Antidepressant Withdrawal and Rebound Phenomena

Abstract

A ntidepressants are among the drugs most frequently prescribed not only in psychiatry but also other medical specialties. In 2017, 1.49 billion defined daily doses of antidepressants were prescribed in the health insurance system in Germany (not including private prescriptions and hospital treatments) (1). In addition to depression, they have also been approved for other indications such as anxiety and obsessive compulsive disorders. Sound knowledge of the side effects and risks of antidepressant medication is essential in order to inform and treat patients.Besides adverse drug reactions during antidepres sant use, adverse phenomena that occur following treatment discontinuation are increasingly becoming the focus of attention. Withdrawal phenomena of this kind were known as early on as in the early 1960s (2, e1). However, awareness of the significance of this topic remains low despite its considerable relevance. It is likely that a third of patients discontinue anti depressant medication within 1 month and 50% of patients by the end of the third month (e2), often without consulting their treating physician. A Danish study showed that the most frequent calls to a national medical advice hotline were accounted for by inquiries relating to antidepressant withdrawal phenomena (e3). It is essential, therefore, to provide patients at the start of treatment with relevant information on the risks of abrupt discontinuation, as recommended by the German clinical practice guidelines on unipolar depression (3).If adverse symptoms occur following discontinuation (or dose reduction) of treatment, a distinction needs to be made between withdrawal syndrome, rebound phenomena, and re-emergence of the primary disorder (Table 1).An accurate differential diagnosis is important, since it has crucial clinical consequences. For example, in the case of transient withdrawal phenomena, one can usually take a wait-and-see approach or treat symptomatically. In the case of disease recurrence, on the other hand, medication may need to be resumed. If pharmaceutical drugs are actually known to be associated with a risk of rebound following discontinuation, this needs to be taken into account as early on as at the time of making the indication and providing patient information.

What I have learnt from helping thousands of people taper off antidepressants and other psychotropic medications

“… 57 , 135 , 154 , 155 Some arrive already wracked by failed withdrawal attempts or adverse reactions to aggressive drug treatment because their prescribers thought they were suffering a dramatic “relapse”, “non-response”, or other psychiatric disorder rather than withdrawal syndrome. 154 , 156 The hyper-reactivity also can be triggered by small amounts of alcohol and neurologically active antibiotics, herbs, even foods and supplements such as caffeine, B vitamins, St. John’s Wort, and fish oil, 34 , 157 , 158 as well as sound, light, and other stimuli (sensory sensitivities recognized as among withdrawal symptoms). 27 …”

“… 2 Furthermore, emotional lability is characteristic of many drug withdrawal syndromes, acute and prolonged 36 , 56 ; it may be coincidental that withdrawal-associated negative emotions sound like “rebound” of original symptoms. 27 , 36 , 156 Like physiological withdrawal symptoms, emotions generated by the neurological chaos of withdrawal often come in intense, sporadic waves, with exaggerated amplitude. 28 , 86 We call them “neuroemotions”; among them may be extreme anxiety, despair, or anger, as well as hypomania or mania.…”

Pregabalin administration and withdrawal affect testicular structure and functions in rats

“…The rebound phenomenon and rebound effects were observed after withdrawal of several drugs including beta blockers, corticosteroids, opioid drugs, antiepileptic, immunomodulatory and antidepressant agents (Fukuyama, Ganchingco, & Bäumer, 2017; Henssler, Heinz, Brandt, & Bschor, 2019; Koracevic et al., 2020; Torres, Torres, Torres, & Torres, 2018; Wilens, Zulauf, Ryland, Carrellas, & Catalina‐Wellington, 2015).…”

Antipsychotic Withdrawal Symptoms: A Systematic Review and Meta-Analysis

“…Occurrence of withdrawal symptoms is not limited to psychopharmacological drugs ( 11 ) such as antipsychotics or antidepressants ( 12 ) or psychiatric patients ( 13 ) but have also been reported in other compounds such as beta-adrenergic receptor antagonists ( 14 ) or alpha-2 adrenergic agents ( 15 ) (used in the treatment of arterial hypertension) and can be expected following the abrupt discontinuation of many drugs ( 14 ). Individuals with antipsychotic withdrawal symptoms typically do not fulfil the addiction criteria as defined by the International Classification of Diseases (ICD-10 ( 11 , 16 ).…”

“…Studies were excluded if there was no information on the exact number of individuals with withdrawal symptoms. Studies were excluded if they did not report daily clinical assessments of the individual (i.e., clinical assessment interval) because short lasting withdrawal symptoms previously reported in antipsychotics ( 4 ) and other psychopharmacological compounds such as antidepressants ( 12 ) otherwise may be missed. Studies with assessments of only single symptoms such as a sleep disorder were excluded.…”