Non-adherence and its consequences: understanding the nature of relapse

The article by Kane et al draws attention to the enormous challenge of non-adherence in treating individuals with psychotic disorders and the need to devise better ways of dealing with it.

Non-adherence is common to most chronic medical conditions, with multiple factors likely contributing simultaneously to its existence in individual patients. Rates of non-adherence are particularly high in those disorders where there may be no immediate consequences of treatment discontinuation (1). For example, one study found that only 50% of patients with hypertension for whom drug treatment is initiated persisted on treatment 1 year later (2). There is a risk that schizophrenia may be considered to fall into this category, as some patients may survive treatment gaps for considerable periods without adverse consequences. However, this is not the case for the majority. Relapse rates are very high after treatment discontinuation, and in many cases recurrences occur within weeks of stopping treatment (3). To make matters worse, there are no reliable early warning signs to assist patients, carers or clinicians in identifying individuals at imminent risk of relapse (4). In fact, when relapses occur, rather than appearing gradually, symptoms typically return abruptly and rapidly reach high levels of severity (5). In other words, an approach of carefully observing patients in whom non-adherence is suspected, with a view to introducing rescue medication at the first sign of recurrence, is unlikely to be effective in real-world settings.

While treatment goals in schizophrenia and other psychotic disorders should include components such as remission and recovery, the need for sustained medication adherence is to a large extent driven by the risks of harm and distress associated with relapse. Although surprisingly few studies have prospectively assessed the consequences of relapse, it is generally recognized that they may be far-reaching. For example, in an international survey conducted by the World Federation of Mental Health, caregivers cited the following consequences of relapse: inability to work (72%), hospitalization (69%), attempted suicide (22%), and imprisonment (20%). Caregivers also reported significant disruption of their own lives (61%), worsening of their own mental health (54%) and worsening of their financial situation (26%) (6). In addition to these psychosocial consequences, there is a risk of biological harm, insofar as disease progression in the form of emergent treatment refractoriness may occur in a subset of patients after each relapse (7,8).

Taken together, all of these factors point to the need for new, more effective strategies for addressing medication non-adherence in psychosis. As pointed out by Kane et al, effectively addressing non-adherence in psychotic disorders poses specific challenges. Two of these challenges demand special attention. The first concerns impairment of insight, which is one of the most prominent manifestations of psychotic disorders (9). The nature of psychotic illness is such that it impairs the individual's ability to recognize the presence of illness and the need for indefinite maintenance treatment – a fact that may not always be sufficiently recognized by clinicians. Therefore, placing the burden of responsibility on patients themselves to maintain sustained medication adherence would be unrealistic. The second consideration concerns the recognition of the very high occurrence of comorbid substance abuse in individuals with psychotic disorders, and the aggravating role it plays in non-adherence (10).

Psychosocial programs addressing adherence should be developed accordingly, taking into account both the impairment of insight and the need to effectively address substance abuse. Similarly, more reliance should be placed on pharmaceutical interventions that improve adherence. More widespread use of depot antipsychotics is indicated, particularly in the early stages of illness when the benefits of continuous treatment are most likely to be observed.

Greater recognition of the extent and impact of non-adherence has not yet translated into widespread changes in clinical practice. In real world clinical settings around the world, few formalized psychosocial interventions addressing adherence exist, and depot antipsychotics are hopelessly underutilized and frequently only considered after many years of illness. In the context of currently available treatments, combining depot antipsychotics with appropriate psychosocial interventions appears to be our best option for effectively addressing non-adherence in psychotic disorders.