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Is Your Antidepressant Effective and Safe?

Is the wave of antidepressant prescribing justified by research evidence?

Antidepressant drugs are by no means our first attempt to lift our mood biologically. Prior to the first antidepressants reaching the market, in the 1950s, biological approaches to treating depression, or ‘melancholia’, had included, to name but a few: poppy extract combined with donkey’s milk, bloodletting, starvation, purgatives, enemas, surprise baths, rotating chairs, standing people next to cannon fire, lobotomies and, still in use today, causing grand mal seizures with electric shocks to our brains (the topic of my previous two posts).

Last year a report by Public Health England1 found that annual antidepressant prescribing had doubled in ten years. In 2018, 7.3 million adults (17% of the adult population) received at least one prescription. That is one in six of us. Although very recent figures for the USA are hard to find, it has, like the UK, experienced consistent annual increases for two decades, and had already passed 37 million (13% of adults) by 2014. Similarly high rates in other countries, including Australia, Canada, Portugal, Sweden, Belgium and Iceland. Rapid increases in recent years have been documented in all 20 OECD countries with available data, which, on average, doubled their prescriptions in just five years.2 The global antidepressants market is expected to grow from $14.3 billion in 2019 to about $28.6 billion in 20203 largely because of the effects of the COVID-19 pandemic.

Public Health England was not the first to report that certain groups are more likely to be prescribed these drugs, including women, older people and people living in deprived neighbourhoods. So about one in every three women over 70 years old in my own London neighbourhood is likely to be on antidepressants. Such findings are the first clue that the causes of the problems for which these drugs are so readily dispensed may be more social than biological. Certainly, the old claim that depression is caused by some kind of chemical imbalance, that is somehow corrected by the drugs, has now been abandoned by most psychiatrists.

Although national guidelines tend to recommend antidepressants primarily for moderate to severe depression, research tells us that millions of people with mild depression, or understandable grief following losses, are being prescribed these drugs.

The international increases in prescribing continue to occur despite significant, longstanding concerns about efficacy and safety. For example, in 2008 Professor Irving Kirsch (Harvard Medical School) and colleagues obtained data on all clinical trials submitted to the Food and Drug Administration for the most widely prescribed antidepressants. They found that ‘the overall effect of new-generation antidepressant medications is below recommended criteria for clinical significance’ with benefit compared to placebo only for a tiny minority of recipients (less than 5%) ‘at the upper end of the very severely depressed category’.3 A more recent meta-analysis,4 of 131 placebo-controlled trials, also concluded that the overall effect size does not reach ‘clinical significance’ and argued that ‘The harmful effects of SSRIs versus placebo for major depressive disorder seem to outweigh any potential small beneficial effects’.

Before discussing those ‘harmful effects’, a word about placebo effects. There is nothing wrong with creating hope and expectations that things will get better. For years I have taught my clinical psychology trainees that they should actively do so, especially in a first session. Placebo is Latin for ‘I shall please’. The fact that a capsule containing no active ingredient is, for 95% of people, just as effective as one containing an antidepressant, speaks volumes about the importance of having someone, especially an expert, listen to one’s problem—even if it’s only for the few brief minutes that typically precede an antidepressant prescription. It also highlights the value of deciding to do something, anything, to address one’s problems, and, even better, actually doing it. All these ‘non-specific effects’ can be overlooked when psychiatrists and GPs exaggerate the effects of their chemicals and when we clinical psychologists inflate the importance of our cognitive therapy techniques or whatever our preferred psychotherapeutic approach is.

If these drugs came with no harmful consequences then it would not matter, at least not to me, that positive outcomes are usually due to placebo effects rather than a biochemical process (or perhaps to a bit of both). But the downsides of these drugs come in many shapes and sizes. Firstly, they can be a missed opportunity to wait and see, and perhaps to learn that most low mood, sadness, feeling depressed—call it what you will—passes with time, and is a natural part of life. As the old saying goes, time can, indeed, sometimes be ‘a great healer’. Imagine a world where nobody feels sad when sad things happen.

Another potential problem is that the act of reaching for the prescription pad can sometimes inadvertently locate the problem entirely or primarily within us as individuals rather than in our life history or current social circumstances. It implies there is something wrong with our biochemistry or our genes rather than helping us identify something depressing going on in our lives and make some changes. On a more societal level this can mask the real causes of depression, such as loss, loneliness, poverty, violence, child abuse, and so on, so that fewer resources are put into primary prevention programmes to address those causes.

Then there are the ‘side effects’. I prefer the term ‘adverse effects’, to put them on the same footing as the positive effects rather than imply, albeit unintentionally, that they are somehow less important. High rates of a broad range of adverse effects have been identified, originally in the biological domain, including nausea, insomnia, diarrhea, dry mouth, dyspepsia, weight gain and sweating, but more recently also in the personal and interpersonal domains.

For example, the largest ‘direct-to-consumer’ survey,5 of 1,431 antidepressant users from 38 countries, found 61% of the respondents reported at least ten adverse effects, most commonly: ‘Feeling emotionally numb’ (reported by 71%), ‘Feeling foggy or detached’ (70%); ‘Feeling not like myself’ (66%), ‘Sexual difficulties’ (66%), ‘Drowsiness’ (63%), and ‘Reduction in positive feelings’ (60%). ‘Suicidality’ attributed to the drugs was reported by 50%.

Unsurprisingly, the longer people had been on the drugs, the higher the rates of adverse effects. More surprisingly, a third did not recall being told anything about any side effects by the prescriber; and less than 5% were told about suicidality or emotional numbing.

Nevertheless, I must strongly caution anyone against coming off, or reducing, their medication on the basis of one blog post. We are only just beginning to understand how many people experience withdrawal effects when coming off antidepressants. Our survey, above, found that 59% reported withdrawal effects. We are still discovering how hard it can be to come off these drugs and how slowly that usually needs to be done. That will be the subject of my next post. In the meantime, there are, in the absence of professionally provided withdrawal services, numerous online resources run by ‘experts-by-experience’, including www.letstalkwithdrawal (UK) and (USA).


1. Taylor, S. et al. (2019). Dependence and withdrawal associated with some prescribed medicines: An evidence review. London: Public Health England.

2. OECD (2017). Antidepressant drugs consumption, 2000 and 2015 (or nearest year).…

3. Kirsch, I. et al. (2008). Initial severity and antidepressant benefits: A meta-analysis of data submitted to the Food and Drug Administration. PLoS Medicine, 5, 260-268.

4. Jakobsen, J. et al. (2017). Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder: A systematic review with meta-analysis and trial sequential analysis. BMC Psychiatry; 17: 58

5. Read J, Williams J. (2018). Adverse effects of antidepressants reported by a large international cohort: Emotional blunting, suicidality, and withdrawal effects. Current Drug Safety; 13: 1763-186

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