I have been known to lament that there’s nothing new under the sun when it comes to depression treatment, and thus, there is little hope for people with true treatment-resistant depression. (And by treatment-resistant depression I mean people who really have tried everything, and there are few in this category.)

But I forget how far we’ve come and how fast. It isn’t fair to say there aren’t new approaches to treatment-resistant depression because there are new approaches being researched and approved every year. Here are a few noted by Current Psychiatry article Innovative approaches to treatment-resistant depression:

1. Genes vs. the Environment

We did think that we would be able to find a “bipolar or depression gene,” just as we’ve found a Huntington’s gene, that would allow for genetic testing of bipolar disorder and depression. Now we know, though, that hundreds of genes make up the cause of bipolar disorder and depression and the environment plays a key role in whether bipolar or depression manifest.

2. From Chemical Imbalance to Inflammatory Process

We once called depression a “chemical imbalance” and even though professionals have known this wasn’t the case for decades we haven’t really had any model that stood in for the chemical imbalance one. Now we’re considering that depression is related to an inflammatory process (yes, anti-inflammatories are being tested) and “studies show levels of inflammatory cytokines and interleukins rise during a depressive episode and decline when the depression remits.”

3. From neurotransmitters to Neuroplasticity and Neurotropic factors.

We once thought that depression was all wrapped up in neurotransmitters like serotonin, but we’re now realizing this is only part of the picture. One of the things we have now realized is that depressed brains shrink and this is likely due to a decrease in brain derived neurotropic factor (BDNF) and other factors involved in neuroplasticity and neurogenesis (the brain being healthy and able to properly create new cells).

4. From Serotonin, Norepinephrine and Dopamine to Glutamate

As I mentioned, we used to think that serotonin was where it was at in terms of the causes of depression. We then widened our net to include the neurotransmitters norepinephrine and dopamine and while all three of these have a role to play in depression, we now realize that glutamate does too. I’ve been saying for a while that I think glutamate is the next big thing in antidepressant medication. We can see an example of that in n-acetlycysteine treatment.

Ketamine IV Infusion Treatment for Depression5. From Pills to Infusions

Personally, I’m not sure this is super-good news because it’s an expensive form of treatment, but we are now looking at intravenous (IV) infusions of medications as well as pills for the treatment of depression. The key example of this is ketamine. A ketamine infusion (NOT the street drug) produces an acute antidepressant response in people within 1-2 hours of taking it, and this includes people with treatment-resistant depression. The antidepressant effect may be due to a surge in BDNF and neuroplasticity changes probably due to the direct concentrations of the drug that are possible through an IV infusion. However, this happens after the acute effects and the mechanism of action for those is not yet known.

6. From Monotherapy to Augmentation Strategies

Well, this isn’t new if you ask me but we are getting more intelligent about it. We now are using more evidence-based research in deciding what drug to add to another in cases of treatment-resistant depression. Additions to antidepressants for depression may be:

 7. From Pharmacotherapy to Neuromodulation

This isn’t overly new either, but the idea is because medication affects all parts of the body, neuromodulation – which affects only the brain – is superior in terms of side effects. Neuromodulation includes:

The theory is that one day deep brain stimulation – where electrodes are implanted directly into your brain – will be as commonly used for treatment-resistant depression as it is in Parkinson’s disease. (DBS, by the way, is very promising for long-term, highly effective treatment of treatment-resistant depression but the test population sizes have been small for obvious reasons.)

New Approaches to Treatment-Resistant Depression

So we are making headway. It’s important to understand that and not give up hope. We learn more about depression every year and new treatments become viable every year so look for one of the above treatments to be available near you sometime soon.