Biology and Psychology

As many of you know, I’ve been busy interviewing for medical residency programs in psychiatry. It’s been wonderful. I love meeting students, residents, and faculty who are passionate about mental health. And the interviews have actually been really fun! I haven’t had anyone really grill me or try to be intentionally difficult. I’ve found that the questions I’ve been asked stretch my intellect and help me to understand my chosen profession better.

One question that keeps coming up is whether I’m looking for a program that is more biological or psychological. I’m not a huge fan of this dichotomy. My understanding of neuroscience is that everything that happens to the brain has a root in biology*, just as everything that happens to a computer is the result of the flow of electrons through physical components. So whether you treat the brain with so-called “biological” or “psychological” interventions, you are absolutely working through biological processes. I like to say that psychotherapy uses the brain’s public API**, while psychopharmacology accesses a lower-level, private API. It’s not a perfect analogy, but I think it’s a nice start.

Beyond the philosophical point that the brain is an inherently biological organ, the fact is that both drugs and therapy have a profound impact on the biology of the brain. Some mental illnesses are treated equally well with medications or psychotherapy (and in many cases, people do better when they receive both). Studies are even beginning to show that either form of intervention can alter the gross structure of the brain. And why shouldn’t they? We don’t have a model for the way that the brain processes and records information that isn’t physical.

I’m a pragmatist. I will use whatever technique I need to to help my patients get better. Ideology matters much less to me than proven effectiveness.

* There is always the possibility that we can’t explain everything about the brain with biological principles. Many people (including me) believe that there is a spirit, soul, energy, or force that at least partially defines who we are. However, that doesn’t mean that we should toss away what we know about the physical world. I once had a brilliant and deeply religious neuroscience professor explain it by saying “I don’t know if the brain is everything, but it seems to be almost everything.” Take that for what it’s worth.

** API means application programming interface. It’s a term that software developers use to describe how one program interacts with another.

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An Ideal Treatment For Depression

Depression is treatable. But that doesn’t mean that treatment is simple, or that many of the current treatments are incredibly effective. In fact, a huge proportion of people do not respond to the first treatment they receive.

While we develop better treatments for depression, I want to propose an ideal approach based upon the best science we currently have. I have not seen any studies that have tested this holistic approach. However, I do know many physicians and therapists who draw upon many of the principles outlined below. Incorporating every aspect of this treatment would be nearly impossible. I’m open to suggestions on how to package this treatment for maximum benefit.

Are you ready? These are the components that I would include in an ideal treatment for depression:

An appropriate workup
On paper, the criteria for diagnosing major depressive disorder are straightforward. A person must meet 5 of 9 criteria, and the presentation can’t be better explained by another disorder. Counting up the criteria is easy, and there is a simple mnemonic that medical students learn to rattle off in their sleep. However, ruling out other causes of depression is much more difficult. Sometimes depression has a physical cause that can be determined with laboratory tests. For example, low thyroid hormone often presents with symptoms of depression. But there are other mimics of major depressive disorder than can only be distinguished through subtle questioning. In some cases, ruling out other diagnoses cannot be done in a single visit. For example, bipolar disorder often begins with depressive episodes, and it is not uncommon for it to take many years before the correct diagnosis is established. Each of the different mimics of depression requires a different treatment approach, and in some cases, the wrong treatment can have catastrophic results. Diagnosis by a competent professional is absolutely critical.

Close follow-up
People with depression should receive close follow-up–especially in the first few weeks of treatment. Frequent return visits allow for quick treatment adjustments, and also allow clinicians to ensure that thoughts of suicide can be kept in check. On occasion, some people respond to certain treatments by becoming more depression, agitated, or suicidal, and it is critical that changes are made quickly.

Evidence-based treatments
An evidence-based treatment is one that has been repeatedly shown to work in well-designed human studies. This doesn’t mean that the treatment makes a huge difference for everyone who uses it. However, evidence-based treatments should form the foundation for an ideal treatment of depression.

Antidepressant medications provide a small but beneficial impact on depression. Even though they work through different mechanisms, they all tend to provide a similar benefit, and so the choice of which antidepressant to use is largely based on side effects and comorbid conditions. If the first one doesn’t work, a second one is usually tried. These drugs are not perfect, but in most cases, the benefits strongly outweigh the risks.

Psychotherapy has also been shown to be effective for the treatment of depression. There are many different forms of psychotherapy, and each has it’s proponents and detractors. For depression, cognitive-behavioral therapy seems to be the most well-studied treatment. The effect tends to be modest with initial treatment, but the odds of success increase if the patient connects well with the therapist. For this reason, I make sure that my patients keep trying until they find someone they work well with. Notably, the combination of psychotherapy and antidepressants is much more effective than either treatment alone.

Electroconvulsive therapy is a treatment where a seizure is induced through electrical current. The patient is under general anesthesia and does not experience any pain. Electroconvulsive therapy is far and away the most effective treatment for major depressive disorder. However, it does entail considerable risks, and so it is generally not recommended as first-line treatment of depression. The treatment carries an unfortunate stigma, but it is incredibly impactful. An ideal treatment plan for depression must include electroconvulsive therapy as an option for severe depression that does not improve after an adequate trial of therapy and medicine.

