Antidepressants are not effective for mild to moderate depression. Why does it matter?

Written By Luisa Cachiaguida
 

 

As a psychiatrist, I wholeheartedly advocate for treatment of mental health symptoms and prescribe psychiatric medications. However, as a holistic psychiatrist, I believe psychiatric medications should be prescribed judiciously, as one treatment tool, instead of as the only tool.

On the Cleveland Clinic website, on the page about antidepressants it says “Antidepressants are usually effective in moderate, severe and chronic depression. They don’t tend to help mild depression.”

In the US, antidepressant medications are the first line treatment for all people diagnosed with major depressive disorder, or depression. “First line” means that they’re the first treatment a patient is recommended to receive upon diagnosis. In England, antidepressant medications are first line for moderately severe to severe depression (as evaluated by the PHQ-9 questionnaire), but not for mild or moderate depression. Why the difference?

First let’s discuss how depression is diagnosed because it impacts treatment recommendations. Clinicians use the DSM-5 to evaluate patients for the presence or absence of depression. There are several different diagnoses under the “depressive disorders” umbrella that include:

  • Major Depressive Disorder (MDD), mild, moderate, or severe

  • Substance-induced depressive disorder

  • Medication-induced depressive disorder

  • Depressive disorder due to another medical condition

  • Persistent depressive disorder

  • Unspecified depressive disorder

As you can see there are a lot of options. Let’s address the different types and then dive into the specifics of MDD mild, moderate, versus severe.

  • Substance-induced depressive disorder: It is well known that some addictive substances or withdrawal from them, for example alcohol, result in symptoms of depression. This diagnosis is given when depression is clearly linked with either substance use or withdrawal. The idea is that the depressive symptoms will dissipate once someone stops using the substance and/or are no longer in withdrawal.

  • Medication-induced depressive disorder: It’s well documented that certain medications cause depressive symptoms. These include oral steroids and topiramate amongst other. This diagnosis is given when depression is clearly linked with the initiation of a medication. The idea is that the depressive symptoms will dissipate once someone stops using the causative medication.

  • Depressive disorder due to another medical condition: It’s well established that certain medical conditions, such as low thyroid, traumatic brain injury, and sleep apnea, lead to symptoms of depression. This diagnosis is given when a medical condition is clearly linked with the start of depressive symptoms. The idea is that the depressive symptoms will dissipate once the underlying condition is treated.

  • Persistent depressive disorder: This diagnosis is specific to those who have suffered from depressed mood and 2 other symptoms (poor appetite or overeating, insomnia or hypersomnia, low energy/fatigue, low self-esteem, poor concentration/decision making, or hopelessness) non-stop for at least 2 years.

  • Unspecified depressive disorder: This diagnosis is given when a person is experiencing significant distress or impairment, but there’s limited information to establish a more precise diagnosis within the depressive disorder category. This diagnosis is often given in emergency rooms where time is limited and then revised after more information is gathered.

Now for the specifics of diagnosing MDD. Major depressive disorder, what is colloquially called depression, is diagnosed by determining that a patient has depressed mood and/or loss of interest or pleasure in almost all activities plus 5 of the following 7 symptoms: unintentional weight loss/gain or change in appetite, insomnia or excess sleep, physical slowing or restlessness, fatigue, a sense of worthlessness or excessive guilt, difficulty concentrating or making decisions, recurrent thoughts of death (not just fear of dying), suicidal ideation, or suicide attempts.

These symptoms must be new or clearly different from the person’s usual state of being. They must last most of the day, everyday for at least 2 weeks straight. Symptoms that are due to a medical condition do not count as depressive symptoms (ie. lack of appetite due to receiving chemotherapy treatment for cancer). The symptoms must cause significant distress or impairment in social, work, or other areas of functioning. Importantly, the depressive symptoms cannot be a result of substance use or withdrawal, a medication, or another medical condition.

