Pretest self-assessment question (answer at the end of the case)
Regarding Lyme disease as a neuropsychiatric illness, which is most accurate?
A. Almost all patients bitten by infected Lyme disease-carrying ticks will develop an easily diagnosable rash
B. Once bitten, most patients will develop clinical Lyme disease
C. Depression as a result of Lyme disease infection is a common clinical presentation
D. Blood antibody testing is often a definitive diagnosis and should be followed by antibiotic treatment
Patient evaluation on intake
48-year-old woman states she has been “depressed and anxious since childhood”
She is extremely worried she will become incapacitated and institutionalized
Psychiatric history
Does not remember any sustained euthymia since her teenage years
Feels as though she has fluctuated between chronic lower-level dysthymia symptoms and has had many MDEs consistent with double depression
Now has full syndrome of MDD symptoms
Additionally, she has uncontrollable worry, racing thoughts, muscle tension, irritability, nightmares, feelings of dread and detachment
– Some of these latter symptoms she attributes to being neglected, but not abused, as a child
She admits to having BN in college
She denies SUD symptoms
Psychotherapy history
Attends eclectic, supportive psychotherapy often and has recently started with a new therapist
Has no history of undergoing organized psychoanalysis, or completing a course of CBT or IPT
Social and personal history
Graduated from college and worked as a teacher until MDD worsened two to three years ago
Has two children but was divorced several years ago
Has brothers who are supportive
Smokes cigarettes and drinks a moderate amount of coffee
Medical history
Denies current medical problems except she is considering being treated for a possible Lyme disease diagnosis as many family members have suffered from this after unknown exposures, although she has not been tested yet
Family history
Mother suffered from treatment-resistant bipolar disorder and was institutionalized often
– The patient reports much fear and currently reliving episodes related to her mother’s symptomatology
– Her mother was often absent in her life because of psychiatric institutionalization
She has two other siblings with bipolar illness
AUD is present in many family members
Medication history
Currently she is taking
In her current MDE occurring over the last two years, she has failed to respond to
Patient evaluation on initial visit
Chronic MDD symptoms with associated, or possibly comorbid GAD or PTSD for many years
MDD progressively more resistant to treatment with each MDE, lasting longer
Possible exposure to tick bites and Lyme disease, but patient does not recollect a bite or a rash
She and her family are particularly concerned as other family members have suffered with Lyme disease
Appears to be compliant with medication management and has attended psychotherapy
Does have passive suicidal ideation, is quite despondent, but is amenable to outpatient treatment and contracts for safety
Reports no current side effects
Current medications
Question
Based on your geographic location, is Lyme disease a reasonable differential diagnosis?
No, there is a very small deer population in my area and chances of deer tick bites are very low
Maybe – I live in a geographic area where more cases are being reported every year
Yes, most cases of Lyme disease are concentrated in a few areas, and most infections occur in the northeast, in the Great Lakes region, and along the Pacific coast of the United States. I live in one of these areas
Attending physician’s mental notes: initial evaluation
This patient has chronic and recurrent MDD
Likely has comorbid GAD and PTSD, or these are at least present in a subsyndromal aspect
There is a possibility that she has an infectious etiology as well
These comorbidities and chronicity of her illness make her prognosis fair at best
She has had several recent therapeutic polypharmacy trials, albeit not always dosed at maximum levels, and has had many monotherapy trials over the years
– This also worsens her prognosis with regard to achieving remission
She does have positive family support and initial indications suggest that she is compliant with treatment, both of which improve her prognosis
Question
Which of the following would be your next step?
Increase the NaSSA antidepressant mirtazapine (Remeron) to the full FDA dose of 45 mg/d to maximize its potential
Increase the BZ alprazolam (Xanax) to a higher dose to treat her agitation and anxiety
Check divalproex (Depakote) levels, and if warranted, increase to make this therapeutic despite the patient not having bipolar disorder
Augment the current medications with yet another agent to enhance antidepressant response
Refer for formal CBT or IPT manualized psychotherapy
Confer with outside clinicians regarding Lyme disease workup and findings
Attending physician’s mental notes: initial evaluation (continued)
This patient seems to be taking standard treatment for resistant MDD
– Good use of multiple antidepressant classes and augmentations with evidence-based agents
– Now is on a moderate dose of an antidepressant
However, there is concern about the use of divalproex (Depakote) as she does not appear to have a bipolar history
– Perhaps it was prescribed for anxiolysis as she is quite agitated at times and failing to respond to BZ
She seems very guilt-ridden and ruminative about her perceived inadequacy
– Will need to continue to investigate if this is delusional
Further investigation
Is there anything else you would especially like to know about this patient?
