by Amy Beausang, PharmD
What Is Depression?
What if you could envision no future? If you felt like there were no answers to your problems, which are overwhelming and without end? Perhaps nothing feels enjoyable or makes you smile. Getting dressed or even getting out of bed may seem an insurmountable task. Or maybe you can’t sleep. You don’t care to eat anymore, or maybe you can’t stop eating. You can no longer make decisions, can’t concentrate. And work? No way. There’s a numbness, an emptiness that you can’t escape. You simply feel worthless and unworthy of love. Like you are in a deep, dark hole and you don’t even have the energy to begin looking for some light or finding a way out. And maybe you begin to think that death would be better than living like this. This is what depression can feel like.
According to the National Institute of Mental Health (NIMH), in 2014, nearly 16 million US adults experienced at least one major depressive episode in the past year. Nearly half of those with severe depressive symptoms report serious difficulties in work, home, and social activities (Pratt & Brody, NCHS Data Brief, Dec. 2014).
How Is Depression Diagnosed?
Many conditions can be diagnosed with laboratory testing. For example, a blood test can help determine if someone has diabetes or anemia. Unfortunately, there are no blood tests to definitively indicate that someone has “depression.” Instead, clinicians have to rely on a rather subjective system for diagnosing depression.
The diagnostic criteria for depression are laid out in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), often referred to as the “bible” of mental health for the United States. To be diagnosed with depression requires having at least 5 of 9 symptoms from the DSM-5 list, and one of the symptoms must be either “depressed mood” or “loss of interest or pleasure.” Symptoms must be present on most days during the same two-week period, and must cause significant distress or impairment in social, occupational, or other important areas of functioning (American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Washington, DC: American Psychiatric Association; 2013).
The DSM-5 criteria also require that the depressive episode not be attributable to the physiological effects of a substance or to another medical condition (DSM-5). This is an important point to remember, because depression may actually be a manifestation of an underlying problem that might seem unrelated. Depression may be a message that there is an issue somewhere that needs attention, and not that the brain is “broken.”
Is Depression Caused by a Chemical Imbalance in the Brain?
This was the prevailing thinking for the last 50 years, even though experts in the field of psychiatry have been arguing against it for decades. In fact, it was by accident that the chemical imbalance theory came about. In the 1950s, researchers observed that medications intended to treat tuberculosis and schizophrenia had the unexpected effects of improving symptoms of depression. In the 1960’s, it was proposed that neurotransmitters like serotonin and norepinephrine are deficient in depression [Schildkraut, Journal of Neuropsychiatry and Clinical Neuroscience, Fall, 1995; Coppen, British Journal of Psychiatry, Nov. 1967), but attempts to definitively prove this hypothesis failed to do so. Over the past couple of decades, various groups openly cast doubt on the “chemical-imbalance theory” (Mendels & Frazer, Archives of General Psychiatry, April 1974; Heninger et al, Pharmacopsychiatry, Jan. 1996; Lacasse & Leo, PLoS Medicine, Dec. 2005; Lacasse & Leo, The Behavior Therapist, 2015). Yet, as recently as 2006, 80% of Americans believed that depression was caused by a chemical imbalance in the brain (Pescosolido et al, American Journal of Psychiatry, Nov. 2010).
Despite the lack of solid, convincing evidence to support it, the chemical imbalance theory is the basis for using the blockbuster medications known as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephine re-uptake inhibitors (SNRIs) to treat depression. SSRIs and SNRIs block the removal of neurotransmitters from their sites of action in the brain. Simply put, these drugs make serotonin (and norepinephrine in the case of SNRIs) more available to act upon brain cells. Over the past 20 to 25 years, the use of SSRIs (like Prozac, Paxil, Zoloft, and Lexapro) and SNRIs (like Effexor, Pristiq, and Cymbalta) has skyrocketed, which leads to two key questions:
- Is depression on the rise?
