By Carol Chuang
Are We Overusing Antidepressants?
Eleven percent of Americans over 12 years old take antidepressants, which is the second most commonly prescribed medication in the U.S., after cholesterol-lowering drugs. Many more women than men use them. About 21 percent of women aged 20 and over take them; among women aged 40-59, the rate is 25 percent.
Antidepressants are psychiatric medications used to treat mood disorders including depression, generalized anxiety disorder, and obsessive compulsive disorder (OCD). The most widely used antidepressants are selective serotonin reuptake inhibitors (SSRIs), a class of drugs that includes medications such as Prozac, Paxil, Zoloft, and Lexapro. Less used but a popular alternative to SSRIs are serotonin-norepinephrine reuptake inhibitors (SNRIs); some of the commonly used medications in this drug class include Effexor and Cymbalta.
With such a high preponderance of usage, some may wonder whether we have become a Prozac nation. Others question if these medications are handed out to patients too casually.
Who Is Prescribing Antidepressants?
In the U.S. nearly 80 percent of antidepressant prescriptions are written by primary care physicians, not psychiatrists. Many depressed patients seen in general practice have not been thoroughly evaluated and may not even meet the full, formal criteria for Major Depressive Disorder (MDD). Instead, they are given the medications for symptoms of mild depression, likely caused by everyday stress, sadness, and sorrow, which may be alleviated by psychotherapy alone. Pediatric use for depression and anxiety has also skyrocketed but it peaked in 2004 when the Food and Drug Administration (FDA) issued a black box warning for SSRIs due to evidence that they may be linked to increased risk of suicidal thinking, feeling, and behavior in young people.
Low Serotonin Levels Don’t Necessarily Cause Depression
SSRIs and SNRIs were developed to treat depression and other mental health conditions caused by an imbalance of neurotransmitter chemicals, particularly serotonin and norepinephrine. This chemical imbalance theory purports that low levels of these chemicals in the brain cause depression. For over two decades, this theory continues to be the dominant paradigm for treating depression.
However, the chemical imbalance hypothesis has its problems and numerous scientific studies conducted in the last 20 years have examined it and rejected it. They found that:
- Not all depressed patients have low serotonin and norepinephrine levels.
- In fact, some have abnormally high levels, while others with no history of depression have low levels of these chemicals.
The significance of this finding is huge, yet it is rarely publicized or taught in medical schools. There are probably various reasons for this but financial is likely to be one of them – antidepressants are a $10 billion industry!
Antidepressants Don’t Always Work
If depression is not caused by an imbalance of serotonin and norepinephrine, then it will explain why antidepressants don’t always work on people who have depression. Countless studies have been done to determine the effectiveness of these medications.
A massive meta-study compiled by the U.S. government that incorporated findings of over 100,000 research studies over a 15-year period concluded that:
- Antidepressants are only effective in around one-third of cases, and partially effective in another third, and have no benefit at all in the remaining third.
- High rate of relapse when depression is treated with drugs alone.
- For many patients, the side effects are more unpleasant than the depression itself, so they discontinue usage.
Likewise, a number of double-blind, randomized controlled studies have come to similar conclusions. They found that:
- The superiority of antidepressants over placebo is clinically significant only for patients who are very severely depressed.
- For those with mild, moderate, and even severe depression, placebos work nearly as well as the medications.
Plus They Have Side Effects
Like most medications, antidepressants have side effects, including nausea, weight gain, loss of sexual desire, fatigue, insomnia, dry mouth, blurred vision, constipation, dizziness, agitation, irritability, and anxiety.
