Rebound effect: when it is linked to psychotropic drugs

By Cristiano Antonino On Mar 13, 2023

‘Rebound effect’: this is a phenomenon that occurs following the abrupt discontinuation of a psychotropic drug and leads to significant negative consequences, including the return and flare-up of the original symptom

What the rebound effect from psychotropic drugs and antidepressants is caused by

The rebound effect is a known effect of psychotropic drugs and is related to the fact that the structures on which the drugs act have become accustomed to functioning differently during the period of treatment.

This modulation leads to the desired curative effects, but the structures on which the drugs have acted need varying amounts of time, depending on the pharmacodynamic and pharmacokinetic characteristics of the active ingredients and the individual, to return to physiologically autonomous functioning after a period of supporting brain activity and, above all, they must be able to do so gradually, returning to full physiology.

The rebound effect has its mirror-image correspondence for some drugs at the start of treatments, particularly with antidepressants, which are usually started at low dosages and then slowly increased.

For example, for anxiety disorders and in particular panic disorder starting immediately with the full dose leads to the risk of a worsening of symptoms instead of an improvement.

The mode of gradual increase (except in limited emergency situations, in which, however, the desired effects in a short time can also be obtained with the temporary use of symptomatic drugs while waiting for the curative effect that takes time to set in) must necessarily be used to reduce the likelihood of side effects or the possibility of causing initial symptomatic worsening effects that are not desired and not related to the drug itself, but to the rapid increase in dose, particularly if already corresponding to the full dose.

The importance of gradualness

The initiation and discontinuation of psychotropic therapy must be followed with particular care and be gradual in the quantitative increase or decrease in dosage and in the speed of the same, which means in the early and late stages more frequent consultation with the medical specialist.

There are detailed and valid recommendations in psychiatry especially for:

antidepressants;
benzodiazepines (of which, due to the specific neuropharmacological mechanism, prolonged use is not recommended, even in the illustrative leaflets, as in some subjects it establishes a mechanism of dependence with withdrawal phenomena as well as a possible rebound of the symptomatology);
antipsychotic and mood-stabilising drugs.

How the rebound effect manifests itself

Rebound side effects may be of the most diverse nature and are related to the nature of the effects on the brain of the drugs (e.g. the specific neuropharmacological systems they affect).

In summary, also looking at the diagnostic criteria available in the literature, side effects

consist of a rapid return of the symptoms for which the drug was administered with a higher intensity;
they are transient with a duration (in the absence of measures such as resuming the drug and scaling it up gradually where possible) of up to 6 weeks
appear within 36-96 hours after discontinuation or sharp decrease in dose;
they are reversible.

Of course, one must always consider that there is no concomitant medical condition that causes those symptoms independently of the drug.

Withdrawal phenomena

We must not confuse these effects with those of withdrawal, because they are of a markedly different quality and concern certain drugs in particular, although today there is a tendency to blur the classificatory boundary between withdrawal and rebound in these cases.

The latter withdrawal phenomena have a common core in a vegetative syndrome with anxiety, tension, tremors, hypertension, muscle cramps, sweating and in the most severe cases even confusional syndromes with cognitive and neurological aspects.

This presentation, which varies from subject to subject and substance to substance, has a common core to all abstinences from alcohol to opiates to benzodiazepines, particularly among psychotropic drugs, and different declinations depending on the substance.

Then there are very rare cases of syndromes caused by abrupt withdrawal such as the serotonergic syndrome for antidepressants, with peculiar activity on serotonin, and the neuroleptic malignant syndrome from withdrawal of antipsychotics, which constitute, in the most serious cases, an emergency in which the clinical picture sometimes has to be managed with hospital medical support because of the physical consequences they may have.