Accessed June 2025. https://psychiatryonline.org/doi/pdf/10.1176/appi.books.9780890424841 4. National Council for Mental Wellbeing. Guide to long-acting medications for clinicians and organizations. June 2025. Accessed June 2025. https://www.thenationalcouncil.org/resources/guide-to-long-acting-medications/ 5. Sajatovic M, Ross R, Legacy SN, Correll CU, Kane JM, DiBiasi F, et al. Identifying patients and clinical scenarios for use of long-acting injectable antipsychotics—expert consensus survey part 1. Neuropsychiatr Dis Treat. 2018;14:1463-1474. 6. SMI Adviser. How can I manage extrapyramidal side effects from long-acting injectable antipsychotics (LAIs)? May 28, 2020. Accessed June 2025. https://smiadviser.org/knowledge_post/how-can-i-manage-extrapyramidal-side-effects-from-long-acting-injectable-antipsychotics-lais 7. Kapczinski NS, Mwangi B, Cassidy RM, et al. Neuroprogression and illness trajectories in bipolar disorder. Expert Rev Neurother. 2017;17(3):277-285. 8. Emsley R, Chiliza B, Asmal L. The evidence for illness progression after relapse in schizophrenia. Schizophr Res. 2013;148(1-3):117-121.