A Two-Column Approach to Depression and Anxiety Treatment

Steven P. Levine, MD, recommends selecting a biologic intervention from column A and a psychotherapy agent from column B to effectively treat depression and anxiety.

There are many options for the treatment of major depression and the spectrum of anxiety disorders, which get lumped together due to their common co-occurrences and therapeutics. While biological interventions include prescriptions medications, nutritional supplements, brain stimulation technologies, and exercise, there are also hundreds of actively practiced styles of psychotherapy — some with greater mainstream acceptance than others.

Study after study confirms that a combination of medication and psychotherapy is more effective than either treatment alone. The agents most frequently chosen for these studies are selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT). Is there something uniquely effective about either of them? Not necessarily, but SSRIs are the most popular first-line choices for anti-depressant/anti-anxiety medications, and the structure of CBT is widely practiced and lends itself to clinical study. But I’ll come back to this.

When we talk about the brain, we inevitably oversimplify because we’re limited by our current knowledge and our need to masticate something so dense and complex into a palatable form. In that spirit, the hippocampus is a putative center of memory and learning, a major component of the emotion regulation system, and the only site of lifelong neurogenesis, which involves the production of new neurons. That all of these significant functions take place within the same structure may not be by accident.

Human memory is similar to computer memory, which makes sense given that we’re the architects of computer memory, and we tend to create things in our own image. Computer memory storage has a finite capacity, and when it’s filled, old memories must be deleted to make space for new ones. The parallel in humans is most dramatically exemplified by the phenomenon of infantile amnesia. By the time we are 4 or 5 years old, we have lost most of our memories from when we were 1, 2, and 3 years old. This coincides with a time of significant neurogenesis — which, in this case, may include the process of clearing sufficient space for the tremendous volume of learning at this point in life.

However, we don’t lose all of those memories — which include stored knowledge, feelings, thoughts, skills, etc. — and similar to a computer’s memory storage, they are never completely erased, since there are traces left behind that can be mined by those who are skilled at doing so. We retain a relatively select few, likely as a result of some special significance or stories told by family members and other people. In this way, “copies” are created, and depending upon the volume and frequency of those copies, they may be more or less likely to be retained over time either consciously or unconsciously. Some may be so frequently repeated that they become overlearned, overrepresented, and highly resistant to escaping one’s memory.

This may partially explain the difficulty in treating depression and anxiety — states in which depressive ruminations and anxious obsessions result in copy after copy after copy of destructive thoughts, memories, and feelings. One of the most notoriously treatment-refractory subtypes of anxiety is obsessive-compulsive disorder (OCD), a condition in which the process of making copies of obsessive thoughts occupies a significant portion of daily life. Left unchecked, the competition doesn’t stand a chance.

Having a good memory is generally considered a laudable quality. Considering the aforementioned, perhaps it’s just as important to be a “good forgetter”. Of course, this doesn’t mean the deletion of one’s memory; instead, it consists of allowing for a diminished representation of negative, harmful memories over time by altering or re-framing and re-copying them in a more useful way, or by filling up the memory storage space with some other new material. This process is a common thread that runs through many of the aforementioned 100 different psychotherapy styles.

The natural process of neurogenesis is a slow one, which is where biologic interventions that we’ll call “column A” choices come in. Although an older hypothesis of depression/anxiety focuses on the monoamine system — or serotonin, norepinephrine, and dopamine — as the agent of change, it’s now believed that even medications affecting this system as a first step ultimately promote plasticity, which is the capacity to repair, grow, and form new connections. With the help of the agents of column A, we can positively influence the rate of neurogenesis and synaptogenesis — defined as the creation of new connections and the repair of damaged connections within the brain — consequently creating a “primed” state, or a classroom of apt pupils (our new cells and connections) waiting to be taught by the agents of psychotherapy, which we’ll call “column B”.

At this time, our selection from column A is similar to the process of throwing a dart in that there are many medicines and procedures that help some people, but we don’t specifically know ahead of time who will respond better to which treatment. However, this situation will likely improve in the near future with additional discoveries of biomarkers and pharmacogenomics.

Column B selections can be more precisely targeted, but in the sense of personalization, since a particular agent isn’t necessarily more effective in all patients. What’s most important is having a detailed model of the mind and applying a consistent method for producing “better” copies. The necessary elements may include a therapist’s skill in guiding the process and the treatment’s “fit” with the patient’s personality and learning style. In fact, it doesn’t have to be therapy at all, as column B could include learning something new, like an instrument, a language, or anything apart from making the same old copies.

Thus, we have an explanation for why the combination of SSRI and CBT — or the introduction of a fertile environment sown with new learning and thought patterns — is more effective than either therapy alone, as well as an answer to why the benefits of strategies that focus solely on promoting neurogenesis and synaptogenesis don’t tend to last after cessation of treatment. So, whenever you’re ordering from the psychiatric menu, please select one agent from column A and another from column B.

Steven P. Levine, MD, is is a board-certified psychiatrist and therapist. He received his psychiatry training at New York Presbyterian Hospital and Memorial Sloan Kettering Cancer Center and currently practices in Princeton, NJ.