Depression: a future pharmacist's thoughts on treatment

Most people are comfortable now with saying depression is real and tangible, because it’s been proven to be “a chemical imbalance in the brain.” It makes sense to the general public and this is how it’s explained to patients to assure them their disease is not their fault. The truth is, we really don’t know what causes depression. Several theories exist, but they all have inconsistencies that can’t be accounted for. This explains why different classes of antidepressants seem to work for different people. Since all theories have their holes, I don’t side with one versus another. Instead, I ask, why is there a chemical imbalance?

We treat depression as a primary disorder, but we’ve got it all wrong. Depression is a symptom of dysfunction on a deeper level. Conventional medicine tends to look at a physiological system and treat with a “divide and conquer” strategy. We identify all the neurotransmitters, receptors, and pathways we can possibly find, and then manipulate them on a micro-scale and expect macro-results. Treatment of depression is the prime example of this.

The most commonly used class of antidepressants, SSRIs, increases the action of circulating serotonin in the brain. Serotonin is a chemical made by the body that is involved in regulating mood, sleep, appetite and almost everything else you could think of. The chemical imbalance that is often used to describe depression generally refers to a deficiency of serotonin. These drugs are the first choice for patients experiencing clinical depression. Response varies greatly among patients and they often have to try several before finding one that helps and/or doesn’t have intolerable side effects. Serotonergic drugs can cause constipation or diarrhea, abnormalities in heart rhythm, sedation, and the most common effect – a dramatic loss of sexual desire. It’s estimated that 60% of patients using serotonin-modulating drugs lose their interest in sex or ability to perform sexually. Some antidepressants have also been thought to increase the risk of suicidal thoughts in young patients. This is considered inconclusive and a very low risk by the FDA, but based on my experience in pharmacy more patients seem to find this problematic than what the literature suggests. Patients who have been through the ringer with psychiatric medications often report “numbing out” from medications or the hindrance of their ability to feel any emotions, even good ones. Mood swings and irritability can also be common with antidepressant use.

Side effects seem to be problematic, but the benefits outweigh the risks, right? Based on the popularity of these drugs, one would certainly assume so. But several reviews of trials suggest that the efficacy of these drugs may be attributed to the placebo-effect. The placebo effect is the phenomenon we see in drug trials in which patients given the control treatment (also known as a sugar pill) have significant improvements in symptoms even though there is no drug being given. A study by Irvin Kirsch et al. reviewed antidepressant drug trials that were both published and unpublished. Published data shows significant differences in effects of these drugs versus the placebo, but when unpublished data from pharmaceutical companies was included in Kirsch’s review, improvements in the placebo group were 82% of what was seen in those being treated with the actual drug. Drug companies must submit all trial data to the FDA when getting the drug approved, but they may only publish what supports the use of their drugs.

Dramatic placebo effects suggest that a large part of depression is psychological, which should be obvious! The rationale for these drugs in the first place has its inconsistencies. For example, drugs that decrease the amount of serotonin in the brain also show improvements in depression in 60% of patients. This is the opposite action of the most commonly used drugs for depression. If a deficiency of neurotransmitters was the main problem, these drugs would make depression worse, but that’s not the case. Additionally, only 25% of depressed patients actually have low levels of the neurotransmitters of interest. Some depressed patients even have abnormally high levels of these chemicals.

The real kicker about the serotonin theory is that 90% of our body’s serotonin is made in the gut. A partnership exists between bacteria and our own cells in the intestines and colon to produce most of the body’s serotonin. If you’ve heard of the fascinating new research area, the gut-brain-skin axis, this is where it stems from. The connection between these systems may explain why depression is commonly presented along with gastrointestinal disorders like IBS and colitis. Many modern foods disrupt the balances of bacteria in the gut; this aligns with the correlation between obesity and/or poor diet and depression. These foods include refined sugar, omega-6 containing foods (vegetable and seed oils), and trans fats.