What about details concerning her past medication treatment?
– Her doses of medications appear to be therapeutic (moderate to high dosages)
– The divalproex is confirmed as being used for anxiety, not bipolar disorder
– She has never misused controlled prescriptions
What about details concerning her possible Lyme disease exposure?
– Has lived most of her life in areas that are prevalent for Lyme disease
– Does not recollect a tick bite
– Does not recollect the typical “bull’s eye” rash
– States multiple family members have developed Lyme disease without known bites/rashes
– Her local internist does not feel this is Lyme disease, which has angered family members who have arranged a visit to a Lyme disease expert in another state for a second opinion, as they feel strongly that it is
– Her present MDE is chronic and has similar features compared to her previous MDEs, which would predate her possible Lyme exposure
Case outcome: first interim follow-up visits four and eight weeks later
At the first follow-up visit, opts to leave the medications as given, to await her laboratory results and levels and collaboration with outside physicians
At the follow-up visit, she acknowledges the same MDD, GAD, PTSD symptoms as in the initial office appointment and agrees to increase the mirtazapine (Remeron) antidepressant to the full 45 mg/d dose and taper off the ineffective divalproex (Depakote)
Now recollects that her trial of lamotrigine (Lamictal) in the past was somewhat helpful and free of side effects
– She asks if this can be restarted and it is titrated slowly per usual guidelines to avoid serious rash complications
Reports that she is having fluctuating anxiety and agitation and reveals that she takes her alprazolam (Xanax) as needed, but sporadically
– She may “take three tablets a day for a few days, then zero tabs, then perhaps one or two….”
– It is possible that on her off-use days she is having rebound anxiety as a side effect
She is convinced to take 2 mg/d routinely to avoid this possible rebound phenomenon, keep consistent drug levels present, and to also provide better longitudinal anxiety control
Shortly after this follow-up visit, she begins seeing a new, psychodynamically oriented psychotherapist who felt she required inpatient psychiatric stabilization, and she was admitted for a 10-day stay
Question
What would you suggest to the inpatient psychiatrist regarding possible treatment options?
Continue mirtazapine (Remeron) full dose as it has not had enough time therapeutically to become effective
Continue to titrate lamotrigine (Lamictal) as it has not reached its usual effective dose as an off-label depression augmentation
Switch the ineffective mirtazapine to a TCA or an MAOI antidepressant
Augment the current medications with an atypical antipsychotic, lithium, or thyroid hormone
Start ECT treatments
Start VNS treatments
Start TMS treatments
Attending physician’s mental notes: second interim follow-up visit at three months
Despite being a little better, the patient still has significant MDD symptoms
She has a clinically meaningful response now in that she is not suicidal, is less anxious, and has better affective range, but she is not a 50% responder yet
She now has side effects of increasing fatigue and sedation
– This type of side effect makes her feel more guilty as she is “able to do less, and is less functional” as a result
She takes medications known to have serious, long-term side effects
– She is warned of, and monitored for, metabolic disorder, which appears not to be a problem now
– She is warned of, and monitored for, TD/EPS, which appears not to be a problem now
– She is warned of, and monitored for, BZ misuse, which appears not to be a problem now
– She is warned of, and monitored for, rashes, which appear not to be a problem now
Case outcome: second interim follow-up visit at three months
The patient returns from hospitalization taking
This regimen differs in that she was augmented with an atypical antipsychotic, her sedative alprazolam (Xanax) was changed to lorazepam (Ativan), and zolpidem-CR (Ambien-R) was added to improve sleep
– The patient now has a moderately better affective range, fewer psychomotor agitation symptoms, and states an absence of suicidal thoughts
– She is felt to be 20%–30% better after her inpatient stay
Question
What would you do next?
Increase the dose of her olanzapine (Zyprexa) augmentation
Switch the mirtazapine to an SSRI, which may mimic the approved olanzapine–fluoxetine combination drug (Symbyax), which is approved specifically for TRD
As she is a partial responder and has failed many therapeutic trials, could combine with a second approved antidepressant such as bupropion (NDRI), or trazodone (SARI), or an SNRI
As she is a partial responder with a minimal response and has failed many therapeutic trials, could augment with a stimulant or a nutraceutical
– L-methylfolate (Deplin) 15 mg/d
– SAMe 400–800 mg twice a day
– N-acetyl cysteine (NAC) 1000 mg twice a day
Continue to wait on the current regimen and PDP for full effectiveness to occur
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