Content sponsored by Otsuka America Pharmaceutical Inc. and Lundbeck for which Gregory W. Mattingly, MD, is a paid consultant.
Despite advances in medicine and psychiatry, Bipolar I Disorder (BP-I) is still one of the most challenging mental health disorders to appropriately diagnose. Experienced clinicians who have worked in this field for years may miss the initial signs and symptoms that differentiate BP-I from other mental health conditions[i]. BP-I, which is a cyclical condition where patients experience bouts of depression and have had at least one manic episode, lasting at least seven days, affects nearly 4.8 million adults in the United States[ii].
According to one large metanalysis, it takes an average of six years for patients to receive a bipolar disorder diagnosis[iii]. However, once a diagnosis is made, providers can help patients work to achieve and maintain mood stability. When talking with my adult patients who are stable with BP-I, I find it important to stress the goals of maintenance therapy, which include the prevention of a recurring episode and symptom reduction[iv]. Since all patients are different, it is important to work directly with each patient to create a comprehensive treatment plan that is best for them[v].
As providers, it’s important that we help patients not only achieve stability for their BP-I symptoms when possible, but also help them understand what it means to be stable and in the maintenance stage.
Typically, patients with bipolar disorder may experience multiple episodes over the course of their illness, with a recurrence occurring approximately every 17–30 months. Successful management of this chronic, recurrent illness depends on maintaining long-term mood stability and the prevention of subsequent episodes of depression and mania[vi]. For patients following a pharmacological regimen who are finding stability, the focus shifts from achieving stability to the maintenance of it, and the goal is to keep their symptoms under control[vii].
When Considering a Long-Acting Injectable
From my experience, there are many people who don’t like to take a daily medication no matter what it’s being used to treat. Many patients with BP-I, are taking other medications for a variety of comorbidities, so it is often not just one pill a day, but several[viii]. Knowing this, I find it important to reiterate the importance of staying on a medication to maintain stability and work with patients to find what works for them.
For appropriate adults in the maintenance phase of treatment of bipolar I who have established tolerability to oral aripiprazole, an option I like to offer is ABILIFY MAINTENA® (aripiprazole). By receiving ABILIFY MAINTENA each month as prescribed, it provides patients an opportunity to take one less daily pill; it is important to note that concomitant oral antipsychotic must be administered for 14 days after the first injection. ABILIFY MAINTENA is available in 300 mg or 400 mg as an extended release injectable suspension.
Long acting injectables may not be appropriate for every patient. Providers should clearly communicate the potential advantages and disadvantages of this type of medication. For example, juxtaposing the idea of removing one pill from a patient’s daily routine, disadvantages include pain at injection site, less flexibility of dose adjustments, and the responsibility of frequent travel to receive the injection, amongst other considerations.
ABILIFY MAINTENA is a prescription medicine given by injection by a healthcare professional for the maintenance monotherapy treatment of BP-I in adults. It’s important to note that ABILIFY MAINTENA has a BOXED WARNING regarding Increased Mortality in Elderly Patients with Dementia-Related Psychosis. Please see IMPORTANT SAFETY INFORMATION below.
INDICATIONS and IMPORTANT SAFETY INFORMATION for ABILIFY MAINTENA® (aripiprazole)
ABILIFY MAINTENA is an atypical antipsychotic indicated for:
- Treatment of schizophrenia in adults
- Maintenance monotherapy treatment of bipolar I disorder in adults
IMPORTANT SAFETY INFORMATION
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 MAINTENA is 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 ABILIFY MAINTENA. 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 MAINTENA, 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 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 aripiprazole if such urges develop.
Orthostatic Hypotension: 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.
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 MAINTENA at the first sign of a clinically significant decline in WBC and in severely neutropenic patients.
Seizures: 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 MAINTENA may impair judgment, thinking, or motor skills. Instruct patients to avoid operating hazardous machinery, including automobiles, until they are certain ABILIFY MAINTENA does not affect them adversely.
Body Temperature Regulation: Use 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 ABILIFY MAINTENA. Use caution in patients at risk for aspiration pneumonia.
Alcohol: Advise patients to avoid alcohol while taking ABILIFY MAINTENA.
