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Help! My Antidepressants Aren’t Working

Treatment must address both environmental and genetic factors.

By Eric M. Plakun, MD

George Rudy/Shutterstock
Source: George Rudy/Shutterstock

The most current research on depression shows that it is most often caused by a combination of both environmental and genetic factors. Treatment for depression, therefore, works best when it addresses both these factors and takes into account an individual’s unique personal history. A common issue with a medication only approach is that it is a "one size fits all" treatment, when depression is different for everyone.

Sharon's story:

Sharon is a 29-year-old woman who suffers from depression, anxiety, and binge eating. Her shaky sense of self has led to a pattern of unstable relationships and trouble with commitments.

Sharon's brother, her only sibling, died when she was 10 and her parents divorced soon after. This was the first time she experienced depression. In her 20s, a series of relationships went badly and she became even more depressed. After becoming preoccupied with suicidal thoughts, Sharon consulted a psychiatrist. She went through trials of two antidepressants but was still depressed.

The psychiatrist had done a thorough evaluation including blood work to rule out thyroid disease or other medical causes of depression. He told Sharon that her depressive episode was superimposed on a longstanding depressive disorder, generalized anxiety disorder, binge eating disorder, and possibly borderline personality disorder. Sharon was bewildered by the list, expecting to be told she had just one problem.

Sharon’s psychiatrist made some sensible decisions in choosing antidepressants. He chose medications that would help not only with depression, but also with anxiety and binge eating.

In their most recent monthly visit her psychiatrist proposed switching to a third drug, but Sharon declined. She had lost confidence that a new medication was the answer.

The problem with medication trials:

Antidepressant medication trials are conducted on patients who are carefully screened, excluding people like Sharon who have other concurrent psychiatric and substance use disorders, and/or histories of suicidality. Therefore, these medications are tested on a select minority of depressed patients, leaving out the 75-80% of patients who have other mental health issues.

The fact is that most antidepressant drugs fail to lead to much reduction in depression symptoms for most patients most of the time, especially for people who have multiple disorders and a history of early adverse experiences like loss, neglect, deprivation, or abuse.

When is therapy the best option?:

Research indicates that chronically depressed patients with early adverse experiences respond more positively to therapy alone than to medication alone. However, a combination of drugs and therapy is more potent than either alone. {Nemeroff CB, Heim CM, Thase ME, et al} So adding therapy to medications is a good strategy. Multiple kinds of psychotherapy have been shown to be effective both for patients with both uncomplicated depression and for complex depression caused by many factors. Psychodynamic therapy in particular is effective with “treatment resistant” depression that has failed to respond to at least two drug trials.

Genes and depression:

The latest research can help us understand the benefit of combined medication and therapy. Although researchers hoped to find genes that cause depression, none have been found in extensive searches. The genetics of depression and most other common mental disorders are quite complex. It is likely that many small genetic components play a role, along with environmental factors like the sort of experiences Sharon had when she was 10 in causing people to become depressed. Since key relationships turn out to play such a significant role in causing depression, it makes sense that a trusting and important relationship like the one with a therapist is a powerful way to engage and make gains.

Since the latest research teaches us that it is both nature AND nurture that account for mental illness, it makes sense that both ought to be part of treatment. Biology alone does not account for the presence of mental disorders like depression. Similarly, drugs alone are inadequate to address the problem.

What helped Sharon?:

Sharon found a new psychiatrist who offered both drugs and psychodynamic therapy in weekly sessions. She is improving as she addresses issues from her early life and sees the impact they are having on her today. The tragic death of her brother and her parents’ subsequent divorce led Sharon to feel she needed to soldier on. But this has kept her from facing and mourning the serious losses she faced so early in life. These were important but missing pieces of her treatment when it was focused on a medication-only approach. The missing pieces are now coming together in a way that is helping her make sense of how early losses led to depression. Putting the losses into perspective is also helping her realize the role they played in her relationship and commitment troubles. She is moving forward in life, and is hopeful about a new relationship. She still takes an antidepressant, but just that one drug, and feels it is helping.

About the Author: Eric M. Plakun, MD is Associate Medical Director and Director of Biopsychosocial Advocacy at the Austen Riggs Center, and former Harvard Medical School clinical faculty member. He is also the editor of two books, including Treatment Resistance and Patient Authority: The Austen Riggs Reader (Norton, 2011)

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