Because there are 9 symptoms possible for diagnosis, there are over 1,000 different combinations of symptoms that are diagnosed as MDD. To make matters more complicated, different diagnoses can exist at the same or different times. For example, people suffering with depressed mood often drink alcohol to cope. If someone dependent on alcohol had never been diagnosed with MDD and first saw a psychiatrist while withdrawing from alcohol, they would be diagnosed with substance induced depressive disorder at that time. After the period of withdrawal ends, the depressive symptoms could either dissipate leaving the patient with no mental health diagnosis or the depressive symptoms could persist, leading to a diagnosis of MDD. If the person returns to drinking regularly they would get diagnosed with both substance induced depressive disorder and MDD. There are a lot of possibilities.

Because not all 9 symptoms must be present to make a diagnosis of depression, there are categorizations of MDD. As per the DSM-5:

  • MDD, Mild indicates that “Few, if any, symptoms in excess of those required to make the diagnosis are present, the intensity of the symptoms is distressing but manageable, and the symptoms result in minor impairment in social or occupational functioning.”

  • MDD, Moderate indicates that “The number of symptoms, intensity of symptoms, and/or functional impairment are between those specified for “mild” and “severe”.”

  • MDD, Severe indicates that “The number of symptoms is substantially in excess of that required to make the diagnosis, the intensity of symptoms is seriously distressing and unmanageable, and the symptoms markedly interfere with social and occupational functioning”.

In clinical practice, symptom scales are most commonly used to categorize the severity of MDD. The most commonly used scale is the PHQ-9 which categorizes MDD severity into minimal, mild, moderate, moderately severe, and severe depression. It makes the following treatment recommendations based on the results:

  • 0–4: None to minimal depression) No treatment

  • 5–9: Mild depression) Watchful waiting; repeat PHQ-9 at follow-up

  • 10–14: Moderate depression) Use clinical judgment about treatment, based on patient’s duration of symptoms and functional impairment

  • 15–19: Moderately severe depression) Treatment with antidepressants and/or psychotherapy

  • 20–27: Severe depression) Treatment with antidepressants and psychotherapy

As you can see, a lot goes into making the diagnosis of depression. Or does it? Most physicians, although well-intentioned, diagnose people with the blanket-term “depression” instead of MDD, mild, moderate, severe or depressive disorder due to another medical condition, for example. The diagnosis matters for two reasons. First, diagnoses are used to select the people who participate in medication trials. People are screened to be included, or, importantly, not included, in the study using these diagnostic criteria. Very commonly people with “insufficient severity of depressive symptoms” are excluded from clinical trials of antidepressants. Simply put, antidepressants are mostly tested on people with moderately severe to severe MDD, not mild to moderate. Unfortunately, this is not spelled out clearly so antidepressants go on to get FDA approval for “MDD” without any severity specifier, making things confusing. Second, the diagnosis matters because it guides treatment. A cough cannot be treated appropriately until the cause is found. If it’s due to asthma, an inhaler is needed; if it’s a bacterial infection, an antibiotic is needed. Someone with depressive disorder due to another medical condition like vitamin D deficiency needs vitamin D supplementation as the first line treatment, not an antidepressant.

The flaw in screening those with mild to moderate depression and those who have both MDD and other conditions such as substance use and medical conditions out of antidepressant trials was attempted to be addressed in the renowned STAR-D trial. The goal was to use fewer exclusion criteria than typically are used in clinical trials to make the results more generalizable to real clinical situations. Although they included people with both MDD and other psychiatric, medical, and substance use disorders, they still excluded anyone with a HAM-D depression rating score under 14. According to this scale, a score of 0–7 indicates no depression, a score of 8–16 indicates mild depression, and a score of 17–23 indicates moderate depression. Although the results showed that about 37% of people taking an antidepressant for moderate to severe depression get better, it still all but excluded those with mild depression.

