This article is Sponsored by Otsuka America Pharmaceutical, Inc. The author is a paid consultant for Otsuka America Pharmaceutical, Inc.

People living with serious mental illness (SMI) are at higher risk for a wide range of chronic physical conditions1, are more likely to visit the emergency department, be admitted to the hospital and have longer hospital stays compared to those without SMI2. Nonadherence to drug treatments for major depressive disorder (MDD)3, schizophrenia and bipolar disorder is common4. Several studies illustrate the problem, estimating that up to half of patients with bipolar disorder4, MDD3 and/or schizophrenia5 do not take their medication as directed.

The Importance of Patient Buy-in and Connections

Treating patients with SMI can be complicated by the illness impairing the person’s ability to properly manage their disorder. Some patients experience anosognosia, a condition that prevents them from recognizing that they have a mental illness, making it challenging to convince them of the need for treatment6. Establishing patient trust and buy-in on the treatment approach is one of the most important steps in caring for patients with SMI. Building that rapport requires working with the patient as a team, and when possible, with the people in their lives who provide support, to engage in shared decision-making and goal-setting7. I have found in my own practice that educating patients about medication options and allowing them to be an active partner in those decisions effectively supports the patient in their journey, rather than simply dictating the medications to be prescribed.

Once a treatment approach is agreed upon, information regarding the patient’s daily experience, such as medication-taking behavior and other lifestyle factors, is essential knowledge for health practitioners, but also for the patient and those supporting them. For clinicians, this information can provide potential insights into how the patient is experiencing their condition, their medication taking behaviors, and can help inform ongoing treatment strategies. For patients, it may provide a more tangible connection between their medication-taking behavior and how it affects the way they feel and their daily functioning. For family members, it can potentially open up a productive dialogue.

The Need for Objective Data

While a strong patient-HCP relationship can help facilitate information sharing, it may not successfully overcome the limitations of patient self-reports traditionally used for assessing a patient’s status. Those with SMI may struggle to accurately recall their medication-taking behaviors which can be particularly challenging as time passes. In my experience, shame and guilt also play a role in a patient misrepresenting their medication use and symptoms. Some of my patients, out of a need to please, will only share good news even if it isn’t what they’re experiencing; other patients I treat feel such guilt they can’t admit they haven’t been complying with their treatment regimen.

Unfortunately, HCPs are not always able to accurately evaluate how well their patients follow treatment recommendations. According to one study, 44% of HCPs treating schizophrenia and bipolar disorder overestimated their patients’ conformity to treatment even when they had a well-established relationship with the patient8.

To gather more objective data that doesn’t rely on long-term memory, I encourage my patients to use a journal when they first start a medication so they can track their medication use, side-effects and symptoms during the course of the day. Because patients often don’t recognize changes in their behaviors and feelings over time, this method can be helpful in clearly illustrating their experience. The drawback is that patients can be inconsistent with their journal entries which presents a similar problem to relying on retrospective self-reports.

Adding Digital Tools to the Toolbox for Information-sharing

The addition of digital tools helps with collecting objective patient data. Rather than patients having to keep track of information that can easily be forgotten, smart phones are readily available. Digital tools can capture patient data, offering an important mechanism for gathering information to help facilitate patient-clinician discussions and help inform treatment decisions.

A digital medicine system I have found especially useful for recording objective and patient-reported data and helping engage patients is the ABILIFY MYCITE® System.

ABILIFY MYCITE, a drug-device combination product comprised of aripiprazole tablets embedded with an Ingestible Event Marker (IEM) sensor intended to track drug ingestion, is indicated in adults for the treatment of schizophrenia; treatment of bipolar I disorder as monotherapy and as adjunct to lithium or valproate for the acute treatment of manic and mixed episodes or maintenance treatment; and the adjunctive treatment of major depressive disorder. ABILIFY MYCITE has not been shown to improve patient compliance or for use in modifying aripiprazole dosage. It should not be used in “real-time” or during an emergency, because detection may be delayed or not occur.

Please see the full INDICATIONS and IMPORTANT SAFETY INFORMATION below, including BOXED WARNING regarding Increased Mortality in Elderly Patients with Dementia-Related Psychosis and Suicidal Thoughts and Behaviors.

