ReviewTherapeutic advances in psychopharmacology2020
May antidepressant drugs worsen the conditions they are supposed to treat? The clinical foundations of the oppositional model of tolerance.
Review in Therapeutic advances in psychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 3 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 3 syntheses or guidelines pooled it, 81 citations in OpenAlex.
- Post-acute withdrawal syndrome (PAWS) after stopping antidepressants: a systematic review with meta-narrative synthesis.Epidemiology and psychiatric sciences · 2025Pooled it
- Pharmacological treatments in panic disorder in adults: a network meta-analysis.The Cochrane database of systematic reviews · 2023Pooled it
- Efficacy of Silexan in patients with anxiety disorders: a meta-analysis of randomized, placebo-controlled trials.European archives of psychiatry and clinical neuroscience · 2023Pooled it
- The neuropsychopharmacology of treatment discontinuation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Public thresholds for antidepressant effectiveness and adverse drug reaction rates: a cross-sectional study.Scientific reports · 2026Article
- The relevance of phenotypic definition in treatment resistant forms of major depressive disorder: a narrative review.Frontiers in pharmacology · 2026Review
- Assessment of the beneficial effects ofFrontiers in neuroscience · 2026Article
- Longitudinal trajectories of major depressive disorder provide further clinical perspectives for precision psychiatry.PCN reports : psychiatry and clinical neurosciences · 2025Review
- The Future of Oncology in Psychiatric Medications.Journal of clinical medicine · 2025Article
- Comparison of effectiveness and side effects of selegiline transdermal system versus oral monoamine oxidase inhibitors and tricyclic antidepressants for treatment-resistant depression.Journal of affective disorders · 2025Article
- [Can antidepressants negatively alter the long-term course of depressive disorders?]Der Nervenarzt · 2025Review
- Use of antidepressant medication is associated with slower response to open-ended psychotherapy for depressed patients.Frontiers in psychiatry · 2025Article
- Paradoxical Depressive Response to Intranasal Esketamine in Treatment-Resistant Depression: A Case Series.The American journal of case reports · 2024Article
- Psilocybin as a Disease-Modifying Drug—A Salutogenic Approach in Psychiatry.Deutsches Arzteblatt international · 2024Review
- Pharmacotherapy and psychotherapy in depression - complementarity or exclusion?Postepy psychiatrii neurologii · 2024Article
- What can the psychoneuroimmunology of yoga teach us about depression's psychopathology?Brain, behavior, & immunity - health · 2024Article
- Design, Synthesis, and Biological Evaluations of Novel Thiazolo[4,5-d]pyrimidine Corticotropin Releasing Factor (CRF) Receptor Antagonists as Potential Treatments for Stress Related Disorders and Congenital Adrenal Hyperplasia (CAH).Molecules (Basel, Switzerland) · 2024Article
- Baseline symptom severity and efficacy of Silexan in patients with anxiety disorders: A symptom-based, patient-level analysis of randomized, placebo-controlled trials.European psychiatry : the journal of the Association of European Psychiatrists · 2024Review
- Article
- The serotonin hypothesis of depression: both long discarded and still supported?Molecular psychiatry · 2023Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.