Bipolar I Disorder Needs Timely Diagnosis and More Treatment Choices

As a nurse practitioner, I work with patients living with a variety of mental health conditions. Given our role in supporting patient care, healthcare professionals have an opportunity to help patients by carefully listening to their experiences and goals, correctly diagnosing patients as early as possible, and bringing our training to bear in helping them navigate their treatment journey to find the right therapy for them.

One challenge I see in my practice is patients who come to me after being prescribed multiple medications over the course of their illness to treat their mental health condition, but are still experiencing symptoms or having adverse effects from their treatment. In cases like these, we often need to dig deeper to ensure that the patient has a correct diagnosis, so we can offer treatment options that might help them.

DIAGNOSIS CHALLENGES

One mental health condition I treat is bipolar disorder. Bipolar disorder is a brain disorder that causes changes in a person’s mood, energy, and ability to function. People with bipolar disorder may experience intense emotional states, called mood episodes, that typically occur during distinct periods of days to weeks. These mood episodes are characterized as manic/hypomanic (abnormally happy or irritable mood) or depressive (sad mood). Bipolar disorder is a category that includes three different diagnoses: bipolar I, bipolar II and cyclothymic disorder.¹

In this article, we focus on bipolar I disorder, which affects about 1% of the U.S. population. The symptoms of bipolar I disorder can often lead to it being initially misdiagnosed. It is estimated that a third of misdiagnosed patients can wait 10 years or longer to receive a correct bipolar disorder diagnosis, which can delay finding treatment that works for them.^2,^3,4

Given the complexity of bipolar I disorder and its many possible presentations, I believe it is important to ask a lot of questions during new patient intake appointments and throughout the course of their treatment. This active listening approach helps me gain a comprehensive understanding of the patient’s experience and can be helpful in identifying symptoms of bipolar 1 disorder, such as a manic episode. The ability to recognize different presentations of the disease helps us arrive at an accurate diagnosis to guide their treatment journey. In my own practice, I take a personal, holistic approach that considers a patient’s lifestyle, family environment, family history, stressors, and more.

HELPING PATIENTS FIND MEDICATION THAT WORKS FOR THEM

My first step when working with a new patient is to take a comprehensive medication history to identify any potential drug interactions and/or side effects they may be experiencing and to assess efficacy. Then we discuss their short- and long-term treatment goals. This helps build trust with the patient, which can help when partnering with them on treatment decisions. I also like to stay abreast of current available treatment options and consider what may work for each patient.

One medication I may consider for appropriate patients with bipolar I is LYBALVI^® (olanzapine and samidorphan), which was approved in 2021. LYBALVI is indicated for the treatment of adults with schizophrenia; or bipolar I disorder for acute treatment of manic or mixed episodes as monotherapy, and as an adjunct to lithium or valproate or as a maintenance monotherapy treatment. It’s important to note that LYBALVI has a boxed warning for increased mortality in elderly patients with dementia-related psychosis and is not approved for the treatment of patients with dementia-related psychosis. Please see additional Important Safety Information below and full Prescribing Information, including Boxed Warning, for LYBALVI.⁵

There are still patients struggling to find the right diagnosis – and the right treatment regimen for them – to help their mental health conditions. Every patient and treatment journey is unique, but by asking the right questions and working together with patients, I believe nurse practitioners are in a position to help find the treatment approach that works for each patient. And I’m honored to have that privilege and that responsibility.

This is Ms. Holliday’s perspective and does not represent the opinion of all clinicians. The information included is not a substitute for professional medical advice. This article is sponsored by Alkermes, Inc.

Please read the Important Safety Information about LYBALVI below. See Prescribing Information and Medication Guide.

IMPORTANT SAFETY INFORMATION AND INDICATIONS

Boxed Warning: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. LYBALVI is not approved for the treatment of patients with dementia-related psychosis.

Contraindications: LYBALVI is contraindicated in patients who are using opioids or are undergoing acute opioid withdrawal. If LYBALVI is administered with lithium or valproate, refer to the lithium or valproate Prescribing Information for the contraindications for these products.

Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis, including stroke, transient ischemia attack, and fatalities. See Boxed Warning.

