Antidepressant discontinuation syndrome is a set of symptoms that can occur after an abrupt cessation (or marked reduction in dose) of an antidepressant medication that was taken continuously for at least 1 month. Symptoms generally begin within 2—4 days and typically include specific sensory, somatic, and cognitive-emotional manifestations. Fre- quently reported sensory and somatic symptoms include ﬂashes of lights, ”electric shock” sensations, nausea, and hyperresponsivity to noises or lights. Nonspecific anxiety and feelings of dread may also be reported. Symptoms are alleviated by restarting the same medication or starting a different medication that has a similar mechanism of action— for example, discontinuation symptoms after withdrawal from a serotonin-norepineph- rine reuptake inhibitor may be alleviated by starting a tricyclic antidepressant. To qualify as antidepressant discontinuation syndrome, the symptoms should not have been present before the antidepressant dosage was reduced and are not better explained by another mental disorder (e.g., manic or hypomanic episode, substance intoxication, substance withdrawal, somatic symptom disorder).
Discontinuation symptoms may occur following treatment with tricyclic antidepressants (e.g., imipramine, amitriptyline, desipramine), serotonin reuptake inhibitors (e.g., ﬂuox- etine, paroxetine, sertraline), and monoamine oxidase inhibitors (e.g., phenelzine, selegi- line, pargyline). The incidence of this syndrome depends on the dosage and half-life of the medication being taken, as well as the rate at which the medication is tapered. Short-acting medications that are stopped abruptly rather than tapered gradually may pose the great- est risk. The short-acting selective serotonin reuptake inhibitor (SSRI) paroxetine is the agent most commonly associated with discontinuation symptoms, but such symptoms oc- cur for all types of antidepressants.
Unlike withdrawal syndromes associated with opioids, alcohol, and other substances of abuse, antidepressant discontinuation syndrome has no pathognomonic symptoms. In- stead, the symptoms tend to be vague and variable and typically begin 2—4 days after the last dose of the antidepressant. For SSRIs (e.g., paroxetine), symptoms such as dizziness, ringing in the ears, "electric shocks in the head," an inability to sleep, and acute anxiety are described. The antidepressant use prior to discontinuation must not have incurred hypo- mania or euphoria (i.e., there should be confidence that the discontinuation syndrome is not the result of ﬂuctuations in mood stability associated with the previous treatment).
The antidepressant discontinuation syndrome is based solely on pharmacological factors and is not related to the reinforcing effects of an antidepressant. Also, in the case of stim- ulant augmentation of an antidepressant, abrupt cessation may result in stimulant with- drawal symptoms (see ”Stimulant Withdrawal" in the chapter ”Substance-Related and
Addictive Disorders”) rather than the antidepressant discontinuation syndrome described here.
The prevalence of antidepressant discontinuation syndrome is unknown but is thought to vary according to the dosage prior to discontinuation, the half-life and receptor-binding affinity of the medication, and possibly the individual’s genetically inﬂuenced rate of me- tabolism for this medication.
Because longitudinal studies are lacking, little is known about the clinical course of anti- depressant discontinuation syndrome. Symptoms appear to abate over time with very gradual dosage reductions. After an episode, some individuals may prefer to resume med- ication indefinitely if tolerated.
The differential diagnosis of antidepressant discontinuation syndrome includes anxiety and depressive disorders, substance use disorders, and tolerance to medications.