Transcript:
Hello, and welcome to NP Psych Navigator’s Clinical Insights series. I’m Chris Lambert, a nurse practitioner board-certified in family medicine. I’m happy that you joined us today as we discuss an important topic, predictors of treatment-emergent affective switch in patients with bipolar I disorder, or BP-1.
As you may know, bipolar disorder is a lifelong mood disorder characterized by recurrent transitions between depressive and manic phases, with periods of euthymia. During the course of their illness, bipolar patients will display symptoms of mania and depression to different degrees.1
Just as a quick review, the symptoms of a manic episode are shown here on the left and can include those such as inflated self-esteem, reduced need for sleep, racing thoughts, and more. On the right side, the symptoms of depression can include daily depressed mood, reduced interest or pleasure in activities, and so on.
In some cases, bipolar patients may experience a sudden change in mood episodes from 1 pole to another, known as an affective switch.3 The switch between manic and depressive episodes may occur over days to weeks, or it may only take a couple of hours, depending on the patient.4
While the specific mechanism behind switching is currently unknown,3 there are some factors that have been found to be associated with affective switch in bipolar I disorder.1
Environmental factors, such as stress, changes in sleep, and seasonal changes, have been implicated as triggers of affective switch.1,3,4
In addition to the environmental factors, the use of certain pharmacological agents has been associated with affective switch. Antidepressant monotherapy, in particular, has been shown to result in mood destabilization that can precipitate a manic switch in some bipolar patients. This type of affective switch is known as a treatment-emergent affective switch, or TEAS.3,6
How often does TEAS occur? To answer that question, let’s first take a step back.
Generally, patients with BP experience symptoms of depression approximately 3 times more than they do manic symptoms during the course of their illness.8,9 In addition, bipolar patients are more likely to seek treatment during a depressive episode rather than a manic episode.10 The depressive symptoms of bipolar disorder are identical to the depressive symptoms of major depressive disorder (or MDD). This can lead to frequent misdiagnoses of BP as MDD. In fact, a survey showed that 60% of bipolar patients reported being initially incorrectly diagnosed with MDD.11
Misdiagnosis of BP can result in bipolar patients being treated with antidepressant monotherapy, which may increase the potential risk of experiencing TEAS.
Coming back to our question about how often TEAS occurs, research has shown that the rate of bipolar patients experiencing a manic or hypomanic switch from antidepressant monotherapy ranges from 20% to 40%.12 In a study called the Systematic Treatment Enhancement Program for Bipolar Disorder, or STEP-BD, which investigated the prevalence and risk factors associated with TEAS, 44% of bipolar patients reported experiencing at least 1 manic switch within 12 weeks of starting an antidepressant therapy.13
It is important to note that the rate of TEAS observed with antidepressant monotherapy can be reduced when an antimanic agent is administered concurrently. In a study with bipolar patients receiving a combination of an antidepressant and a mood stabilizer, the rate of manic switch was reduced to 14%.12,14
In another study comparing the rate of manic switch in bipolar patients receiving acute treatment of an antidepressant monotherapy versus an antidepressant plus a mood stabilizer, the risk of TEAS was found to be increased in the antidepressant monotherapy group, with a hazard ratio of 2.83, while the risk was unchanged in the group receiving an antidepressant plus a mood stabilizer, with a hazard ratio of 0.79.6 The results of these studies highlight the need to appropriately manage the symptoms of bipolar disorder. Due to the increased risk of TEAS, antidepressant monotherapy is not recommended and not approved for treating depressive symptoms in bipolar patients.15,16
Affective switch can have negative consequences on patient outcomes.
Studies have shown that bipolar patients who experience affective switch are more likely to have comorbidities and are at a higher risk of developing substance abuse problems.3
In a 10-year follow-up study, bipolar patients with affective switch had a greater number of previous hospitalizations, a longer time to recovery, and a greater likelihood of psychomotor retardation.17 TEAS, in particular, is associated with a higher risk of rapid cycling. Rapid cycling refers to when a patient experiences 4 or more mood episodes within a year that meet the criteria for a major depressive, mixed, manic, or hypomanic episode. These episodes are distinguished by partial or full remission for at least 2 months or an episode switch to the opposite polarity.3,6,15
Therefore, it is important for healthcare providers to understand and be aware of possible predictors of affective switch in bipolar patients.
So, what are potential predictors of affective switch? Studies have shown that affective switch in patients with BP can be associated with certain clinical and demographic characteristics.
One example is BP patients who experience mood episodes with mixed features. This can be associated with a greater likelihood of switching mood states.18-20
The term “mixed features,” which is defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, or DSM-5, as the presence of at least 3 symptoms of opposite mood polarity,4 refers to the occurrence of manic and depressive features simultaneously.21
In addition, research has shown that a higher number of previous switches, a lower age at onset, a history of rapid cycling, and a history of substance use were risk factors for affective switch in bipolar patients.20,22
Lastly, according to several studies, the risk of experiencing affective switch may be higher for patients with bipolar I disorder than for patients with bipolar II disorder.23
Studies have also identified potential risk factors specifically for TEAS. They include a shorter duration of illness, exposure to multiple antidepressant trials, a family history of bipolar disorder, and a history of antidepressant-associated manic switch.13,24,25
In addition, risk factors for TEAS may also include low response to previous antidepressant therapy and the use of certain types of antidepressants.25,26
The high rate of misdiagnosis of bipolar disorder as MDD, as discussed earlier, highlights the importance of screening patients diagnosed with MDD for bipolar disorder. Considering the increased risk of TEAS in patients receiving antidepressant therapy, this becomes even more important in the management of both of these conditions. Both the Rapid Mood Screener and Mood Disorder Questionnaire screening tools can be helpful in this regard.27,28 The Rapid Mood Screener, as an example, is shown on the screen here.
It is important for healthcare providers, or HCPs, to monitor for signs of affective switch in bipolar patients upon starting new pharmacotherapy, especially an antidepressant monotherapy.
Regular monitoring of the patient’s mood symptoms can help HCPs and patients recognize a sudden shift in affective states or signs of mixed features, which have been identified as a potential predictor of an affective switch. A quick and easy way for a patient to assess the current presence and severity of their depression is to complete the 9-item Patient Health Questionnaire (PHQ-9).29 Using a mood tracker may also help identify trends in symptoms.30 Remember to educate patients and their caregivers on how to recognize early signs of affective switch,16 including those of TEAS.
In conclusion, it is important for HCPs who are treating patients with antidepressant therapy to consider the possibility of TEAS for the following at-risk patient groups: first, bipolar patients being treated with an antidepressant for their depressive symptoms, and second, patients who are currently diagnosed with MDD and are being treated with an antidepressant, but who you suspect have underlying bipolar disorder.26,31 Using screening tools can help identify patients with bipolar I disorder who may be initially misdiagnosed with MDD.27
HCPs should monitor patients’ symptoms regularly for signs of an affective switch associated with an antidepressant therapy and make adjustments to their treatment plan if necessary. Enlist your patients, as well as their caregivers — with permission of the patients, of course — to partner with you in monitoring for signs of TEAS.
I hope that you found this video on the possible predictors of TEAS in bipolar patients informative for your clinical practice and patient care. Thank you for joining me today!
