3 overlooked causes of treatment-resistant depression

Treatment-resistant (refractory) depression has been a hot topic for decades (eg, Freyhan, 1978; Nierenberg & Amsterdam, 1990; Voineskos, 2020). Unfortunately, as Voineskos noted, treatment-resistant depression is generally defined as patients who have failed two antidepressant trials. This condition apparently allows little consideration other than biological intervention.

Gerd Altmann/Pixabay

Source: Gerd Altmann/Pixabay

Knowing that mental illness tends to be a biopsychosocial equation (i.e., Tripathi et al., 2019), it is not surprising that the treatment resistance concept primarily considers a pharmacological perspective. Amazing. Some researchers have begun investigating the efficacy of psychotherapy combined with pharmacology for treatment-resistant depression cases. For example, Van Bronswijk et al. (2019) compared 22 pharmacology studies. and psychotherapy vs that’s all Pharmacological interventions for difficult-to-treat cases. They found the former to be more effective and suggested that psychotherapy should be included in treatment-resistant depression guidelines.

Additionally, if someone has been told depression is tolerant, it’s worth considering what they were tested for. Depression is often a secondary effect of a larger problem, and both prescribers and therapists may be focused solely on relieving symptoms of depression. It stands to reason that little improvement will occur if activation issues are not resolved. It’s like constantly trying new painkillers to try and calm the pain instead of removing a big thorn.

As the reader can imagine, to say that debilitating depression is tolerable means that it is “untreatable.” This can add to the problem of iatrogenic disease, exacerbating the depression and hopelessness of the initial diagnosis.

Below are three other areas to consider if someone’s depression is seemingly treatment-resistant.

personality pathology

People with personality disorders often have comorbid depression. In 1996 Tase wrote, “The role of personality disorders in the management of treatment-resistant chronic depressive states is one of the least studied but more interesting topics in the treatment of mood disorders.” rice field. This is not surprising given the chronic effects of markedly maladaptive interpersonal styles in individuals with personality disorders. However, there is still relatively little research in this sector.

This relationship between depression and personality is easily explained by avoidant personality disorder (AVPD). People with AVPD have a prevalent pattern of negative self-evaluation in comparison to others, which leads to social inhibition. In effect, they feel unworthy and nobody wants to be associated with them, so why bother to be scrutinized? They lack self-confidence and motivation and tend to fail to achieve what they want because they believe they will either fail or be subject to strict scrutiny. An acquaintance of mine with her AVPD, who recognized this pattern herself, once said: “I’m just a dreamer.”

It is easy to imagine that such a view of life drives people into depression. Naturally, health care providers may assume that inhibitions and lack of self-confidence are due to depression, and thus work sharply to alleviate symptoms of depression. Unfortunately, depression is downstream of her AVPD, and in the absence of definitive research into personality complications, direct studies of depression are likely to provide tenuous stability at best. Indeed, Banyard et al. (2021) conducted a meta-analysis and stated: [personality disorder] Improvement tended to be slower than untreated patients. [personality disorder] After CBT for depression. ”

Health care professionals concerned about treatment-resistant depression may want to consider whether personality plays a role. Depression is not uncommon as a symptom of Diagnostic Statistical Manual (DSM) personality disorders, particularly Borderline Personality Disorder, Histrionic Personality Disorder, Avoidant Personality Disorder, and Dependent Personality Disorder (DSM-5). Other personality styles not included in the DSM (such as depressive, passive-aggressive, and suicidal) (i.e., Millon, 2011) are also often depressive.


The impact of trauma is devastating, and it is not surprising that depression is highly correlated with trauma and PTSD (e.g., Shalev et al., 1998; Afzali et al., 2017). In addition to this, not all traumatized people report it (i.e., U.S. Centers for Disease Control, 2023), so it is reasonable to speculate that treatment does not necessarily introduce trauma. . Similarly, not everyone who acknowledges trauma during therapy is willing to work on that trauma. Considering the foregoing, we see how depression maintains a fertile bed for chronic flowering.

depression essentials

For health care providers who have an intuition that trauma is just around the corner but not on the surface, it may be helpful to ask aloud whether there are buried conflicts the person has not yet shared. do not have. For example, “Alex, we have been battling depression for months. seems to have locked you in depression.”

Health care providers with obstinately depressed patients with known but unaddressed trauma may wish to carefully consider their approach to trauma work. Educating patients about the correlation between depression and trauma can be an effective start, and can prove to be a “double-step” to resolve. Resolving the trauma can lift the clouds of depression.

Gerd Altmann/Pixabay

Source: Gerd Altmann/Pixabay

circadian rhythm

In 2009, researchers Kalman and Kalman published a study called “Depression as a chronobiological disease.” This illustrates the complex relationship between our synchronicity with our natural rhythms and depression. Since then, circadian rhythms and mood have become burgeoning topics in depression research (eg, Robillard et al., 2018; Walker et al., 2020; Crouse et al., 2021). Some researchers, such as Boehler et al. (2021), conducted animal studies and found that biogenetic complications within the suprachiasmatic nucleus, the part of the brain that sets circadian rhythms, may contribute to depression. found to be a contributing factor (Ma & Morrison, 2022) and may soon provide further insight into the human experience.

The underlying hypothesis is that circadian rhythm disruptions cause significant sleep disturbances and/or other hormonal imbalances, the downstream effects of which are mood disorders (e.g., Vadnie & McClung, 2017; Lamont et al.). al., 2022).

Anyone who’s ever been sleep deprived knows that one night’s insomnia can lead to moodiness, poor concentration, and fatigue. Now imagine if a person’s circadian rhythm is equivalent to a slipping timing belt in a car. Just like a car, it can become chronically ill. Lack of sleep combined with constant moodiness, poor concentration, and persistent fatigue can lead to disinterest in previously enjoyed activities, loneliness, and, if chronically tired, suicidal thoughts. is even triggered. This is an image of depression, but rooted in sleep or chronobiological pathology.

Health care providers who care for patients who have had little success with antidepressants or psychotherapy despite good efforts may also consider referring the patient to a sleep specialist. This is especially true given his history of working three shifts like a pilot and frequently crossing time zones, with irregular sleep patterns built into his life. It applies.

Disclaimer: The content provided in this post is for informational purposes only and is not intended to diagnose, treat, or prevent any illness from you or anyone you know. This information should not replace individualized care or intervention by private health care providers, or formal supervision in the case of physicians and students.

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