4 Ways to Cope With Bipolar Uncertainty

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The first of this trio of essays noted that research studies conducted after the 2013 DSM-5 found the following symptoms common in bipolar mixed states:

• Agitation, both psychic and physical
• Irritability
• Nonstop ideas and distractibility
• Anxiety
• Decreased sleep

These have been dubbed “The 4 A’s”: anxiety, anger, agitation, and attention problems (plus extreme insomnia). With these symptoms, bipolar mixed states overlap almost completely with those of posttraumatic stress disorder (PTSD) with depression, generalized anxiety disorder (GAD) with depression, attention deficit disorder (ADD) with depression, and borderline personality disorder.

This essay presents 4 means of coping with the diagnostic uncertainty that results from this overlap.

1. Gather More Data

While the symptoms of these conditions overlap almost completely, 4 other domains of information do statistically differentiate bipolar depressions from depression (including when comorbid with PTSD, GAD, ADD and borderline): (1) a family history of bipolar disorder; (2) early age of depression onset (teens/early 20s); (3) episodic illness course or postpartum onset; and (4) highly adverse reactions to antidepressants.^1,2

Therefore, one way of coping with the difficult differential posed by depression with 1 or more of the mixed state symptoms described in Part 1 (including anxiety, anger, agitation, attention problems; and extreme insomnia) is to make sure to gather all relevant data. No diagnosis should be proffered until they are obtained and evaluated.

But the sheer volume of information one is expected to gather in an initial interview can interfere with establishing trust and rapport through open-ended questions and accurate reflective listening. Using questionnaires to gather some of this information is efficient but can be cumbersome: how much can you ask a patient to divulge before meeting you in person? For a short questionnaire designed to capture mood symptoms and family history, age of onset, illness course, and response to antidepressants, consider “MoodCheck”, described in Psychiatric Times in 2017 and available for direct download (no profit or industry connections).³

2. Recruit the Patient (And Perhaps Family)

Shared decision-making involves more than simply explaining treatment pros and cons. It includes understanding the patient’s beliefs and fears and social milieu. For example, is PTSD a preferred diagnosis because it places causality outside the patient? Is ADD preferred because it is a simple explanation for struggling in school? How much stigma is attached to the word bipolar, in the patient’s mind, and their family’s, and their community?

With these insights in hand or in development, a good clinician helps the patient (and perhaps family) understand the diagnostic challenge of mixed states. One might say “There are a couple of ways to explain your symptoms. No single diagnosis is obvious. We have to consider several” (enumerating those most likely, including bipolar without mania). Another variation: “You do not have bipolar disorder, but you do not have plain depression either. You may be somewhere in between.”

When time is limited, especially in an initial interview, it is almost impossible to be this deliberate explaining a complex differential. But many patients, if they leave with limited information, will turn to the internet. Unguided searching can easily lead to misimpressions. You could create your own website, or a handout of recommended sites to direct your patients’ searches. For that list, consider a site built recently for patients with depression that emphasizes all the themes in the essay you are reading now (no profit, no advertising).⁴

3. Start With Psychotherapy, Including Digital Therapeutics

New tools for psychotherapy, discussed here, make it more available, and thus a realistic alternative to medication. Psychotherapies have lower risks than medications, even if targeting the “wrong” diagnosis; indeed, several are likely to help even when misdirected.

In the face of diagnostic uncertainty, you can offer or refer the patient to a psychotherapy specific for the most likely diagnosis, or therapy likely to benefit any of several diagnostic possibilities. For example, some therapies are PTSD-specific, focusing on trauma, while basic cognitive-behavioral therapy (CBT) may still be of benefit in PTSD through components such as stress management and mindfulness skills. Similarly, CBT is likely to help a patient whose depression is mixed, or even bipolar II depression. A meta-analysis of 409 trials found CBT equally effective as medications for depression in the short term, and better in the long term.⁵

Unfortunately, unless you have a solid referral network, it can be difficult to confidently refer patients for psychotherapy. The best local therapists are often not routinely taking new patients. For online therapy, some websites allow a patient to choose a particular kind of therapy, but you cannot control the quality.

