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.
Author
- Colin Davidson
Professor of Neuropharmacology, University of Central Lancashire
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.
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.
Colin Davidson has previously received funding from the NIH (USA) and the European Community for projects related to drug abuse. His PhD, on the SSRI paroxetine, was sponsored by GSK. He is currently a consultant on psychoactive substances for the UK Defence Science Technology Labs and is a member of the Advisory Council on the Misuse of Drugs (UK). The views expressed here are his own.
