Decisional reversal after antidepressant initiation: The role of early subjective experience in clinical practice

Adherence to antidepressant treatment remains a major challenge in the management of depressive disorders. Although pharmacological efficacy is well established, non-adherence and early discontinuation remain common. Recent evidence suggests that adherence to antidepressant treatment in depressive disorders remains highly variable and is influenced by multiple sociodemographic and clinical factors. ¹ A population-based cohort study further reported an overall antidepressant adherence rate of only 31.02%, highlighting the magnitude of the problem in real-world care. ² Earlier studies also suggest that discontinuation during the first months of treatment is frequent.^3,4 Educational interventions and shared decision-making strategies attempt to address this by improving understanding of treatment options and expected outcomes. However, studies of decision aids in depression suggest that improvements in knowledge, decisional comfort and patient involvement do not necessarily translate into improved medication adherence or clinical outcomes.^5,6 This distinction raises the possibility that persistence may depend on processes occurring after the initial decision has been made.

This discrepancy suggests that treatment continuation may depend on factors beyond the initial decision to start medication. A clinically relevant factor is the patient’s early subjective experience after treatment initiation. We present this as a conceptual hypothesis derived from the integration of existing evidence on antidepressant non-adherence, early activating effects, nocebo-related interpretation and the limited effect of decision aids on treatment persistence. We do not propose that adverse effects merely reduce tolerability; rather, they may act as interpretative signals that lead patients to reconsider whether starting the medication was the correct decision.

During the first phase of antidepressant therapy, particularly after initiation of selective serotonin reuptake inhibitors (SSRIs), patients may report increased anxiety, restlessness, agitation, sleep disturbance and emotional discomfort. ⁷ These effects are usually transient and precede therapeutic improvement. Clinically, however, the temporal sequence matters: patients may feel worse before they feel better.

In routine care, many patients do not evaluate treatment through probabilistic reasoning but through immediate experiential feedback. When symptoms intensify shortly after starting medication, the treatment may be perceived as harmful or not right for them. Expectation and interpretation strongly influence perceived drug effects and tolerability. ⁸ Early bodily or emotional changes may therefore acquire meaning beyond their pharmacological intensity. The key point is not simply that early adverse effects are unpleasant, but that they may be interpreted as evidence that the treatment decision itself was mistaken. Early discontinuation may therefore reflect a reinterpretation of treatment initiation rather than a failure of tolerability.

This process may manifest as a reversal of the treatment decision rather than simple intolerance. Medication beliefs and subjective interpretation are major determinants of adherence behaviour. ⁹ In this sense, the problem is not only the decision made at initiation, but how the patient reinterprets that decision during the first days of treatment.

Pre-treatment decision aids operate primarily before medication exposure, improving understanding of risks and benefits before patients encounter the subjective experience of taking the medication. Adherence, however, may also depend on affective and interoceptive experiences occurring afterwards. If early sensations contradict expectations, patients may reinterpret the treatment as inappropriate despite having initially agreed to it. Although physician communication is associated with adherence, communication before initiation may be insufficient if early subjective experiences are subsequently interpreted as evidence that treatment is inappropriate. ¹⁰

If treatment discontinuation is partly driven by reinterpretation of early subjective experiences, then interventions acting exclusively before treatment initiation may have limited impact on persistence. This perspective may help explain why decision aids improve decisional conflict, knowledge or patient involvement but fail to consistently improve adherence or clinical outcomes.^5,6 The early treatment phase may represent a critical period during which the original decision must be maintained long enough for benefit to emerge.

This hypothesis is testable. Prospective studies could measure early activating symptoms, patient attributions (e.g., “the medication is harming me” or “starting treatment was a mistake”), decisional reinterpretation and subsequent discontinuation. Such studies could also examine whether anticipatory guidance and early follow-up attenuate decisional reversal.

Addressing this phase may improve treatment persistence. Clinicians can provide anticipatory guidance describing possible transient worsening, normalise early discomfort and emphasise its temporary nature. Early follow-up contact may allow clinicians to identify activating symptoms, clarify patient attributions and reframe transient discomfort before discontinuation occurs. This is consistent with evidence that structured monitoring and telephone-based care management can improve depression care after antidepressant initiation. ¹¹ Slower dose titration in anxious patients and phase-specific counselling strategies may further support persistence.

This perspective is limited by its conceptual nature and by the absence of prospective studies directly evaluating decisional reinterpretation following antidepressant initiation. The proposed mechanism should therefore be understood as a testable explanatory model rather than as an established causal pathway.

Antidepressant non-adherence may therefore depend not only on the initial decision to start treatment but also on how patients interpret and are supported through the early subjective experience of starting it.