- How well do these blockbuster drugs work to treat depression?
Is Depression on the Rise?
It would seem so, based on the increasing use of antidepressants over the last couple of decades. Data from a national survey show a trend of steadily increasing antidepressant use among US adults aged 20 years and older: doubling from almost 7% during the 1999-2000 survey to 13% during the 2011-2012 survey. This same survey shows that antidepressant use is more common in women than in men (Kantor et al, JAMA, Nov. 3, 2015). A separate report found that about 1 in 4 women between the ages of 40 and 59 reported taking an antidepressant (Pratt et al, NCHS Data Brief, Oct. 2011).
While the use of antidepressants has clearly increased over the decades, this rise in use may not be due to an increase in the prevalence of depression. A Canadian study of antidepressant prescribing trends found that nearly half (45%) of prescriptions for antidepressants were written for “off-label” use, i.e., a use that was not approved by either the Canadian or United States regulatory agencies (Wong et al, JAMA, May 24-31, 2016). A separate study in the US found that 69% of people taking SSRIs-the most commonly prescribed class of antidepressants-had never suffered from major depression (Takayanagi et al, Journal of Clinical Psychiatry, Jan. 2015). This finding was confirmed in yet another study published just this year in JAMA Internal Medicine. The study found that only 30% of adults treated for depression were actually “positive” for depression based on a screening test (Olfson et al, JAMA Internal Medicine, Oct. 2016).
Indeed, antidepressants are currently being prescribed to treat many different conditions including insomnia, nerve pain, fibromyalgia, migraines, hot flashes, premenstrual syndrome (PMS), sexual dysfunction, attention deficit hyperactivity disorder (ADHD), eating disorders, arthritis, and irritable bowel syndrome. Antidepressants-in particular, SSRIs-seem to have become “all-purpose” medications. All the more reason we need to know as much as we can about the benefits and risks of antidepressants.
How Effective Are Antidepressants for Treating Depression?
In 1977, the FDA created specific guidelines for the evaluation of antidepressant drugs (Hanrahan & New, Mental Health Clinician, Jan. 2014). This document still serves as a loose framework for antidepressant drug development in the United States, even though it is considered outdated and in some respects, quite vague. For example, the recommended duration for studies is very broad, noting that they may last days to weeks, with at least one study being at least six weeks or longer.
Most antidepressants have been approved based on the results from two studies, each typically lasting for 6 to 8 weeks. It is important to note that most of the approved antidepressants have undergone multiple studies. The number of “negative” studies (those that fail to show a difference between the investigational drug and placebo, for example) does not necessarily affect whether the FDA grants approval for a drug, as long as two of the studies show adequate effect in the eyes of the FDA.
Direct guidance from the FDA on how to measure the effectiveness of an antidepressant in clinical studies is lacking. Studies may use a number of different depression “rating scales” which are used to “score” the severity of depression. In addition, there is no criteria regarding the level of improvement or change in the depression score that is necessary to deem that an antidepressant has meaningful effectiveness. This makes it difficult to estimate the real benefit of antidepressant use against the potential side effects and health risks.
Benefits and Risks of Antidepressants:
In recent years, researchers have re-examined data from numerous clinical trials to gain a clearer understanding of the effectiveness of antidepressants in the treatment of depression (Kirsch et al, PLoS Medicine, Feb. 2008; Fournier et al, JAMA, Jan. 6, 2010). They did so by conducting what are known as “meta-analyses” of clinical trial data. This means that data from multiple studies were combined in attempts to gain a better sense of the magnitude of antidepressant effectiveness.
Results from these meta-analyses suggest that antidepressants show little benefit (if any) over placebo for people whose depression is rated as mild to moderate. In other words, those with mild to moderate depression who received a placebo improved just as much as those who received the actual antidepressant. For those with severe depression, there tended to be a larger effect of antidepressant therapy compared to placebo(Kirsch et al, PLoS Medicine, Feb. 2008; Fournier et al, JAMA, Jan. 6, 2010). Thus, there appears to be a significant “placebo effect” when it comes to treating depression.
