If Antidepressants Don’t Work

I decided to write this article as a response to the many cases I encounter when antidepressants don’t help people with a diagnosed major depressive disorder.

For these people the situation when drugs fail to produce relief from this debilitating experience is dire, but it doesn’t have to be.

The hopelessness and helplessness that set upon failure of prescribed drugs add to already existing depressive condition, cause despair and even suicidal thoughts.

I’m not a psychiatrist, I don’t prescribe drugs, so don’t take this text as any sort of medical advice: it’s not.

I’m a coach and a clinical psychologist, and I want to offer a wider view on depression with one main goal: to show that medication treatment failure doesn’t make one resistant to treatment and doesn’t make the case hopeless.

What is Major Depressive Disorder

Let’s start with understanding what MDD (major depressive disorder) actually is.

First of all, we all can be in a bad mood, we can endure acute stress and its consequences, we all can be sick and tired of things, demotivated, sad, etc. If this state is transient, if it is a response to an actual life situation (e.g. sadness after loss of a friend) and if you can effectively cope with it (e.g. a long restful sleep does away with tiredness and demotivation), this is not MDD. It’s just a natural part of human experience.

Depression is diagnosed based on the following criteria in the DSM-V (a handbook that doctors use for diagnosis). To be diagnosed with MDD a patient should observe 5 or more of these conditions “nearly every day”:

Frequent depressed mood

Loss of interest / pleasure

Weight loss or gain

Insomnia or hypersomnia

Psychomotor agitation or retardation


Feeling worthless or excessive / inappropriate guilt

Decreased concentration

Thoughts of death / suicide

In addition, all four of these should be reported:

Symptom cause significant impairment of normal functioning

They should not be attributed to the use of substances

They should be explained by other psychiatric disorders, such as schizophrenia

There should be no history of manic or hypomanic episodes.

I am giving you these details to make an important point: Major Depressive Disorder (just like many other mental disorders, such as ADHD or PTSD) is not a disease in the conventional sense.

And therefore they can’t be treated like conventional bodily diseases.

Conventional somatic disease is when something wrong happens to our known biological functions. For instance, skin disease called “impetigo” (often happens to children), is caused by bacteria and the skin’s response to that bacteria.

This is when drugs work perfectly: we apply antibiotics to the skin, kill the bacteria, and the skin quickly heals.

Depression is NOT a disease in this sense. We don’t really know what exactly causes it. Yes, there is a physiological explanation to depression, claiming that depression is caused by serotonin imbalance. This theory was suggested in 1965 by Joseph Schildtkraut as a hypothesis. The many researches and experiments conducted since then didn’t prove this hypothesis. However the hypothesis, although unproven, made its way into pharmaceutical commercials. (ref. Lacasse and Leo, 2005 )

Depression is a syndrome: meaning, it is a set of symptoms without one exactly established cause for them. Usually what causes depression is a complex combination of physiological, cognitive, psychological, developmental processes interweaved with each other.

This is exactly why attacking one possible biochemical cause (the function of the drugs) doesn’t guarantee successful treatment. Not because the patient is treatment resistant, but because such is the nature of a syndrome.

But Antidepressants Helped My Friend…

When I mention that since depression is a syndrome and not a disease, nothing can be guaranteed about medication treatment the most popular response I get is:

“But antidepressants helped my friend / cousin / Facebook friend / all other patients of my psychiatrist”.

Remember, the criteria of depression include exaggerated sense of worthlessness and guilt. Depressed people would rather blame antidepressant treatment failure on themselves, than acknowledge that its success is never guaranteed for anyone in the first place. Such is the nature of the syndrome. It is important to recognize it, and not mistake such thoughts for true analysis of chances to recover.

Therefore labeling depressive patients as “treatment resistant” is a) fairly easy b) fairly harmful.

Why do antidepressants help in some cases and don’t help in others? 

There can be many explanations, I’ll offer some:

1 — Maybe in some cases the core reason for depression is an imbalance of serotonin reuptake, and medications that address this problem actually prove to be effective.