My goal in pointing this out is not to deny that people seeing their doctors are suffering or to deny people antidepressant prescriptions. Rather I aim to shine a light on the fact that antidepressants are being widely prescribed without a second thought. This is largely a result of the commonly held, and widely-marketed, belief that antidepressants are the only way to “fix” our brain’s biochemistry. This narrow-minded approach has precluded physicians from telling patients that brain biochemistry is impacted in a myriad of ways and that there are many causes and contributors to depression. For example, a recent theory of depression states that it is linked to brain and body inflammation. Most patients with psychiatric symptoms are not screened for the many causes and contributors to depression which provide various treatment options outside of medication, leaving them to falsely think that antidepressants are the only treatment.

Many doctors think that since antidepressants are about as effective as but not statistically significantly better than placebos in mild to moderate depression, there’s no harm in prescribing them. I disagree. Placebos have no side effects, they do not result in the body building a tolerance thus causing withdrawal symptoms when stopped, and at the end of the study the participants receiving placebo are told. Trial participants are not kept on a placebo for months on end and when ineffective told that they need to try a different kind of placebo to see if that one works. That doesn’t seem like a fair comparison to me.

The American Psychiatric Association recommends antidepressants as the first line treatment for all MDD, regardless whether it’s mild, moderate, or severe. (I am making the distinction between moderate and moderately severe because the PHQ-9, which is the most widely used depression screening tool, differentiates it in this way.) NICE, the National Institute for Health and Care Excellence, is a UK organization that provides national guidance and advice to improve health and social care. Based on research on antidepressant effectiveness and outcomes, they put out the following guidelines for treatment of MDD.

For mild to moderate depression, it states “Do not routinely offer antidepressant medication as first-line treatment for less severe depression, unless that is the person's preference.” Instead they recommend the following treatments, in order:

  • guided self-help, group cognitive behavioral therapy, group behavioral activation, individual cognitive behavioral therapy, individual behavioral activation, group exercise, group mindfulness and meditation, interpersonal psychotherapy, SSRI antidepressants

For moderately severe to severe depression, they recommend individual cognitive behavioral therapy + antidepressant as first line.

Why the difference in treatment guidelines? One major difference between the US and England is socialized vs private healthcare. The goal of private insurance is to make money. Prescription medications make insurance and pharmaceutical companies A LOT of money. Antidepressants alone are a $15.6 billion market in the US. And that’s not accounting for any other psychiatric medications.

The clearest indication that pharmaceutical companies are for profit in the US? TV commercials. In Europe, pharmaceutical companies are banned from advertising medications. Pharmaceutical companies also regularly give money to government entities, which regulate the FDA. Pharmaceutical companies are the ones funding their own research on medications. Doctors are given lunches, talks, and free items by pharmaceutical drug reps to increase their exposure, leading to more prescriptions. Socialized healthcare systems must prioritize using medical resources judiciously, thus careful evaluation of medication effectiveness and outcomes is performed. I say this not to extol socialized medicine, but rather to highlight the hidden motivators for medication prescription that shape treatment guidelines in different healthcare systems.

Why does the difference in treatment guidelines matter? Because the widespread prescription of antidepressants isn’t alleviating people’s suffering the way it promises. Because antidepressants have side effects that affect quality of life. Because antidepressants cause physical tolerance resulting in withdrawal symptoms when stopped. Because people who are already hopeless end up thinking there’s nothing left for them because antidepressants didn’t work for them.

Rates of depression and suicide have significantly increased over the last 30 years while antidepressants have been the first line treatment in America. That’s not to say that antidepressants are causing depression, but rather, that if they were as effective as the way they’re marketed to be, the rates would not keep increasing. It also matters because if we continue down this path, insurance companies will not change what medical services they cover. For example, gender reassignment was only covered by insurance companies after a lot of attention from the media was placed on the issue.

So where do we go from here?

Given all we know about antidepressants, ideally doctors would make more accurate mental health diagnoses and discuss treatment options for depression including, and outside of, medication. When discussing medications, they would let patients know that there is a low likelihood that antidepressants will be effective in mild or moderate MDD, and be clear about the possible side effects and that their body will likely become tolerant to them making it physically difficult to stop them if they wanted to.