Theoretically effective treatments
There are many treatments that might be successful based upon theoretical or anecdotal evidence. In some cases, small studies may have shown some benefit. Unfortunately, a lot of these treatments don’t have a sponsor with the funding to prove or disprove their efficacy. However, those with minimal risk should absolutely be considered as adjuncts to the evidence-based therapies found above.

Healthy diet


Quality sleep

Weight loss

Obtaining and maintaining meaningful work

Spirituality and meditation

Practicing gratitude


Quality relationships

Nutritional supplements may also be effective. It’s really not fair to lump all nutritional supplements into one category. Most products that have been tested aren’t any better for you than a placebo. However, there are some supplements that show encouraging results in smaller studies. As with any other medication, talk to your doctor before taking a nutritional supplement.

Addressing socially mediated risks for depression
People who live in poverty, have a history of abuse, or suffer from chronic medical conditions are also at risk for depression. There is no easy answer to any of these problems, but it seems clear that finding effective methods to fight poverty, protect people from the horrors of abuse, and provide affordable, high-quality healthcare are critical elements for preventing and treating depression.

There must be a better way to treat depression. I’m grateful that we have antidepressants and psychotherapy, but I believe that there is so much more that can be done to help people overcome depression. I look forward to innovation that can help us produce and implement better treatments for depression!

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Depression is not a chemical imbalance

Depression is not a chemical imbalance–that’s what the best data on the subject suggests.

Now please don’t misunderstand me. I believe that major depressive disorder is inherently biological. I just remain unconvinced that brain chemistry alone tells us much about depression. At it’s best, the “chemical imbalance hypothesis of depression” is an outdated theory. More cynical observers might say that it’s an oversold marketing message.

The belief that depression is a chemical imbalance comes from a misunderstanding of the monoamine theory of depression. According to this theory, depression is caused by dysfunction in one of the monoamine neurotransmitter systems. These neurotransmitters–serotonin, norepinephrine, and dopamine–are certainly related to mood, but changing the absolute levels of these chemicals in the brain has not been consistently shown to affect mood. Correlation (as I’m sure you’ve heard) isn’t causation.

The most convincing argument against the chemical imbalance hypothesis comes from clinical research into antidepressants. The most commonly prescribed antidepressants are the selective serotonin reuptake inhibitors, also known as the SSRIs. Within hours of taking these drugs, the effective level of serotonin is increased at every serotonin-containing synapse in the brain. But unfortunately, patients who take SSRIs feel no better than patients taking placebo for at least 2 weeks (and realistically, it takes most people 4-6 weeks to really start feeling any effect at all). If depression was caused by a simple chemical imbalance, we’d expect a much more rapid response. And this long time to effect happens with all FDA approved antidepressants, regardless of their action on the serotonin, norepinephrine, or dopamine systems. (I’ve heard some well-meaning doctors tell their patients that the drugs take 4-6 weeks to reach a significant dose in the bloodstream. However, the vastly different half-lives of these drugs and the remarkable consistency in their time to effect argues strongly against this explanation.)

So what causes depression? Depression seems to be related to dysfunctional brain circuitry. A depressed person may very well have problems with one of the monoamine neurotransmitter systems, but it is the system that is impaired, not necessarily the chemical concentration. For recovery to occur, neurons in the brain must find a way to appropriately reconnect with each other.

Thankfully, the brain is remarkably resilient. While as many as 20-40% of the population will experience at least one episode of major depressive disorder, a surprising number recover without any treatment. This isn’t to say that treatment doesn’t work (it does) or that the risk of untreated depression is trivial (it isn’t). It’s just to point out that the brain has mechanisms in place to rebuild dysfunctional synapses. And if you really want to kickstart recover, every known treatment for depression has been shown to increase the levels of neuronal growth factors. The most well known of these factors is brain-derived neurotrophic factor (BDNF), and it is increased by antidepressants, talk therapies, electroconvulsive therapy, and even experimental treatments like ketamine. However, the diverse targets of these therapies may trigger growth in different regions in the brain, which could explain why certain people respond better to one treatment than another. In most cases, the best initial treatment is a combination of antidepressants and cognitive-behavioral therapy.

Why does it matter that we stop talking about depression as a chemical imbalance? For one, an accurate understanding of science matters. When you realize that depression is caused by impaired brain circuitry, it makes sense that depression arises from a combination of genetic, environmental, and psychological factors. On a more human level, calling depression a chemical imbalance trivializes the disorder. A chemical imbalance sounds like something that can be rapidly reversed. It makes us think that there is a magic pill that can quickly fix things. It’s the biological equivalent of the words “why can’t you just snap out of it.” Overcoming depression–especially severe depression–takes time and appropriate treatment. Finally, thinking of depression as a problem with circuitry helps us conceptualize depression as a complex set of disorders with unique causes, manifestations, and treatments. It gives us a reason to approach all sufferers as individuals that cannot be treated with a one-size-fits-all approach.