Digital therapeutics (DTX) include websites and apps that provide a kind of psychotherapy. Web-based versions of CBT have been shown to be nearly as effective as a live therapist, particularly if guided with some minimal support.⁶ Online therapies for PTSD also have shown efficacy, although patients are more likely to drop out if the intervention focuses on stabilization (as do the majority of such programs) when they are looking for trauma-focused work.⁷

Some of the best studied versions of online CBT rely on patient motivation to work through the modules.⁸ Completion rates have been as low as 10% in some of these studies.⁹ By contrast, newer DTX programs “push” adherence with programmed messages and limited text-based support. With these, 1 industry-sponsored study demonstrated almost 90% adherence after 12 of 16 sessions.¹⁰

In that industry-sponsored study, the absolute difference in the primary outcome measure (MADRS) vs an active control condition was small. But all patients were already on an antidepressant and the control was a very plausible version of the treatment app, perhaps limiting improvement and separation. Data from further research will be of great interest. In the meantime, it appears that the push technology represents a major advance vs older DTXs.

As a final reason to more deeply consider adding DTX to your toolkit, note that Medicare and Medicaid Services have proposed new CPT codes that would pay for prescribing and managing these tools. (In an important twist, only “FDA-approved” programs would be allowed, thus excluding several existing programs that have not sought such approval). Code GMBT1 would allow clinicians to bill for giving DTX to patients and teaching them how to use it. The idea is to make DTX rather like giving a vaccine. Code GMBT2 covers the first 20 minutes of “monthly management services,” such as reviewing the data from the DTX device.¹¹

4. Compare Treatment Risks

If beginning with a medication treatment rather than a psychotherapy, a fourth means of coping with diagnostic uncertainty is to help the patient compare the risks of treatment options associated with possible diagnoses. This approach is detailed in Part 3 of this series.

Concluding Thoughts

Because of overlapping symptoms, distinguishing mixed states from other common presentations of depression can be nearly impossible. This essay describes 4 means of coping with that uncertainty, including respective clinical tools: gathering data using a broad but brief questionnaire; patient education, augmented with reliable internet sources; starting with a psychotherapy, including DTX; and patient education comparing treatment risks.

Dr Phelps is retiring from 30 years of treating complex mood disorders, and recently founded another website, DepressionEducation.org. He is the bipolar disorder section editor for Psychiatric Times® and the author of A Spectrum Approach to Mood Disorders for clinicians and Bipolar, Not So Much for patients and their families.

References

1. Mitchell PB, Goodwin GM, Johnson GF, Hirschfeld RM. Diagnostic guidelines for bipolar depression: a probabilistic approach. Bipolar Disord. 2008;10(1 pt 2):144-152.

2. Phelps J, Angst J, Katzow J, Sadler J. Validity and utility of bipolar spectrum models. Bipolar Disord. 2008;10(1 pt 2):179-193.

3. MoodCheck. Depression Education. Accessed November 7, 2024. https://depressioneducation.org/depression-section-page-1/questionnaire-moodcheck/

4. Depression Education. Accessed November 7, 2024. https://depressioneducation.org/

5. Cuijpers P, Miguel C, Harrer M, et al. Cognitive behavior therapy vs. control conditions, other psychotherapies, pharmacotherapies and combined treatment for depression: a comprehensive meta‐analysis including 409 trials with 52,702 patients. World Psychiatry. 2023;22(1):105-115.

6. Karyotaki E, Efthimiou O, Miguel C, et al. Internet-based cognitive behavioral therapy for depression: a systematic review and individual patient data network meta-analysis. JAMA Psychiatry. 2021;78(4):361-371.

7. Blackie M, De Boer K, Seabrook L, et al. Digital-based interventions for complex post-traumatic stress disorder: a systematic literature review. Trauma Violence Abuse. 2024;25(4):3115-3130.

8. MoodGym. Accessed November 7, 2024. https://www.moodgym.com.au/

9. Twomey C, O’Reilly G. Effectiveness of a freely available computerised cognitive behavioural therapy programme (MoodGYM) for depression: meta-analysis. Aust N Z J Psychiatry. 2017;51(3):260-269.

10. Rejoyn. Clinician brief summary. Otsuka America Pharmaceutical, Inc. 2024. Accessed November 7, 2024. https://www.rejoynhcp.com/Clinician-Brief-Summary.pdf

11. Anderson M. What CMS’s proposed reimbursement codes could mean for the digital therapeutics industry. HealthCare Brew. July 22, 2024. Accessed November 7, 2024. https://www.healthcare-brew.com/stories/2024/07/22/cms-proposed-reimbursement-codes-digital-therapeutics-industry