In regards to providing treatment options outside of medication, this begins with a shift in mindset around depression and what causes it. Depression is a multifactorial condition. This means that it results from a combination of different causes and contributors, both physical and non-physical. The multifactorial nature makes mental health treatment complex. Acknowledging this complexity is where most depression treatment falls short. Broadly speaking, depression can result from a combination of two overarching domains - physical and non-physical, which contain the following categories:

  • Physical Domain

    • Metabolic Dysfunction (metabolism refers to all the biochemical reactions that occur within the body to maintain life)

    • Brain and Body Neglect

  • Non-Physical Domain (not an exhaustive list)

    • Distressing experiences, past and ongoing

    • Disempowering thought patterns

    • Weak support systems

    • Inadequate time in (offline) social connection

Within the Physical Domain, Metabolic Dysfunction includes:

  • Blood sugar dysregulation and insulin resistance

  • Low vitamin D, omega 3 fatty acids, or iron levels

  • Abnormal magnesium, zinc, copper, iron or lithium levels

  • High mercury or lead

  • Protein indigestion

  • Intestinal bacterial imbalance

  • Methylation imbalances and low B vitamins, including B12 and B9

  • Thyroid dysfunction

  • Celiac disease and gluten intolerance

  • Specific food intolerances

  • Sleep apnea

Within the Physical Domain, Brain and body neglect includes:

  • Low nutrient diet

  • Insufficient sleep

  • Insufficient water intake

  • Insufficient movement

  • Inadequate stress recovery (reflected as low heart rate variability)

  • Exposure to toxins (from seed oil-laden processed foods to pesticides)

  • Addictions (to social media, the news, and substances like caffeine, alcohol, nicotine, and cannabis)

This shift in approach then leads to a new evaluation process for anyone presenting with depression. It’s an extensive work up, with lab work and lifestyle audits and questionnaires, but is completely worth it. Because once someone’s unique combination of causes and contributors are uncovered, multiple treatment options outside of medication are revealed. Medication may or may not be a part of the treatment plan, but if so, it will have clearer goals instead of vaguely hoping that it’ll generally decrease depression symptoms.

The current conventional mental health model provides psychiatric medication and talk therapy as the two main treatment options for depression. Psychiatric medications, the first line treatment option, does not address the physical domain components. Talk therapy, the other mainstream treatment option, mainly addresses the non-physical domain of depression causes and contributors and is a crucial part of depression treatment. It’s time to appreciate the various causes and contributors to depression and include treatments like nutrition, sleep, exercise and stress recovery coaching, addiction treatment, education on decreasing toxin exposure and supplementation of nutrient deficiencies in depression treatment, alongside or outside medication treatment.

Ideally, this shift in approach would lead to changes in treatment guidelines and insurance-covered psychiatric evaluations and treatments. On an even broader scale it might lead to changing laws about the availability of processed and sugar-laden foods or it might make social media platforms have a disclaimer that the app is addictive. Big problems need big solutions.

The above is a glimpse into a holistic psychiatrist’s treatment approach. It’s been helpful to many, especially to those who

  • have been failed, partially or wholly, by psychiatric medication

  • want to avoid psychiatric medication

  • want to come off psychiatric medication

Brain-Body Psychiatry brings you better mental health treatment through holistic psychiatry.

We all need guidance, support, and accountability in making the changes that achieving mental health requires. If you’re interested in this approach, I am very excited to work on this together.

With care,

Dr. Luisa Cacciaguida

Sources:

Disclaimer:

This blog post is intended to be informative and does not replace individual medical advice. Always consult with your healthcare provider or a professional for any personal medical decisions or concerns you may have. Everyone's health situation is unique and should be evaluated by a healthcare professional.

This blog post is designed as a general guide. This is not a substitute for personalized medical advice, nor is a patient-physician relationship established in this blog post.

Luisa Cachiaguida
Previous

Unlocking Natural Mental Health: How Functional Psychiatry Goes Beyond Symptoms
Next

You probably haven’t heard of these treatment options for Long COVID