Placebo Effect and Depression:
Studies have shown that placebo response rates average 31-45%, compared to 50% with antidepressants (Walsh et al, JAMA, April 10, 2002; Stolk et al, Annals of Pharmacotherapy, Dec. 2003). One meta-analysis concluded that the placebo response rate was as high as 82% (Kirsch et al, PLoS Medicine, Feb. 2008). Within this decade, major pharmaceutical companies have announced their cessation of depression research, with one CEO explaining that it was difficult to show that a drug works even with large-scale studies (van Gerven & Cohen, British Journal of Clinical Pharmacology, July 2011).
The intention of sharing this perspective is not to negate the fact that some people feel that antidepressants have helped them tremendously. There is no denying that some people have severe depressive symptoms, and antidepressants may be an option that works for them. However, because these drugs are prescribed so widely and for so many different indications, it is important to be informed when it comes to potential benefits and risks of antidepressants.
What Are the Risks Associated with Antidepressants?
While some people do find that antidepressants have helped them, others may feel no better, or even worse after starting an antidepressant. Or, maybe certain symptoms of their depression have improved, but other unpleasant effects have developed. Antidepressants-especially SSRI’s-commonly make people feel “flat” or “apathetic”. Other effects include insomnia, anxiety, agitation, loss of libido or other sexual problems, irritability, fatigue, weight gain, weight loss, headache, nausea, and diarrhea, among others (Ferguson, Primary Care Companion to the Journal of Clinical Psychiatry, Feb. 2001).
Interactions with Antidepressants and Serotonin Syndrome:
When taking antidepressants, it is important to check if other medications that also affect serotonin are being used at the same time, due to the risk of serotonin syndrome. Think of serotonin syndrome as “serotonin overload.” This can happen when high doses of drugs that increase serotonin are used, or when multiple drugs that affect serotonin are used together. Symptoms of serotonin syndrome range from mild (jitteriness, restlessness, muscle twitching) to very serious (high fever, severe muscle spasms, heavy sweating, seizures, uneven heartbeat, passing out) (Volpi-Abadie et al, Ochsner Journal, Winter 2013). Full-blown serotonin syndrome is very rare, but it is worth knowing what to watch for, especially when taking several agents that may impact serotonin levels. Some of the riskier combinations involve taking an SSRI or SNRI with tramadol (Ultram), certain opioid pain relievers (fentanyl, methadone), certain drugs used to treat Parkinson’s disease (selegiline [Eldepryl], rasagiline [Azilect]), and the muscle relaxant metaxalone (Skelaxin). [You can read more about antidepressant interactions here.]
In 2004, the FDA notified antidepressant manufacturers that product labeling for antidepressants should include a “black box warning” to caution prescribers, patients, and caregivers about an increased risk of suicidal thinking and behavior in children and adolescents taking antidepressant medications. In 2007, this black box warning was updated to include young adults ages 18 through 24. These labeling changes stemmed from an FDA analysis of more than 20 short-term studies, which ultimately demonstrated increased rates of suicidal events with antidepressants compared to placebo. The decision to conduct this analysis came years after case reports of patients committing suicide or experiencing “intense suicidal preoccupation” within a short time after starting an antidepressant. This is one of several reasons why antidepressants have come under intense scrutiny.
[What are the benefits and risks of antidepressants during pregnancy? Read more here.]
Antidepressant Withdrawal Syndrome and the Importance of Slow Tapers:
Some antidepressant studies have gone on to assess the longer-term effects of these medications in people who responded to the active drug during the main period of the study. These “responders” were re-randomized (reassigned) to either continue receiving the antidepressant or to switch to placebo. Such studies have reported higher rates of depression relapse among those who were reassigned to placebo. These results were interpreted as proof that antidepressants prevent relapses, and that depression returns when people stop taking them.
