The Present and Future of Treatment for Depression

Almost seven percent of the U.S. population, 16 million people, had at least one major depressive episode in the last year. Many more family members, friends, and coworkers are affected.

What’s best practice for treating depression? And what’s on the horizon?

For answers, in today's The Eminents interview, I turned to Dr. Thomas Insel, Director of the National Institutes of Mental Health (NIMH.) He is a member of the Institute of Medicine of the National Academy of Sciences and recipient of the Outstanding Service Award from the U.S. Public Health Service. I interviewed him today.

Marty Nemko: Let’s start with basics. How would you define depression?

Thomas Insel: Actually, “depression” can be a misleading term. It implies it’s sadness rather than a brain disease. Sadness, for example, when divorcing, can be healthy coping with the pain of existence. But when you have major depressive disorder, you can’t experience sadness. You’re paralyzed. People like Andrew Solomon in his book, The Noonday Demon, make that painfully clear.

MN: Some people get divorced, have deaths in the family, etc., but quickly rebound, while much smaller trauma spirals other people down into a deep pit. How clear are we that depression is primarily caused by physiology/genetics rather than by a person’s experiences?

TI: That’s a little like asking if a penny is really heads or tails. It’s both. The modern view of depression brings an understanding of environment, molecular genetics, and neuroscience together. We experience the world through changes in our brain and our brains work through molecules, cells, and circuits. Depression involves all of these.

MN: What can we now confidently state about the molecular basis of depression?

TI: We can say that it’s more complex than when we viewed depression as a chemical imbalance. Recent science recognizes severe depression as a disorder of specific brain circuits. But we haven’t yet mapped the relevant circuits at a molecular or cellular level. So we have much more to do.

MN: That’s what the Human Connectome Project is doing.

TI: Right. I think it will be transformative. It’s the neuroscience analogue to the Human Genome Project: It provides the reference maps of our brains instead of our genomes.

MN: Abnormality in the glutamatergic system is being seen by some as causal not only of depression but of bipolar, schizophrenia, and in cognitive functioning. What’s the latest on that?

TI: Genetics is giving us a new picture of the biology of mental disorders. Surprisingly, the usual suspects for risk like serotonin and dopamine receptors, transporters and synthetic enzymes are not showing up. But glutamate signaling and several post-synaptic proteins that none of us knew about keep showing up across a range of diagnostic categories.

MN: What's the state of the art for treatment of depression?

TI: Most people with mild-to-moderate depression are significantly improved with standard drugs like SSRIs (Prozac, Zoloft, Celexa, etc.) and/or structured cognitive-behavioral therapy (CBT) practiced well, which, alas, it often isn’t.

MN: Why is CBT often practiced poorly?

TI: Too few universities’ training programs rigorously train and test its students on it. Too often, students are still trained as they were in the 1960’s. We have effective psychotherapies but we lack any process for knowing who is providing these with fidelity.

MN: How should someone choose a CBT therapist?

TI: Too few therapists have ample numbers of reviews on Yelp or that might be a good place to start. But certainly, ask the therapist about their training in CBT, whether their program is indeed structured, and what is the typical outcome for patients like you. Also, get a sense of whether the two of you will likely be compatible.

Depression Essential Reads

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MN: What about for more disabling depression with severe agitation?

TI: Medication can be life-saving. No it’s not isn’t as useful as giving an antibiotic for infection but it’s helpful.

MN: What’s a clinical innovation you’re excited about?

TI: Web-based and mobile CBT. Many people don’t want to take time off work and pay the fees to see a therapist. Mobile addresses that.

MN: Can software really take the place of a human clinician?

TI: I asked that question of an expert in the area, Marsha Linehan, and she admonished me: “For many people under 30, their core relationship is with their device.” And recent research suggests that apps—at least for social phobia--may even be more effective than a live therapist—perhaps because they’re inexpensive and accessible 24/7.

MN: Is there a new drug you’re excited about?

TI: While not yet approved for general clinical use, ketamine shows that depression can be effectively treated in hours rather than weeks. Early reports suggest it may be valuable, not as a long-term cure, but, for example, in acute suicide prevention.

MN: Many patients have to try multiple medications to find one or a combination that works well enough. Do you have a sense of how long it will be before physicians will be able to use biomarkers to predict what medications, if any, will work for a particular individual?

TI: A recent imaging paper provided a fingerprint for who will do better with CBT and who will do better with medication. But these are still early days. The ultimate predictor may be a biosignature made up of many data points not a single image or blood test.

MN: Media portrayals of electro-convulsive therapy such as in One Flew Over the Cookoo’s Nest have created bias against it. What’s the reality?

TI: For severe depression with agitation, ECT is the treatment with the highest efficacy –80% show remission or significant improvement. ECT today is not like what you see in the movies –there is no evident seizure activity.

MN: Some people try herbal remedies for depression such as St. John’s wort. What’s the current evidence on the efficacy of so-called "alternative" treatments?

TI: I know of no evidence to support the use of alternative treatments for life-threatening depression but the standard treatments are still not 100% effective, so we need to keep an open mind to new possibilities.

MN: Is it realistic to hope that in the next decade or two, depression will be a largely preventable and/or easily manageable disease?

TI: Preventable? Unlikely. Treatable and manageable? Already, if well-treated, 80% of people can manage depression reasonably. For many people, the main problem is not lack of therapies but lack of competent therapists.

Marty Nemko’s bio is in Wikipedia.