This model of depression isn’t perfect, and my explanation is, of course, a gross oversimplification. But when we recognize that depression is a circuit problem, it enables us to take some responsibility for rebuilding and maintaining the circuitry that brings us happiness. This is what cognitive-behavioral therapists have been telling us all along. By learning how to combat the thought and behavior patterns that worsen depression, you can help yourself rebuild the faulty circuits within your own head. Conquering depression often takes the help of competent professionals, but recovery without learning to help yourself is almost impossible.

Guidelines for alcohol use

In a recent post, I talked about the importance of behavioral change in preventing early death. This post is the fourth in a series looking at the evidence behind changing health-related behaviors. Previous posts in this series include:

9 surprising facts about weight loss.

Every doctors visit should include smoking cessation counseling.

Medications for smoking cessation

Although heavy drinking is associated with liver failure, brain damage, violence, risky sexual behavior, and motor vehicle accidents, most adults can consume moderate amounts of alcohol without adverse health effects. Some studies even suggest that appropriate levels of alcohol consumption may even be associated with small improvements in certain health outcomes. Of course, there is nothing wrong with being a teetotaler, and weighing the risks and benefits of any alcohol consumption is an important individual decision. If you do choose to drink alcohol, you should consider expert guidelines for appropriate consumption.

In the United States, Dietary Guidelines for Americans recommends no more than 7 standard drinks per week for women, or 14 drinks per week for men. It is also recommends that on any given occasion, women should consume no more than 3 drinks, and that men should consume no more than 4 drinks. There are certain people that should never drink–including pregnant women, children and adolescents, people who cannot limit their drinking, and individuals with certain health conditions (including severe liver disease and illnesses requiring treatment with medications that interact with alcohol). In the United States, one standard drink is considered to be 14 grams of alcohol–the approximate amount found in 12 ounces of beer, 5 ounces of wine, or a 1.5 ounce shot of 80 proof liquor.

Interestingly, drinking recommendations vary significantly around the world. Wikipedia has a really nice summary of recommendations from different countries. In the next few posts, I’ll be looking at some of the evidence behind interventions for people who abuse alcohol.

Why I’m Blogging

I hear a lot of good and bad things about blogging. Some people say it’s a waste of time–and I certainly see how it could be. I started blogging with a modest goal: to enhance my own learning. Writing makes me encapsulate what I learn into meaningful chunks. I can’t promise that what I’ve written will be helpful to anyone else, but it has been extremely useful to me. Now that I have a few posts under my belt, I’ve decided to lay out three main goals from this blog.

1. To learn how to write. My training has focused on technical writing–and I finally feel like I’m becoming comfortable with that style. I love how technical writing emphasizes clear communication of complex concepts. I can’t imagine a better format for writing as a professional. However, my skill at writing to a broader, non-technical audience is much weaker. I struggle to explain what I think with clarity. Hopefully, this blog will help me learn how to write in a crisp, authentic way.

2. To connect with others. There are so many smart people working on difficult problems within the behavioral health community, and I want to learn from them. I believe that there is immense innovation in the pipeline from patients, consumers, doctors, therapists, allied health professionals, academics, and entrepreneurs, and I want to be here as it unfolds. If you’re reading this, I’d love to get to know you better!

3. To advocate for better behavioral health. Behavioral health is misunderstood and often maligned–even within the broader healthcare community. There are many voices for good, and I want to add mine to the conversation. I don’t have many answers, but I am passionate about finding and implementing better solutions.

Medications for smoking cessation

In a recent post, I talked about the importance of behavioral change in preventing early death. This post is the third in a series looking at the evidence behind changing health-related behaviors. Previous posts in this series include:

9 surprising facts about weight loss.

Every doctors visit should include smoking cessation counseling.

As I discussed last week, even brief counseling interventions dramatically increase smoking cessation rates. This effect can be multiplied even further by providing appropriate medications.

There are essentially two main medication strategies for smoking cessation. The first is to replace nicotine from cigarettes with a nicotine-containing gum, lozenge, patch, inhaler or nasal spray. There are some subtle differences between each form, but they all appear to be similarly effective and they increase quit rates by 50-70%.

The second medication strategy for smoking cessation is to use medications such as buproprion, nortriptyline, or varenicline. Bupropion and nortriptyline are considered antidepressant medications, but their effect is probably not related to their antidepressant properties (in fact, other antidepressants have not been shown to be effective for smoking cessation). Both bupropion and nortriptyline produce similar quit rates to nicotine replacement therapies. Varenicline, however, is not an antidepressant. It is thought to work by weakly binding to nicotine receptors, thereby decreasing cravings for nicotine. This is a newer drug, but the early data suggests that varenicline may be the most effective medication yet for smoking cessation.

Every medication has risks and should be discussed with a doctor before starting, but these drugs have been helpful for many people who quit. It would be wonderful if these treatments were offered to more people!