However, we now know that it isn’t necessarily the depression that is coming back once the antidepressant is stopped. Instead, when antidepressants are stopped abruptly or the dose is reduced too quickly, “withdrawal syndrome” may occur, and many of the symptoms can resemble some of those seen in depression.
Discontinuation or Withdrawal?
In response to an antidepressant, the brain “recalibrates” or adapts to changes in neurochemistry. When an antidepressant is stopped or the dose reduced, the brain again makes adjustments in attempts to “rebalance”. If the drug is discontinued abruptly or the dose reduced too rapidly, this readjustment process cannot keep pace, and the result is withdrawal syndrome (Haddad, Journal of Psychopharmacology, 1998, vol 12, no. 3). It is important to note that some psychiatric experts use the term “discontinuation syndrome. Others feel that this term minimizes the effects of SSRI or SNRI withdrawal, and argue that the term “withdrawal syndrome” more adequately conveys what is happening in the body (Chouinard & Chouinard, Psychotherapy and Psychosomatics, Feb. 21, 2015).
Not everyone who stops taking an antidepressant will experience withdrawal syndrome, but for some people, the experience can be quite severe. As mentioned previously, sometimes the symptoms that occur after reducing or stopping an antidepressant are misinterpreted as a recurrence of depression. This can lead the physician and patient to conclude that the antidepressant should be continued unnecessarily.
The development of new symptoms and/or new feelings after an antidepressant is stopped or the dose is reduced provides a clue that withdrawal syndrome is occurring rather than a return of the depression itself. Withdrawal symptoms vary from person to person, but may include the following: flu-like symptoms, abdominal cramping, trouble sleeping, irritability, headache, blurred vision, stomachache, nightmares, dizziness, electric shock sensations, crying spells, muscle jerks, lethargy, light-headedness, nausea, anxiety, numbness, diarrhea, vertigo, tingling or burning sensations, and low mood, among others(Chouinard & Chouinard, Psychotherapy and Psychosomatics, Feb. 21, 2015).
How Common Is Withdrawal Syndrome?
Studies report rates of withdrawal syndrome ranging from 20% to 50% of patients. The likelihood of experiencing withdrawal syndrome is higher with some antidepressants than others. For example, paroxetine (Paxil) is associated with higher rates of withdrawal syndrome compared to fluoxetine (Prozac). A key reason that fluoxetine may carry a lower risk of withdrawal syndrome is because it takes the body much longer to completely clear fluoxetine, so the decline in drug levels is much more gradual than with other antidepressants (Rosenbaum et al, Biological Psychiatry, July 15, 1998).
Certain factors have been associated with an increased chance of experiencing withdrawal syndrome from SSRIs. These include taking the medication for longer than two months, abrupt dose reduction or discontinuation, female gender, and experiencing withdrawal syndrome in the past (Coupland et al, Journal of Clinical Psychopharmacology, Oct. 1996; Bogetto et al, CNS Drugs, 2002, vol. 16, no. 4; Schatzberg et al, Journal of Clinical Psychiatry, 1997, vol. 58, Supplement 7).
Because withdrawal syndrome can cause unnecessary and avoidable suffering, it seems prudent to follow a conservative approach when it comes to tapering off antidepressant therapy. However, very little guidance exists regarding how to actually do this. Even the official FDA-approved prescribing information (PI) leaflets for marketed antidepressants are quite vague when it comes to discontinuation of antidepressant therapy. They typically offer a general recommendation of “gradual reduction in dose rather than abrupt cessation” but no product-specific information is offered. It seems a great oversight by the industry not to conduct adequate studies on how to discontinue antidepressants in efforts to minimize withdrawal syndrome, especially now that antidepressants are being used to treat so many different conditions. Someone who begins taking Cymbalta for nerve pain, for example, and doesn’t derive pain relief after a few months of treatment may decide to just stop taking the drug without awareness of the risk for experiencing withdrawal syndrome.
