A new article in the magazine Neuropsychopharmacology indicates that brain stimulation treatments such as electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) were among the most effective treatments for treatment-resistant depression, usually defined as severe depressive symptoms that did not improve despite treatment with at least two standard interventions. The study examined the results of 25 different standard treatments in studies involving more than 10,000 participants. Also one of the most effective treatments was ketamine. Minocycline, a drug perhaps better known as an acne treatment, was, at least to this psychiatrist, a bit of a surprise.
Electroconvulsive therapy was perhaps the first treatment for major depression to be developed. Hungarian psychiatrist Joseph Ladislav von Meduna published a report in 1935 that artificially induced seizures in patients with severe depression led to dramatic improvements for many. Improvements in anesthesia techniques in subsequent decades have made the treatment much safer, and it remains a treatment of choice for certain forms of major depression.
Like ECT, transcranial magnetic stimulation (TMS) is also a brain stimulation treatment, but it delivers much smaller bursts of electrical energy using magnetic pulses. The survey also gave high marks to a new version of TMS called theta burst stimulation (TBS), in which the magnetic pulses are delivered at frequencies that mimic the natural electrical rhythms of the brain.
Ketamine Targets glutamate, one of the brain’s communication chemicals or neurotransmitters, but one that other antidepressants don’t have much effect on.
Minocycline, in addition to the antibiotic effects that make it useful for treating acne, also has neuroprotective effects, protecting brain cells from a damaging process known as oxidative stress. This toxic process is caused by dangerous molecules that are created during many chemical reactions in the body and are not sufficiently neutralized by the body’s defenses against them.
In general, antidepressants work by changing the levels of chemicals in the brain neuroamines. These are the nitrogen-containing molecules that serve as chemical messengers in the brain. Serotonin is probably the best known. Since the first of these antidepressants, imipramine, was introduced in the 1950s, every subsequent drug has essentially been a variation on this theme. While these medications are very effective for some people with depression, as this post shows, there is a subset of depressive disorders where targeting neuroamine levels simply doesn’t work.
Brain stimulation treatments such as ECT, TMS and TBS appear to directly stimulate underactive areas of the brain and restore a normal balance between electrical activity and brain function. Ketamine also appears to stimulate brain cells directly, albeit through chemical rather than electrical effects. The neuroprotective effect of minocycline is also consistent with the idea that underactive neurons in certain parts of the brain cause some cases of major depression. (By the way, lithium, the “magic bullet” for so many people with bipolar disorder, also works through neuroprotective mechanisms.) Minocycline appears to provide a layer of protection that allows these neurons to function normally again.
Understanding how these new treatments treat depression will undoubtedly stimulate more research into the pathological mechanisms of mood disorders and result in even more new treatments for these debilitating diseases.
