The concept of adherence is contiguous to that of compliance: compliance is defined as. “an amicable or serene agreement” and rather antithetical, as, “the act of giving in to pressure, demand, coercion… so servile.. accordance to satisfy formal requirements… promoted by official or legal authority”. The adherence is defined as, “the act of forming a stable and trusting attachment (for a party, principle, cause)” [4].

From a semantic point of view, the two terms emphasize the fact that the subject is placed in a different position in relation to the agreement. The compliance presupposes the liabilities and the coercive characteristic of the action, induced by a hierarchically superordinate authority; however, adherence always seems to catch a glimpse of the assignment as a superordinate entity, but not experienced as coercive.

In the medical field these terms, in the course of time, have evolved from the point of view of the meaning and, consequently, also in the characteristics of their use: Sackett in 1976 defined the compliance as “the degree of coincidence of the behavior of a subject with the prescription” [5]; in 1986 Babiker spoke of “complex phenomenon that represents the subject’s personal contribution to the management of their disease” [6]; Blackwell in 2000 speaks of “the degree to which the patient follows the doctor’s prescription”. In 1996, Hatcher, for the first time, combines the concept of compliance to that of the therapeutic alliance, calling it “a collaboration in which contribute, with varying degrees of activity, both the physician and the patient in an intersubjective dialogue”, introducing the concept of partnership [7].

In 1991 [8], Probstfield used, for the first time, the terms adherence and nonadherence to refer to a therapeutic relationship in which the emphasis is shifted to the participation of the patient in the therapeutic choices. Focusing on the patient, the indexes of subjective perceptions and patient satisfaction are gaining greater value in the assessment of response to therapy and participation in treatment.

Subjective perceptions and patient satisfaction are elements that must be distinguished from the more general assessment of the drug’s effectiveness on symptoms and the side effects objectively demonstrated. To confirm this observation there is the fact that, with the same effectiveness and incidence of side effects, many interruptions of treatment are to be related to low scores in ranges of subjective well–being and patient satisfaction [9]. A significant step forward was made with the introduction of informed consent, which is an instrument through which the patient expresses his desire to join the therapeutic program.

Within the informed consent, the terms adhesion and adherence must a fortiori be distinguished. The adhesion is, as has been said, a general acceptance a priori of the treatment proposed, before it has started, while adherence refers to a contract in which patients, after having experienced the effects of the treatment, express their intention to continue it.

Through the expression of informed consent, the evaluation of subjective perceptions of patients and the expression of their satisfaction for the ongoing treatment, it establishes a negotiation and dialogue between informed patient and caregiver, that is the person who takes care of the patient (e.g., relative, assistant, medical-nursing staff).: This involves the active involvement of the subject in establishing treatment goals, and therefore, the establishment of a therapeutic alliance (see Table 1).

The interaction is called dynamic because each of the factors listed may vary over time within the therapeutic relationship. Examples of this include the introduction of a new drug, suspension and/or reduction of the previous treatment, the decision to start psychotherapy in the course of a drug in a psychological relationship.

Satisfaction and well-being are subjective experiences: the way patients experience drugs and sensations that patients experience when taking psychopharmacological therapy appears to be an essential clinical data for both the overall understanding of the patient’s attitude towards therapy and for predicting the adherence to treatment [10]. In addition to the factors previously considered, these feelings have a significant impact in maintaining adherence. The patient’s attitude towards the drug by psychopathological conditions, clinical severity of the subject and the side effects.

As neuroleptics were introduced into clinical practice, patients, in the position of influencing the selection of therapy, have now spoken of the “unpleasantness”. The side effects that mostey affect adherence in a negative way are: extrapyramidal symptoms (akathisia in particular), weight gain, sexual dysfunction and, more generally, the negative sensations related to the treatment [11–14]. In fact, despite the side effects of drugs are a cause of discontinuation of therapy, response and subjective well-being to treatment with antipsychotics are the most important predictors for adherence [12, 13, 15].