Important Considerations Before Tapering Antidepressant Therapy:
First and foremost, it is important to discuss any possible changes to medications with your doctor beforehand. You’ll want to be clear on the benefits and risks of antidepressants and of stopping the drugs. Enlisting the support of a qualified health professional before attempting an antidepressant taper can be tremendously helpful in easing the process. As previously mentioned, some people have no withdrawal symptoms, while others may experience severe symptoms for months to years. It simply is not possible to accurately predict what each individual’s experience will be. This is why it is crucial to have an open and knowledgeable professional helping you through the process in a responsible, safe manner. Never try quitting without support, and never stop an antidepressant “cold turkey.”
Many doctors will suggest taking a pill every other day for a few weeks and then spacing them out further. There is very little basis for this approach and it can make things worse. Thus, a slow, conservative tapering strategy is the best approach to consider.
Information on Tapering Antidepressant Therapy:
A resource that may be helpful for healthcare professionals and consumers who seek additional guidance on tapering antidepressant therapy can be found at RxISK.org, a Canadian-based organization whose mission is “Making medicines safer for all of us”. One of the founding members of RxISK.org is David Healy, MD, an internationally respected psychiatrist, psychopharmacologist, author, and professor of psychiatry at Cardiff University in Wales. Dr. Healy has written extensively about antidepressant withdrawal, and this guide to stopping antidepressants provides valuable information regarding withdrawal symptoms, tapering strategies, and approaches for handling complex or difficult withdrawal cases.
Why “Getting in Shape” Before Beginning an Antidepressant Taper Makes Sense:
Ever thought about running a race or completing some other type of physical challenge? You probably would never consider running a marathon without properly training for it-without putting in the miles, eating the right foods, and getting plenty of good sleep. Failing to do those things would likely result in an unpleasant experience on race day.
Perhaps antidepressant tapers should be approached in a similar manner-by being in the best possible shape before even beginning the process. Incorporating regular and enjoyable exercise, eating real food and minimizing processed food, and getting enough quality sleep can help ease the tapering process. Conversely, being overly stressed, tired, sedentary, and stuck in poor eating habits can make it very difficult to go through an antidepressant taper, and probably should not be attempted until positive lifestyle changes can be implemented.
Non-Drug Strategies That Can Help Prevent and Treat Depression:
Exercise:
Will a walk around the block make all problems disappear? No. However, getting regular exercise can certainly benefit people experiencing depression, and may even help prevent depressive episodes from occurring. A 16-week study comparing the effects of regular exercise (about 45 minutes of walking or jogging 3 times per week), sertraline, or both in people with depression found that exercise was equally effective in reducing symptoms (Blumenthal et al, Archives of Internal Medicine, Oct. 25, 1999). A follow-up to this study was conducted 6 months after the original study ended. The researchers found that the effects of exercise outlasted those of antidepressants. People who exercised regularly after completing the original study-regardless of which group they had initially been assigned to-were less likely to relapse into depression (Babyak et al, Psychosomatic Medicine, Sep-Oct. 2000). And, as we all know, exercise yields multiple other benefits for our bodies.
The challenge with exercise is that depression can zap all motivation to actually do it. When someone feels depressed, the last thing they want to hear is that they “should be” exercising because it will help. It can feel impossible. It may feel difficult enough to get out of bed, much less pull on some exercise wear and go to a gym or even outside.
A previous People’s Pharmacy article has shared some strategies for getting hooked on exercise. While some of them might seem darkly laughable to someone going through depression, others might actually help. Like not letting anyone, even yourself, “should” you when it comes to exercise. The word “should” often brings feelings of guilt, shame, and failure-feelings that someone with depression typically has too much of to begin with, and feelings that will not foster a desire to exercise.
