Författare: Colin Davidson Professor of Neuropharmacology University of

Robert F. Kennedy Jr. has been sworn in as the US health and human services secretary, despite saying a few things that raised eyebrows during his confirmation hearing. One of those things was the claim that some people have a harder time coming off antidepressants than they do coming off heroin. He was referring specifically to the current generation of antidepressants called selective serotonin reuptake inhibitors, or SSRIs.

RFK Jr. is known for saying controversial things about medicine, but is he right on this count?

Coming off SSRIs can indeed be difficult, causing “SSRI discontinuation syndrome” in some people. The syndrome is characterised by flu-like symptoms, including dizziness, nausea, headaches and tiredness. In most cases, the symptoms are mild and short-lived.

People trying to come off antidepressants who experience these types of symptom sometimes believe their depression has returned, and will start taking their antidepressant pills again. Differentiating between returning depression and SSRI discontinuation syndrome can be difficult. And it can lead to people continuing to take their antidepressant medication even though they no longer need it.

Evidence suggests that SSRIs with short half-lives (where the drug is rapidly broken down in the body) are more likely to cause discontinuation syndrome. These drugs include paroxetine and fluvoxamine, which cause discontinuation syndrome in about 7% of people. Antidepressants with a long half-life – such as sertraline and fluoxetine – only cause the syndrome in about 2% of people.

Other studies suggest that discontinuation syndrome may be as high as 40% when people stop taking SSRIs abruptly.

The situation is further complicated in that some SSRIs, when broken down by the body, have active metabolites. These metabolites can have similar effects to the SSRI and effectively prolong the half-life of the drug.

So fluoxetine, which has quite a long half-life and an active metabolite, rarely triggers discontinuation syndrome. On the other hand, paroxetine has a short half-life and no active metabolites and is the SSRI most likely to cause withdrawal effects, accounting for about 65% of cases.

The simplest explanation for discontinuation syndrome is that coming off these drugs leads to an abrupt and rapid reduction in serotonin, the neurotransmitter thought to mediate the initial antidepressant effects. This is a gross oversimplification, but appropriate levels of serotonin make you happy and relaxed, while low levels make you sad and anxious.

This serotonin discontinuation theory is supported by studies in rats, although other neurotransmitters are almost certainly involved.

How does this compare to heroin withdrawal?

Heroin activates a protein found in the brain, spinal cord and gastrointestinal tract called the mu opioid receptor. When activated, these receptors reduce the perception of pain by blocking pain signals in the nervous system.

More users of heroin experience a withdrawal syndrome compared to users of SSRIs. Around 85% of opioid users who inject the drug experience severe withdrawal symptoms when they come off it. As with SSRIs, opioid withdrawal syndrome severity depends on how long they have been used for and the half-life of the specific opioid.

The half-life of heroin is very short, which would suggest that it will cause severe withdrawal symptoms. However, heroin produces two active metabolites when it is broken down in the body, 6-MAM and morphine, which, like heroin, activate mu opioid receptors.

But these metabolites do not activate the mu opioid receptor to the same extent as heroin. So in most cases of heroin withdrawal, significant symptoms occur as mu opioid receptors quickly shift from a state of high to low activation, leading to severe effects.

Symptoms include drug craving, anxiety, nausea, diarrhoea, stomach cramps, fever and increased heart rate. These are all caused by changes to opioid receptors in the brain and gut. The gastrointestinal symptoms tend to be shorter lasting, whereas the psychological symptoms, such as anxiety and irritability, can last for years.

Withdrawal from heroin often requires treatment with methadone or buprenorphine, two drugs that activate the mu opioid receptor but which have long half-lives.

Typically, someone trying to come off heroin would go to the pharmacist and get a daily dose of methadone or buprenorphine. This is so-called substitution therapy because the new drug (methadone) substitutes for heroin.

Methadone has many advantages over heroin, including that it is free (no need for criminality to get money for heroin), clean (no need to use potentially dirty needles or potentially contaminated heroin) and less addictive, with reduced side-effects.

Heroin withdrawal is a relatively more common and more serious condition. But individual patients can still have a terrible time coming off SSRIs and a relatively easier time coming off heroin.

How do you come off SSRIs?

To come off SSRIs with minimal chance of a withdrawal syndrome, especially for the short-acting SSRIs, you should taper off the dose. This means that you would take progressively smaller and smaller doses over several weeks or months before coming off completely. Recent medical advice suggests that the tapering should be over a longer period than originally thought, and the final doses should be much lower.

You could also switch from a short-acting SSRI to one with a long half-life like fluoxetine, and then taper off fluoxetine, which should be easier than tapering off paroxetine.

It might be easier tapering off fluoxetine as it has a long half-life.
Stephen Barnes/Medical/Alamy

Doctors should also consider “nocebo” effects. Just as doctors can increase placebo effects by being positive about a treatment, they can also increase negative effects (nocebo effects) by focusing on potential side-effects. So if your doctor focuses too much on a potential SSRI withdrawal syndrome, you will be more likely to experience negative effects.

In addition to tapering off SSRIs very slowly, several drugs are available to mitigate the withdrawal effects of SSRIs. These include anxiety-reducing drugs, such as benzodiazepines, and antiemetic drugs, such as ondansetron for nausea.

