Pretest self-assessment question (answer at the end of the case)
If a manic spell is instigated by initiation of an antidepressant, which of the following is likely to happen?
A. The induced mania will be more severe
B. The induced mania will last longer
C. The induced mania will be less severe and shorter in duration
D. None of the above
Patient evaluation on intake
26-year-old man with a chief complaint of being “depressed, more or less”
Mainly experiences MDEs of varying lengths and severities, occurring since he was a teenager
Asks for a consultation because he has legal issues concerning an altercation that occurred recently
Psychiatric history
Significant MDEs consistent with recurrent MDD are evident
– Some MDEs have been incapacitating and have interfered with school and work
– Seems to have good inter-episode recovery, which allows him to return to class and work
When in the middle of an MDE, he admits to most MDD symptoms
– Except he does not have suicidal thoughts
– Admits to decreased sleep, despondent thoughts and mood, low interest in activities, poor energy and cognition
– Says his self-esteem drops as he feels disgruntled, rejection-sensitive, and is guilt-ridden for no apparent reason
He admits to SAD symptoms where he
– Is often nervous around new people and acquaintances
– Experiences anticipatory anxiety and will avoid certain social events
– The SAD appears separate from the MDEs where these anxiety symptoms occur regardless of his affective state
The main reason for consultation is that he has a legal issue regarding drinking while driving that he feels was likely fueled by psychiatric symptoms
– At the time of the infraction, he had been started on an SSRI for the MDD and SAD symptoms
– With this, he felt invincible and that the law did not apply to him
– During this episode he was also in an altercation at a bar when he purposefully antagonized another patron
This is extremely out of character for his usually quiet, socially anxious demeanor
Despite being a shy, avoidant, SAD person during this period, he lost all anxiety, fear, and avoidance tendencies
– During these spells, he experienced a moderate amount of talkativeness, distractibility, racing thoughts, hyperactivity, hyposomnia, impulsivify (flirting, drinking more than usual, fighting) and grandiosity (becomes invincible, arrogant, back-talking, and challenging of authority [police, bystanders, etc.])
These mood-elevating events were complicated by the fact that AUD criteria were likely met during these times
– While in college, he admitted to heavy alcohol use on weekends
– When depressed, he may use cannabis intermittently
Has now completed college and has few friends in the immediate area
Family is very supportive
Wants to be a writer, specifically a news reporter, and is planning on applying to graduate school
Currently presents in a euthymic state at his first office appointment
Social and personal history
Graduated high school and college
Is not gainfully employed but is considering graduate school now
Drug and alcohol history as noted
He does not smoke and uses low amounts of caffeinated drinks
His family is supportive
Medical history
There are no acute or chronic medical issues
Family history
GAD is reported for his mother
No bipolar family members
Medication history
Via his PCP, he has had two short SSRI trials with sertaline (Zoloft) 50 mg/d and paroxetine (Paxil) 20 mg/d, both of which caused mood elevations with problematic behaviors and drinking
Took a few doses of mood stabilizing divalproex sodium (Depakote) but was too sedated to continue its use
Prescribed the BZ anxiolytic clonazepam (Klonopin) in the past without misuse
Psychotherapy history
None
Patient evaluation on initial visit
Recurring MDD since late teens with comorbid SAD are evident
Possible hypomanic spells in last two to three years versus antidepressant-induced activating side effects versus alcohol intoxication-induced mood disorder
All mood elevations reported seem secondary to SSRI and/or alcohol use
He has not had a chance to be compliant with medication treatment due to side effects
He has no suicidal ideation and no signs of psychosis
He is euthymic now and functioning well psychosocially
Current medications
None
Question
What does a family history of, or lack thereof, bipolar disorder mean clinically?
Nothing, as there is no clear bearing on risk of bipolar disorder or treatment outcomes
Risk of bipolar disorder appears clear as family, twin, and adoption studies have provided evidence for a strong genetic component to bipolar disorder
– Particularly, twin studies demonstrated higher concordances for the disorder among monzygotic identical twins, as compared with dizygotic fraternal twins, with an estimated heritability >80%
– People with a first-degree relative with bipolar disorder have a 13.63-fold increased risk of developing bipolar disorder themselves
Attending physician’s mental notes: initial evaluation
This patient is somewhat complex given his MDD, SAD, and AUD comorbidities
He has had two spells consistent with hypomania symptomatology, but the origin of these symptoms might be due to the SSRI treatments, his alcohol abuse, or frank onset of bipolar illness
He has no family history of bipolar disorder, which seems to decrease his bipolar risk 13-fold
His multiple SSRI-induced activations are often considered to be bipolar disorder prodromes or sentinel events and are troubling
Many bipolar patients appear to be unipolars with anxiety problems in their young adult years but progress toward bipolar disorder as they age
He is undertreated in that he has not had a full trial of any psychotropic
Question
Which of the following would be your next step?