Also, reframing one’s perception of exercise may help when in the midst of depression. Look back at the study that was just discussed. The participants weren’t running 5 miles a day or going to an intense boot camp class. They were walking 3 days a week. They warmed up for 10 minutes, walked at a steady clip for 30 minutes, and then cooled down for 5 minutes. If this seems overwhelming, it can be broken up into smaller chunks to make it more manageable.
Stop Ruminating:
The word “ruminate” means “to chew the cud, as a ruminant.” Cows, for example, are ruminants. A cow takes a bite of grass or hay, then chews and swallows it. But that’s not enough to really digest tough grasses, so the cow actually regurgitates this “cud” -kind of like “controlled vomiting”. This allows the cow to chew it again and swallow it again to improve digestibility.
Humans have a tendency to ruminate in a different way, especially on negative thoughts and experiences. We “chew” on them in our minds, and then we regurgitate them, bringing them up again to chew on some more, over and over. This is particularly prominent in depression, and often involves ruminating about feelings of inadequacy or worthlessness, which can lead to anxiety and deepening depression. In short, rumination intensifies a negative mood and ramps up the brain’s stress response. Dr. Stephen Ilardi, author of The Depression Cure-a book that emphasizes therapeutic lifestyle changes (TLC) for overcoming depression-explains how rumination is toxic for humans, and offers 3 steps to breaking the rumination cycle: (1) Notice (2) Decide (3) Redirect. [You can listen to an interview with Dr. Ilardi here.]
- Notice when you are ruminating-practice catching yourself as it’s happening.
- Decide to shift your attention elsewhere. You have the capability to choose whether to keep ruminating over the negative or to stop it.
- Redirect your attention to something else that will take you out of the rumination cycle.
This could be getting out in nature. It could be listening to upbeat music, working on some type of puzzle, reading a good book, or exercising. It could be anything that engages your brain. Dr Ilardi also suggests that it could be a shared activity. This means having someone that you can do things with, and it doesn’t necessarily involve actually conversing with that person. Conversation when you are ruminating often leads to sharing that rumination with someone else and “chewing” on it endlessly. But merely having someone there with you to share the space-whether it’s on a walk, watching a movie together, or taking a gym class-can help snap the rumination cycle. Having someone that can do something with you without requiring conversation can be very helpful.
Be Mindful:
“Mindfulness” may seem like an overused buzzword these days, so much so that its significance has been lost. Simply defined, mindfulness is paying attention to one’s experience right now, in the present moment. The mind is prone to wander, but we can train ourselves to take note of where the mind goes-without judgment or becoming caught up in it-so that we can then calmly return to the present moment. Focusing on the breath is one way to return to mindfulness. Studies have shown mindfulness-based cognitive therapy (MBCT) to be as effective as maintenance antidepressant therapy in preventing relapse of depression (Kuyken et al, The Lancet, July 4, 2015; Segal et al, Archives of General Psychiatry, Dec. 2010). Of note, these studies involved discontinuation of antidepressants for those in the MBCT groups (specific tapering protocols were not described), which we now know is associated with withdrawal symptoms that may be misinterpreted as depression relapse. Thus, by design, these studies may have underestimated the true effectiveness of MBCT.
The aim of MBCT is to interrupt the automatic processes that often trigger an episode of depression. Specifically, MBCT seeks to teach people to disengage from deeply ingrained dysfunctional thoughts that are common with depression. Typically, MBCT consists of an 8-week, group-based program that incorporates mindfulness exercises (breathing, yoga, daily homework) with full attention to what one is doing moment-by-moment. A major advantage of MBCT is that it has no side effects, and can be used in conjunction with other therapies.
