1 Boring Old Man

Plot summary: The life of spoiled Robert Merrick is saved through the use of a hospital’s only pulmotor, but because the medical device cannot be in two places at once, it results in the death of Dr. Hudson, a selfless, brilliant surgeon and generous philanthropist. Merrick falls in love with Hudson’s widow, Helen, though she holds him responsible for her husband’s demise. One day, he insists on driving her home and makes a pass at her. She gets out and is struck by another car, losing her sight. He watches over her and visits her during her recuperation, concealing his identity and calling himself Dr. Robert. When he finds out that she is nearly penniless, he secretly pays for specialists to try to restore her vision. Finally, she travels to Paris and is told that her eyesight is gone forever. Robert follows her, confesses his true identity and proposes marriage. She forgives him, but goes away, not wanting to be a burden to him. Years later, Robert has become a brain surgeon. He learns that Helen urgently needs an operation, which he performs. When she awakens, her sight has miraculously returned.

Those were the days when the big screen could resolve any tragedy into a triumph of the the human spirit – as in Lloyd C. Douglas’ 1935 Magnificent Obsession. We know this theme best from Scarlett’s 1939 soliloquy, "Tomorrow is another day!" in Gone with the Wind. We’d moved a long way from the Greek Tragedies or Shakespeare where tragic character flaws lead to inevitable ruin. The 1930s were a time when the themes of redemption in the cinema offered temporary respit from the terror and hardship of the Depression, the inklings of the coming War. But in practice, an obsession only becomes magnificent if it prevails against all odds. Otherwise, it’s just an obsession – clinging to an idea well beyond the time when the evidence has clearly negated any  chance of success.

Which logically brings us to the story of the modern antidepressants [SSRIs, Bupropion, and SNRIs]. Eli Lilly’s Prozac came on the scene in 1987, around the time I was beginning a private practice. We all remember the excitement of the time. The tricyclic antidepressants had been around for a long time and most of us thought of them as treatment for the severe depressions. Although the DSM-III had thrown those syndromes into the wastebasket of Major Depressive Disorder, we still remembered their names [Melancholia, Involutional Depression, Post-partum Depression, etc.] and still used the terms [because the patients were still there in spite of their un-naming]. But the tricyclics were, at best, only maybe drugs in the more common depressed patients we saw. Prozac changed all of that, followed by an army of me-too antidepressants. In short order, all Depressions were Major Depressive Disorders, and the treatment for Major Depressive Disorder became the antidepressant du jour. In a more subtle way, depression itself became biology, neuroscience, chemical imbalance. Prior to that, the consensus had been that many of the severe depressive syndromes were biologic, but that moniker was extended to all depression after the coming of Prozac and friend.

As cracks began to appear in House SSRI, there was a concerted effort to un-see them [matching the persistent un-naming of the classic depressive syndromes]. Decreased libido, erectile dysfunction, anorgasmia, akisthisia, suicidal thinking, withdrawal syndromes – one by one, they were resisted vigorously as they appeared by both the pharmaceutical industry and their psychiatric Key Opinion Leaders – a story you know all too well. But then the foundation began to crack as well when the efficacy itself came into question. It came slowly. "They don’t work as well as we’d like" became "they don’t work very well" on the way to "Do they even work at all?" To the clinical neuroscientists who had put all of their eggs in that basket, that was an intolerable progression. Thus was born the magnificent obsession that these hallowed medications just had to work – maybe they were just being given in the wrong way; maybe they needed to be augmented, sequenced, or combined; maybe there’s a biosignature that will predict who will respond.

RATIONALE FOR THE GOAL OF FULL REMISSION
Evidence for the efficacy of antidepressant medications and brief, time-limited formal psychotherapies, although robust, is largely based on a significant reduction [rather than complete remission] of depressive symptomatology. Most randomized, controlled efficacy trials [RCTs] do not document full symptomatic remission and restoration of psychosocial and occupational functioning to premorbid levels in their evaluations of comparative efficacy. However, evidence from efficacy studies suggests that patients who fare best during continuation phase treatment are those who have attained the most complete symptomatic remission at the end of the acute phase. Thus, clinically, acute phase treatment is most successful if a full symptomatic remission, rather than just a response, results at the conclusion of the acute phase…

Clinician-rated symptom measures, while time-consuming, provide a firm basis for making strategic [e.g., switching or augmenting treatment] or tactical [e.g., dose adjustments, starting side effect treatments, etc.] decisions. Thus, the routine use of clinical rating scales seems justified.

