Category: bipolar disorder

Within the last few months, a generic formulation of Latuda (lurasidone) has become available. Should you consider prescribing it for adult Bipolar I Depression?

Previously, this medication cost >$1,200/month and was thus out of reach for most patients and/or required insurance pre-authorization. Now that the price of lurasidone has fallen dramatically, it is worth comparing this medication to quetiapine, which is also generic and also has an FDA indication for adult Bipolar I Depression.

There aren’t very many head-to-head trials, but in meta-analyses of monotherapy for adult Bipolar I Depression, both lurasidone and quetiapine appear to be efficacious. Several published treatment algorithms consider both medications to be first-line options as monotherapy for this indication. In other studies, lurasidone has demonstrated efficacy for adult Bipolar I Depression when used as an adjunct to lithium or divalproex and, indeed, Latuda garnered FDA-approval for adjunct use for this indication.

FDA package inserts are available on the FDA approved drugs site. Package inserts contain a lot of useful information and are likely underutilized in our era of quick, app-based, medication references. When comparing the data reported in the package inserts for lurasidone and quetiapine, lurasidone appears to have a lower incidence of the antipsychotic-associated metabolic syndrome (weight gain, new-onset diabetes, new-onset hyperlipidemia, etc.). Lurasidone, at least at low doses, is also felt to be less sedating than quetiapine. However, when compared to quetiapine, lurasidone appears to have a higher incidence of parkinsonism, akathisia, and other D2 blockade-mediated side effects. For more details on the side effects of these medications, including information on the Black Box warnings, QTc prolongation, monitoring of the metabolic syndrome, and other adverse effects, please refer to your own medication reference material or the free sites available via Heal WA.

Another important difference between lurasidone and quetiapine is that lurasidone needs to be taken with a >350 calorie meal. This dramatically increases the absorption of lurasidone. However, food insecurity is a problem experienced by many people in our society, and it is important to ask your patients if they have regular access to a >350 calorie dinner.

Lurasidone dosing is usually initiated at 20mg/day. Though the FDA max dose is 120mg/day, some studies of adult Bipolar I Depression suggest that high-end dosing does not necessarily increase efficacy but might increase the risk of side effects. The mean (SD) lurasidone dose was 64.1 (14.4) mg in a 24-week open label study authored by Ketter et al for the journal Depression and Anxiety. Thus, rather than automatically pushing the lurasidone dose to the top end, it could be useful to first give the patient a good trial in the middle of the dosing range.

If you would like more information on the treatment of adult Bipolar I Depression, please call the Psychiatry Consultation Line (877-WA-PSYCH) and one of our psychiatrists would be happy to review the options with you.

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Author

Ryan Kimmel, MD
Professor, University of Washington School of Medicine, Department of Psychiatry and Behavioral Sciences
Chief of Psychiatry, University of Washington Medical Center
Medical Director, Psychiatry Consultation Line

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Bipolar Disorder — Screening and Diagnosing in Primary Care
UW Psychiatry and Addictions Case Conference series (UW PACC)*
Presenter: Joseph Cerimele, MD, MPH
The objectives of this presentation are to describe1) the clinical epidemiology of individuals with bipolar disorder in primary care settings; 2) techniques to improve the recognition of bipolar disorder in primary care patients; and 3) clinical characteristics of patients with bipolar disorder in primary care. 

*The UW Psychiatry and Addictions Case Conference series (UW PACC) is a free, weekly teleconference that connects community providers with UW Medicine psychiatrists and addictions experts. Sessions include both an educational presentation on an addictions or psychiatry topic and case presentations where providers who participate receive feedback and recommendations for their patients.

When it comes to treating adults with bipolar disorder, gabapentin appears to be everything you’d want in a medication…except for efficacy.

Prescribers wish that gabapentin had utility in bipolar disorder because gabapentin isn’t a P450 substrate, is renally excreted, and is generic and thus relatively affordable. Unfortunately, gabapentin does not demonstrate efficacy in randomized trials for bipolar disorder and current treatment guidelines do not emphasize its use. Despite of the lack of evidence, reviews of gabapentin prescribing patterns in the United States show that this medication is still being used with alarming frequency for bipolar disorder.

There are now five medications with specific, FDA approval for acute bipolar depression. Moreover, there are at least a dozen medications with FDA approval for acute mania. Many of these options are available in generic formulations.

Instead of reaching for gabapentin as a potential intervention for bipolar disorder, please call the Psychiatry Consultation Line (877-WA-PSYCH) and one of our psychiatrists would be happy to review treatment options that have better evidence.

