A type of depressive syndrome that I don't think you mention is chronic, low grade depression that in my opinion is related to chronic systemic inflammation caused by multiple medical problems. I work with a lot of patients who have several chronic conditions such as diabetes, hypertension, or heart disease. They tend to present with a low grade type of depression characterized by low energy and motivation, fatigue, anhedonia, low mood, poor sleep, and isolation. They don't seem to have anything in their presentation or history that would trigger me to think of bipolar, melancholia, or neurotic depression. There is some evidence looking at the role of chronic inflammation in mood issues. I haven't found them to respond very well to "traditional" depression treatments such as SRIs or cognitive behavioral therapy Often they come to me already on duloxetine (Cymbalta) for chronic pain issues or may have been started on citalopram, sertraline, or other SRIs by primary care. If the mechanism is more inflammatory, it may not be a surprise that their depressive symptoms aren't responding to these medications. Sometimes I use bupropion for the stimulant like effects, but I haven't found a good solution for most of them. What are your thoughts in these patients?
The question of depression and inflammation is interesting. As you note, there may be kinds of depressive syndromes that are based in medical causes that are unrelated to manic-depressive illness (bipolar or unipolar depression), and unrelated to specific subtypes of depression such as mixed depression, melancholia, or neurotic depression. All the above depressive presentations are part of what might be called “primary” depressive illnesses, or, for want of a better word, “psychiatric” causes of depression. Medical illnesses can cause “secondary” depression in persons who do not have the “primary” psychiatric causation of family genetics. In those medical cases, the depressive syndromes are caused by various factors. Perhaps the most common is so-called “vascular” depression, which involves brain micro-infarcts leading to white matter abnormalities. This condition is associated highly with diabetes and/or hypertension, and monoamine agonists (antidepressants) are less effective in these vascular depressive conditions, as opposed to primary depressive conditions.
You raise another major medical cause of depression, which is known inflammatory disease. Some would argue that all depression involves inflammation, which is present in the pathophysiology of depressive states. Cytokine activity is increased, natural killer cell activity is decreased, and various changes are present in the kynurenine system which many think relate to the link between inflammation and depression. Many monoamine agonists have anti-inflammatory effects in persons with depressive syndromes; in other words, when their depression improves, their inflammatory states normalize with monoamine agonists.
However, the reverse doesn’t seem to be the case: anti-inflammatory agents that are not monoamine agonists (like NSAIDs) have been studied in acute depressive episodes and...