The Three Dimensions of Side-Effects (3D-SE)™

A key feature of adherence programmes is the recognition that we understand and take account of the three dimensions of side-effects: physical, psychological and behavioural.

Physical Dimension of side-effects

Adherence programmes must provide practical support to help patients to manage the physical side-effects that they experience as a result of their treatment such as increased blood pressure, diarrhoea, fatigue, appetite changes and nausea. The adherence programmes should focus on how to manage side-effects (including sign-posting to clinical support) and how to reduce their impact on daily living.

Psychological Dimension of side-effects

Addressing physical symptoms is important but dealing only with this domain seriously limits the effectiveness of the programme in terms of patient acceptability and its impact on adherence/persistence. More detailed investigations into concerns about medication show that, for many patients, concerns go well beyond the experience of ‘side-effects’. Many patients who do not experience side-effects are still concerned about future side effects or that the medication is doing ‘silent’ harm or that taking the medicine now will lead to adverse-effects in the longer term.

Non-specific effects (nocebo component) are often caused by specific pharmacological effects of medication. However, psychological factors such as expectations and conditioning also contribute to side-effects. Around 20-25% of chemotherapy patients experience nausea or vomiting before drug administration, indicating the importance of non-pharmacological factors in side effect experiences.

In recent studies concerns about medication have been shown to be the single most significant predictor of the subsequent reporting of side effects. At first sight these findings may seem startling: ‘patients who start out with strong concerns about the medicine subsequently experience more severe side-effects’. However, we should not be too surprised because side-effects such as dizziness, headache and fatigue are commonly reported in the placebo arm of clinical trials, this is commonly referred to as the ‘nocebo effect’. The nocebo effect; the evil twin of the placebo response also operates for active drugs. Just as a component of the beneficial effect of a drug is non-specific (the ‘placebo’ response), so is an aspect of the negative effects (the ‘nocebo component’).

Behavioural Dimension of side-effects

Non-adherence/non-persistence is often a hidden problem. Patients are often reluctant to express doubts and concerns about treatment or to tell healthcare professionals that they are not adhering to regimen because they fear that this will be negatively perceived (e.g. doubt about the medicine will be perceived by the doctor as a doubt in them). A common behavioural response to the experience of side effects (or even concern about side-effects in the absence of specific side-effects) is to take less of the medicine or even to stop altogether, without telling the HCP.