In this regard, it is useful to remember that the line between side effects and subjective effect is very thin, and is difficult to detect in the patient’s report; however, it is important that in the clinical interview is thoroughly investigated, because frequently, patients tolerate serious side effects well if they do not identify their subjective feelings as particularly unpleasant. The subjective experience is often found in the patient’s idea of his or her illness and what is the idea of recovery or, more simply, to “be better”. The most frequent unpleasant sensations reported by patients taking psychiatric drugs recall “feeling strange and drawn, without feelings, difficulty thinking” [12, 15]. In summary, it is believed that some unpleasant sensations that arise during treatment represent a specific element in its own right, usable in order to provide nonadherence, and then to implement strategies which limit the interruption of therapy. The clinical importance of the study of subjective responses lies, no doubt, in the ability to accurately predict sufficient adherence to treatment in patients with schizophrenia, as well as, according to Dworkin, to recognize subjective feelings to treatment as an indicator of initial symptomatic response [16]. The earliest evidence dates back to the end of the 1990s; Singh and Smith in 1973 reported that patients with dysphoria during treatment with haloperidol had a negative outcome over time [17]. More recent studies have confirmed that the occurrence of negative feelings after 24 to 48 hours of treatment with neuroleptics significantly correlated with poor adherence within 3 weeks or less in response to treatment [12]. Another study conducted on a fairly large sample of patients (150 subjects) with a diagnosis of chronic schizophrenia showed that slightly more than half of the participants did not follow the therapy. Among them, the patients did not differ by sex, age, and total time of hospitalization, but a significant negative correlation was observed between subjective experiences (assessed with the Drug Attitude Inventory-DAI) and poor adherence; also almost all patients (80 %) within the sample had a pattern of adherence in accordance with the type of subjective response reported [12]. Recently, other experiences have allowed us to observe that the attitude and feelings of the patient toward medication, assessed with specific scales such as the Drug Attitude Inventory (DAI), Subjective Well–Being under Neuroleptic Scale (SWN), and Rating of Medication Influences (ROMI) are not explained by the overall severity of positive or negative symptoms: not necessarily in sicker patients observed an approach to the treatment worse than those with milder symptoms and it always show that the feelings related to the treatment and the way in which the subject experiences the relationship with the drug are something autonomous, not closely related neither to the state of the disease nor to side effects. This data is very important and should be constantly kept in mind: an improvement of psychopathological picture, in fact, is not always associated with a similar improvement in subjective well-being, or to a greater adherence to therapy by patients.

The relationship between doctor and patient, fundamental in all branches of medicine, is in psychiatry, the core of the therapeutic program and ensures the therapeutic continuity. The therapeutic relationship between doctor and patient was found to be significant for adherence to treatment in all psychiatric conditions. The therapeutic relationship was investigated as it was emphasized by Freud. He wrote that, “The first aim of treatment consists of fixing [the patient] for the treatment and the person of the physician”. A discontinuity in treatment does not merely indicate an interruption in the assumption of drugs, but represents an important signal that something in the doctor–patient relationship has changed or is changing. This relationship is peculiar, and as a matter of fact, even in a doctor-patient relationship that is primarily based on psychopharmacological prescription, the simple drug prescription has the value of “relational act” and necessarily involves the construction of a relationship that takes into account the drug use, giving to therapist and patient roles that turn around this central element. Therefore, in choosing a therapeutic program the primary target to be achieved (if the diagnosis is correct and the chosen drug effective) is to ensure the appropriate therapy intake, at the right doses and for the prescribed time, which in turn, affects response, remission, relapse, recurrence and the possible development of resistance and / or chronicity, which will shape the course of the disorder. In fact, neither the accuracy of diagnosis, nor the right medication can provide sufficient guarantees about therapeutic adherence. The ability to predict, within certain limits, adherence to treatment can occur only if the physician has a thorough knowledge of his/her patient: he/she must have much information about his/her previous history, personality traits, capacity of insight, his attitude toward drugs in general, and psychiatric ones in particular, his illness idea: the nature of it and the extent to which it has changed his life, what he means by his idea of getting better, the family and social network, how they establish and maintain, if this happens, significant emotional ties (attachment style). To pursue this objective, the interview is the spatial, temporal, and mental location, to collect all the elements and to lay the foundations for the creation of a therapeutic field. As mentioned above, in psychiatry any type of doctor–patient counseling, and in particular the first interview, is already a relational and therapeutic act. In order to achieve this objective, the interview represents the spatial, temporal, and mental place to collect all of the elements in play and to lay the foundation for the creation of a therapeutic field.

As mentioned above, in psychiatry any type of doctor–patient meeting, even and especially the first interview, is already an act and relational therapy.

The points on which the therapist must focus during the first interview are:

The follow-up interviews are meant to the monitoring of drug treatment and to strengthen the collaborative approach established in the first interview, through the following steps:

The prescription is at the same time the official start of drug therapy and the endpoint of a path that has developed through the execution of all previous diagnostic and therapeutic acts, from which now, largely depends on the outcome of the prescription. The context where the prescription happens is a relationship between doctor and patient which is human and dynamic and goes beyond the symptoms to shape the “therapeutic field”, an area of intersubjectivity, which is the result of this dynamic interaction between factors that belong to the patient and the therapist, and influence, in various measure, the achievement of an adequate therapeutic alliance. This latest is defined as the relational base on which a therapeutic project is built, a relationship of trust and cooperation with mutual sharing of skills, objectives, and methods, that has a crucial effect on adherence to pharmacological or psychotherapeutic treatment, issues which areas fundamental as they are problematic for all medicine and for psychiatry in particular.

The therapeutic alliance is also defined as a relationship to which both doctor and patient contribute, with varying degrees of activity. It is the relational collaboration established between the physician and the patient with the aim of building a relationship of trust and mutual cooperation. On this relational base, a treatment plan is built, and allows the patient and the physician to plan together the course of treatment articulated in the time and manner necessary to address the specific disorder.

