The extraordinary media hype over the latest meta-analysis of antidepressants puts the discussion of these drugs back years. Despite the fact that 9% of the UK population are taking antidepressants (1), and rates of prescribing have doubled over the last decade (2), the authors of the analysis are calling for yet more prescribing. John Geddes suggested in The Sun newspaper that only 1 in 6 people are receiving adequate treatment for depression in high income countries. In The Guardian he estimates that 1 million more people require treatment with antidepressants in the UK, but by my maths, if 9% are already taking them and they only represent 1 in 6 of those who need them, then 54% of the population should be taking them. I make that another 27 million people!
The coverage was almost universally uncritical, and said little about the terrible adverse effects that some people can suffer while taking antidepressants, or while trying to get off them. Even The Guardian claimed that the new ‘groundbreaking’ study will ‘put to rest doubts’ about antidepressants.
But there is nothing groundbreaking about this latest meta-analysis. It simply repeats the errors of previous analyses. Although I have written about these many times before, I will quickly summarise relevant points.
The analysis consists of comparing ‘response’ rates between people on antidepressants and those on placebo. But ‘response’ is an artificial category that has been arbitrarily constructed out of the data actually collected, which consists of scores on depression rating scales, like the commonly used Hamilton rating Scale for Depression (HRSD). Analysing categories inflates differences (3). When the actual scores are compared, differences are trivial, amounting to around 2 points on the HRSD which has a maximum score of 54. These differences are unlikely to be clinically relevant, as I have explained before. Research comparing HRSD scores with scores on a global rating of improvement suggest that such a difference would not even be noticed, and you would need a difference of at least 8 points to register ‘mild improvement’.
Moreover, even these small differences are easily accounted for by the fact that antidepressants produce more or less subtle mental and physical alterations (e.g. nausea, dry mouth, drowsiness and emotional blunting) irrespective of whether or not they treat depression. These alterations enable participants to guess whether they have been allocated to antidepressant or placebo better than would be expected by chance (4). Participants receiving the active drugs may therefore experience amplified placebo effects by virtue of knowing they are taking an active drug rather than an inactive placebo. This may explain why antidepressants that cause the most noticeable alterations, such as amitriptyline, appeared to be the most effective in the recent analysis.
Antidepressant trials often include people who are already on antidepressants. Such people may experience withdrawal symptoms if they are randomised to placebo, which, given that almost no antidepressant trial pays the slightest attention to the problems of dependence on antidepressants, are highly likely to be classified as relapse.
The analysis only looks at data for eight weeks of treatment, whereas in real life people often take antidepressants for months or even years. Few randomised, placebo-controlled trials have investigated long-term effects, but ‘real world’ studies of people treated with antidepressants show that the proportion of people who stick to recommended treatment, recover and don’t relapse within a year is staggeringly low (108 out of the 3110 people who enrolled in the STAR-D study and satisfied the inclusion criteria) (5). Moreover, several studies have found that the outcomes of people treated with antidepressants are worse than the outcomes of people with depression who are not treated with antidepressants (6;7), even in one case after controlling for the severity of the depression (as far as possible) (8). The huge increase in prescribing of antidepressants over the last three decades has been accompanied by a substantial rise in the numbers of people who are in receipt of long-term disability benefits due to depression and related disorders in the UK, and this is at a time when benefits for other disorders, like back pain, have been reducing (9).
Calling for antidepressants to be more widely prescribed will do nothing to address the problem of depression and will only increase the harms these drugs produce. Adverse effects of the most commonly used SSRI antidepressants include sexual dysfunction, which in rare cases seems to persist after discontinuation of the drug (10), agitation, suicidal and aggressive behaviour among younger users (11), prolonged and severe withdrawal effects (12) and foetal abnormalities (13) with some drugs. Thankfully the more severe effects are probably rare, but they will become a more significant problem if prescribing rates increase further. The harm caused by encouraging people to consider themselves as having a disease requiring long-term medical treatment is difficult to quantify.
As the debate around the coverage highlighted, many people feel they have been helped by antidepressants, and some are happy to consider themselves as having some sort of brain disease that antidepressants put right. These ideas can be reassuring. If people have had access to balanced information and decided this view suits them, then that is fine. But in order for people to make up their own minds about the value or otherwise of antidepressants and the understanding of depression that comes in their wake, they need to be aware that the story the doctor might have told them about the chemical imbalance in their brain and the pills that put it right, is not backed up by science, and that the evidence these pills are more effective than dummy tablets is pretty slim.
Many people will be wondering why on earth we are reacting to the increasing burden of human misery in this way. Why are we not asking why it is that so many people in the modern world feel miserable and stressed? What are the pressures that people are under that make coping with life difficult? I could name many – insecure or inadequate employment, finances and housing, loneliness, increasing pressure to perform and reach ever higher targets at work and school, loss of meaning in life and the disappearing nature of community in many areas. These are the things we need to focus on to stem the ‘epidemic of depression’ – not doling out ever more placebos with side effects!
(1) Lewer D, O’Reilly C, Mojtabai R, Evans-Lacko S. Antidepressant use in 27 European countries: associations with sociodemographic, cultural and economic factors. Br J Psychiatry 2015 Sep;207(3):221-6.
(2) NHS Digital. Antidepressants were the area with largest increase in prescription items in 2016. Cited 2018 Feb 23;Available from: URL: http://content.digital.nhs.uk/article/7756/Antidepressants-were-the-area-with-largest-increase-in-prescription-items-in-2016
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(11) Sharma T, Guski LS, Freund N, Gotzsche PC. Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports. BMJ 2016 Jan 27;352:i65.
(12) Fava GA, Gatti A, Belaise C, Guidi J, Offidani E. Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review. Psychother Psychosom 2015 Feb 21;84(2):72-81.
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