Concomitant Medication: Dosage adjustments are recommended in patients who are CYP2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors for greater than 14 days. Avoid concomitant use of CYP3A4 inducers with 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 ≥5% and at least twice that for placebo) were increased weight, akathisia, injection site pain, and sedation.
Injection Site Reactions: In a short-term, clinical trial with ABILIFY MAINTENA in patients with schizophrenia treated with gluteal 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.
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 ABILIFY MAINTENA, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms. Consider the benefits and risks of ABILIFY MAINTENA and possible risks to the fetus when prescribing ABILIFY MAINTENA to a pregnant woman. Advise pregnant women of potential fetal risk.
Lactation: Aripiprazole is present in human breast milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother and any potential risks to the infant.
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 U.S. FULL PRESCRIBING INFORMATION, including BOXED WARNING.
Learn more at www.abilifymaintenahcp.com.
The Importance of Provider-Patient Communication
Ultimately, it is important that providers create a space for their BP-I patients to feel empowered to speak honestly about their symptoms and treatment plan[ix]. For those living with this condition, maintaining stability is important and we as providers, need to ensure that patients know there are maintenance treatment options out there that may help as they continue to work on managing their BP-I.
[i] Phillips, M. L., & Kupfer, D. J. (2013). Bipolar disorder diagnosis: challenges and future directions. Lancet (London, England), 381(9878), 1663–1671. https://doi.org/10.1016/S0140-6736(13)60989-7
[ii] Tandon R. (2015). Bipolar and Depressive Disorders in Diagnostic and Statistical Manual of Mental Disorders-5: Clinical Implications of Revisions from Diagnostic and Statistical Manual of Mental Disorders-IV. Indian journal of psychological medicine, 37(1), 1–4. https://doi.org/10.4103/0253-7176.150796
[iii] Dagani, J., Signorini, G., Nielssen, O., Bani, M., Pastore, A., Girolamo, G., & Large, M. (2017). Meta-analysis of the Interval between the Onset and Management of Bipolar Disorder. Canadian journal of psychiatry. Revue canadienne de psychiatrie, 62(4), 247–258. https://doi.org/10.1177/0706743716656607
[iv] Shah, N., Grover, S., & Rao, G. P. (2017). Clinical Practice Guidelines for Management of Bipolar Disorder. Indian journal of psychiatry, 59(Suppl 1), S51–S66. https://doi.org/10.4103/0019-5545.196974
[v] Krupnick, J., Sotsky, S., Simmens, S., Moyer, J., Elkin, I., Watkins, J., & Pilkonis, P. (1996). The Role of the Therapeutic Alliance in Psychotherapy Pharmacotherapy Outcome: Findings in the National Institute Of Mental Health Treatment of Depression Collaborative Research Program. Journal of Consulting and Clinical Psychology, 64(3), 532–539. https://doi.org/10.1037/0022-006X.64.3.532
[vi] Malhi, G., McAulay, C., Das, P., & Fritz, K. (2015). Maintaining mood stability in bipolar disorder: a clinical perspective on pharmacotherapy. Evidence-Based Mental Health, 18(1), 1–6. https://doi.org/10.1136/eb-2014-101948
[vii] Shah, N., Grover, S., & Rao, G. P. (2017). Clinical Practice Guidelines for Management of Bipolar Disorder. Indian journal of psychiatry, 59(Suppl 1), S51–S66. https://doi.org/10.4103/0019-5545.196974
[viii] Sinha, A., Shariq, A., Said, K., Sharma, A., Jeffrey Newport, D., & Salloum, I. M. (2018). Medical Comorbidities in Bipolar Disorder. Current psychiatry reports, 20(5), 36. https://doi.org/10.1007/s11920-018-0897-8
[ix] [ix] Krupnick, J., Sotsky, S., Simmens, S., Moyer, J., Elkin, I., Watkins, J., & Pilkonis, P. (1996). The Role of the Therapeutic Alliance in Psychotherapy Pharmacotherapy Outcome: Findings in the National Institute Of Mental Health Treatment of Depression Collaborative Research Program. Journal of Consulting and Clinical Psychology, 64(3), 532–539. https://doi.org/10.1037/0022-006X.64.3.532