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

Exercise

Quality sleep

Weight loss

Obtaining and maintaining meaningful work

Spirituality and meditation

Practicing gratitude

Mindfulness

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.

Conclusion
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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Anatomy of an Android app launch: The CBT Keeper experience

In June of 2013, I was finishing a medical research fellowship when I came up with the idea behind CBT Keeper. CBT Keeper was imagined as a simple Android app that would allow users to implement the basic principles of cognitive-behavioral therapy to help them fight back against depression and anxiety. Although I had almost no experience with programming, I decided that I would learn to design and build the app myself. I believed (and still believe) that the world needs more high-value, low-cost mental health resources, and learning how to build this app has been a great introduction into the business of software. I can’t predict exactly what my future projects will be, but I am enthusiastic about the potential that software products have to empower mental health consumers and professionals.

Now that CBT Keeper is on the market, I thought I’d share a few thoughts about the progress I’ve made. This post is more for me than for anyone else, but I thought it would be valuable to lay out some raw numbers. Data can be empowering or paralyzing, but I hope that this data gives me a baseline upon which I can build in the future.

Bare Metrics:

Estimated hours spent building the app: 400 (including learning how to code and all of the associated marketing so far)

Number of weeks available in beta: 23

Downloads in beta: 1595

Number of weeks since full-market release: 2

Total downloads (including beta): ~8100

Revenue from in-app purchases: ~$450 (30% of that goes to Google or Amazon)

In-app purchase conversion rate: 2.2%

Average revenue per in-app purchase: $2.54

Revenue from advertising: $70

Estimated Gross profit: $385

Approximate gross profit per download: $0.048 (many in-app purchases come later, so it’s likely a little bit higher).

Things that surprised me:

Being an amateur developer is incredibly fun. Once you realize that the only thing holding you back is the time to read and try things out, it’s amazing what you can build.

Marketing is much, much harder than making an app. This shouldn’t have surprised me, but publishing one app has given me a ton of ideas about how I will incorporate marketing elements into the next one from day one of development.

A single news source can do wonders for a free app. I pitched a ton of sites and only had one response, however, that single article drove almost 5000 downloads. I’ll be leaning heavily on this fact to drive future campaigns.

If you have a mission, people will be happy to pay for your app. My mission is to make CBT fun, easy to use, and available to everyone. I had always heard that conversion rates from free to paid are approximately 0.5-1.0% on Android, but CBT Keeper has consistently driven rates over 2%. Not only that, but the app has a “pay what you want feature,” allowing users to spend $1.99, $4.99, or $9.99 to remove ads and password protect the journal entries users make. It has been delightful to see how many people chip in more to help me fulfill my mission.

For developers only: Don’t even think about using android.app.Fragment. This seems to be implemented poorly by several Android OEMs and produces errors that everyone but me can reproduce. Instead, you MUST use  android.support.v4.app.Fragment. This error alone dropped the app from 4.8 to 3.5 stars at launch. We can work with a 3.5, but I’d much rather have the credibility of a higher ranking going forward.

Future directions:

1. Polish CBT Keeper on Android and incorporate some of the key feedback given by users. There’s a lot of feedback I will have to ignore, but many important points do keep bubbling to the surface again and again.

2. Expand marketing efforts with giveaways on major Android blogs. Paid acquisition on a per-user basis is completely unfeasible, but I want to see what kind of ROI we can drive with a more mass-market approach.

3. As more revenue comes in, hire a developer to build the app for iOS. I had thought about doing this on my own, but I’d rather focus my efforts on learning from users rather than learning a new framework. Plus, having the app on both major platforms will provide excellent opportunities to promote it on sites dedicated to mental health consumers and professionals.

4. Reinvest proceeds into more great mental health tools! I still have a little less than 5 years of training before I can really devote a substantial portion of my time to Euthymic Labs, but I want to keep learning and developing things that make an impact.

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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.