It is an FDA-approved digital medicine system that automatically logs when a patient takes their medication, their activity levels (measured in steps) and the time spent resting (determined by body position). It also enables patients to manually input additional information on their mood and sleep quality, as well as reasons for why they missed a medication dose. This can provide clinicians with insight into a patient’s ingestion data and the quality of their sleep.

The impact of the ABILIFY MYCITE System on treatment adherence has not been demonstrated. Some factors, such as connectivity, transmitter malfunction, or device availability, may impact the consistency and reliability of data detection, collection and transmission. Only functions related to tracking drug ingestion have been evaluated or approved by FDA.

The information gathered about these factors is presented in the MYCITE® Dashboard, a web portal, that can be viewed by the clinician and shared with family members or other support people in their lives.

For some of my patients and their families it has been very impactful. For example, I’ve found in my practice that the system can be particularly helpful for young adults whose parents are still very much involved in their care but who are trying to gain their independence. Being able to review the dashboard may allow the family to have a more meaningful dialogue about the information while limiting the need to question them about whether they are taking their medication.

This digital medicine system may not be right for all patients. HCPs know their patients best and can determine which patients may want to engage in measuring their medication ingestion.

For patients living with SMI and their HCPs, having this type of data can help inform those important treatment discussions and decisions.

INDICATIONS and IMPORTANT SAFETY INFORMATION for ABILIFY MYCITE® (aripiprazole tablets with sensor)

INDICATIONS

ABILIFY MYCITE, a drug-device combination product comprised of aripiprazole tablets embedded with an Ingestible Event Marker (IEM) sensor intended to track drug ingestion, is indicated in adults for the:

  • Treatment of schizophrenia
  • Treatment of bipolar I disorder as monotherapy and as adjunct to lithium or valproate for:
    • Acute treatment of manic and mixed episodes
    • Maintenance treatment
  • Adjunctive treatment of major depressive disorder

Limitations of Use: ABILIFY MYCITE has not been shown to improve patient compliance or for use in modifying aripiprazole dosage. It should not be used in “real-time” or during an emergency, because detection may be delayed or not occur.

IMPORTANT SAFETY INFORMATION

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

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

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults. Those on antidepressant therapy should be monitored closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber. The safety and effectiveness of ABILIFY MYCITE have not been established in pediatric patients.

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

Cerebrovascular Adverse Events, Including Stroke, in Elderly Patients with Dementia-Related Psychosis: 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 aripiprazole.

Neuroleptic Malignant Syndrome (NMS): NMS is a potentially fatal symptom complex reported in association with administration of antipsychotic drugs, including ABILIFY MYCITE. 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 ABILIFY MYCITE, 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 in total cumulative dose of antipsychotic drugs. TD can develop after a relatively brief treatment period, even at low doses, or after discontinuation. If antipsychotic treatment is withdrawn, TD may remit, partially or completely. Prescribing should be consistent with the need to minimize TD.

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 anti-diabetic 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 ABILIFY MYCITE if such urges develop.

Orthostatic Hypotension: ABILIFY MYCITE 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.

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 MYCITE at the first sign of a clinically significant decline in WBC and in severely neutropenic patients.

Seizures: ABILIFY MYCITE 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 MYCITE may impair judgment, thinking, or motor skills. Instruct patients to avoid operating hazardous machinery, including automobiles, until they are certain ABILIFY MYCITE does not affect them adversely.

Body Temperature Regulation: Use ABILIFY MYCITE 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 ABILIFY MYCITE. Use caution in patients at risk for aspiration pneumonia.

Dosage Adjustments and Cytochrome P450 Considerations: For patients with schizophrenia and bipolar I disorder taking ABILIFY MYCITE who are:

  • Known CYP2D6 poor metabolizers, administer half the recommended dose
  • Known CYP2D6 poor metabolizers taking concomitant strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin), administer a quarter the recommended dose.
  • Taking strong CYP2D6 (e.g., quinidine, fluoxetine, paroxetine) or CYP3A4 inhibitors, administer half the recommended dose.
  • Taking strong CYP2D6 and CYP3A4 inhibitors, administer a quarter the recommended dose. When co‑administered drug is withdrawn, adjust ABILIFY MYCITE dosage to its original level.
  • Taking strong CYP3A4 inducers (e.g., carbamazepine, rifampin), double recommended dose over 1 to 2 weeks. When co‑administered drug is withdrawn, reduce ABILIFY MYCITE dosage to original level over 1 to 2 weeks.

