David Nutt – biography
Imperial College London

Antidepressants have a peculiar place in the public mind. Almost every family in the UK will have someone taking these drugs; yet, the media are often very hostile to them with disparaging terms such as “happy pills” used to cast aspersions on their efficacy and utility [1]. Moreover, claims that they may cause suicidal ideation particularly in young people have lead to warning labels in the USA. Yet, despite the repeated media criticism, the use of antidepressants continues to be widespread. So what are the reasons for this?

The first is that they are effective and the disorders they are used to treat are very common. Depression is predicted to be largest cause of disability in the world by 2020 [2] and is now exceeding that of cardiovascular disease in many western countries (making it number one there already). Moreover, several of the anxiety disorders are also in the top ten causes of disability, and these also respond very well to antidepressant treatment.

In their primary target of depression, the antidepressants are effective treatments of the acute phase with a number needed to treat (NNT) of about 6, which compares favourably with treatments in other branches of medicine. However, when used in the long term to prevent recurrence of depression, they become even more effective with an NNT of 3 [3]. This makes them one of the most effective of any medicine: for comparison the NNT of statins to prevent the recurrence of a myocardial infarction is about 20.

Similar efficacy is seen in their secondary indications of the treatment of anxiety disorders. Moreover, the desire of many countries to reduce the prescribing of benzodiazepines has lead to a switch to the new antidepressants, particularly the selective serotonin reuptake inhibitors (SSRIs) that have greater efficacy and are much freer from problems such as abuse and withdrawal [4]. Although the SSRIs take several weeks to work and can even worsen anxiety at the start of treatment after a few weeks, they become very effective anxiolytic treatments with efficacy exceeding that of the benzodiazepines. The SSRIs also have uses in other indications such as pain, some sleep disorders and some sexual problems (particularly SSRIs for premature ejaculation).

There are other factors underlying this increase in use. The most important one is that the newer antidepressants are extremely safe drugs. Before their invention, the most commonly used antidepressants were those of tricyclic structure such as amitriptyline and duselepin. However, these are very toxic in overdose due to their combination of noradrenaline reuptake blocking properties and marked anticholinergic actions on the heart. At the peak of their use, they were the most common cause of drug overdose death in the UK, and still today kill hundreds of people a year [5]. Patients with depression are at very high risk of suicide, and before the onset of the SSRIs, many used their antidepressants to kill themselves.

The newer generation of antidepressants exemplified by the SSRIs, but also including venlafaxine, duloxetine, mirtazapine and agomelatine, are orders of magnitude safer than the tricyclics in overdose and much preferred by psychiatrists for this reason. In practice, it is extremely difficult to kill oneself with an overdose of these medicines alone and the cases of suicidal ideation have been minimal and have not lead to actual suicides. The very enhanced safety and tolerability profile of these newer antidepressant drugs has lead to a greater use of them in the depressed population because patients’ compliance with medication is enhanced and doctors are more comfortable prescribing them. This in turn has resulted in a reduction in suicide rate in many countries where their use has become widespread [6].

Despite this, depression is still under-treated with up to half of all patients not being appropriately diagnosed or treated [7]. Efforts to improve this situation are underway, and are more necessary today than was the case a few years ago because depression and suicide rates in Europe are on the rise as a result of the economic downturn [8]. It therefore appears to be the case that the use of antidepressants is large and growing but still inadequate to meet the needs of the population.

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References

1. Nutt DJ: The unhappy saga of ‘happy pills’. J Psychopharmacol 2003, 17:251-252.
2. Murray CJ, Lopez AD: Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. Lancet 1997, 349:1498-1504.
3. Geddes JR, Carney SM, Davies C, Furukawa TK, Kupfer DJ, Frank E, Goodwin G: Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet 2003, 361:653-661.
4. Nutt DJ: Death and dependence: current controversies over the selective serotonin reuptake inhibitors. J Psychopharmacol 2003, 17:355-364.
5. Nutt DJ: Death by tricyclic: the real antidepressant scandal? J Psychopharmacol 2005, 19(2):123-125.
6. Isacsson G, Holmgren A, Osby U, Ahlner J: Decrease in suicide among the individuals treated with antidepressants: a controlled study of antidepressants in suicide, Sweden 1995– 2005. Acta Psychiatr Scand 2009, 120(1):37-44.
7. Lecrubier Y: The diagnosis and treatment of depression. CNS Spectr 2008, 13(Suppl. 11):5-9.
8. Stuckler D, Basu S, Suhrcke M, Coutts A, McKee M: Effects of the 2008 recesson on health: a first look at European data. Lancet 2009, 378:124-125.

DOI: 10.1016/j.coph.2011.12.001

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