In a new article in European Neuropsychopharmacology, researchers Mark Horowitz and David Taylor provide guidance for tapering psychiatric drugs, whether for full discontinuation or to reduce the dose. They suggest a slow, individualized taper to minimize withdrawal effects.
“The general principle when reducing or stopping psychiatric medications is as follows. Make a small reduction, monitor for withdrawal effects or destabilization of the patient, then ensure stability before making further reductions. Reductions should probably be made in smaller and smaller increments because of the pharmacology of the drugs; the final dose before completely stopping will need to be very small.”
A 2018 survey found that 84.6% of people who tried to discontinue an antidepressant experienced withdrawal symptoms, which lasted for over a year for 47% of them. Antidepressant withdrawal can include anxiety, tearfulness, dread, numbness, brain zaps (described as similar to “electric shocks”), nausea, vomiting, diarrhea, dizziness, fatigue, insomnia, nightmares, sexual problems, confusion, and amnesia.
Long-term use of psychiatric drugs causes the body to adapt to the presence of these drugs; when the drugs are removed from the system, the adaptations remain. This causes withdrawal.
“There is no reason to think that the brain or body can return to its pre-drug state in a manner of weeks after adaptation to years or decades of medication exposure,” write Horowitz and Taylor. They add, “Reports from patients of long-lasting effects are often dismissed because the drug is ‘out of the system.’ However, it is adaptations to the drug which persist, causing the brain to register a lack of the anticipated input from psychiatric drugs, which manifests as withdrawal effects.”
Some people may require months or even years to slowly decrease their dose before eventually stopping the drug. The researchers write:
“Withdrawal effects (and relapse) might be minimized by stopping psychiatric drugs over a period long enough for underlying adaptations to the drug to resolve.”
According to the researchers, based on studies of the drugs’ effects on the brain, psychiatric drugs impact the brain along with a hyperbolic relationship. That is, at low doses, small adjustments have huge impacts—but at high doses, even large adjustments have less of an impact.
“The relationship between dose of a psychiatric drug and its effects is hyperbolic,” they write. “This is a consequence of the law of mass action: when there are few molecules of a drug present at the site of action, every additional molecule has a large incremental effect, but when higher concentrations are present each additional molecule has less and less effect, as receptors become saturated.”
This means that dose reductions should not be linear (reduced by the same amount each time, e.g., 40, 30, 20, 10, 0 mg). Instead, one strategy is to reduce the current dose by 10% each time, especially ensuring that the last adjustment—to full discontinuation—is very small.
“For most psychiatric drugs, this means that the final dose required before completely stopping will be very small, much smaller than commonly used doses, and in many cases much smaller than available tablet formulations,” they write.
If the final doses are smaller than those available, then what are patients to do? Horowitz and Taylor suggest liquid formulations and tapering strips can fill that void. Many psychiatric drugs are already available in liquid form, which enables very small doses. However, tapering strips are just beginning to become more widely used.
Horowitz MA, & Taylor D. (2021). How to reduce and stop psychiatric medication. European Neuropsychopharmacology, 55, 4-7. https://doi.org/10.1016/j.euroneuro.2021.10.001 (Link)