Depression - Future Prospects

While great advances have been made through specifically targeting serotonin, other neurotramitters are also implicated in depression.

Brain scans can help reveal the emotional state of a patient [Harvard].

Measurements in people and in animal models indicate that inhibitors of noradrenaline or dopamine reuptake may help people for whom SSRIs are ineffective.

In 1997, reboxetine was the first noradrenaline reuptake inhibitor to be launched in the UK; others are in preclinical and clinical trials. Medicines that prevent the selective reuptake of more than one monoamine transmitter may also provide new antidepressants. The recently approved duloxetine blocks the reuptake of both serotonin and noradrenaline, as does venlafaxine. Bupropion has some effects on dopamine reuptake, another monoamine neurotransmitter implicated in depression. Other drugs that affect the reuptake of the three monoamines to varying degrees are in development.

Although monoamine neurotransmitter reuptake inhibitors are good antidepressants, a deficit in the activity of these neurotransmitters is probably not the primary cause of depression. Work in animals and in patients indicates that stress-induced release of corticotropin-releasing factor (CRF) in the brain may also be involved in depression. When rats are injected with CRF, they develop symptoms reminiscent of depression. Molecules that interfere with the action of CRF have been developed and their ability to block the behavioural effects of CRF tested in rats. Some of these potential antidepressants have now entered early clinical trials.

Another avenue to find better antidepressant drugs has come from work on pain relief. In the search for painkillers that work by targeting a small protein called substance P, scientists discovered that their candidate painkillers were changing the behaviour of rats and mice in the same way as antidepressants. This work too has now progressed into patients.

Researchers are also looking for ways to boost the production of brain-derived neurotrophic factor (BDNF). BDNF keeps brain cells healthy throughout life. They are doing this because established antidepressants increase concentrations of this growth factor while stress decreases it. Thus, depression may be caused or worsened by a gradual loss of brain cells on exposure to stress and boosting production of the growth factor could reverse that loss.

Finally, a better understanding of the mechanism that tells us when to sleep may suggest new ways to deal with depression. Our circadian rhythms, as they are known, tell us not only when to sleep but also when to be active. They are often disrupted in depression. Research in people, other mammals and even fruit-flies and sea-slugs is beginning to throw light on how this aspect of our biology is controlled and may lead to new treatments, particularly for bipolar disorder.

Next Section: Role of Animals