Commonly Observed Adverse Reactions (incidence ≥5% and at least twice that for placebo) in adult patients:

  • Schizophrenia: akathisia
  • Bipolar mania (monotherapy): akathisia, sedation, restlessness, tremor, and extrapyramidal disorder
  • Bipolar mania (adjunctive therapy with lithium or valproate): akathisia, insomnia, and extrapyramidal disorder
  • Major depressive disorder (adjunctive treatment to antidepressant therapy): akathisia, restlessness, insomnia, constipation, fatigue, and blurred vision

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

Skin Irritation for MYCITE Patch: Symptoms of skin irritation localized at the site of the MYCITE Patch may occur. In clinical studies, 12.4% of patients (n=61) experienced skin rashes at the site of patch placement.

Pregnancy: Neonates exposed to antipsychotic drugs, including ABILIFY MYCITE, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms. Consider the benefits and risks of ABILIFY MYCITE and possible risks to the fetus when prescribing ABILIFY MYCITE to a pregnant woman. Advise pregnant women of potential fetal risk. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ABILIFY MYCITE during pregnancy. For more information contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.

Lactation: Aripiprazole is present in human breast milk; however, there are insufficient data to assess the amount in human milk, effects on the breastfed infant, or effects on milk production. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for ABILIFY MYCITE and any potential adverse effects on the infant 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).

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.

©2022 Otsuka America Pharmaceutical, Inc. All rights reserved.
FEBRUARY 2022 12US21EBP0124

References
1. Mental Health and Chronic Diseases. CDC. (2012, October). https://www.cdc.gov/workplacehealthpromotion/tools-resources/pdfs/issue-brief-no-2-mental-health-and-chronic-disease.pdf 2. Ronaldson, A., Elton, L., Jayakumar, S., Jieman, A., Halvorsrud, K., & Bhui, K. (2020, September). Severe mental illness and health service utilisation for Nonpsychiatric Medical Disorders: A systematic review and meta-analysis. PLOS Medicine. https://doi.org/10.1371/journal.pmed.1003284
3. Sansone RA, Sansone LA. Antidepressant adherence: are patients taking their medications? Innov Clin Neurosci. 2012;9(5-6):41-46. 4. Stephenson JJ, Tunceli O, Gu T, et al. Adherence to oral second-generation antipsychotic medications in patients with schizophrenia and bipolar disorder: physicians’ perceptions of adherence vs. pharmacy claims. Int J Clin Pract. 2012;66(6):565-573. doi:10.1111/j.1742-1241.2012.02918.x 5. Haddad PM, Brain C, Scott J. Nonadherence with antipsychotic medication in schizophrenia: challenges and management strategies. Patient Rel Outcome Meas. 2014;5:43-62. doi:10.2147/PROM.S42735 6.Anosognosia. NAMI. (n.d.). https://www.nami.org/About-Mental-Illness/Common-with-Mental-Illness/Anosognosia 7. Lehman, A. F., Lieberman, J. A., Dixon, L. B., McGlashan, T. H., Miller, A. L., Perkins, D. O., Kreyenbuhl, J., American Psychiatric Association, & Steering Committee on Practice Guidelines (2004). Practice guideline for the treatment of patients with schizophrenia, second edition. The American journal of psychiatry161(2 Suppl), 1–56. 8. Stephenson, J. J., Tuncelli, O., Gu, T., Eisenberg, D., Panish, J., Crivera, C., & Dirani, R. (2012, May 11). Adherence to oral second‐generation antipsychotic medications in patients with schizophrenia and bipolar disorder: Physicians’ perceptions of adherence vs. Pharmacy claims. Wiley Online Library. https://doi.org/10.1111/j.1742-1241.2012.02918.x