La ressource mondiale en matière de preuves scientifiques sur l’expérimentation animale

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Antidepressants

Depression is a debilitating disease, and a major illnesses affecting modern society. The World Health Organization  predicts that by 2020 depression will be the second most common cause of lost working time in the entire worldANCHOR. Current estimates are that:

– Depression carries a risk of suicide, even for patients receiving treatment; and the risk for untreated individuals is greaterANCHOR.

– Approximately one fifth of the population will suffer at least one episode of clinical depression resulting in a significant social and economic burden on societyANCHOR. Progress in the understanding of depression and other mental illnesses has come through a combination of chance observations and clinical studies in human beings, and experimental work on the chemistry of the brain in animals.

Research has provided doctors with at least four major classes of drugs which can be used to treat depression. However, not all patients respond to these treatments and problems still exist with a time-lag before beneficial effects are seen.

Discovery of antidepressants
Drug treatments
The need for future research
References

Discovery of antidepressants

Studies in the 50s and 60s provided a possible biochemical explanation for the cause and potential treatment of depression. The serendipitous discovery that certain drugs used to treat other disorders, such as tuberculosis, could also change mood provided a major breakthroughANCHOR. Around the same time, experiments in both humans and animals (rats, mice and non-human primates) were providing the first evidence that changes in the levels of chemical messengers in the brain, 'neurotransmitters', could alter an individual’s emotional state. These studies provided the first theory of the cause of depression, which is still the basis of current researchANCHOR.

Our current understanding of the way the brain controls our mood and motivation has been achieved through a combination of experiments using healthy volunteers and patients as well as experiments performed in laboratory animals. These experiments primarily use rats and mice although a small number of experiments are also carried out using non-human primates. The basic brain pathways and chemical processes that control mood and motivation are found in all mammalian species enabling researchers to translate findings from species, such as rats and mice, to the human diseaseANCHOR ANCHOR. Rodent models of depression have been crucial in testing hypotheses relating to the cause and treatment of depression, enabling researchers to develop newer and more effective treatmentsANCHOR ANCHOR.

See related webpage 'antidepressants: the role of animal models' (link on the right)

Drug treatments

Drugs developed to treat depression act by increasing the amount of certain chemicals in our brains. These neurotransmitters communicate between nerve cells. Our brains contain many different neurotransmitters, but the two that are particularly important in depression are serotonin and noradrenaline. It is believed that in depression not enough of these chemicals are available and antidepressant drugs act to increase their levels in the brain.

The first drugs developed were monoamine oxidase inhibitors and tricyclic antidepressants, but both types of drug cause significant side-effects and can be dangerousANCHOR. Prozac was designed by computer in the 80s, then experiments using rats confirmed that the drug was more selective in its actions. This means it has fewer side effects and improved safety.

Prozac and other drugs which are also selective serotonin re-uptake inhibitors (SSRIs) are now the biggest group of drugs being prescribed to patients with depression. SSRIs work by blocking the reabsorption of serotonin by nerve fibres, thus raising the level of serotonin in the fluid around brain cells. This new generation of antidepressants was tested in rats, whose brain tissue was analysed for the presence of neurotransmitters after giving the drugs. Their very specific nature means that they have fewer side effects. Further clinical studies have also shown that these antidepressants can be used to treat other diseases such as anxiety, panic disorder, eating disorders and obsessive compulsive disorder.

The need for future research

The development of SSRIs was a huge advance in treating depression. Other drugs have since been developed that interact with both the serotonin and noradrenaline systemsANCHOR.

Although these drugs have provided very significant improvements in the treatment of depression, around 40% of patients do not show any improvement in their symptoms. An additional problem is that these drugs do not work quickly with a delay of between 4 and 6 weeks common. So there is still an important clinical need for further research.


Références

  1. Lopez AD and Murray CC (1998) The global burden of disease, 1990-2020. Nat. Med., 4, 1241.
  2. http://www.nimh.nih.gov/health/topics/suicide-prevention/index.shtml
  3. Doris A, Ebmeier K, Shajahan P (1999) Depressive illness. The Lancet, 354, 1369.
  4. Slattery DA, Hudson AL, Nutt DJ (2004) Invited review: the evolution of antidepressant mechanisms. Fundam. Clin. Pharmacol., 18, 1.
  5. Schildkraut JJ (1965) The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry 122, 509.
  6. Huhman KL (2006) Social conflict models: can they inform us about human psychopathology? Horm Behav. 50, 640.
  7. Berton O and Nestler EJ (2006) New approaches to antidepressant drug discovery: beyond monoamines. Nature Rev Neurosci, 7, 137.
  8. McArthur R and Borsini F (2006) Animal models of depression in drug discovery: a historical perspective. Pharmacol Biochem Behav 84, 436.
  9. Fuchs E and Fliugge G (2006) Experimental animal models for the simulation of depression and anxiety. Dialogues Clin Neurosci 8, 323.
  10. Slattery DA, Hudson AL, Nutt DJ (2004) Invited review: the evolution of antidepressant mechanisms. Fundam. Clin. Pharmacol., 18, 1.
  11. Slattery DA, Hudson AL, Nutt DJ (2004) Invited review: the evolution of antidepressant mechanisms. Fundam. Clin. Pharmacol., 18, 1.

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