Another link we seem to be missing is immune function and how that affects depression. Over 30 years ago, it was discovered that increasing the levels of cytokines in patients causes new-onset depression in over ¼ of patients. Cytokines are cells that signal immune-responsive inflammation as a result of insult or stress. Some cytokines including tumor necrosis factor, several types of interleukins, and interferons are increased in patients being treated for autoimmune diseases, and the rises correlate with depressive symptoms. This evidence has been shadowed by the prevailing chemical imbalance theory, nonetheless. Despite resistance toward the evidence, depression is often more common in patients with autoimmune diseases like rheumatoid arthritis, multiple sclerosis, and Parkinson’s disease which supports the connection between inflammatory processes and depression.

Fortunately, there are strategies we can use to adapt to the stressors that can spiral into depressive symptoms. I have personal experience with weaning off of the popular medication Prozac by adopting these strategies into my everyday life. Withdrawal from antidepressants can be dangerous. Always consult with your doctor before making changes to your treatment regimen.

  1. Support Your Gut: Increase your intake of fermented foods rich in healthy bacteria to support the microbes in your gut that produce serotonin. My favorite fermented foods include sauerkraut, kimchi, kombucha, raw cheese, and grass-fed full-fat yogurt. You may also opt for a daily probiotic recommended by your doctor or pharmacist. Feeding the bacteria is at least as important. Food for the bacteria is called prebiotic fiber which can be found in onions, leeks, garlic, green bananas, and asparagus. When rebuilding gut health some people may have symptoms of something called serotonin syndrome. The gut starts to produce serotonin at a normal, functioning level resulting in too much Serotonin syndrome may present as nausea, vomiting, fever, muscle spasms, or confusion. Serotonin syndrome is a medical emergency and should be evaluated immediately.

  2. Psychological Stress: Implement daily meditation, prayer, or relaxation practices. The American way of life is incredibly demanding and has normalized a state of extreme emotional stress. Extreme stress is NOT normal and can be mitigated with individualized management techniques. Cognitive behavioral therapy is also beneficial for most participants, and clinical guidelines even recommend it for every person who is prescribed antidepressants.

  3. Sunlight: Seasonal Affective Disorder is a well-known phenomenon in which people exhibit depression symptoms during winter months when less sunlight is available. Humans evolved outdoors and rely on sunlight to produce Vitamin D. You can read my post about Vitamin D here. Despite fear-mongering about sun exposure and skin cancer, 15-20 minutes daily of unprotected sun exposure is a healthy amount for most people.

  4. Exercise: Several studies have shown that exercise can be at least as effective as antidepressants. Exercise does not have to be intense to reap the mood-boosting benefits. A simple 30 minute walk outdoors can be sufficient. It would also help with Suggestion 3!

  5. Nutrition: Reducing your intake of inflammatory foods can decrease the response involving cytokines as discussed regarding immune reactions. Avoidance of refined sugar, vegetable oils, trans fats, and refined grains (or those that aren’t sprouted and properly-prepared) can decrease inflammation that may be contributing to some depression cases.

  6. Accept Sadness: I wouldn’t suggest that clinical depression is the same thing as a bad mood. However, the availability of treatment for mental disorders supports our refusal to work through emotions. Emotions are part of the human experience: both good and bad ones. Direct-to-consumer marketing of prescription drugs (illegal in almost all developed countries besides the U.S., might I add) has convinced us that the best way to treat depression is by swallowing a pill. Once daily medication use is incredibly easy, but not necessarily the best option. Using the strategies laid out previously can help move through emotional states mindfully and healthfully. Our medical model of treating disease is not appropriate for chronic disease – especially mental disorders.

Antidepressant use can be helpful for many, and it was even a bridger for me in overcoming my anxiety. I wish I would have educated myself sooner, though, because the side effects were unbearable. So I’m passionate about raising awareness that drugs are not the only answer, and the benefits from their use have been overstated by pharmaceutical companies that collect the $13 billions dollars per year Americans spend on these drugs. You can start incorporating the strategies I’ve presented even if you’re still using an antidepressant. Always keep your provider involved in your decisions, but be your own advocate in doing what is best for your mental health. The easiest way out is not always the best option.

Be well!