The measurement of symptomatic outcome will also help clinicians inform managed care and other administrators as to whether or not ongoing continuation treatment is indicated. In addition, our own experience, having measured outcome in clinical practice for over 20 years, strongly suggests that patients are highly receptive to this brief assessment. They seem to be reassured that the clinician is attending to the symptomatology that caused them to seek treatment…

So in the 16 years since publishing the Treatment of Depression to Remission, Rush and Trivedi masterminded four major implementations of their concept of measurement-based care using sequencing algorithms or combination therapy aiming for remission [TMAP, STAR*D, IMPACTS, CO-MED]. All four studies were government financed [expensive undertakings]. One was part of a huge pharmaceutical fraud. All four were failed studies. Rarely mentioned is the fact that the algorithms themselves were all arbitrary sequences created by the authors based on… I don’t know what they were based on. One might have thought that they had amassed enough evidence to conclude that measurement-based, evidence-based,, remission-bound, algorithmic treatment wasn’t working out so well after all. And these studies spanned a period when there was a growing consensus that the antidepressants were much less efficacious and more toxic than advertised – by anyone’s measure.

Report by the ACNP Task Force on response and remission in major depressive disorder.
^{by Rush AJ, Kraemer HC, Sackeim HA, Fava M, Trivedi MH, Frank E, Ninan PT, Thase ME, Gelenberg AJ, Kupfer DJ, Regier DA, Rosenbaum JF, Ray O, and Schatzberg AF; ACNP Task Force.}
Neuropsychopharmacology. 2006 Sep;31(9):1841-53.
[full text on-line]

^{This report summarizes recommendations from the ACNP Task Force on the conceptualization of remission and its implications for defining recovery, relapse, recurrence, and response for clinical investigators and practicing clinicians. Given the strong implications of remission for better function and a better prognosis, remission is a valid, clinically relevant end point for both practitioners and investigators. Not all depressed patients, however, will reach remission. Response is a less desirable primary outcome in trials because it depends highly on the initial (often single) baseline measure of symptom severity. It is recommended that remission be ascribed after 3 consecutive weeks during which minimal symptom status (absence of both sadness and reduced interest/pleasure along with the presence of fewer than three of the remaining seven DSM-IV-TR diagnostic criterion symptoms) is maintained. Once achieved, remission can only be lost if followed by a relapse. Recovery is ascribed after at least 4 months following the onset of remission, during which a relapse has not occurred. Recovery, once achieved, can only be lost if followed by a recurrence. Day-to-day functioning and quality of life are important secondary end points, but they were not included in the proposed definitions of response, remission, recovery, relapse, or recurrence. These recommendations suggest that symptom ratings that measure all nine criterion symptom domains to define a major depressive episode are preferred as they provide a more certain ascertainment of remission. These recommendations were based largely on logic, the need for internal consistency, and clinical experience owing to the lack of empirical evidence to test these concepts. Research to evaluate these recommendations empirically is needed.}

If these recommendations were adopted for daily practice, clinicians would need to:
1. specifically and repeatedly measure core criterion depressive symptom severity to guide the implementation and timely modification of treatment,
2. conduct sufficient visits or measurements to establish that 3 consecutive weeks of minimal to no symptoms [ie, remission] has or has not been achieved,
3. systematically inquire about the magnitude and types of side effects and overall side-effect burden, so as to accurately gauge whether the dose or type of treatment needs modification in order to achieve remission in a time-efficient fashion, and
4. follow the trajectory of symptom change [or lack of change] such that treatments [dose, type] can be modified in a timely fashion, hopefully informed by empirically defined triage points.
The use of a depressive symptom measure to assess the nine criterion symptom domains that define an MDE by DSM-IV-TR would become routine.

Measurement-based care for unipolar depression
^{by Morris DW and, Trivedi MH}
Current Psychiatry Report. 2011 13(6):446-58.

^{This article outlines the role of measurement-based care in the management of antidepressant treatment for patients with unipolar depression. Using measurement-based care, clinicians and researchers have the opportunity to optimize individual treatment and obtain maximum antidepressant treatment response. Measurement-based care breaks down to several simple components: antidepressant dosage, depressive symptom severity, medication tolerability, adherence to treatment, and safety. Quick and easy-to-use, empirically validated assessments are available to monitor these areas of treatment. Utilizing measurement-based care has several steps-screening and antidepressant selection based upon treatment history, followed by assessment-based medication management and ongoing care. Electronic measurement-based care systems have been developed and implemented, further reducing the burden on patients and clinicians. As more treatment providers adopt electronic health care management systems, compatible measurement-based care antidepressant treatment delivery and monitoring systems may become increasingly utilized.}

Performance improvement CME: algorithms and EMRs in depression
^{by Shelton RC and Trivedi MH}
Journal of Clinical Psychiatry. 2011 72(9):e29.

