Clinical trial of deep brain stimulation for depression

Depression is a common neuropsychiatric disorder which affects at least 1 in 7 adults. The condition can have a major effect on patients' quality of life, and is a major cause of both disability and suicide.

Many patients with depression can be treated effectively with antidepressant medications, such as the specific serotonin re-uptake inhibitor (SSRI) fluoxetine (more popularly known as Prozac). However, a significant proportion of patients - up to 20% - do not respond to these drugs, or to other forms of treatment.

Now a study published online in the journal Biological Psychiatry suggests that patients with treatment-resistant depression could benefit from a technique called deep brain stimulation, in which an electrode is implanted into the brain.

Deep brain stimulation (DBS) is an experimental surgical technique which involves the implantation of a device called a brain pacemaker into a specified area of the brain. The device is attached by a thin wire to a small battery which is often placed under the skin on the chest. It generates rhythmic pulses of electricity which modulate the activity in the targeted brain region.

In 2002, the U.S. Food and Drug Administration approved DBS as a treatment for Parkinson's Disease, a neurodegenerative disease characterized by muscle rigidity and tremors, and since then has been used to successfully alleviate those symptoms in approximately 40,000 patients with that condition.

DBS has also been used to treat other conditions such as chronic pain and Tourette's Syndrome. And it is not the first time that it has been used to treat depression: in 2005, the same team reported their results from a trial involving 6 patients and last year, researchers from the Cleveland Clinic in Ohio reported their preliminary data from a trial involving 17 patients.

The current study is the largest clinical trial to date of the efficacy of DBS as a treatment for severe depression. Between May 2003 and November 2006, Andrez M. Lozano and his colleagues implanted electrodes into the brains of a total of 20 patients (9 men and 11 women) with major depressive disorder, all of whom were referred to the researchers from hospitals or community psychiatrists, after failing to respond to antidepressants, psychotherapy or electroconvulsive therapy.

The surgery, carried out at Toronto Western Hospital, involved implanting the electrodes into a region of the brain called the subcallosal geniculate cingulate gyrus (SCG), which is thought to be involved in regulating mood and has been shown in functional neuroimaging studies to be over-active in depressed patients.

The SCG was identified in the patients by magnetic resonance imaging; holes were then drilled on both sides of the patients' skulls, and the electrodes inserted through them. The precise locations at which the researcher left the electrodes were determined by behavioural tests - the patients were given a local anaesthetic prior to the surgery, and so remained conscious throughout the procedure. They could therefore report how their mood changed with electrical stimulation of different parts of the SCG.

12 out of the 20 patients reported significant long-term improvements in their condition. This was corroborated by neuropsychological assessments which measured, among other things, the patients' mood, anxiety levels and sleeping patterns. These improvements were observed within 1 month and, importantly, persisted for at least 12 months after the treatment, by which time 7 of the patients had gone into full remission.

However, the exact mechanism by which DBS exerts its effects at the cellular level is unknown. PET scans performed following the treatment suggested that the alleviation of symptoms was caused by stimulation of the SCG white matter (which contains bundles of nerve fibres), leading to both activation and inhibition of multiple distant brain areas. But other studies have targeted other regions of the brain, such as the nucleus accumbens, at it remains to be seen which of these substrates is the optimal target for treatment of depression. It is also unclear why 8 of the patients did not respond to the treatment.

Even so, the study shows that DBS can improve many of the symptoms of severe depression, and that it is a safe procedure that was tolerated well by the patients involved: although the surgical wound became infected in 3 of the patients, and 1 of them experienced a seizure on the evening of the surgery, 7 patients reported no adverse effects whatsoever, and none of those who did not respond to the treatment reported a worsening of their condition.

Related:

• Growing new brain cells to treat depression: A clinical trial
• Severe depression treated with deep brain stimulation
• Deep brain stimulation evokes long-lost memories
• Brain implant cures drug-induced gambling addiction
• Electrode implant stimulates consciousness

Lozano, A. M., et al (2008). Subcallosal Cingulate Gyrus Deep Brain Stimulation for
Treatment-Resistant Depression. Biol. Psychiatry. DOI: 10.1016/jbiopsych.2008.05.034.