Two developments in the world of psychiatry this year – the “debunking” of the serotonin theory of depression and Thomas Insel’s new book, Healing: Our Path From Mental Illness to Mental Health – struck me as addressing related issues. This got me thinking about how I came to practice psychiatry over forty-two years and what’s important in moving forward as a profession.
I’m sure many of you have seen or read about the recent study out of UK (Molecular Psychiatry, July 20th) debunking the serotonin theory of depression. In essence the study, a meta-analysis, showed no correlation between taking alleged serotonergic agents and actual serotonin levels. Quoting senior author Mark Horowitz, PhD, Batya Yasgur in Medscape wrote, “We found no consistent evidence…that there is an association between serotonin and depression, and we found no support for the hypothesis that lower serotonin activity or concentrations are responsible for depression. It is not an evidence-based statement to say that depression is caused by low serotonin. If we were more honest and transparent with patients, we should tell them that an antidepressant might have some use in numbing their symptoms, but it’s extremely unlikely that it will be the solution or cure for their problem.”
Having gone to medical school and completed my psychiatry residency in the mid-1970’s, I was well aware of the catecholamine hypothesis of depression in an era of tricyclic antidepressants and MAOI’s. At that time most clinical psychiatrists were practicing psychotherapy, as well as prescribing medication, using a bio-psycho-social approach to care. With the advent of reputed selective serotonin-reuptake inhibitors in the 1990’s (which conveniently paralleled the explosion of managed care and the need for quick cures), psychiatrists and primary care physicians had a simple and convenient “chemical imbalance” theory of depression and other mental disorders. A depressed or anxious patient could simply take Prozac or Zoloft, etc. and be cured of their ills in a few weeks. No matter that much of the data showed that such medications were barely superior to placebo. We and our patients had a plausible and simple explanation for their distress that was much easier to swallow (pun intended) than a complicated analysis of their current situation, their past histories, or worse, their fear that they were mentally or morally weak. The chemical imbalance explanation, never a true theory but only a hypothesis based on scanty and sometimes fanciful information, was heartily promoted by pharmaceutical advertising to the public and by drug reps to doctors. Their audience was often primary care physicians, who happen to be the docs who prescribe most of these drugs because of patient resistance to seeing a psychiatrist or inability to find one. How nice to have a simple solution in a pill! Psychiatrists, including myself, who may have been more skeptical of such solutions because of their training, were not immune to offering simple solutions to complex problems in order to give hope to a patient in distress, comply with managed-care expectations, or prove our worth as “medical model” specialists. In any event, more than 80% of the public today believes that low serotonin levels may be the cause of depression.
An article by Ruairi Mackenzie subsequently appeared in Technology Networks (July 22nd issue, reprinted in MDedge) entitled “A Popular Theory About Depression Wasn’t ‘Debunked’ by a New Review”. It was, in my opinion, a somewhat disingenuous defense of psychiatry by declaring, “Psychiatry gave up on the ‘chemical imbalance’ theory long ago” but it “forgot to tell the public.” The article quotes a number of academic psychiatrists, pharmacologists and researchers pooh-poohing the chemical imbalance theory as ancient history. That may be true, but the majority of psychiatrists are, like me, on the front lines treating patients and their families. We are subject to the aforementioned pressures, plus time pressures, to explain things with simplicity and certainty. While most of my colleagues and I believe that SSRI’s and other psychiatric medications have demonstrable therapeutic effects, it is more difficult and time consuming to have an honest dialogue around the facts that a) we don’t really know how the medication works, b) here are the expected benefits and the expected side-effects, and c) we still have to understand how and why your mind works the way it does and what you can do to help it work better.
Having previously read Ellen Barry’s review of Thomas Insel’s new book, Healing: Our Path From Mental Illness to Mental Health in the New York Times (February 22nd issue), I couldn’t help relating it to the serotonin brouhaha. In an article entitled, “The ‘Nation’s Psychiatrist’ Takes Stock, With Frustration” she explains Insel’s second thoughts on his work as director of NIMH for 13 years, prior to leaving in 2015. Though Insel calls the advances in neuroscience in the past 20 years “spectacular”, he admits that they haven’t yet benefited patients because of ineffective delivery of care, gutting of community mental health services, and reliance on police and jails for crisis services. Though the U.S. leads the world in spending on medical research, he says, we suffer dismal outcomes in people with mental illness.
Quoting Insel, Barry writes that during his tenure, NIMH “bet big on genomics” but that after 20 years the role genes play in major mental illness, such as schizophrenia and bipolar disorder, has turned out to be extraordinarily complex. Insel recounts a moment at a conference when, confronted by the parent of a schizophrenic son, he realized that all the talk about DNA and neurobiology amounted to nothing in comparison to the suffering and mortality of millions of patients who were not receiving services. Dr. Allen Frances, a critic of NIMH’s approach, has made the point that “thirty years of fascinating pieces of science… hasn’t helped a single patient.”
