Adherence to treatment in schizophrenia is generally regarded as central for optimizing recovery [1]. However, non-adherence remains a significant clinical problem, with rates of non-adherence approximately 50% [2]. Non-adherence is linked to relapse, rehospitalisation and poor quality of life. Meanwhile, the therapeutic relationship (TR) between patient and clinician has been found to be important for treatment adherence in other psychiatric conditions. The TR has been extensively studied since it was highlighted by Freud [3]. He wrote that “The first aim of the treatment consists in attaching [the patient] to the treatment and the person of the physician”. Since then, the TR has been described as the “quintessential integrative variable” across different forms of psychotherapy [4] and has been consistently found to predict the outcome of therapy [5]. In psychiatric treatment outside formal psychotherapy, the TR is a more global concept [6]. It tends to be used to denote the quality of the whole relationship rather than specific aspects such as the collaborative bond or the transference relationship [6]. Nonetheless, there is increasing evidence that the TR also predicts outcome of complex psychiatric treatment across diagnoses and treatment settings [7]–[14].

Previous research in psychiatry has investigated the predictive role of the TR with respect to so-called distal outcomes of treatment such as symptom change and social functioning. Few studies have investigated whether the TR is associated with proximal treatment outcomes, e.g., engagement and adherence. This is of interest given the suggestion that a causal chain links each outcome measure in a continuum to the next more distal outcome measure [15], e.g. that adherence to medication leads to better symptom levels, and is important for designing interventions to influence specific outcomes in the treatment chain.

In a recent study by Day et al. [16], the TR was found to predict attitudes towards antipsychotic medication. Various studies have found that a more favourable TR is linked with better adherence to medication in other psychiatric disorders, namely depression [9], [17] and bipolar disorder [18]. Moreover, Holzinger et al. [19] found that patient's assessment of the TR was associated with adherence as reported by patients themselves. It remains unclear whether the TR also predicts adherence to medication when adherence is not based on self-report. Since previous research has shown that the clinician and patient perspective on the quality of the TR are not the same in psychiatric treatments [20], both perspectives need to be considered.

There are two main findings from this study. Firstly, the TR is associated with adherence to, not just attitudes towards, antipsychotic medication in the treatment of schizophrenia. Secondly, although only weakly correlated with each other, both patient and clinician perspectives of the TR are independently associated with adherence. In the depot subgroup, where the assessment of adherence is more objective and hence more reliable, the clinician's perspective remained significantly associated with adherence whereas the patient's perspective was significant at the 10% level.

With over 450 patients, this is the largest study to date to investigate the association between the TR in the treatment of schizophrenia and adherence to antipsychotic medication. It used the same assessment instruments in community mental healthcare settings across six European countries. The associations between the TR and adherence were seen after adjusting for symptom levels and possible clustering effects of patients treated by the same clinician and were not influenced by country. A limitation is that adherence was, in some cases, assessed by the clinician [29] who also rated their relationship with the patient. It should be considered that a clinician's ratings of the TR and medication adherence may not be independent of each other, i.e., their TR ratings are influenced by their estimations of medication adherence and their estimations of adherence may be influenced by the relationship they have with the patient. However, the assessment of adherence was based on collateral information from depot, supervised drug intake, drug tests and other clinicians (psychiatrist, general practitioner, pharmacist) and informal carers in the majority of cases. Moreover, the association between TR and adherence held true in a sub-sample of patients on depot medication where the assessment of adherence is objective and independent of any potential rater bias.

The sample is not necessarily representative for all patients with schizophrenia in community mental health care. Most patients had been in treatment for many years and were, on the whole, well engaged in treatment. Those who agreed to participate in the study, both patients and clinicians, may have had better TRs. Thus, there may have been a selection bias, including fewer patients with shorter treatment histories and poorer TRs. However, the TR ratings reported by patients (mean 8.0) in the current study are similar to those reported in other studies, e.g. a mean of 8.1 in outpatients with schizophrenia [34]. Moreover, length of time in treatment was not associated with the quality of the TR from either patient or clinician perspective. Finally, the associations are cross-sectional so causal relationships may not be inferred.

Patient and clinician ratings of the TR were only weakly correlated with each other, which in other studies has also been found in relation to needs for care [28]. It may be seen as intriguing that, despite the fact that patient and clinician perspectives on the TR are only weakly inter-correlated, both are independently associated with adherence. Hence, each perspective must be capturing some distinctive aspects. The patient's rating may be tapping into a subjective assessment of the social and personal experience of the relationship with their clinician. If they get along well with their clinician, they may be more willing to follow the clinician's advice on treatment. Clinicians have different views of the TR with a given patient. They may compare it to relationships with other patients and consider how the patient is functioning more generally. In turn, how well a patient is functioning may coincide, to some degree, with adherence to treatment.

In the current study, the clinician's perspective had a somewhat stronger association with adherence than the patient's perspective. This is in contrast to psychotherapy, where the patient's perspective appears to be most strongly related to outcome [30]. It is, however, consistent with other findings in psychiatry, which have measured both the patient's and clinician's perspectives. These studies suggest that the clinician's perspective may be more strongly related to outcome in complex psychiatric treatment of depression [17] and schizophrenia, psychosis or major affective disorder [7], [31]. It may be the case that clinicians rate the TR higher when patients adhere to their recommendations, i.e., they view their relationship with these patients more positively because they are more adherent. On a speculative note, this may also be related to the degree to which treatment is oriented to the needs of the patient as identified by themselves, which is stronger in psychotherapy, versus the needs of the patient as identified by the service, which is stronger in psychiatric treatment of patients with severe mental illness.

As mentioned above, the findings do not imply causality and could be interpreted in different ways. A better TR may lead to better adherence or better adherence may lead to a better TR or both. Future prospective studies with first episode samples would help to disentangle the direction of the effect. The associations might also be explained by other factors. One possibility is that those patients who form better relationships with their clinicians do so because they can and will also do better on a range of outcomes, in this case, more likely to adhere to medication. This might be an index of their individual potential rather than anything to do with the potential of the relationship per se to influence treatment outcomes. Bentall et al. [32] examined whether the TR indirectly mediates or has a direct causal influence on outcome in a large trial of cognitive behaviour therapy for psychosis. They found that the relationship had a direct causal influence on outcome, which was not explained by other factors influencing patients' potential to form a good TR.

Future studies might explore how to achieve better TRs. Little is known about what makes good relationships and how they might be improved, with a few intervention studies showing promising results [21], [33]. In the light of the current findings, studies developing and testing interventions that focus on collaboration in relationships and specifically on talk about medication may be indicated.