They are not addictive the same way substances like heroin or alcohol are, but people can still develop a physical dependence if they stop taking the drugs abruptly and may experience rather unpleasant withdrawal symptoms such as:
- Insomnia or vivid dreams
- Flu-like symptoms, including achy muscles and chills
- Electric shock sensations
- Return of depressive symptoms
Compelling Evidence: Inflammation As A Contributing Factor To Depression
There is a huge body of research connecting depression and inflammation. In one of the most conclusive findings, a study in JAMA Psychiatry determined that brain inflammation was 30 percent higher in clinically depressed patients. The research team pointed out that previous studies have only looked at biomarkers of inflammation in the blood; this is the first to find definitive evidence in the brain.
Scientists have long known that inflammation is at the root of nearly every modern disease, including allergies, Alzheimer’s, arthritis, asthma, autoimmune disease, cancer, cardiovascular disease, and diabetes. So it is not a huge surprise that depression is also linked to inflammation.
Researchers found that people with clinical depression have elevated levels of inflammatory biomarkers such as cytokines in the blood. Cytokines cruise through the bloodstream, damaging tissue, causing plaque buildup in the arteries, and sometimes even promoting the growth of tumors.
Cytokines can also travel to the brain, possibly via the vagus nerve which connects the gut and the brain. Specialized immune cells in the brain called microglia become activated in inflammatory states and they too, secrete cytokines.
Neuroinflammation alters neurotransmitter pathways and brain circuits. In the early 1980s, researchers have already discovered that inflammatory cytokines produce a wide variety of psychiatric and neurological symptoms mirroring characteristic signs and symptoms of depression.
Known Causes Of Inflammation
If inflammation is a contributing factor to depression, it is critical to understand how we get inflammation in the first place. This correlation has the potential to suggest both therapeutic and preventative approaches to combating depression.
Stress and traumatic life events
Researchers reported that acute negative life events, chronic psychological trauma, and exposure to childhood trauma hugely increase the risk of developing clinical depression and mood symptoms. There is very strong evidence that different types of psychosocial stressors may stimulate the pro-inflammatory cytokine network in the brain.
There have been substantial changes to dietary patterns over the last 50 years. We have swapped a diet high in fiber, nutrient-dense foods, and omega-3 fats (all anti-inflammatory) to one that is high in refined carbohydrates, sugar, and unhealthy refined vegetable oils (all highly pro-inflammatory). Since 2009, there have been numerous studies reporting inverse associations between diet quality and common mental disorders in children and adults across cultures.
Many studies found that exercise is an effective treatment strategy for depression. Regular exercise protects against the development of new depressive and anxiety disorders while physical inactivity during childhood is associated with an increased risk of depression in adulthood.
Without doubt, obesity is an inflammatory state. Inflammatory cytokines are found in abundance in fat cells.
With the prevalence of obesity increasing to epidemic proportions, studies have demonstrated a close relationship between obesity and depression. Obesity predisposes one to depression, while depression also predisposes one to obesity. A recent meta-analysis found obesity to increase the risk of later depression by 55%, whereas depression increased the risk of developing obesity by 58%.
Another diet-related cause of inflammation is gut permeability or “leaky gut”. Under normal circumstances, immune cells are geographically separated from gram negative bacteria in the gut, which are part of the normal gut flora. However, if there is a loosening of the tight junction barrier in the gut wall, toxins produced by gram negative bacteria called lipopolysaccharides (LPS) may get into the bloodstream, causing immune cells to respond and produce pro-inflammatory cytokines. Since the gut and brain are connected by the vagus nerve, mental disorders are highly associated with gut permeability.
The most common causes of leaky gut are:
- Food sensitivity, such as gluten (a protein found in wheat, rye, and barley) and dairy.
- Chronic gut infections, such as parasites, Cryptosporidium, Clostridium difficile, Blastocystis hominis, and Helicobacter pylori.
Cigarette smoke contains many thousands of chemicals, many of which induce inflammatory responses in the body and direct damage to cell tissues in the brain. Studies showed that smoking may increase one’s susceptibility to developing depression.