There are two different types of therapeutic alliance. In the first type, called “helping alliance”, the patient perceives the therapist as “warm, helpful and supportive”, in this case it may run the risk of reducing the relationship in terms of “demand-response”, whereby the patient “asks” and the doctor, colluding, “provides” the drug. In this case it is important to insist on engaging the patient in a reciprocal relationship, in which he must take the most active and proactive attitudes, even with respect to dose adjustments and decisions on drug. The second type of alliance, called “working alliance”, is based on a sense of common work, that targets the containment of the discomfort that hinders the patient. Key points of this type of alliance are the sharing of similar interpretations of the etiology and for the reasons of hardship by the therapist and patient, combined with the feeling of a positive evolution in the ability of cooperation of the patient in the treatment program, through the acquisition of therapeutic tools borrowed from the progress of the relationship with the therapist.

It is possible to foresee a third type of alliance, which in successive stages, is found to shift from a helping to a working alliance during the gradual, but steady, development of the therapeutic relationship [8]. The “intersubjective alliance” [18, 19] is a new concept derived from psychotherapy, later adapted to the pharmacological therapeutic relationship. To develop an effective and appropriate patient–physician relationship, the psychiatrist must always be aware of working with a people who have their own personality, feelings, sensitivity and intelligence, apart from symptoms and illness. Psychoanalytic theories suggest that the quality of the therapeutic relationship is linked training to interpersonal relationship training of unconscious reactions such as transfert and controtransfert. Since the beginning of his studies, Freud had understood that the work of revelation, which is essential for the success of psychoanalysis, required a collaborative attitude and cooperation between patient and therapist. Placing inside the “irrepressible positive transfert” (conscious positive feelings toward the analyst, who helps the patient to overcome the resistance), Freud used the term “rapport” to refer to this important aspect of patient–therapist relationship and called it the “vehicle for the success” [20]. Transfert is defined as the shift of thoughts, feelings, desires, and behaviors of the patient, originally facing significant characters of his childhood world, on the therapist. Through this shift, the patient turns the memories into present life: in the analysis space. However, the controtransfert is, however, the wide range of reactions that the doctor may have toward the ill. It may take the form of positive or negative feelings (e.g., a doctor who has feelings of anger, hostility, antipathy toward the patient, tends to assume a destructive and ineffective attitude in the relationship) [21]. According to Freud, the conditions for withdrawal of the setting (opacity, silence) create frustrating situations for pulses so that they win the obstacle of resistance, actualized in the analytic relationship. In contrast, in the cognitive model, the conditions of interpersonal security, offered by the therapeutic relationship, promote the awareness and development of autoriflessive more heuristics activities. The experience of a positive relationship with the therapist can change the negative forecasts of the patient’s interpersonal patterns. Such corrective interpersonal experiences concern the affective and cognitive side and the disposition of the action. Looking at the therapist the patient can assimilate ways of acting more useful than those usually adopted. The therapeutic outcome is most significantly correlated with the therapeutic relationship rather than the different psychotherapeutic techniques [22].

In this complex model of prescription, focused on relationship, the attachment styles emerge as central points. As the therapist and the drug represent attachment figures and the patient is a caregiving figure, each of them enters the relationship with their Internal Working Models (IWM) and behavioral patterns, which must be taken into account in the construction of a prescription to optimize adherence. Attachment theory also contributes to the understanding of working alliance by providing a framework to conceptualize the way in which therapist and client factors interact in determining the quality of the relationships. There is empirical evidence to suggest that therapist attachment style is influential in the development of a therapeutic relationship [23].

The attachment system has its basis in the innate propensity of human beings to form strong emotional bonds with their figures of reference, which Bowlby calls “particular others” [24, 25]. The evolutionary purpose of the attachment system is to find a caregiving figure that the subject perceives as strong and reliable. This attachment system is established according to the different qualities of the mother-child relationship, resulting in several “attachment styles”, with varying characteristics depending on different dynamic and circular patterns of demand (attachment) and answer (caregiving). Attachment style is the way in which each individual assumes the innate propensity to form affectionate bonds with others. The attachment developed within the infant-caregiver relationship is thought to form the “secure basis” of future relational dynamics.

Research by developmental psychologist Mary Ainsworth in the 1960s and 1970s, through the protocol of the Strange Situation, reinforced the basic concepts and introduced the concept of the “secure basis”. As such, she developed a theory which included a number of attachment patterns in infants: secure attachment, insecure-anxious avoidant attachment and insecure-anxious ambivalent attachment. Infants who are “securely attached” use their caregiver as a secure basis while exploring new surroundings; such infants seek contact with, and are comforted by, caregivers after separation. Infants described as “anxious-ambivalent” have difficulty using the caregiver as a secure base; these infants seek, then resist, contact with caregivers after separation. Finally, infants with an “avoidant attachment” style do not exhibit distress upon separation and do not seek contact after the caregiver’s return.