Precipitation of Severe Opioid Withdrawal in Patients who are Physiologically Dependent on Opioids: LYBALVI can precipitate opioid withdrawal in patients who are dependent on opioids, which can lead to an opioid withdrawal syndrome, sometimes requiring hospitalization. LYBALVI is contraindicated in patients who are using opioids or undergoing acute opioid withdrawal. Prior to initiating LYBALVI, there should be at least a 7‑day opioid-free interval from last use of short-acting opioids, and at least a 14-day opioid-free interval from the last use of long-acting opioids. Explain the risks associated with precipitated withdrawal and the importance of giving an accurate account of last opioid use to patients and caregivers.

Vulnerability to Life-Threatening Opioid Overdose: Attempting to overcome opioid blockade with high or repeated doses of exogenous opioids could lead to life-threatening or fatal opioid intoxication, particularly if LYBALVI therapy is interrupted or discontinued, subjecting the patient to high levels of unopposed opioid agonist as the samidorphan blockade wanes. Inform patients of the potential consequences of trying to overcome the opioid blockade and the serious risks of taking opioids concurrently with LYBALVI or while transitioning off LYBALVI. In emergency situations, if a LYBALVI-treated patient requires opioid treatment as part of anesthesia or analgesia, discontinue LYBALVI. Opioids should be administered by properly trained individual(s) and patient should be continuously monitored in a setting equipped and staffed for cardiopulmonary resuscitation. Patients with a history of chronic opioid use prior to treatment with LYBALVI may have decreased opioid tolerance if LYBALVI therapy is interrupted or discontinued. Advise patients that this decreased tolerance may increase the risk of opioid overdose if opioids are resumed at the previously tolerated dosage.

Neuroleptic Malignant Syndrome, a potentially fatal reaction. Signs and symptoms include hyperpyrexia, muscle rigidity, delirium, autonomic instability, elevated creatine phosphokinase, myoglobinuria (and/or rhabdomyolysis), and acute renal failure. Manage with immediate discontinuation, intensive symptomatic treatment, and close monitoring.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), a potentially fatal condition reported with exposure to olanzapine, a component of LYBALVI. Symptoms include a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. Discontinue if DRESS is suspected.

Metabolic Changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Any patient treated with LYBALVI should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required anti-diabetic treatment despite discontinuation of the suspect drug. Measure weight and assess fasting glucose and lipids when initiating LYBALVI and monitor periodically.

Tardive Dyskinesia (TD): Risk of developing TD (a syndrome of potentially irreversible, involuntary, dyskinetic movements) and the likelihood it will become irreversible increases with the duration of treatment and the cumulative dose. The syndrome can develop after a relatively brief treatment period, even at low doses, or after discontinuation. Given these considerations, LYBALVI should be prescribed in a manner that is most likely to reduce the risk of tardive dyskinesia. If signs and symptoms of TD appear, drug discontinuation should be considered.

Orthostatic Hypotension and Syncope: Monitor orthostatic vital signs in patients who are vulnerable to hypotension, patients with known cardiovascular disease, and patients with cerebrovascular disease.

Falls: LYBALVI may cause somnolence, postural hypotension, and motor and sensory instability, which may lead to falls, and consequently, fractures or other injuries. Assess patients for risk when using LYBALVI.

Leukopenia, Neutropenia, and Agranulocytosis (including fatal cases): Perform complete blood counts in patients with a history of a clinically significant low white blood cell (WBC) count or history of leukopenia or neutropenia. Discontinue LYBALVI if clinically significant decline in WBC occurs in the absence of other causative factors.

Dysphagia: Use LYBALVI with caution in patients at risk for aspiration.

Seizures: Use LYBALVI with caution in patients with a history of seizures or with conditions that lower the seizure threshold.

Potential for Cognitive and Motor Impairment: Because LYBALVI may cause somnolence, and may impair judgment, thinking, or motor skills, caution patients about operating hazardous machinery, including motor vehicles, until they are certain that LYBALVI does not affect them adversely.

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

Anticholinergic (Antimuscarinic) Effects: Olanzapine, a component of LYBALVI, was associated with constipation, dry mouth, and tachycardia. Use LYBALVI with caution with other anticholinergic medications and in patients with urinary retention, prostatic hypertrophy, constipation, paralytic ileus or related conditions. In postmarketing experience, the risk for severe adverse reactions (including fatalities) was increased with concomitant use of anticholinergic medications.