You can also call the PCL for advice regarding differential diagnosis, non-pharmacologic interventions, and treatment monitoring. In complicated clinical scenarios, discussing a patient’s care with a colleague can help you formulate a more comprehensive treatment plan.  

The PCL is a free resource for healthcare providers in Washington State to consult with a psychiatrist about their adult patients with mental health or substance use conditions. Learn more at pcl.psychiatry.uw.edu.

If you are considering using a medication for bipolar disorder, please first review your own reference material for full details on indications, side effects, dosing, monitoring requirements, and drug interactions. For reference, we most often use Micromedex, UpToDate, or Epocrates. Additionally, there are free databases available to Washington providers at heal-wa.org/professions.

Author

Ryan Kimmel, MD
Professor, University of Washington School of Medicine, Department of Psychiatry and Behavioral Sciences
Chief of Psychiatry, University of Washington Medical Center
Medical Director, Psychiatry Consultation Line

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Managing Bipolar Depression in Primary Care
UW Psychiatry and Addictions Case Conference series (UW PACC)*
Presenter: John S. Kern, MD
The objectives of this presentation are to 1) recognize the predominant role of depressive episodes in the morbidity associated with bipolar disorder; 2) summarize the outcomes of the SPIRIT study; and 3) apply an orderly approach to the care of bipolar depression.

*The UW Psychiatry and Addictions Case Conference series (UW PACC) is a free, weekly teleconference that connects community providers with UW Medicine psychiatrists and addictions experts. Sessions include both an educational presentation on an addictions or psychiatry topic and case presentations where providers who participate receive feedback and recommendations for their patients.

Clinicians call the Psychiatry Consultation Line with a range of questions about individuals with suspected or diagnosed bipolar disorder, which affects an estimated 4.4% of U.S. adults at some time in their lives. Bipolar disorders, sometimes referred to as manic-depressive disorders, are mood disorders that include manic or hypomanic symptoms and depressive symptoms. Accurate diagnosis of bipolar disorder can be difficult, and once a diagnosis is made, clinicians can face numerous decisions regarding acute episode treatment, maintenance treatment, monitoring response, monitoring for adverse effects, and treatment adjustments. These “points to consider” may help as you encounter similar clinical scenarios.

Assessment and Diagnosis

Common PCL Question: How can I assess for bipolar disorder in my primary care practice?

• A structured assessment can help collect information that any clinician would need to inform diagnosis of bipolar disorder.
• The Composite International Diagnostic Interview (CIDI) instrument can contribute to a structured assessment by assessing for lifetime experience of manic symptoms. It is important to remember that positive screening results do not equal a clinical diagnosis. In one study in primary care, about 45% of people screening positive on the CIDI, and 15% of people screening negative, were diagnosed with bipolar disorder by a psychiatrist. However, this instrument can help to collect information that might lead clinicians to ask more questions about bipolar disorder in those with a positive screen. PCL psychiatrists can assist with questions about administering structured tools such as the CIDI.
• Some clinicians also find it useful to have structured tools to assess age of onset of mood symptoms, past mood symptoms and episodes, peripartum mood symptoms, response to medications including to antidepressant medications, family psychiatric history, drug and alcohol use, and other clinical problems, since historical points other than manic symptoms might raise clinical suspicion for bipolar disorders.

Common PCL Question – What questions can I ask patients about past manic symptoms?

• One strategy to consider in clinical questioning is to ask about discrete periods of concurrently elevated or irritable mood AND increased energy. Then, once identifying a period when that occurred, inquiring about associated hypomanic or manic symptoms.

Common PCL Question – Is there a bipolar disorder spectrum, and does this apply to my patient?

• Some individuals experience hypomanic symptoms that do not reach the level of severity of a hypomanic or manic episode.
• Diagnostic and Statistical Manual of Mental Disorders (DSM-5) classification includes categories of cyclothymia (subsyndromal hypomanic and depressive symptoms most days over two years), and Other specified bipolar and related disorder due to short-duration hypomanic episodes (i.e. 2-3 day duration), and insufficient number of hypomanic symptoms to reach episode-level (i.e. 3 symptoms). 
• Additionally, major depressive episodes in major depression can occur with mixed features (concurrent hypomanic symptoms) though the difference in this case is that the individual with major depression with mixed features has never previously experienced a hypomanic or manic episode.
• Mood fluctuations or ‘swings’ can occur in the absence of bipolar disorder diagnosis. Consider alternate explanations.
• Visit Psych Education for more information on bipolar spectrum.