He is euthymic, thus do nothing and await any symptom relapse, then choose an appropriate medicine to match his affective state
Collect collateral information from relatives to better delineate his mood elevations to determine if he is bipolar I, II, or neither
Start a mood chart to observe in real time any mood swings that he might develop to better delineate his diagnosis
Issue a rating scale such as the MDQ to better delineate his bipolar diagnosis
Start an approved mood stabilizer for presumed bipolar II disorder
Start another antidepressant for his SAD, while watching for mood elevation in real time
Start a BZ sedative for his SAD to avoid mood-elevating side effects that have been noted previously when he used SSRIs
Attending physician’s mental notes: initial evaluation (continued)
This patient seems to be either very sensitive to excessive mood-elevating side effects from his SSRI treatments, or he is a relatively new bipolar II disorder patient
Collateral information suggests that his two hypomania spells were clearly preceded by SSRI use and excessive alcohol use
His behavioral and legal problems occurred after the mood elevation was noted
He has no family history of bipolar illness and these facts seem to point toward SSRI-induced hypomanic-like side effects
However, it is also likely that these ominous “SSRI side effects” are likely signs of pre-bipolar disorder emergence, a bipolar prodrome, also known as “pre-bipolaring”
He is currently drug and alcohol free while euthymic
Further investigation
Is there anything else you would especially like to know with regard to treating this patient?
Are there any bipolar II approved medications?
– No
Are there any well-established guidelines specifically to help in these situations of pre-bipolaring?
– No
Are some antidepressants safer with regard to lower risk of hypomanic escalation?
– Yes, SSRI and NDRI (bupropion) antidepressants seem safer than TCA, MAOI, and possibly SNRI classes
Some studies suggest that SSRI may work as well as lithium stabilization in bipolar II patients
– However, this may be at odds with the fact that antidepressants are felt to allow patients to worsen from bipolar II to bipolar I disorder more often, or convert patients to mixed features or rapid cycling specifiers
Case outcome: first interim follow-up visit three months later
Patient is educated about his presumptive bipolar II diagnosis as a worst case scenario
Instructed to maintain a usual sleep–wake schedule and avoid marked amounts of caffeine or alcohol
Agrees to release information for his family so that there can be better monitoring of his treatment and symptoms between visits
As there are no clear guidelines for treating bipolar II disorder, he is instructed about bipolar I treatment options, and that conservative approaches would consider treating him as if he were a bipolar I patient
This might lower the chance of depressive and hypomanic relapses, and might prevent escalating to a bipolar I diagnosis in the future
He is re-evaluated for DSM-5 mixed features specifier, and he has not yet met the criteria
Question
What is the chance that this presumptive unipolar MDD patient will develop a bipolar disorder, or if he is a presumptive bipolar II patient, that he will worsen and progress to bipolar I disorder?
Not much risk as these are separate disorders
Some risk if we consider him unipolar now, as longitudinal studies suggest that 27% of severely depressed unipolar MDD patients will develop bipolar II and 19% bipolar I disorders, respectively
Some risk if we consider him a bipolar II patient as he may escalate into a bipolar I disorder
Case outcome: first interim follow-up visit three months later (continued)
There is clear risk of escalation from MDD to bipolar II disorder, and also from bipolar II to a full syndromal bipolar I disorder
– If one were to assume his legal problems were to have resulted from mood elevation symptoms and not his AUD, then he would have enough psychosocial dysfunction to warrant the bipolar I diagnosis now
Several mood stabilizing treatments are offered and initially are refused
Between sessions, he researches the medication options and now asks to start lamotrigine (Lamictal) as it is approved for bipolar maintenance treatment and seems to have “fewer side effects” when compared to other mood stabilizers such as lithium, divalprox (Depakote), olanzapine (Zyprexa), etc.
– There is less organ damage risk, neuromuscular side-effect risk, and metabolic syndrome risks with lamotrigine
– He is titrated according to regulatory guidelines to 200 mg/d, over six weeks, to avoid severe rash risks
He misses his one-month appointment but does attend at three months
– There have been no hypomanic episodes
– Feels moderately depressed
– SAD continues at a mild level
– There are no side effects
He is taking some miscellaneous college higher-level courses and feels the depression is interfering, and requests treatment specifically for this
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