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CLINICAL DEPRESSION
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TABLE OF CONTENTS
V. SUCCESSES AND ADVERSE EVENTS
Depression is a term commonly used to refer to a downturn in mood characterized by a loss of pleasure and an overwhelming sense of sadness or hopelessness. Depressed patients are often restless, irritable, and, in many instances, constantly struggle to overcome suicidal thoughts. Though many individuals often feel sad or upset, clinical depression as the medical community defines it refers to a state of melancholia or despair that has lasted for a relatively long period of time – anywhere between a few months to several years, depending on the patient – and has advanced sufficiently to the point of being disruptive and harmful to the individual’s daily activities and social functioning.
Depression is a common but serious illness affecting 9-12% of the American population – approximately 17.6 million Americans per year. The prevalence of the disease is largely due to the fact that it is overdetermined: there is no single known cause for depression. Rather, it arises from a combination of genetic, biochemical, environmental, and psychological factors.
Depression can arise when the limbic system, the part of the brain responsible for regulating human emotions and responses to external stimuli, fails to properly respond, thereby affecting the patient’s mood and behavior. The limbic system includes numerous parts of the brain, most notably the amyglada, which is responsible for facilitating a sense of satisfaction, fear, and social interaction, and the hypothalamus, which regulates body temperature, sleep, appetite, stress response through the controlled production and release of hormones. Abnormal levels of these hormones can affect physical activity and mood. In short, the limbic system controls an individual’s emotional response to stimuli. A failure to respond properly may lead to depression.
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Furthermore, neurotransmitters such as serotonin, norepinephrine, and dopamine are known to play a significant role in the regulation of emotions. In healthy individuals, these neurotransmitters can be found in the brain in specific concentrations. Should they be produced or consumed in abnormal quantities, they may create a chemical imbalance that causes depression. For example, reduced serotonin levels are believed to cause depression.
Studies have shown that depression sometimes tends to run in families, suggesting that individuals with a large number of depressed relatives are more likely to become depressed. Women are also more likely to suffer from depression than men. It is important to remember, however, that anyone can become depressed, and it is likely that multiple genes coupled with environmental stimuli act together to increase risk of depression.
Personal circumstances and events often trigger depressive episodes. The death of a loved one, a traumatic event, or even high levels of stress at home or work can cause depression. It is important to note that how much an individual is affected by environmental factors is largely dependent on their own personal constitution.
Deep Brain Stimulation is a relatively new method of treatment that has the potential to improve the lives of a large number of depressed patients. It is important to note, however, that DBS is only recommended for those patients whose depression does not respond to more conventional therapies. This refractory depression constitutes approximately 20% of all cases. The use of DBS on depressed patients was spurred by its success in treating patients with Parkinson’s disease. Furthermore, interest in DBS as a treatment for depression has been encouraged by the increased popularity of both invasive and non-invasive neurostimulation techniques, which has in turn been encouraged by increasingly beneficial discoveries concerning the pathologies of several psychiatric disorders.
Due to its recent discovery, the use of DBS to treat depression is still far from comprehensive clinical trials. Since the treatment shows real promise, however, several major institutions are conducting trials. As of 2006, 50 patients worldwide had received DBS as a therapy to treat obsessive-compulsive disorder or depression.
When treating depression with DBS, the implantation and programming of the neurostimulator and leads are very similar in practice to its use in patients with Parkinson’s or epilepsy. What differs, however, is the specific area of the brain targeted by the stimulation. The two most significant studies concerning the use of DBS to treat depression each targeted different areas of the brain:
- Mayberg et al., 1999
- Schlaepfer et al., 2007
Targeted Area: White matter close to subgenual cingulate in Brodmann area 25
Reason: The area has been linked to acute induced sadness; it is a metabolically overactive region in refractory depression, improvement after treatment is marked by decreased metabolic activity in the region
Targeted Area: Ventral striatum and nucleus accumbens
Reason: Ventral striatum is greatly involved in normal and abnormal reward processes, nucleus accumbens acts as a bridge between the emotion and motor control, ventral striatum is conveniently located to modulate activity in other regions of the brain
Deep Brain Stimulation is only used as a last resort in treating depression. Numerous other methods, each with a different level of efficacy, have been used to treat depression. Chief among these treatments are medications, psychotherapy, and, in some cases, electroconvulsive therapy. All three have been shown to help depressed patients, but, as can be expected, results vary between individuals and methods.
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The drugs prescribed to depressed patients are typically neurotransmitters that work to normalize the levels of serotonin, norepinephrine, or dopamine in the brain. The newest and most popular drugs are Selective Serotonin Reuptake Inhibitors (SSRIs) that work to increase the levels of serotonin in the brain. Common prescribed medications are Prozac, Celexa, and Zoloft. Monoamine oxidase inhibitors (MAOIs) are also used occasionally, but too often they have undesired side effects.
Psychotherapy, or “talk therapy” involves meeting with a professional, often a doctor or psychiatrist, to discuss life changes and new ways of thinking and behaving. Though it may be the best treatment option for mild to moderate depression, psychotherapy is most often used in conjunction with drugs in more severely depressed patients.
In more extreme and unresponsive cases of depression, electroconvulsive therapy (ECT) is often used. This treatment is similar to DBS, the biggest difference being that in ECT, the electrical shock is administered externally and stimulates the surface of the brain instead of having the electrodes implanted into the brain.
Though the possible side effects of DBS may seem drastic, when compared to the adverse effects caused by the other common treatments for depression – medications and psychotherapy – DBS appears to be a very potent and effective form of treatment. Psychotherapy is often ineffective in treating severe depression, while antidepressants cause numerous, sometimes fatal, side effects including insomnia, agitation, sexual problems, and even suicidal thoughts, especially in adolescents. For this reason, DBS, though a much more invasive procedure, offers the advantage of being effective, yet fully reversible. It can also be easily tailored to fit the need of each unique patient. It is important to note, however, that the lifelong monitoring and treatment offered by DBS may not be ideal for everyone.
Overall, the few trials that have been conducted suggest that DBS is a very promising treatment for depression. A study conducted by researchers by researchers from the University of Toronto on six patients with refractory depression showed significant improvements in the patients’ health, accompanied by a feeling of calmness and connectedness. All patients showed improved moods during the six-month study, and four of the six even experienced long-term remission of their depression. These results were perfectly consistent with the other research. In general, using DBS on a depressed patient has very quickly improved their mood and general state of being. The efficacy of the treatment has even been validated by showing that depressive symptoms appear and disappear when the neurostimulator is turned off and on, suggesting that the electrical impulses are, in fact, responsible for the patients’ improved condition.
Adverse events in the use of DBS to treat depression are usually a result of the surgical implantation of the device and not the actual treatment itself. The most common side effects include bleeding in the brain (hemorrhage) and infection; though in some instances the patient may suffer from delirium, unwanted mood changes, movement disorders, lightheadedness, or insomnia. Most often, however, these side effects only occur during the first several days post-implantation and end when the therapy has been formatted to best suit the patient.
Cleveland Clinic - Neurological Institute
University of Toronto - Research page
Emory University - Research page