It’s common to read or hear people say they’re “addicted” to all sorts of things, like chocolate, but there’s a difference between addiction and adaptation. Adaptation can also be called “dependence” or the fancier “neuroadaptation.”
This can foster a discussion about whether you can be addicted to antidepressants, which by extension, could mean it’s difficult to discontinue them. Presumably, that would point to withdrawal symptoms being the obstacle to “getting off” them. Comparing them in terms of which one is more difficult to quit (as noted in the news lately) is fraught with difficulty.
Because I’m a retired psychiatrist, I searched the medical literature to refresh my knowledge about the issue. It turns out, according to a recent review, that it’s important to distinguish between dependence (neuroadaptation) and addiction.
The thing about addiction is that it’s about misusing or abusing substances in a compulsive way despite adverse consequences. Medical students used to remember it (for exams) as the 4 C’s: compulsion, craving, control (the loss of), and consequences (negative). I remember one doctor who added another c: conniving (to obtain substances).
On the other hand, dependence is marked by the adaptation of brain receptors to a substance and which doesn’t involve any of the c’s. This is the way to differentiate addiction from dependence, the latter being a consequence of taking antidepressants. One recent review article does a pretty good job of explaining this:
“Physical dependence to antidepressants may occur in some patients, caused by adaptation of the brain to long-term use of the medication. As pharmacologically defined, this physical dependence is a distinct phenomenon from addiction, and is manifested by a drug withdrawal syndrome.” — Horowitz MA, Framer A, Hengartner MP, Sørensen A, Taylor D. Estimating Risk of Antidepressant Withdrawal from a Review of Published Data. CNS Drugs. 2023 Feb;37(2):143-157. doi: 10.1007/s40263-022-00960-y. Epub 2022 Dec 14. PMID: 36513909; PMCID: PMC9911477.
The authors make the point that pretty much all antidepressants can cause dependence if you take them long enough. But with the possible exception of tranylcypromine (Parnate), they don’t lead to abuse or addiction. That was an interesting reminder. Parnate has a chemical structure similar to amphetamine and there are old case reports describing patients who usually have other substance use disorders abusing Parnate.
Anyway, antidepressants can lead to dependence which can be detected only if they stop using them. Withdrawal can be extremely uncomfortable and can last weeks to months, uncommonly for years.
Withdrawal syndromes vary among different substances. Alcohol and heroin can cause severe withdrawal that has to be managed in a hospital. That’s not to say it’s impossible to suffer antidepressant withdrawal serious enough to warrant hospitalization, but it would be rare. Partly that’s due to the difference in neuroreceptors.
Serotonergic receptors, for example, can be occupied by serotonergic antidepressants and lead to dependence mediated by neuroadaptation. If the antidepressant is abruptly stopped, there will be withdrawal, partly depending on the chemical half-life of the drug. Withdrawal can be marked by headache, dizziness, falls, electric shock sensations, and suicide attempts, for example.
Opioid and benzodiazepine withdrawal are mediated by opioid and Gamma Amino Butyric Acid (GABA) receptors respectively. Withdrawal symptoms can include but are not limited to tremor, sweating, seizures and delirium for benzodiazepine withdrawal, and muscle jerks, sweating, bone pain, nausea and vomiting, diarrhea, and muscle spasms for opioids such as heroin. Both may require medical detoxification in a hospital.
Who’s to say which withdrawal syndrome is worse? They’re both bad.
There’s not a lot of scientific literature out there on antidepressant withdrawal. The authors of the article cited above ended up with only 11 papers over a 20-odd year span after their search.
On average, antidepressants with shorter half-lives tend to be associated with withdrawal. Table 5 in the article cited above identifies the ones with lower to higher risk. Table 6 is a preliminary effort to categorize the level of risk to develop antidepressant withdrawal for an individual patient.
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