Pretest self-assessment question (answer at the end of the case)
Which of the following is not an invasive surgical treatment for resistant depression?
A. TMS
B. VNS
C. ECT
D. DBS
E. EpCS
F. A and C
G. B and D
H. All of the above
Patient evaluation on intake
55-year-old woman with a chief complaint of unremitting depression for 30+ years
Psychiatric history
Onset of depression in her 20s
Questionable recurrent depressive episodes versus a single, chronic unremitting episode. Patient cannot recollect a two-month symptom-free period or any clear inter-episode recovery
MDD symptoms have never been mild enough to allow gainful employment, likely ruling out persistent depressive disorder plus MDD, which is often called “double depression”
Meets melancholic MDD specifiers with severe anhedonia (patient was housebound and essentially bedridden), worse symptoms in the morning, marked psychomotor retardation (a simple depression symptom screening took 15 minutes to complete due to thought slowing), and weight loss (patient’s weight was 90 lbs)
History includes at least two psychiatric hospitalizations. She has had no suicide attempts
Review of psychiatric systems revealed no formal anxiety disorder, psychosis, mania, eating disorder, SUD
She has received eclectic, supportive psychotherapy in the past, but her mental state at this presentation made reciprocal talk therapy almost impossible
There is no evidence of clear personality disorder
Failed to respond to adequately dosed
– Fluoxetine (Prozac) 60 mg/d and sertraline (Zoloft) 200 mg/d SSRI monotherapies
– Venlafaxine-XR (Effexor-XR) 225 mg/d SNRI therapy
– Bupropion-SR (Wellbutrin-SR) 400 mg/d NDRI therapy
– Mirtazapine (Remeron) 45 mg/d NaSSA therapy
– TCA trials in distant past
– Course of ECT (electroconvulsive therapy)
Social and personal history
Married and has a son
High school educated and has not been gainfully employed outside raising children
Grew up with outside relatives as both parents died when she was younger
Does not drink alcohol, smoke cigarettes, or use addictive drugs
Medical history
Coronary artery disease (CAD)
Irritable bowel syndrome (IBS)
GERD
Hyperlipidemia
Family history
Eating disorder (likely anorexia nervosa [AN]) in a sibling
Current psychiatric medications
Current medical medications
Question
Based on what you know about this patient’s history and current symptoms, would you consider her to be suffering from TRD or do you think she would be refractory (will never respond) to treatment altogether?
What conventional antidepressant-type treatments might you suggest?
Lithium augmentation
Thyroid augmentation
Taper off medications and use an MAOI
Try ECT again
Try ketamine infusion therapy
Try transcranial magnetic stimulation (TMS)
Try vagus nerve stimulation (VNS)
Try deep brain stimulation (DBS)
Try magnetic seizure therapy (MST)
Attending physician’s mental notes: initial evaluation
The patient has melancholic MDD that is chronic and surprisingly has no other psychiatric comorbidities, which is relatively uncommon in this patient population
Patient has marked psychomotor slowing: a symptom of melancholia or subtle psychotic depression? Could this be considered “psychiatric parkinsonism”?
As she has had more than two years of unremitting symptoms without any full inter-episode recovery, this makes her depression chronic
She should also be considered resistant as she has failed antidepressants from several different classes (TCA, SSRI, NDRI, SNRI, ECT) and augmentation strategies (olanzapine, dextroamphetamine, topiramate)
She is treatment resistant so far, but she has not had some of the leading empirical augmentation strategies (lithium, thyroid) or an MAOI trial
She also has utilized supportive psychotherapy well, but not formal CBT, IPT, or PDP
Her regimen at her first outpatient visit is complicated and minimally effective. The prescriber could streamline her medications and discontinue ineffective medications as the current medications seem to be fairly well maximized
She could be sent for neurostimulation treatment (VNS, DBS, TMS) given her medication failures and high treatment resistance, but ECT has already failed
Further investigation
Is there anything else you would especially like to know about this patient?
What medical details about this patient are you concerned about?
At the first visit, her weight was very low. Is she medically stable? Could she tolerate ECT or other neurostimulation treatments?
Her medications seem contradictory in that she is on a weight gaining olanzapine (Zyprexa), but weight-losing topiramate (Topamax) and dextroamphetamine (Dextrostat)
She has hyperlipidemia and CAD for which she is being treated. (Of note is that these were medications upon admission to author’s service in 2000 and many of the warnings and guidelines about the atypical antipsychotic inducing metabolic disorders were not available until 2003–2004.)
