How to Taper Antidepressants: Understand the Hyperbolic Curve Before It Hits You

Many start tapering off psychiatric drugs feeling encouraged and with a renewed sense of possibility. The first reductions go smoothly – a few withdrawal symptoms maybe, but nothing unmanageable. But then, suddenly, things get worse. Panic. Insomnia. Flu-like symptoms. Dizziness. Anxiety. Constant inner restlessness. Akathisia. Crying spells. Brain zaps. Depressed mood. What’s happening?

The answer lies in something called hyperbolic tapering and receptor occupancy. While these terms sound technical, the concept is simple: the effect a psychiatric drug has on your brain doesn’t reduce in a straight line as you lower the dose. Instead, most of the effect is packed into a surprisingly small portion of the dose – meaning that part requires especially careful, gradual tapering to avoid withdrawal.

Understanding this is crucial if we want to stop antidepressants safely and avoid mistaking withdrawal for relapse. Here’s how it works.

What is hyperbolic tapering?
The term hyperbolic refers to the shape of a curve. Specifically, the one that forms when we plot dose against effect (called receptor occupancy) on a graph. Receptor occupancy is simply a measure of how much the drug activates or blocks target receptors in the brain at different doses. This can be measured using brain imaging technology and visualized on a graph as follows:

(For occupancy data on more drugs, see Sørensen et al. 2022, Molecular Psychiatry, 27(1):192-201 – it’s open access!)

The graphs show that the relationship between dose and effect is a curve, not a straight line. The higher the dose, the more receptors are blocked – but only up to a certain point. There’s a saturation point – a plateau – for each drug, beyond which no additional effect occurs. The brain’s receptors are already quite saturated at relatively low doses, here at approximately 40 mg sertraline, 50 mg venlafaxine, 30 mg duloxetine, and 5 mg escitalopram.

But don’t be misled by the seemingly low numbers. These so-called “low” doses are anything but – they’re highly potent.

In plain terms: Most of the drug’s action lies in a very small portion of the dose range. Specifically, in the first milligrams above zero, as shown by the steep initial rise and then flattening of the occupancy curves. That bend in the curve is where withdrawal symptoms typically become significantly worse – or emerge altogether. This explains why so many people feel fine tapering at higher doses, but then hit a wall at “lower” doses. It’s not in your head. It’s in the curve.

The solution? Slow down the taper. Reductions in the 3-10% range of the current dose (not the original dose) are typically needed to respect the steep part of the curve. Consequently, crossing zero may take years, simply because the nervous system is so sensitive to even minor changes toward the end. You can think of it this way: the less medication is in your system, the more the drug can detect any changes.

It's Not the Dose – It’s the Effect
The whole point of tapering – as opposed to just stopping – is to give the brain time to gradually adapt to the drug’s absence. If we reduce the dose too much at once, moving faster than the brain can keep up, the body responds with withdrawal symptoms. Sometimes subtly, sometimes explosively. This is not a return of a supposed underlying illness – it’s withdrawal: the drug leaving our system too quickly for it to adapt. Therefore, the body speaks to you through unpleasant symptoms. Or screams. And if you or your prescriber don’t understand the curve, it’s easy to misread what’s happening.

Because it’s not the dose (the X-axis) as such we want to reduce gradually; it’s the effect that dose has on the brain (the Y-axis).

Hyperbolic tapering simply means following your drug’s occupancy curve all the way down to zero mg. This means dose reductions must become smaller and smaller – and, at some point, much smaller – as we approach zero. It also means that, while the main message here is to taper slower than we were taught, it may not be necessary all the way from the beginning. At higher doses, a reduction might not impact brain chemistry much and can often (though not always) be a bit larger. Starting the 3-10% reductions at this point may prolong the taper unnecessarily. But at lower doses, the same reduction can cause a large drop in effect – and trigger withdrawal – even if it looks small on paper.

Why the Last Milligrams Matter Most
Think of it this way: each time you lower your dose, you take a step to the left on the curve, toward lower receptor occupancy. However, the impact of a reduction on brain chemistry – and whether withdrawal symptoms occur, and how severe – depends on where you are on the curve. That is, what dose you’re on. A reduction might:

· cause no or minimal change in occupancy (and thus no symptoms),

· cause a small or moderate change (mild or moderate symptoms), or

· cause a major drop (severe and potentially protracted symptoms).

Example time. Say you’re on 100 mg of something and reduce by a fixed amount of 10 mg each time (don’t do that). What’s important to understand is that the next 10 mg you remove will consistently be a larger reduction than the previous 10 mg. If you keep making same-size cuts, eventually one of them will hit much harder than the last – and that’s when you’ve found your bend in the curve.

Where Does the Curve Bend? What Graphs Can and Can’t Tell Us
Here’s the tricky part: the “bend in the curve” – where tapering gets harder – isn’t the same for everyone. While the shape of the curve is universal for all, the exact dose where the steep part begins can vary to some degree from person to person. This is because individual factors like metabolism, genetics, smoking, age, diet, and other meds all affect a drug’s journey from mouth to brain and how it behaves in the body.

The graphs show average occupancy based on group data – not the exact occupancy for everyone. We can't just look at the graph, read off our true occupancy, and know exactly what size reduction is safe for us. What we can see is the overall shape and pattern: A plateau at moderate-to-high doses, and a steep cliff near zero. Therefore, we can’t know exactly when we’ll need to slow down – only that we eventually will.

Knowing this can help you and your prescriber design a taper plan that makes sense – or understand why your last attempt failed. Just remember: the plan must be flexible and patient-led. Always.

In summary:

We know that reductions must get smaller as we taper, and eventually, much smaller. We just don’t know exactly when. If your taper started out easy and then suddenly got unexpectedly hard, this might be why. You hit your “bend” and dropped too far below it in one go. That’s not your “illness returning” – it’s your body telling you it needs a ladder with smaller steps for a gentler descent.

The Technical Part
While the principle of hyperbolic tapering is simple, doing it in real life can be challenging, as we have to go far below the smallest tablet available before it’s safe to jump to zero. Put simply, the pills at the pharmacy aren’t designed for tapering: the dose is too high. Even half or a quarter of the lowest standard available dose can still cause a large drop in effect.

Because standard doses don’t match the brain’s needs, many people find themselves needing to cut, crush, weigh, or dissolve their pills to create the small reductions required. This has long been known in the layperson withdrawal community. The Inner Compass Initiative, SurvivingAntidepressants.com, Benzobuddies, and Facebook groups like Cymbalta Hurts Worse and many more all understood this long before academia caught up. Only recently has it entered the scientific mainstream – through the hard neuroscience of receptor occupancy studies, which apparently are required before anyone will listen to patients.

NB: While this article focused on antidepressants, it's important to emphasize that the shape of the occupancy curve is essentially the same across all psychiatric drugs, including SSRIs, SNRIs, tricyclics, benzodiazepines, Z-drugs, antipsychotics, mood stabilizers, and mirtazapine. This follows from a basic biological principle known as the law of mass action. As a result, the same hyperbolic tapering principle applies universally.

Closing Suggestion
If this article helped you understand tapering better, please consider sharing it. Most people – including many clinicians and prescribers – have never been taught this. Not because we lack the knowledge, but because it hasn’t made it into most guidelines yet – with rare exceptions like The Maudsley Deprescribing Guidelines and the ASAM Joint Clinical Practice Guideline on Benzodiazepine Tapering,

It’s time we understood why tapering safely takes time – and why the fastest way is often to go slow. Let’s change the conversation around withdrawal together. Talk to your doctor about hyperbolic tapering today – but be prepared: your roles may be reversed ;)