More Cautious Antidepressant Prescribing Needed by Doctors

Rob Hicks

December 21, 2021

In a new review published online in the Drug and Therapeutics Bulletin, the perceived benefits and harms associated with antidepressant use are discussed by UK experts. They suggest that ongoing uncertainties about the effectiveness of antidepressants, together with the potential for severe and long-lasting withdrawal symptoms, should prompt doctors to exhibit more caution and prescribe these drugs less frequently.

In their review, "Newer generation antidepressants and withdrawal effect: reconsidering the role of antidepressants and helping patients to stop", the authors, Dr Mark Horowitz of the division of psychiatry, University College London, London, and Michael Wilcock, pharmacist at Royal Cornwall Hospitals NHS Trust, Truro, say: "Increasing knowledge about the difficulty that some patients have in stopping antidepressants should lead to more cautious prescribing practice - with antidepressants given to fewer patients, for shorter periods of time."

They argue that existing trial data often don’t assess outcomes that matter most to patients, for example, social functioning and quality of life, and focus only on symptom measures instead.

The Rise of SSRIs/SNRIs

Selective serotonin reuptake inhibitors (SSRIs) have been around since the 1980's, with serotonin and norepinephrine reuptake inhibitors (SNRIs) arriving shortly after in the early 1990's, and both classes of drugs have since dominated the antidepressant market. The prescribing of these classes of drugs has risen in England over the years with an estimated 7.8 million people issued at least one prescription in 2019-20. This equates to around 1 in 6 adults, say the authors, highlighting that prescription rates of antidepressants are 50% higher in women.

In their review the authors suggest that while for those with severe depression there might be a role for antidepressants, for those with mild to moderate depression the cons may outweigh the pros. They raise the sobering thought that there is "no clinically relevant difference between antidepressants and placebo" for the outcomes that are of greatest relevance to patients, including overall quality of life.

For children and teenagers, the authors say the findings are even less convincing, they say. "A recent Cochrane review found that no antidepressant had a clinically significant effect compared with placebo, leading the authors to question whether they should be used at all," they report. They add that between 2005 and 2017 the number of 12- to 17-year-olds prescribed antidepressants more than doubled.

Withdrawal Symptoms Often Severe, Long-Lasting, and Affect Quality of Life

The authors comment on study findings that in a population of primary care patients on antidepressants for an average of one year, around two-thirds had at least one adverse effect, with around one in three having three of more adverse effects. Around 1 in 5 patients on SSRIs report daytime sleepiness, dry mouth, profuse sweating, or weight gain, with a quarter reporting sexual difficulties. Around one in ten report nausea, muscle spasms or twitching, constipation, diarrhoea, restlessness, or dizziness. They add that the prevalence of side effects may be even higher among those taking antidepressants for more than three years, and can include emotional numbness and mental 'fogginess'.

They highlight that withdrawal symptoms – such as anxiety, insomnia, depression, agitation, and appetite changes - are common, and can be severe and long-lasting. These withdrawal symptoms can also interfere with social functioning and professional life, particularly if treatment is stopped abruptly, further affecting a person’s quality of life.

In 2019 the Royal College of Psychiatrists issued a position statement in response to the recognition that antidepressant withdrawal effects are more common, more severe, and more long-lasting than previously thought. In it they recommend that patients be informed of this risk by prescribers before antidepressants are initiated. In its updated 2019 guidance the National Institute for Health and Care Excellence (NICE) said: "While the withdrawal symptoms which arise when stopping or reducing antidepressants can be mild and self-limiting, there is substantial variation in people’s experience, with symptoms lasting much longer (sometimes months or more) and being more severe for some patients."

Patient Support Needed

The authors emphasise, however, that: "Withdrawal from antidepressant therapy should not be imposed on patients, but those who are prepared to undergo this process should be supported to do so."

Patients attempting to stop antidepressant use, particularly long-term users, may very well need additional help, they say. However: "There are currently no dedicated NHS services to support antidepressant de-prescribing."

They conclude: "There continues to be considerable uncertainty about the benefits of  antidepressant use in the short- and long-term, particularly in regard to the lack of a clinically significant difference between antidepressant and placebo treatment."

They recommend: "In light of this uncertain balance of benefits and harms, we should re-visit the widespread – and growing – prescription of antidepressants."

https://dtb.bmj.com/content/early/2021/12/13/dtb.2020.000080

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