^{Major depressive disorder is difficult to treat due to its chronic and recurrent nature and the poor performance of most pharmacologic treatment options. To improve patient outcomes, clinicians should become familiar with moderators of antidepressant response, implement measurement-based care, and follow treatment algorithms. The use of electronic medical records and computerized decision support systems may improve documentation and facilitate clinicians’ adherence to current standards of care. This Performance Improvement activity focuses on improving treatment outcomes for antidepressant therapy through familiarity with moderators of antidepressant response and the use of treatment algorithms, measurement-based care, and electronic medical records.}

Trivedi’s NIMH study [EMBARC]:
^{This study began as a comparison among Citalopram, Bupropion, and Cognitive Behavior Therapy [RePORTER], but by the time it was registered as a Clinical Trial [July 25, 2011], it had become a comparison among Citalopram, Bupropion, and Placebo. [clinicaltrials.gov]. It has the SMART design motif [sequential multiple-assignment randomized trial], meaning that non-responders are then switched to the other treatment. So it’s another drug sequencing scheme. It now has a name and a website [EMBARC – Establishing Moderators/Mediators for a Biosignature of Antidepressant Response in Clinical Care]. They plan to "…assess a comprehensive array of carefully selected clinical (i.e. anxious depression, early life trauma, & gender) and biological (i.e. genetic, neuroimaging, serum, epigenetic & qEEG) moderators and mediators of outcome. Using innovative statistical approaches the identified moderators and mediators will then be used to develop a differential depression treatment response index (DTRI)… The DTRI will help clinicians match treatments to patients with MDD, resulting in timely selection of treatments best suited for individual patients."}

Overview of the Use of Dimensions in DSM-5
^{Dimensional assessments are being proposed for inclusion with existing categorical diagnoses in DSM-5 to provide a basis for measurement-based care. The principal goal is to provide additional information that assists the clinician in assessment, treatment planning, and treatment monitoring. Some dimensional assessments may be useful before a formal diagnostic evaluation is conducted, such as assessing for depression in primary care, identifying features like suicidal ideation, or rating personality traits; some may be useful for refining the diagnosis; others may be specific measures useful once a diagnosis is established, such as severity ratings of the condition that could be used to establish a baseline measure of severity and then track its change over time. A full range of dimensional assessments is being considered for recommendation to clinicians and other users of DSM-5, and the technology may extend from paper-based self-report questionnaires through computerized adaptive testing. These various assessments and instruments may have value in many settings, including primary care and specialized care clinics. Many of these dimensional assessments will be specific for a given disorder, but an effort to assess factors that may be relevant in any patient’s treatment is also being undertaken.}

I’ll leave you on your own to read further about what they have in mind. But it’s the same thing I’ve been trying to talk about in this whole post – the magnificent obsession with the idea that if the entire process of treatment is under tight control with algorithms and measurements, outcome will be improved. It sounds to me more like a plan to make mental health care something that anyone can do using a computer and patient rating scales. It’s an extrapolation of the notion of Managed Care carried to an extreme. And perhaps that’s exactly what it is, explaining why the idea persists even though its track record in every one of the alphabet studies where it has been implemented is abysmal. In the study most like what they’re proposing here, IMPACTS, they couldn’t even get their doctors to do it, much less look at the outcome. And yet they persist. Surely there’s a reason that this idea won’t die.

1. Depressed people are easily diagnosed from the DSM-x symptom list.
2. The treatment is antidepressant medications picked by an algorithm.
3. The progress can be followed using a questionnaire.
4. Based on the results, medications are adjusted using the algorithm.

The magnificent obsession with measurement-based, evidence-based, algorithmic treatment is good for the insurance carriers. We know it’s good for the pharmaceutical industry in that every depressed person is automatically a customer. Is it good for psychiatrists? Hardly. It aims for psychiatrists to become obsolete except as algorithm expeditors. But the point is really "Is it good for patients?" Not according to the studies of Drs. Rush and Trivedi. Not according to the Clinical Trials that pepper our literature. In spite of the injunction to treat to remission, the patients drop out like flies or report only minor improvements on their collective questionnaires at the very best. And  even looking at the placebo responses in clinical trials, the non-drop-outs improve too. So it’s not going to come out like the book or the movie – the Magnificent Obsession. It’s going to come out like it has for  Drs. Rush and Trivedi repeatedly – a failed clinical trial – perpetuating the overvaluing and over-prescription of medication to the detriment of sick people. And it’s going to burden practitioners with more hassle and external control, until the only psychiatrists left standing are the KOLs who are out hustling primary care physicians to take it over.

More to the point, why is the DSM-5 Task Force incorporating this injunction to practice measurement-based, evidence-based, algorithmic care into our diagnostic system of all places? It’s certainly not based on results. Who told the APA that it was their job to shape the future practice of psychiatry using a diagnostic classification revision? Or to move the treatment of depression into primary care? Since when was a diagnostic manual a vehicle for introducing a system that benefits the insurance and pharmaceutical industries but neither the psychiatrists nor patients? And what does such a system do for the psychologists, the social workers, and the counselors whose treatment has nothing to do with these simplistic medication/questionnaire/algorithm fantasies of non-practicing psychiatrists, having used our manual thinking it was an authoritative compendium of mental illnesses?