The Deceptive Manifestations of Treatment Resistance in Depression: A New Look at the Problem

Fava, Giovanni A.; Cosci, Fiammetta; Guidi, Jenny; Rafanelli, Chiara

doi:10.1159/000507227

Cited by 39 publications

(58 citation statements)

References 77 publications

(119 reference statements)

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“…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.…”

Section: Resistance To Antidepressant Drugsmentioning

confidence: 99%

“…21 "Treatment resistance" thus prompts switching and augmentation of AD. Yet, these therapeutic strategies may trigger a "cascade iatrogenesis", instead of reconsideration of the entire process 21 : was treatment appropriate in the first place? Clinical outcome is the result of several interacting variables: living conditions, patient characteristics, illness features and previous therapeutic experience, self-management (the degree of collaboration of the patient in behavioural and lifestyle terms), and treatment setting (e.g.…”

Section: Resistance To Antidepressant Drugsmentioning

confidence: 99%

“…physician's attitude and attention, illness behavior). 21 Some of these factors may be therapeutic, whereas other factors may be counter-therapeutic. In some patients the interactive combination of treatment variables may lead to clinical improvement; in other cases, the net result will produce no effect; in another segment of the clinical population, it may cause worsening of the condition.…”

Section: Resistance To Antidepressant Drugsmentioning

confidence: 99%

“…Such confusion is increased by the assumption that treatment was right in the first place and failure to respond is blamed on patients’ characteristics. 21 “Treatment resistance” thus prompts switching and augmentation of AD. Yet, these therapeutic strategies may trigger a “cascade iatrogenesis”, instead of reconsideration of the entire process 21 : was treatment appropriate in the first place?…”

Section: The Clinical Foundations Of the Model Of Oppositional Toleramentioning

confidence: 99%

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

Fava

2020

Therapeutic Advances in Psychopharmacology

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In recent years there has been a considerable debate on antidepressant drugs. Continued drug treatment with antidepressant medications may stimulate processes that run counter to the initial acute effects of a drug. The oppositional model of tolerance may explain loss of treatment efficacy during maintenance treatment and the fact that some side effects tend to occur only after a certain time. These processes may also direct the illness into a treatment-unresponsive course, including manifestations of bipolar disorder or paradoxical reactions. When drug treatment ends, oppositional processes no longer encounter resistance, resulting in potential onset of new withdrawal symptoms, persistent post-withdrawal disorders, hypomania, and resistance to treatment if it is reinstituted. In all these cases, antidepressant medications may constitute a form of iatrogenic comorbidity, which increases chronicity and vulnerability to depressive episodes. Antidepressant medications are essential drugs for the treatment of major depressive episodes. They are less likely, however, to provide protection for relapse prevention. Current prescription practices need to be reformulated in light of consideration of vulnerabilities and adverse effects of treatment. The oppositional model of tolerance provides a conceptual framework for weighing all these elements in the individual case. The model does not appear to apply to all patients who undergo treatment with AD, but only to a part of them. Studying the variables that are associated with such occurrence in certain patients and not in others would be one of the most important tasks of current therapeutic research. Current diagnostic systems in psychiatry do not consider the iatrogenic components of psychopathology, and can be applied to only patients who are drug free. They are suited for a patient who no longer exists: most of the cases that are seen in psychiatric clinical practice receive psychotropic drugs and such treatment is likely to affect prognosis and treatment choices.

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Section: Resistance To Antidepressant Drugsmentioning

confidence: 99%

Section: Resistance To Antidepressant Drugsmentioning

confidence: 99%

Section: Resistance To Antidepressant Drugsmentioning

confidence: 99%

Section: The Clinical Foundations Of the Model Of Oppositional Toleramentioning

confidence: 99%

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

Fava

2020

Therapeutic Advances in Psychopharmacology

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“…However, hypothetically, prolonged antidepressant exposure could also cause permanent neurophysiological alterations, comparable with tardive dyskinesia after long-term antipsychotic use, 33 with unremitting, chronic, withdrawal symptoms. 30,34 In any case, the neurophysiology of protracted withdrawal is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Protracted withdrawal syndrome after stopping antidepressants: a descriptive quantitative analysis of consumer narratives from a large internet forum

Hengartner

Schulthess

Sørensen

et al. 2020

Therapeutic Advances in Psychopharmacology

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Background: Protracted withdrawal syndrome (PWS) after stopping antidepressants (frequently also referred to as post-acute withdrawal syndrome or PAWS) has been described in a few case reports. However, a detailed quantitative analysis of specific symptom manifestations in antidepressant PWS is still lacking. Methods: We extracted patient narratives from a large English-language internet forum SurvivingAntidepressants.org , a peer support site concerned about withdrawal from antidepressants. PWS was ascertained based on diagnostic criteria proposed by Chouinard and Chouinard, specifically ⩾6 months of continuous antidepressant use, with emergence of new and/or more intense symptoms after discontinuation that last beyond the initial 6 weeks of acute withdrawal. We assessed medication history, outcome of PWS, and the prevalence of specific symptoms. Results: In total, n = 69 individual reports of protracted withdrawal were selected for analysis. At time of the subjects’ most recent reports, duration of PWS ranged from 5 to 166 months, mean = 37 months, median = 26 months. Length of time on the antidepressant causing protracted withdrawal ranged from 6 to 278 months, mean = 96 months, and median = 79 months. Throughout the withdrawal experience, affective symptoms, mostly anxiety, depression, emerging suicidality and agitation, were reported by 81%. Somatic symptoms, mostly headache, fatigue, dizziness, brain zaps, visual changes, muscle aches, tremor, diarrhea, and nausea were reported by 75%. Sleep problems (44%) and cognitive impairments (32%) were mentioned less frequently. These broad symptom domains were largely uncorrelated. Conclusion: PWS or PAWS from antidepressants can be severe and long-lasting, and its manifestations clinically heterogeneous. Long-term antidepressant exposure may cause multiple body system impairments. Although both somatic and affective symptoms are frequent, they are mostly unrelated in terms of occurrence. Proper recognition and detection of PWS thus requires a comprehensive assessment of medication history, duration of the withdrawal syndrome, and its various somatic, affective, sleep, and cognitive symptoms.

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Brexpiprazole versus placebo or other antidepressive agents for treating depression

Ralovska

Koychev

Crescenzo

et al. 2021

Cochrane Database of Systematic Reviews

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The Deceptive Manifestations of Treatment Resistance in Depression: A New Look at the Problem

Cited by 39 publications

References 77 publications

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

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

Protracted withdrawal syndrome after stopping antidepressants: a descriptive quantitative analysis of consumer narratives from a large internet forum

Brexpiprazole versus placebo or other antidepressive agents for treating depression

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