Periodontal disease is an inflammatory disease that involves infections of the structures around the teeth, which include the gum, periodontal ligament, and alveolar bone. Periodontal disease is associated with high levels of systemic inflammatory cytokines. It is a significant predictor of other inflammatory illnesses, such as cardiovascular disease, and may also increase the risk of depression as well.
Research has demonstrated that chronic sleep deprivation results in impairments in immune functioning, characterized by increased levels of pro-inflammatory cytokines. It is estimated that up to 80-90 percent of individuals who suffer from a major depressive disorder experience sleep disturbances. Studies have suggested that sleep disturbances may also predispose individuals to subsequent development of mood disorders.
There is a high prevalence of vitamin D deficiency in developed countries. Low vitamin D is linked to many diseases including osteoporosis and cancer. Vitamin D receptors are present in key brain areas and vitamin D plays a major role in circadian rhythms and sleep. Vitamin D has a regulatory effect on immunity too. In human studies, supplementation greatly reduces inflammatory markers associated with depression.
Strategies To Overcome And Prevent Depression
Check for inflammation
Depression can be a devastating illness. For very severe depression, studies show that antidepressants appear to be rather helpful in alleviating symptoms. But if your depression is milder, antidepressants may only be just as good as placebos. Therefore, it is worthwhile to check your inflammation level by getting a blood test forC-reactive protein (CRP), which is made by the body in response to high levels of inflammatory cytokines.
Depression is a sign that your body and your life are out of balance. Unless you address your stress, it is difficult to return your life to balance. Both mindful meditation and cognitive therapy have been proven to be extremely helpful in combating depression.
Change your diet and lifestyle
- Trade in the processed and sugary foods for an anti-inflammatory diet that consists of fatty fish like wild Alaskan salmon, leafy greens, fermented vegetables, cultured foods such as unsweetened yogurt and kefir, berries, garlic, and green tea.
- Make sure you have at least 30 minutes of physical activity everyday.
- Get a minimum 7-8 hours of quality sleep daily.
Take supplements to lower inflammation
- High quality animal-based omega-3 fish oil (3 g daily if you have depression)
- Vitamin D3 (5,000 I.U. daily) with vitamin K2 (for bone and heart health)
- Probiotics (for gut health)
- Curcumin (active component of turmeric)
Other supplements to lessen depressive symptoms
- Vitamin B12 and folate (vitamin B9)
Studies found a link between deficiencies in these B vitamins and depression. Vitamin B12 is found mainly in animal proteins; hence, vegans are more susceptible to B12 deficiency. Folate is found in abundance in dark leafy greens and beans. If you have symptoms of depression and you know that you are not eating enough of these foods, you should consider incorporating them in your daily diet. If you are a vegan, you need to take a B12 supplement.
The following amino acid supplements should only be taken after consultation with a knowledgeable healthcare practitioner and a completed neurotransmitter test. For some individuals, these amino acids may help to alleviate the symptoms of depression by balancing the body’s neurotransmitter levels. However, it is still critical to address the underlying causes of depression (as mentioned above).
- 5-HTP (5-Hydroxytryptophan) or L-tryptophan
L-tryptophan is first converted to 5-HTP, which is then converted to serotonin in the brain. Some people cannot tolerate 5-HTP, they will have to use L-tryptophan instead. For those who have low serotonin levels and are either negative, obsessive, worried, irritable, sleepless, or have low self-esteem, 5-HTP and L-tryptophan have a positive effect on sleep, mood, anxiety, and carbohydrate cravings.
- L-Tyrosine and DLPA (D,L-Phenylalanine)
For those who have low norepinephrine, epinephrine, and dopamine, and have a flat-tired type of depression and crave stimulants like caffeine and sugar, L-tyrosine and DLPA will help you feel more energized, improve mood and drive, and increase mental focus.
- GABA (Gamma amino-butyric acid)
For those who feel wired, stressed, and overwhelmed, GABA will help with anxiety and stress, reduce excess stimulation, and improve sleep.