Hyperprolactinemia: LYBALVI elevates prolactin levels. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds.

Risks Associated with Combination Treatment with Lithium or Valproate: If LYBALVI is administered with lithium or valproate, refer to the lithium or valproate Prescribing Information for a description of the risks for these products.

Interference with Laboratory Tests for Opioid Detection: LYBALVI may cause false positive results with urinary immunoassay methods for detecting opioids. Use an alternative analytical technique (e.g., chromatographic methods) to confirm positive opioid urine drug screen results.

Most Common Adverse Reactions observed in clinical trials were:

- Schizophrenia (LYBALVI): weight increased, somnolence, dry mouth, and headache
- Bipolar I Disorder, Manic or Mixed Episodes (olanzapine): somnolence, dry mouth, dizziness, asthenia, constipation, dyspepsia, increased appetite, and tremor
- Bipolar I Disorder, Manic or Mixed Episodes, adjunct to lithium or valproate (olanzapine): dry mouth, weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia, paresthesia

Concomitant Medication: LYBALVI is contraindicated in patients who are using opioids or undergoing acute opioid withdrawal. Concomitant use of LYBALVI is not recommended with strong CYP3A4 inducers, levodopa and dopamine agonists. Reduce dosage of LYBALVI when using with strong CYP1A2 inhibitors. Increase dosage of LYBALVI with CYP1A2 inducers. Use caution with diazepam, alcohol, other CNS acting drugs, or in patients receiving anticholinergic (antimuscarinic) medications. Monitor blood pressure and reduce dosage of antihypertensive drug in accordance with its approved product labeling.

Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with LYBALVI. Inform patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to LYBALVI during pregnancy.

Renal Impairment: LYBALVI is not recommended for patients with end-stage renal disease (eGFR of <15 mL/minute/1.73 m²).

To report SUSPECTED ADVERSE REACTIONS, contact Alkermes at 1-888-235-8008 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

LYBALVI is indicated for the treatment of:

Schizophrenia in adults
Bipolar I disorder in adults
- Acute treatment of manic or mixed episodes as monotherapy and as adjunct to lithium or valproate
- Maintenance monotherapy treatment

Please see accompanying full Prescribing Information, including Boxed Warning, for LYBALVI.

LYBALVI is available as 5 mg/10 mg, 10 mg/10 mg, 15 mg/10 mg, and 20 mg/10 mg tablet.

Tarrah Holliday Bio:

Tarrah Holliday, based in Atlantic, IA, is a Masters-prepared ANCC board-certified Psychiatric Mental Health Nurse Practitioner (PMHNP-BC), with experience in inpatient and outpatient settings, providing services to approximately 2,400 patients. She works with two crisis stabilization centers, four residential substance abuse treatment centers and 17 mental health care facilities. Primary diagnoses she treats are schizophrenia and bipolar disorder, and she has vast experience in treating patients. Her professional goal is to reframe the conversation from mental illness to brain health to help patients increase acceptance in seeking treatment.

References: 1. American Psychiatric Association. What are bipolar disorders? Accessed March 15, 2024. https://www.psychiatry.org/patients-families/bipolar-disorders/what-are-bipolar-disorders 2. Merikangas KR, et al. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry. 2007 May; 64(5): 543–552. 3. McIntyre RS, Laliberté F, Germain G, et al. The real-world health resource use and costs of misdiagnosing bipolar I disorder. J Affect Disord. 2022;316:26-33. 4. Hirschfeld RMA, et al. Perceptions and impact of bipolar disorder: How far have we really come? Results of the National Depressive and Manic-Depressive Association 2000 Survey of individuals with bipolar disorder. J Clin Psychiatry. 2003 February; 64:(2):161-174 5. LYBALVI [prescribing information]. Waltham, MA: Alkermes, Inc.

ALKERMES^® is a registered trademark of Alkermes, Inc. LYBALVI^® is a registered trademark of Alkermes Pharma Ireland Limited, used by Alkermes, Inc., under license.

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