Dr. Joshua Gordon, current head of NIMH and an advocate of basic research, faults Insel for not acknowledging some of the “wonderful things” that have been done with neurobiological research. He cites as examples the use of ketamine for treatment-resistant depression and brexanolone for postpartum depression. Such examples, however, belie his point. Controversy still surrounds the usefulness of ketamine, especially under the current “Wild West” delivery systems that have popped up in unmonitored clinics. Brexanolone, which has to be given by infusion in a medical setting, costs $34,000 for a single dose, so it’s unlikely to get much use.
Jump to the July 22nd New York Times, where Ezra Klein (The Ezra Klein Show) interviewed Dr. Insel. It’s an interesting, wide-ranging discussion that includes a lot that is of special interest to adolescent and young adult psychiatrists, and it is worth reading (or listening to). The main points of the discussion are as follows:
§ While we are having a crisis of mental illness, with 1 in 5 people having a mental disorder, the prevalence of severe mental illness, defined by disability (e.g., bipolar disorder, schizophrenia, severe depression, PTSD), has remained about 1 in 20.
§ In people less than age 24, the numbers have been increasing, especially since the pandemic. Depression, anxiety disorders, eating disorders, and suicide are on the rise in this group, especially amongst LBGTQ youth.
§ The mental health crisis is not one of prevalence but one of care. Our ability to help people recover has gone down, not up. While we have very good treatments – medications, psychotherapies, rehabilitation – population data shows we are having more suicides, more disability and more people with mental illness incarcerated or homeless.
§ While the problem is medical, the solutions are social, relational, environmental, and political.
§ The promise of President Kennedy’s Mental Health Care Act of 1963 was never realized. Housing for patient’s discharged from state hospitals was never adequately available. CMHCs failed to live up to their mission of treating the sickest patients rather than on healthier ones using psychoanalytic psychotherapy. Funding for the program dried up in the 1980’s under Reagan and never came back, except for some reversal under the recently enacted gun legislation.
§ What we need now for seriously mentally ill people, in addition to medication and psychotherapy, are recovery services, also called ‘enhanced care management’, that engages people, builds trust, and helps them get to a ‘clubhouse’ where they can be around people, get job training, or get help returning to school.
In the interview Klein challenges Insel with the fact that more people are getting more treatment but death and disability continue to rise. Insel acknowledges this paradox but explains that while we have effective treatments – medications as well as psychotherapies – they’re effective only if they’re given in the right way, at the right dose, at the right time, to the right person. But, he adds, we’re not very good at doing that. Most people in practice, he says, have minimal training in the therapies that are most effective for various disorders. While Insel acknowledges that studies show the therapist is more important than the therapy, he believes it is both, not just one or the other.
In my view the chemical imbalance theory and Insel’s new book both describe a tendency in our profession to promise more than we can deliver, be it the benefits of medication along with certainty of how they work, or the promise of neurobiological research in curing mental illness. This is not to say that medication and research are not worthwhile. However if we fail to be clear about the complexity of the brain, the limits of our understanding, and that we don’t have simple solutions for complex neurobiological or societal problems, we do our patients and ourselves a disservice. Giving false hope may leave our patients disappointed, angry, and despairing. It may also leave the clinician feeling like a failure or a fraud.
So what’s a psychiatrist to do? In reflecting on my own career, I navigated our messy and complicated world by keeping in mind the following:
§ As a treatment team leader, clinical administrator, teacher, and practitioner I tried to model honesty and acceptance of controversy and uncertainty with my staff, students and patients.
§ I’d do my best to examine problems and issues from various angles, refraining from dogmatism or promoting false certainty in the service of comfort, convenience, or control. For example, I’d explain to staff that while a hospitalized teenager with impulsive aggression might have a bipolar disorder or a conduct disorder or complex PTSD, medication for bipolar disorder might help their symptoms. Nevertheless they would also need therapy and, possibly, change in a toxic environment.
§ In my office and outpatient clinic work with patients and families I’d be open and succinct about what I knew and what’s known in the field. When I’d make a conjecture about the cause of a problem, I’d add that I might be wrong. If a patient was looking for a “medication cure”, I’d be modest in my prediction that it would help unless it was clear to me that they could really benefit. In that case I would be much firmer in my recommendation. If I could provide the psychotherapy a patient needed, I’d offer my services. If not, I’d refer them.
With the above approach I felt I was being straightforward, honest, practical and doing good – or at least doing no harm. And I was also better able to sleep at night.
Dr. Bauman is a 1995 ABAP Emeritus Diplomate with a long and successful career in clinical and administrative psychiatry, presently serving on the ABAP Board of Directors.