Choose Healthy Food:
In recent years, there has been growing interest in the relationship between dietary patterns and mental health. A study involving just over 1,000 women ages 20 to 93 found that a “traditional” diet that emphasized vegetables, fruit, meat, fish, and whole grains was associated with lower odds of developing major depression or anxiety. Conversely, a “western” diet of processed or fried foods, refined grains, sugary products, and beer was associated with a higher likelihood of psychological symptoms (Jacka et al, American Journal of Psychiatry, March 2010). Another study of over 10,000 Spanish participants suggested that a Mediterranean dietary pattern was protective against depression (Sanchez-Villegas et al, Archives of General Psychiatry, Oct. 2009). A separate study in middle-aged women also linked a Mediterranean dietary pattern with a lower incidence of depression symptoms (Rienks et al, European Journal of Clinical Nutrition, Jan. 2013). Further studies will likely provide even more information on dietary patterns that may help prevent depression, but it is likely that generally avoiding processed and sugary foods and emphasizing “real” foods like vegetables, healthy fats, legumes, fruits, and healthy proteins will benefit the whole body, brain included.
Step into the Light:
Bright light therapy using a “light box” is a well-known, effective approach for treating seasonal affective disorder (SAD), a type of depression that typically occurs during fall and winter when there is less sunlight (American Psychological Association, June 26, 2006). A 2016 study in JAMA Psychiatry suggests that bright light therapy may also help those with non-seasonal depression. The 8-week, randomized, placebo-controlled study was conducted in 122 people with depression of at least moderate severity. Study participants were divided into four treatment groups to receive either: light therapy for 30 minutes in the morning, fluoxetine (Prozac®), light therapy plus fluoxetine, or placebo (a “fake” light box + placebo pill). Bright light treatment alone or in combination with fluoxetine was more effective than placebo or fluoxetine alone for treating nonseasonal depression (Lam et al, JAMA Psychiatry, Jan. 2016).
If getting natural sunlight (even overcast skies are beneficial) on a regular basis isn’t possible, using a light box might be worth discussing with your doctor. Experts typically recommend bright light therapy in the morning rather than the evening, to avoid disruption of the sleep cycle that can worsen depression symptoms. To receive maximum benefit, the light box should provide 10,000 lux of light (lux is a measure of brightness). As a comparison, the brightness of sunlight on a “sunny” day is anywhere from 10,000 to 100,000 lux. Typical indoor lighting is only about 100 lux. Other features to look for when considering a light box include ultraviolet (UV) light filtration, and the design preference that will work best for you on a daily basis.
It is important not to stare directly into the light box, as this can strain and possibly damage the eyes. The most common side effect of the light box is headache. People with bipolar depression should check with their doctor before using a light box, as there is a possibility of developing manic symptoms with bright light therapy (irritability, extreme happiness, high energy, talkativeness, racing thoughts, insomnia).
Could There Be an Underlying Cause of Depression?
Thyroid, Vitamins, Hormones and Medications:
For decades, we have been inundated with the “chemical imbalance” theory of depression-to the extent that underlying causes of depression may be overlooked. For example, those with hypothyroidism may be particularly susceptible to depression (Kirkegaard & Faber, European Journal of Endocrinology, Jan. 1998). One assessment of six clinical trials showed that 52% of those with treatment-resistant depression had subclinical hypothyroidism (in which the “free” thyroid hormones, T3 and T4, are low, but TSH is normal) compared to 5% of those in the general population (Sintzel et al, Encephale, May-June 2004). Another study correlated subclinical hypothyroidism with more severe depression (Berent et al, Molecular Biology Reports, online Jan. 18, 2014). Deficiencies in vitamin B12 and vitamin D have also been linked to depression (Seppala et al, BMC Psychiatry, May 24, 2013; Anglin et al, British Journal of Psychiatry, Feb. 2013; Shaffer et al, Psychosomatic Medicine, April 2014).
