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

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.

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

“… 24 This may be the iatrogenic neuropsychiatric precondition various authors have linked to “pseudo-resistance”, “acquired resistance”, “treatment-resistance”, and “tardive dysphoria”. 24 , 75 , 168 – 174 …”

When Anxiety and Depression Coexist: The Role of Differential Diagnosis Using Clinimetric Criteria

“…In the long-term treatment of depression, when loss of clinical effect occurs, an increase in dosage is unlikely to yield lasting remission [48], as was found to be the case with this patient. Thus, in this case, citalopram was tapered and discontinued, with the help of clonazepam [49] since withdrawal symptoms occurred despite tapering [34].…”

Successful use of tapering strips for hyperbolic reduction of antidepressant dose: a cohort study

“… 28 It has been pointed out that continued drug treatment with antidepressant medications may stimulate processes that represent a reversal of the initial acute withdrawal effects of a drug. 7 The ‘oppositional model of tolerance’ has been invoked to 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 steer the mental disorder into a development of treatment-unresponsiveness, which may also include expressions of bipolar disorder or paradoxical reactions.…”

“… 3 Given high rates of long-term prescribing, particularly in deprived areas, 4 withdrawal and inability to discontinue antidepressant medication represent a significant public health problem, 5 particularly given persisting doubts about real-world effectiveness 6 and indications that continued drug treatment with antidepressant medications may stimulate processes that run counter to the initial acute withdrawal effects of a drug (the oppositional model of tolerance). 7 Patient surveys suggest current inadequacy of healthcare systems to recognise and manage prescribed drug withdrawal with tapering medication, and patient feedback, 5 , 8 , 9 which is matched by research showing that only a small minority of general practitioners feel sufficiently knowledgeable about withdrawal. 10 As a result, tens of thousands of patients resort to social media groups that are filling the void left by health services.…”