2 — In some cases medications are taken alongside with other psychotherapy approaches, and it’s hard to tell what exactly facilitated recovery.

3 — Research of antidepressant efficacy repeatedly demonstrates significant placebo effects. For example, a meta-analysis of FDA research published in Psychotherapy and Psychosomatics (Pigott et.al., 2010) concludes that antidepressants are only marginally efficacious compared to placebos. Depressed people may respond to the feeling that they are in control of the situation better than to the actual biochemistry of medication.

If someone followed a prescribed antidepressant treatment and is feeling better, it is great, and we can only be happy and grateful for their success in fighting depression. But this success doesn’t imply that those who didn’t respond to medical treatment are hopeless.

So What Can We Do about Depression if Drugs Don’t Work

Now, let’s see what exactly can be done to approach depression.

The following approaches are based on “Clinical Handbook of Psychological Disorder” by David Barlow.

Understand “Cognitive Schemas”

“Schemas” are cognitive pictures or narratives of reality and yourself in this reality. Depression is associated with maladaptive cognitive schemas, that 1) suggest a priori negative “truth” about oneself 2) are triggered by certain situations 3) are extremely emotional 4) are usually resulting from dysfunctional developmental experiences.

Understanding those inner narratives about the world and yourself in it often helps to correct and replace them with more adaptive schemas and overcome depression. CBT practitioners are trained to work with such schemas.

Experience collaborative and interpersonal relationships

Lack of supporting relationships is the tragic reality for depressed people, and depression often results from damaged relationships. When a depressed person is placed in supportive collaborative environment, receives respect and consideration, reminded of their abilities and potential, comforted and understood in their emotional struggle, chances for recovery are higher.

Take control over automatic thoughts

A lot of painful and destructive experiences in depressed states come from automatic thoughts. These are attitudes, interpretations of events and self assessments that we don’t intentionally think through, but that appear in our minds automatically. Automatic thoughts are very powerful because they form how we perceive reality and how we respond to it.

Automatic thoughts in depressed people are maladaptive and negative.

Understanding them, defining them, and developing the skill of correcting those negative automatic thoughts with more functional and adaptive ones help in depression.

Behavioral activation: scheduling activities and accountability

Probably the best known sign of depression is physical inactivation: a depressed person stays in bed, not wanting to do anything, including basic hygiene. Any task and chores seems too hard and meaningless at the same time.

This is when behavioral activation helps: with support of a professional a depressed person plans the actions that they can commit to, schedule them very specifically, and relearn the skill of following the plan.

If the planned actions turn out to be too much of a challenge, the plan is corrected accordingly.

The goal of this approach is not to get stuff done, but to reactivate the nervous system of a depressed person to a functional state through small achievements. Scheduled activities help obtain more pleasure and greater sense of accomplishment from activities on a daily basis.

Somatic stress relief techniques, such as breathing, massage, aromatherapy, exercises

Sometimes depression is a response to intense stress, and intense stress has a physiological aspect to it. Physiologically stress is activation of the sympathetic autonomic nervous system that is designed to prepare the body to effectively fight or flight.

If the real situation doesn’t imply physical fighting or running, then activating the parasympathetic (safe and relaxed) mode of the nervous system is a good idea.

That’s why the physical effect of relaxation and breathing techniques can be life-changing for a depressed person.


To conclude this article I want to emphasize that depression is a complex condition.

It can have many causes, and it certainly creates many consequences. Those consequences — failed relationship, damaged careers, etc., — feed back into depression through stress, frustration, more reasons to think negatively about self and life.

Therefore recovery of depression is a complex, multi-stage process that starts with recovering basic functions, addressing organic conditions, continues with building new coping skills and adaptive cognitive schemas, and ends with building new Self, achieving desired goals and creating desired life conditions.

It is a true Hero’s Journey, it takes courage and support to embark on one, and there is no “one-fits-all” route for this journey.

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