No Free Lunch

April 2, 2021
John J. Miller, MD

Psychiatric Times, Vol 38, Issue 4, Volume 04,

The more tools we have in our treatment toolbox, the greater the likelihood that we will ultimately find a treatment (or combination of treatments) to improve a given patient’s functioning and quality of life.

FROM THE EDITOR

The phrase “no free lunch” has its root in the mid-1800s United States. Beginning in that time period, bars and saloons offered free food at their establishments as long as you bought a drink. The merchants knew that their generous investment in free food for their customers would pay for itself many times over with the profits made from the beverages. Simply put, nothing is for nothing.

In the practice of medicine, we are all too familiar with this simple concept: No matter what benefit our treatment plan provides for our patients, there is always a cost. Our ethical responsibility is to provide informed consent to our patients about the potential benefits, side effects, adverse effects, and rare serious risks from any agreed-upon treatment plan. Ideally, our menu of possible treatments should be comprehensive and should include many elements that go beyond the scope of our expertise, including the option of no treatment.

A Case Study of Depression

Let’s look at a common psychiatric disorder—a major depressive episode—and review the treatment complexities that are involved. Our first task is to complete a comprehensive psychiatric evaluation, collecting a treasure trove of information that often directs our recommended treatment options. We must consider the many possible etiologies that, on the surface, look like a straightforward major depressive episode, such as: various medical conditions, newly started medication or over-the-counter remedy, substance-use disorder, drug withdrawal, bereavement, an adjustment disorder, or depression secondary to another primary psychiatric disorder (such as obsessive-compulsive disorder or an anxiety or sleep disorder).

Once we have established that our patient indeed is having a primary major depressive episode, the next task is to differentiate if it is secondary to unipolar depression or bipolar depression, as the treatment recommendations will be very different for each.

Let us review a partial list of the possible treatment interventions (Table).1 Evidence exists to support each of the listed interventions, and our patient may have a strong preference that may not include treatment with us. For many patients, a combination of several of these treatment modalities can be initiated concurrently. Over time, especially if the depression is treatment resistant, additional treatments may be explored until 1 or more of the following occurs for our patient: They reach the ideal goal of full remission from their depressive symptoms; improve from the simple passage of time; have a major change in life circumstances that helps propel them out of their depression; fire us (and hopefully see another clinician); or accept the persisting residual symptoms; or dies.

So, what about no free lunch? Each of the listed treatment interventions, including the patient’s option of no treatment, is accompanied by a plethora of potential benefits side effects (also known as adverse events), and, in some cases, the possibility of serious and even life-threatening risks. With no crystal ball, our responsibility is to inform our patient of all these possibilities and ensure that they are competent and understand this discussion. Then, we agree upon a plan with appropriate monitoring. Over my 30 years of clinical practice, my patients have taught me about many unusual side effects that I never could have predicted. Additionally, it is not uncommon that I am surprised by the treatment choice that a patient makes. My clinical philosophy has evolved to include the recognition that the more tools we have in our treatment toolbox, the greater the likelihood that we will ultimately find a treatment (or combination of treatments) to improve a given patient’s functioning and quality of life.

In this issue, we present 2 important series of articles related to psychiatry’s toolbox: a debate over the use and effectiveness of electroconvulsive therapy (ECT), and an exploration of psychiatric medications’ possible side effects. In the spirit of these articles, I would like to share a few of my memorable patient responses to treatment.

ECT for Psychotic Depression

I was in private practice 25 years ago when I was asked to evaluate a man, aged 72 years, who was brought to me by his family for an emergency evaluation. He had a history of recurrent severe major depressive episodes, often complicated by mood-congruent psychotic delusions. Because this man presented virtually mute to my office, his family provided his history and current symptoms.

According to the family, he had suffered 5 previous severe depressive episodes over the prior 20 years and had not responded to aggressive trials of pharmacotherapy. There were no identifiable psychosocial stressors; when he was not depressed, he lived independently and was high functioning. His depressive episodes began unpredictably and rapidly progressed to severe depression accompanied by hopelessness, worthlessness, helplessness, amotivation, and poor functioning. He ultimately would stop eating, make no eye contact, and sit at home “like a log.” In addition, he developed delusions that he was full of sewage and rotting from the inside out. He believed he would die, but he was not suicidal.

This was a psychiatric emergency, as he had stopped eating and drinking and was virtually mute with delusions compromising his competence. I arranged for admission to our local community hospital’s inpatient psychiatric unit, and my colleague, who had treated the patient for similar presentations with ECT in the past, began ECT the following morning.