Treatment

Common PCL Question – Where do I start with choosing a medication treatment for a patient diagnosed with bipolar disorder?

• Consider the current mood state. The most commonly experienced mood state in individuals with bipolar disorder is depression with one or more concurrent hypomanic symptoms.
• There are relatively few FDA-approved or evidence-based medication treatments for bipolar depression and guideline-suggested first-line treatments include quetiapine, lurasidone, lamotrigine and lithium.
• A greater number of medication treatment options exist for treatment of manic episodes, and guideline-suggested first-line treatments include lithium, quetiapine, risperidone, olanzapine, divalproex (avoid use of divalproex in women of reproductive potential) and aripiprazole.

Common PCL Question – My patient is diagnosed with bipolar disorder. Can I prescribe treatment with an antidepressant?

• Uncertainty remains about effectiveness of antidepressant medications in treatment of individuals with bipolar disorder. Expert guidelines suggest avoiding antidepressant treatment when two or more concurrent hypomanic symptoms are present, when past antidepressant treatment was associated with onset or worsening of hypomanic symptoms or anxiety symptoms, during an episode with mixed features or in individuals who experience predominantly mixed features episodes, or as monotherapy.
• If someone is already taking an antidepressant medication, and is not experiencing remission of depression or is experiencing anxiety symptoms or hypomanic symptoms, a reasonable next step is to taper and discontinue treatment with the antidepressant medication.

Common PCL Question – What can I add to this treatment plan that is not a medication?

• Consider other treatment options including bright light therapy for bipolar depression (administered in midday rather than upon awakening). This treatment was not associated with treatment-emergent hypomanic symptoms in a clinical trial.
• Psychotherapy options include treatments specific to bipolar depression, and maintenance treatment psychotherapies including strategies to normalize life patterns to reduce risk of mood episode recurrence and improve quality of life.

Monitoring

Common PCL Question – I started this treatment, what can I do next?

• When caring for individuals diagnosed with bipolar disorder it is important to monitor the effect of any treatment decision. The patient may also have specific treatment goals to monitor.
• Mood episode recurrence is common, and subsyndromal mood symptoms can occur chronically, which are associated with recurrence.
• Monitoring symptom severity and frequency as part of measurement-based care could be accomplished with validated patient-reported measures such as the Patient Health Questionnaire-9 for depressive symptoms, and the newer Patient Mania Questionnaire-9 for manic symptoms.

Common PCL Question – What laboratory studies or other monitoring should I do?

• Some medication treatments such as lithium, quetiapine and other antipsychotic medications require monitoring treatment for a therapeutic medication serum concentration (lithium and divalproex), and for adverse effects such as serum metabolic studies, weight/ body mass index, tremor, or other motor phenomena such as akathisia or involuntary movements. These measurements are usually done at baseline, and every 3-6 months depending on the clinical circumstance. Some individuals treated with antipsychotic medications should have baseline and interval EKG monitoring to measure QTc interval.

Conclusion
Assessment, diagnosis, treatment selection and monitoring can be complicated when caring for individuals with suspected bipolar disorder.  Psychiatrists on the Psychiatry Consultation Line can help clinicians reason through next steps in assessment, treatment decisions, and monitoring. Even in complicated clinical scenarios, discussing a patient’s care with a colleague can lead to a path forward.

For additional reading on bipolar disorder, visit Psych Education by Dr. Jim Phelps.

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Author
Joseph Cerimele, MD
Assistant Professor, University of Washington School of Medicine, Department of Psychiatry and Behavioral Sciences
Director, Psychiatry and Behavioral Sciences Grand Rounds

References
Pacchiarotti I, et al. The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders. Am J Psychiatry. 2013;170:1249-1262.

Goodwin GM, et al.  Evidence-based guidelines for treating bipolar disorder: Revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2016;30:495-553.

Yatham LN, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. 2018;20:97-170.

Cerimele JM, et al. Bipolar disorder and PTSD screening and telepsychiatry diagnoses in primary care. Gen Hosp Psychiatry. 2020;65:28-32.

Cerimele JM, et al. The Patient Mania Questionnaire (PMQ-9): a Brief Scale for Assessing and Monitoring Manic Symptoms. J Gen Intern Med. 2021; Jun 18. doi: 10.1007/s11606-021-06947-7. Online ahead of print.