Premenstrual Dysphoric Disorder:
Many women experience symptoms of depression, anxiety, and mood swings with hormone changes that occur during their menstrual cycles. Sometimes the symptoms are disabling and last for 2 or more weeks every month. In the late 1990’s, this syndrome became known as “premenstrual dysphoric disorder” (PMDD). Around this same time, Eli Lilly produced results from clinical trials showing that fluoxetine was effective in the treatment of PMDD. Today, antidepressants such as fluoxetine and sertraline are frequently prescribed for PMDD. While they may help some women, these drugs are not addressing the potential hormone imbalances that are thought to drive these cyclical symptoms. It is important to discuss the benefits and risks of antidepressants for PMDD with the prescriber. Non-drug approaches like magnesium, calcium, stress management, alcohol avoidance, caffeine reduction, chaste tree berry, and vitamin B6 have been shown to help with symptoms of premenstrual syndrome (PMS) and PMDD (Bhatia & Bhatia, American Family Physician, Oct. 2002).
When looking for underlying causes of depression, it is important to consider any medications being taken. Those implicated in drug-induced depression include certain anticonvulsants, antimigraine agents, antipsychotics, oral contraceptives, corticosteroids, and cardiovascular agents, among others (Botts & Ryan, Depression, in: Tisdale, JE, ed. Drug-Induced Diseases: Prevention, Detection and Management, second edition. Bethesda, MD: American Society of Health-System Pharmacists, 2010). For example, approximately 1 out of every 4 people receiving interferon, an agent commonly used to treat chronic hepatitis C, will develop drug-induced depression (Udina et al, Journal of Clinical Psychiatry, Aug. 2012). While the quality of evidence linking certain drugs to depression varies among agents, it is always important to investigate medications as a potential contributor.
From Chemical Imbalance to Inflammation: An Emerging Theory on Depression:
Although the idea that inflammation contributes to depression has been around for a long time, recent years have seen a burgeoning interest in the link between inflammation and depression. Indeed, a growing body of evidence now suggests a connection between depression and a low-grade, chronic inflammatory state. Research has shown that when inflammation is induced in humans, it is associated with anxiety, depressed mood, and memory problems (Reichenberg et al, Archives of General Psychiatry, May 2001). Studies have shown that otherwise healthy people with depression have increased levels of markers of inflammation in their blood (Raison et al, Trends in Immunology, Jan. 2006). A recently published study in JAMA Psychiatry was perhaps the first definitive study showing a link between neuroinflammation (inflammation within the brain) and depression. In this study, researchers determined that an inflammatory marker in the brain was 30 percent higher in clinically depressed people (Setiawan et al, JAMA Psychiatry, March 2015).
In summary, future research will surely provide a better understanding of the connection between inflammation and depression, and perhaps other, yet unknown, contributors to depression. This will hopefully lead to effective approaches for treatment and prevention. While current antidepressants such as SSRIs have shown benefit for some people, it appears that their effectiveness has been misrepresented and even overinflated in several clinical studies. In contrast, the potential for adverse effects and withdrawal symptoms from these widely prescribed drugs may have been underestimated. Understanding the benefits and risks of antidepressants is not easy, but it is crucial.
Antidepressants should not be stopped abruptly, and fortunately we now have resources to help with antidepressant tapering for prescribers and consumers who are considering discontinuation of therapy. For people with depression, it is important to consider any possible underlying causes, such as hypothyroidism or hormone imbalance. It is heartening to see research showing that lifestyle changes such as regular exercise, exposure to natural light, eating unprocessed foods, and practicing mindfulness are each effective therapies for reducing depression. Perhaps the most important thing to remember? If you are dealing with depression, you may feel like you are alone, but you are not. Even when self-isolation seems like the only action you can take, finding the strength to contact someone, even if it is just to “be” there and not say a word, can truly help.
About the Author:
Amy Beausang is a Doctor of Pharmacy (PharmD) with Community Care of North Carolina. Amy also helps people make changes that just might enable them to reduce their need for prescription medications (always responsibly and in conjunction with their prescribers). For more information, visit http://amybeausang.com/
Amy Beausang, PharmD, Health Coach