She has a family history of eating disorders and collateral information about her typical eating habits and body habitus should be collected
– Preliminarily, she does not appear to suffer from AN
Obtaining a nutrition or dietary consultation might be warranted as she is mostly immobile, bedridden, and her caloric intake is low
– This may also help to determine if the patient is in a “failure to thrive” situation where an inpatient admission might be warranted
Obtaining routine blood laboratory analyses and a discussion with her PCP is warranted, to determine medical stability for future treatment with psychotropics, neurostimulation techniques, and also to rule out medical causes of her depression
Question
Based on what you know about this patient’s history, current symptoms, and treatment responses, do you think that a bona fide, formal trial of established psychotherapy is warranted?
Yes, a referral for PDP is warranted
Yes, a referral for CBT is warranted
No, this patient has had many years of supportive, eclectic style psychotherapy and further psychotherapy intervention is unlikely to be effective
No, specific psychotherapies are no better than eclectic psychotherapies in treating MDD
No, this patient’s cognitive impairment and psychomotor slowing would likely make psychotherapy ineffective
Attending physician’s mental notes: initial evaluation (continued)
The patient is clearly depressed and seems to have had no clear benefit to monotherapy antidepressant treatments nor to her current aggressive augmentation regimen
The patient may be psychotic given her marked cognitive impairment, but the current high-dose olanzapine (Zyprexa) use and past ECT trial likely rules out depressive psychosis, leaving her profound thought slowing and vegetative symptoms likely due to severe MDD without psychosis but with melancholic features
She has a history of thorough antidepressant trial follow-through where full, therapeutic dosing has been utilized. Her husband is supportive and a good historian about her medical interventions
Pharmacy records confirm her medication trials
– Note that in the absence of a good historian or available medical records from previous providers, most pharmacies can print out medications dispensed, going back several years. This is often an easy way to tabulate how treatment resistant a patient is while confirming their medication trial history
The patient really needs to be evaluated medically before more aggressive treatment is prescribed
Case outcome: interim follow-ups through three months
The patient is medically cleared without any concerns
– Lipids are well controlled
– Cardiac state is stable
– Laboratory test results are normal
– Nutritionally, she is meeting her minimal requirements despite her current weight and stature
Psychotherapy was halted due to psychomotor and cognitive impairment
A second trial of ECT was attempted. It was unclear if first trial was bilateral and conducted for at least 12 sessions. This second trial was also ineffective
A reduction and streamlining of medications was refused as patient and spouse felt the medications were helpful to some degree, and feared a clinical worsening despite her current severe symptoms
An inpatient stay was considered but her medical health was stable and she was not a danger to herself as her spouse is able to meet her instrumental activity needs
TMS and DBS options were experimental and not readily available at the time. However, VNS was available at a local study site and this was more vigorously considered
Question
Considering her current medication regimen, what types of clinical monitoring might you utilize in the outpatient office setting?
Routine measurement of weight and abdominal girth due to the use of an atypical antipsychotic
Routine blood pressure monitoring due to the use of noradrenergic stimulant medication and the atypical antipsychotic
An understanding with the primary care clinician that they will help monitor these as well and be responsible for continued treatment and monitoring of the patient’s pre-existing hyperlipidemia. If not, independent monitoring of laboratory test results should occur in the psychiatric setting
Topiramate (Topamax) has warnings about acidosis and requires blood draws to establish good renal function and then an absence of bicarbonate wasting over time. Patients on this medication should also be warned about acute eye pain and vision changes due to glaucoma, and about a loss of sweating (oligohydrosis) and risk of heat stroke and further weight loss
Attending physician’s mental notes: four months
Much collateral clinical information has been collected but no treatment changes issued as yet
She has failed to achieve remission with multiple antidepressants, psychotherapy, and ECT
Informed consent regarding lithium or thyroid augmentation was provided versus an experimental course of VNS
At the time, VNS was not an approved treatment and two experimental open-label pilot studies showed good tolerability and reasonable effectiveness in highly treatment-resistant MDD patients
Clinically, the patient perceived the offered medication augmentations to have end organ damage issues and the MAOI medications to have too many drug interaction issues. She was despondent that her previous medications had manipulated her brain monoamines excessively and to no avail. Hence, she had lost faith in pharmacotherapy
The patient visited a VNS study team and was felt to be a good candidate for VNS given that
– VNS is indicated for the adjunctive long-term treatment of chronic or recurrent depression for adult patients who experience MDEs and have not had an adequate response to four or more adequate antidepressant treatments
– These four trials could be medications, psychotherapies, or ECT. This patient has had more than double the amount of qualifying treatment trials
– Present data would suggest that patients who have failed four medications (even with ECT) have very poor chances of achieving remission and then maintaining it, making experimental VNS a more viable option
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