2019/2020
Francisca Caiado de Bragança
Treatment in Schizophrenia: factors for adherence
Mestrado Integrado em Medicina
Área: Psiquiatria e Saúde Mental
Tipologia: Monografia
Trabalho efetuado sob a Orientação de:
Professor Doutor Manuel António Fernandez Esteves
Trabalho organizado de acordo com as normas da revista:
Comprehensive Psychiatry
Francisca Caiado de Bragança
Treatment in Schizophrenia: factors for adherence
Treatment in Schizophrenia: factors for adherence
Francisca Caiado de Bragança1, Manuel António Fernandez Esteves21Faculty of Medicine, University of Porto, Porto, Portugal; Alameda Prof. Hernâni Monteiro, 4200-319 PORTO, Porto, Portugal
2 Department of Clinical Neuroscience and Mental Health, Faculty of Medicine, University of Porto, Porto, Portugal; Alameda Prof. Hernâni Monteiro, 4200-319 PORTO, Porto, Portugal
Corresponding author:
Francisca Caiado de BragançaFaculdade de Medicina da Universidade do Porto
Alameda Prof. Hernâni Monteiro, 4200-319 PORTO, Porto, Portugal E-mail: franciscabraganca@hotmail.com
Abstract
This narrative review analyzes the existing scientific evidence on factors related to medication adherence in schizophrenia.
Using PubMed as the database, a research was conducted targeting articles published between 2009 and 2019, written in English or Portuguese, about predictors of antipsychotic compliance in schizophrenia.
Factors affecting adherence have been generally subdivided into 4 categories: disease-related, patient-related, medication-related and environmental-related. Factors which were found to be consistently associated with poor adherence include poverty, high symptom burden, high levels of hostility, poor insight, presence of substance abuse, negative attitudes toward medication and antipsychotic side-effects. On the other hand, variables such as neurocognitive dysfunction, type of antipsychotic, social support and demographic parameters often yielded contradictory results.
Variables consistently associated with non-adherence should be assessed in clinical practice and strategies put in place to correct them or dampen their effect. Since conflicting results are often found regarding several studied variables, future research should aim at identifying further predictors of adherence in order to better guide clinicians and maximize the patient’s benefit of treatment.
1. Introduction
Schizophrenia is a disabling chronic illness that affects aproximatelly 0,5%-0,7% of the adult population worldwide.1 Typically developing in late adolescence and early adult life, it is caractherized by cognitive changes, lack of insight, and both positive and negative symptoms, reflecting, respectively, a distortion and excess or a reduction in normal functions.2 3 4 The primary treatment, adressing symptom burden and relapse risk,5 includes both antipsychotic medication and psychossocial interventions, such as cognitive-behavioral, compliance and family therapy and psychoeducation.24
Adherence to treatment is not an all or nothing phenomenon.6 Although both adherence and compliance are plausible terms to describe the extent to which a patient takes the medication prescribed by an healthcare provider, some authors prefer the term adherence, as compliance generally involves deliberate treatment engagement. As the two may be imperfect, both will be used interchangeably in this review.
Since schizophrenia is a chronic mental illness and adherence tends to be worse with a prolonged disease course, non-adherence to antipsychotics is one of the most important aspects of treatment.7 8 Patients’ low insight for the disease makes this problem even more pronounced, with the decreased motivation to be treated being the cause of highly detrimental consequences to the patient.8
In the literature, poor adherence in schizophrenia has been shown to be a strong predictor of relapse, which is two to five times more likely to occur in non-compliant patients.9 Non-adherence has also been associated with poor symptom outcome, substance abuse, longer inpatient treatment, increased re-hospitalization, social alienation, arrest, violence and greater economic burden.410 Besides this, non-adherent patients are more likely to suffer from neurocognitive, occupational and social dysfunction and ultimately to become a danger to themselves and others.1112
In this setting, rates of non-adherence vary between 70% to 95%,13 although naturalistic studies point to rates between 25 to 50%.14 In the CATIE study, a double-blind trial that included 1493 patients, 74% of patients discontinued their medication within 18 months, with no distinction between first and second generation antipsychotics.3
Medication adherence is, in this way, a central aspect in the management of these patients, and the factors affecting it have been studied for several years now.10 While for some the evidence consistently points to a direction of impact, for others the results are many times inconsistent and contraditory.7 Putative predictors have been generally categorized as disease-related, medication-related, environmental-related and patient-related.14 The aim of this narrative review is to study how these factors affect antipsychotic adherence in schizophrenia.