RFK Jr. has made several debatable statements related to health, including, for example, on vaccinations. On this occasion, though, concerning antidepressants, there is considerable evidence that coming off of SSRIs can be very difficult. But, for most people, it is unlikely that it would be as difficult as coming off heroin. Läs mer…

Under the UK’s Pharmacy First initiative, people are encouraged to see their pharmacist before consulting their GP – especially for minor ailments. It’s a tough four-year course to become a pharmacist in the UK, so you’re in good hands if you seek their advice.

However, on stepping in to any community pharmacy, you might be surprised by the welter of products on sale – from decongestant drugs to homeopathic remedies – that have little or no evidence to support their effectiveness.

For example, oral phenylephrine has been shown to be ineffective as a nasal decongestant. Following a review of the evidence, late last year, the US Food and Drug Administration advised that oral versions of the drug (pills, soluble powders and syrups) should no longer be sold as a treatment for a blocked nose.

Phenylephrine is the main decongestant ingredient in many over-the-counter cold remedies.

Meanwhile, the UK’s Medicines and Healthcare Products Regulatory Agency’s chief safety officer, Alison Cave, said there are “no safety concerns” over phenylephrine products and “people can continue to use as directed”. Although safety is not what’s in question. Effectiveness is.

The flu drug oseltamivir also has little evidence of effectiveness – at least in otherwise healthy people. The UK government, however, still recommends its use in seasonal flu outbreaks.

A recent meta-analysis of 33 clinical trials, with a combined 19,000 patients, showed that oseltamivir, and similar antivirals, might be useful if given to patients who are at a high risk of severe disease. However, they only worked if given within 48 hours of exposure to the flu virus. These drugs had little or no effect on most people who are at low risk or who look for treatments after the 48-hour window.

In 2017, the World Health Organization (WHO) downgraded the status of oseltamivir from “essential” to “complementary”.

The WHO strongly advises against giving oseltamivir to people with “suspected or confirmed non-severe seasonal influenza virus infection”. The drug doesn’t seem to help people at low risk of severe flu and can have unpleasant side-effects.

What about supplements and other non-medicines?

Of course, pharmacies don’t just sell drugs. They also sell supplements, such as vitamins and minerals, herbal medicines and homeopathic remedies.

Although more than half the UK population takes a multivitamin or dietary supplement, scientists still debate their benefits. A recent large study found that taking a daily multivitamin doesn’t appear to be associated with a mortality benefit.

On the other hand, taking a vitamin D supplement is recommended for those with a deficiency – especially during the dark winter months. Studies have shown that it may reduce the risk of heart attacks and strokes in older people. And people with periods can benefit from vitamin C as it helps with iron absorption.

Medicines in the UK must demonstrate safety, quality and efficacy – but these criteria don’t apply to supplements, herbal medicines and homeopathic products. These products only have to demonstrate safety and quality.

The Royal Pharmaceutical Society states that there is “no evidence from randomised controlled trials for the efficacy of homoeopathy over placebo, and no scientific basis for homoeopathy”. However, it was only as recently as 2017 that the NHS agreed to cease providing homeopathic treatments.

If the evidence says that they don’t work, why do people take these products?

Placebo effects may be part of the reason. The person may believe that the treatment will work and this may lead to them thinking that they feel better. Most of these products are sold for self-limiting conditions and are aimed at helping people feel better while they recover.

Many of these products are sold for self-limiting conditions.
fizkes/Shutterstock

Pharmacies have always sold complementary therapies, although these products have changed with the times. You won’t find tonic wine anymore, and there’s much less call for malt extract with cod liver oil.

So why do UK pharmacies sell products with little or no evidence of effectiveness?

Data from Community Pharmacy England suggests that 90% of the income of the average pharmacy comes from the NHS. But, over the last ten years, that funding has seen a 30% real-term cut, even in the face of new services, such as Pharmacy First.

Is it any wonder then that community pharmacies are moving into private services, such as weight loss, and expanding the range of lifestyle products they sell?

Also, many pharmacists work for larger companies and these companies might value profit over evidence-based treatments. Their shops can be crammed with dubious products with high profitability.

This conflict between pharmacies making a profit and providing the best treatment options and advice is not new and is something that Australia struggled with quite recently, leading to calls for pharmacies to drop products that lack evidence.

As long as pharmacies face NHS spending cuts and have to rely on the sale of products that have little or no evidence for their efficacy to remain afloat, the situation is unlikely to change. In the meantime, ask questions about anything you are considering buying. You can be reassured that if a product isn’t right for your condition, your pharmacist will tell you.

The Conversation offered the Royal Pharmaceutical Society the right of reply and Elen Jones, the society’s director for England and Wales wrote:

“Community pharmacies are the ideal place for open conversations with patients to ensure they make informed decisions about their health, including discussing any questions about the evidence of a product’s clinical effectiveness …

”In the case of homeopathy, the RPS is clear that it has no scientific evidence to support its clinical efficacy beyond a placebo effect and does not endorse it as a form of treatment. Pharmacists should advise people considering homeopathic products about their lack of efficacy beyond placebo and also advise that individuals do not stop taking their prescribed medicines when considering using a homeopathic product.

”Offering a variety of products can be an opportunity for patients to access the pharmacy as a ‘gateway to healthcare,’ encouraging them to seek advice for conditions because they trust their pharmacist. Pharmacists play a crucial role in providing evidence-based care daily, guiding patients towards treatments that are safe and clinically effective, with patient care and safety always as the highest priority.” Läs mer…