There was a dramatic change after the patient’s first ECT treatment: He wanted a meal, and his delusions virtually vanished. After 3 ECT treatments in the hospital, he significantly improved and continued his course of ECT as an outpatient.

I eventually learned that this was his usual presentation. He never responded to a litany of medications, but he did respond rapidly to ECT treatments. His long-term treatment consisted of 1 ECT treatment a month. However, he tested the fates every once in a while and chose to stop his ECT treatments, which was always followed by a severe delusional depressive relapse.

Dr Miller, You Are Fired

Several years after completing my residency training, I was working in a private group practice when I completed a seemingly straightforward psychiatric evaluation on a woman in her late 40s. She presented with a moderate episode of depression, with significant insomnia and anxiety. I discussed treatment options with her; she was already in psychotherapy with a therapist in our practice. We agreed on a trial of nefazodone, hoping to take advantage of its sedating properties to help her sleep, as well as decrease her anxiety.

Three days later she came in to see me for an emergency appointment. I quickly found myself being criticized and cursed by this woman. She reported that since starting the nefazodone, both her anxiety and insomnia had worsened. She fired me and transferred to another psychiatrist in our practice who put her on a different antidepressant. She responded nicely with full resolution of her depression and associated symptoms.

I was befuddled. At the time, my understanding and experience with nefazodone was that it was a reasonable antidepressant that helped insomnia and lowered anxiety.2 Nefazodone also had the advantages of relative weight neutrality and minimal sexual dysfunction. As psychiatry’s collective experience with nefazodone grew, however, we learned that a tiny minority of patients hypermetabolize nefazodone to a molecule called metachlorophenylpiperazine (mCPP), usually a minor metabolite. In this small subgroup of patients, mCPP causes anxiety, panic attacks, central nervous system stimulation, and dysphoria. I learned important psychopharmacology from my experience with that patient; with subsequent patients, I always discussed the rare but possible risk of unpleasant side effects from nefazodone.

From a Lamb to a Lion

During my second year of residency in psychiatry at the University of Massachusetts Medical Center, I worked on the locked inpatient unit. I admitted a man in his early 60s who reported a lifelong history of recurrent unipolar major depressive episodes. When depressed, he could not function in his job, withdrew from his social relationships, became hypersomnic, was paralyzed by anxiety, and felt full of guilt and negative self-judgment. He reported that historically heresponded best to imipramine, which he usually continued for about 6 months after the depressive episodes resolved, and then discontinued it. At the time of this admission, he had been off all psychiatric medications for more than 2 years. So, I started him on imipramine.

On the morning of his third hospital day, as I walked onto the locked unit, this patient ran toward me with exuberance, praising me for turning him “from a lamb into a lion.” The staff told me he had been up all night calling old friends and business customers. Having never been hypomanic or manic in the past, he was excited and delighted over his perceived newfound exceptional functioning.

However, as is common in mildly manic patients, he remained fully competent to decide his fate. Despite a lengthy team meeting with him, in which we explained in great detail that the imipramine had flipped him into a manic state and shared the risks and unpredictability that accompanied mania, he insisted on discharge. We had to allow him to leave against medical advice.

I can still see him walking toward me that morning with such excitement and appreciation, all the while feeling dread about having prescribed the medication that transformed this man from having a major depressive episode with poor functioning into an individual with hypomania who had no insight into the impulsivity and regretful adventures that would likely come his way.

Conclusions

All experienced clinicians have had similar encounters to these. The blessing of the field of medicine is that we have numerous treatment options to draw upon, established by a solid evidence base and the accumulation of our aggregate clinical experience. The curse is that each patient is unique in ways that we cannot predict, and we have no control over how a particular patient will respond to treatments. Just as our patients have no free lunch when beginning our prescribed treatment, we have no free lunch when recommending what that treatment should be.

Dr Miller is medical director, Brain Health, Exeter, New Hampshire; Editor in Chief, Psychiatric TimesTM; staff psychiatrist, Seacoast Mental Health Center, Exeter; Consulting Psychiatrist, Exeter Hospital, Exeter; Consulting Psychiatrist, Insight Meditation Society, Barre, Massachusetts.

References

1. Miller JJ. Antidepressants, part 1: 100 years and counting. Psychiatric Times. 2017;34(10):23-26.

2. Davis R, Whittington R, Bryson HM. Nefazodone. a review of its pharmacology and clinical efficacy in the management of major depression. Drugs. 1997;53(4):608-636. ❒

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