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Depression: Major Depression & Unipolar Varieties
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Mark Dombeck, Ph.D.

People get over most minor sad moods as a matter of course, but clinical depression is another thing entirely. It can come on without warning or as a response to difficult situations and experiences. It can hang around for several weeks and remit spontaneously, or it can linger for years. If it does remit, it can come back to bite again at a later time. It is not an overstatement to say that depression can be utterly disabling in its severe forms.

Scientists have labored for years to find effective remedies for depression, and some very significant treatment approaches have been developed. The first of these to become available was psychotherapy, which emerged at the turn of the last century. The original format of psychotherapy (Psychoanalysis a la Freud) was limited in its efficacy and availability. It was expensive, involving frequent sessions with the therapist, focused on people's past more than their present symptoms, and was only capable of truly helping a minority of patients. But these failings did not take away from the core truth to be found therein: that some forms of mental difficulty, minor depressions among them, were caused by 'inner conflicts' and that fixing those 'inner conflicts' through talking could produce symptom relief.

The watchword for any treatment is how well it works; how much it can help fix a problem. Psychotherapy went through an evolutionary process throughout the next hundred years, changing in format and focus, and undergoing systematic scientific study. What has emerged are modern forms, some specialized just for depression, and known to work well for many of people who undertake them. Cognitive behavioral therapy for depression, for instance is one such result. It is practical, short term in duration and symptom-focused, aimed at helping people to feel better now rather than repair their damaged childhoods. Its designers wanted to isolate the active ingredients of effective therapy and concentrating them into an easier to swallow (and afford) package, and in this goal they succeeded. Therapy is still expensive and still demanding on the attention span, but today it also largely works.

A pharmaceutical revolution occurred during this therapy evolutionary process. The 'Tricyclics' – the first widely available medicines with anti-depressant effects - went on the market at mid-century. These medicines came complete with a range of side effects and were fairly lethal when taken en-mass (as in an overdose or suicide attempt) but they did help lift depressed mood in many cases and so were utilized. Where previously people had seen depression as a moral failing, or weakness, over time it became to be seen as a biological illness. A newer and safer generation of such medicines – the SSRI's – was introduced in the 1980s and became even more widely used. In addition to being safer, the newer generation of medicines were also in some ways more focused on specific brain chemical systems implicated for depression. Their name says it all – “selective serotonin reuptake inhibitors”. They were, in fact, a class of medicines designed specifically to target the neurotransmitter Serotonin.

Still another approach to treating depression was developed during the 1930s and 40s when it was noted that some psychiatric patients seemed to show symptom improvements after experiencing seizures similar to those that occur naturally in epilepsy. At first the seizures were initiated through chemical means (e.g., by manipulating patient's insulin levels), but very shortly on it was found to be safer and easier to produce the required seizures with electricity. Thus was born Electro convulsive Therapy or ECT. ECT remains very much in use today, but for the most part it is reserved for the most severe, treatment resistant cases of depression. Though safer than ever, it still involves induction of seizures, and this is still less safe than psychotherapy, and anti-depressant medication.

Useful as they are, anti-depressant medications, psychotherapy, and ECT are blunt instruments, in large part having their effect across the entire brain. What is needed for the future are more precisely targeted treatments that can effect specific areas and subsystems of the brain primarily responsible for allowing depression (and similar illnesses) to develop and be maintained while sparing others. For example, antidepressant side-effects like erectile dysfunctional and dampening of sexual arousal might be avoided with a more specifically targeted formulation. Progress towards more targeted treatments is ongoing. Just this past week, a news report suggests that a next step towards that destination may have arrived.

A team of scientists in Canada have successfully treated several patients with highly treatment resistant depressions by using direct deep brain stimulation. Instead of broadly treating patients with talk, chemicals or electricity, these doctors have implanted electrodes into a particular region of several patient's brains - the subgenual cingulate (BA25) region – they believe to be most responsible for sustaining severe depression. Wires connect the implanted electrodes to a power source which continually drips small amounts of electrical stimulation directly into that specific part of the brain, forcing it and areas it connects to within the brain to activate differently. Though electricity is involved, this is not like ECT. No seizures are created. Rather, direct application of electricity stimulates the tissues at BA25 to activate in a more normal pattern than before. Because the whole brain is connected together, the whole brain changes how it activates for the better as a result of the beneficial changes at BA25.

Six patients were treated with this electrode approach. According to the report (appearing this month in the journal 'Neuron'), four of the patients have benefited considerably. This remarkable finding is all the more remarkable because these same patients were not responsive to more commonly available treatments. The strong suggestion is that faulty activity at BA25 is a cause of the more general brain dysfunction involved in severe depression, but knowing this for sure will require a lot more research and replication.

This direct stimulation of BA25 technique is a research protocol for the time being. It is not available at your local doctor's office. Much research needs to be done to understand the risks and the benefits of such a treatment. In all likelihood, direct BA25 stimulation will never be a widely available treatment. For one thing, brain surgery is involved; not something you'd want to go through if there were alternatives. For another, the area that seems to be dysfunctional in severe treatment resistant depression may not be dysfunctional in more run of the mill depressions. To the extent that this becomes an available treatment it will likely be reserved for those patients who aren't helped by other means, just as gastric stapling surgery is reserved for those obese people who cannot lose weight through other means.

 

More likely to be available in the near future are similar brain stimulation techniques including electrical vagus nerve stimulation and 'transcranial' magnetic stimulation.  Like the BA25 technique, these other experimental techniques apparently produce antidepressant effects by stimulating focal areas of the brain with current (magnetic fields). Although they are not quite so targeted as described in the Neuron article, they look to be far safer. Really, there is no telling. The research will have to be done before we'll know for sure.

One thing is sure: whether it is a surgical, medical or psychotherapeutic technique for treatment that is next up for discussion in the media, it will be judged not just by how well it works, but also by how much more 'focused' and 'precise' that technique is compared to its predecessors. We like precision today. More and more focus and precision is what we're wanting from our treatments.