Failure to Respond after Reinstatement of Antidepressant Medication: A Systematic Review

Abstract

Background: Following remission of an anxiety disorder or a depressive disorder, antidepressants are frequently discontinued and in the case of symptom occurrence reinstated. Reinstatement of antidepressants seems less effective in some patients, but an overview is lacking. This systematic review aimed to provide insight into the magnitude and risk factors of response failure after reinstatement of antidepressants in patients with anxiety disorders, depressive disorders, obsessive-compulsive disorder (OCD), or posttraumatic stress disorder (PTSD). Method: PubMed, Embase, and trial registers were systematically searched for studies in which patients: (1) had an anxiety disorder, a depressive disorder, OCD, or PTSD and (2) experienced failure to respond after reinstatement of a previously effective antidepressant. Results: Ten studies reported failure to respond following antidepressant reinstatement. The phenomenon was observed in 16.5% of patients with a depressive disorder, OCD, and social phobia and occurred in all common classes of antidepressants. The range of response failure was broad, varying between 3.8 and 42.9% across studies. No risk factors for failure to respond were investigated. The overall study quality was limited. Conclusion: Research investigating response failure is scarce and the study quality limited. Response failure occurred in a substantial minority of patients. Contributors to the relevance of this phenomenon are the prevalence of the investigated disorders, the number of patients being treated with antidepressants, and the occurrence of response failure for all common classes of antidepressants. This systematic review highlights the need for studies systematically investigating this phenomenon and associated risk factors.

Iatrogenic Factors in Psychopathology

“…A second example of iatrogenic comorbidity is concerned with resistance to a psychotropic drug that was previously effective [42, 57]. There is considerable confusion regarding the term “resistance” in mood disorders, since it is applied to either depressive illness (i.e., an episode which does not respond to drugs or psychotherapy) or to lack of response to a previously effective pharmacological treatment when it is started again after a drug-free period.…”

Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications

“…However, both relapse and recurrence have 2 clinical features different from withdrawal syndromes: (1) the gradual onset of the original symptoms and illness, while drug withdrawal produces acute, abrupt return; (2) symptom severity as before drug treatment, while drug withdrawal produces greater severity [10]. On the other hand, Fava et al [24] suggested that withdrawal from psychotropic medications can be associated with modifications of the illness course such as switching to mania as well as other forms of tolerance [24] such as loss of antidepressant clinical effects [25], resistance when the same medication is administered again [26], and general refractoriness to treatment [25, 27, 28].…”

May antidepressant drugs worsen the conditions they are supposed to treat? The clinical foundations of the oppositional model of tolerance

“…The former use is the most common, but the latter also occurs in a considerable number of cases. 21 In a recent systematic review on lack of response to re-challenge, 22 the range of response failures was broad (between 4.9% and 42.9% across studies). In a large observational study, 23 failure to respond to the same medication that was used in a previous episode was found to occur in a quarter of cases.…”