2. Methods
A research was conducted using the PUBMED database on the 10th September 2019, using the following query: ((((("schizophrenia"[MeSH Terms]) OR schizophre*)) AND ((("risk factors"[MeSH Terms]) OR predictors) OR reasons)) AND (((("treatment adherence and compliance"[MeSH Terms])) OR "medication adherence"[MeSH Terms]) OR non adherence)) AND "antipsychotic agents"[MeSH Terms]. Articles were included if written in English or Portuguese, published between 2009 and 2019, related to humans.
The database returned a total of 181 references. After reading the title and abstract, 115 articles were excluded for not being related to the theme. After the full reading of the remaining 66 articles, 27 were excluded due to information that did not apply to this study. To this total of 39 articles, 10 were added after a hand search of relevant content found in references of selected articles. Thus, 49 articles were included in this review.
3. Results
3.1. Disease-related factors
3.1.1. Illness duration
A shorter illness duration was found to be significantly associated with higher rates of treatment discontinuation.5 In fact, patients with less than a five-year disease course were found to be 2,7 times more likely to discontinue medication in comparison to those with a course of over five years.5 Patients early in the course of disease seem to have less insight, which is a strong predictor of non-adherence. However, illness duration may also act as a proxy for other factors such as duration of maintenance therapy.9 A longer duration of maintenance therapy has been shown to predict higher adherence.15
3.1.2. Symptomology
The efficacy of antipsychotics in decreasing symptom burden is consistently considered the core driver of the patient’s decision to comply with therapy.16 Studies go further to state that symptomatic worsening during treatment is a stronger predictor of discontinuation than medication intolerance.1617
However, the degree of improvement in specific symptom clusters appear to be more relevant in this behavior.17 Positive symptoms improvement has been pointed as the most important symptom cluster predictor of treatment compliance.16171819 Besides this cluster, only improvement in hostility levels and depressive symptoms predicted adherence.17 Hallucinations and delusions of grandiosity impair the patient’s ability of acknowledging the need to take the medication, making them reluctant to adhere.20 On the other hand, improvement of negative symptoms hasn’t been a consistent predictor of adherence.1720
The positive valorization of symptoms has been an understudied subject, since most patients seeking treatment refer more detrimental than advantageous effects.21 However, positive attitudes or ambivalence toward symptoms exists and have been found more frequently in positive symptoms such as hallucinations and delusions.2122 Some patients describe psychosis as fascinating, with an undisputable risk of attachment to their delusional narratives.21 22 Paranoid patients convinced to be in possession of special powers have high self-esteem, which can be a barrier to comply with treatment.22 Auditory hallucinations of benevolent content have been associated with decreased
compliance, especially when patients perceive paranoia as a survival strategy.21 22 A study assessing the way patients perceive the possible gain from illness showed that 28% of patients discontinue their medication due to increased necessity of “importance and power”, desire of “becoming another person” or “missing voices”.21 It is, thus, crucial to assess how patients feel about their symptoms, in order to better guide the choice of therapy.22
3.1.3. Neurocognitive dysfunction
Cognitive dysfunction is a robust feature of schizophrenia and has been pointed out as a strong predictor of functional outcome,7 although there is still debate as whether it does so independently or through non-compliance.14 Though studies assessing neurocognition and adherence have reached different conclusions,7 14 15 memory impairment and executive dysfunction have been found to be the most relevant predictors of non-adherence in schizophrenia.14
In the memory field, adherent patients exhibit an overall better memory performance, especially in verbal memory,14 while non-adherent patients have a worse immediate recall ability, which hinders their capacity to comply.14 In fact, forgetting to take the medication has been reported as the most frequent reason for non-adherent behavior.239
In relation to executive functioning, patients that don’t adhere to antipsychotic medication show significantly lower scores in tests evaluating attention, abstraction, and cognitive flexibility.14 15 They also display impaired task-shifting abilities, which reflects dysfunction in domains such as planning, problem solving and conceptualization,14 and this has also been correlated to non-adherence.15
Other studies, however, have reached opposite conclusions, with non-adherent patients exhibiting a higher level of neurocognition, exemplified by better verbal learning and memory skills, executive functions and a higher IQ.7 Authors speculate that patients with a higher cognitive performance may have a stronger belief in their ability to cope without medication, and hence choose to discontinue it.7
In the field of language, verbal fluency has been found to be one the most impaired cognitive domains in schizophrenia.15 A study has found that language impairment, reflected by poor performances in verbal fluency tests, conferred a moderate risk for non-adherence.15
Despite the debate around this topic, it is generally accepted that cognitive dysfunction in schizophrenia impacts adherence both through decreased motivation and impaired ability to engage in therapy.14
The premorbid functioning level of a patient who develops schizophrenia and its impact on adherence is understudied and subject to conjecture.14 Those with higher premorbid intellectual function, itself affected by the neurodevelopmental nature of schizophrenia, are thought to better deal with the neural insult of the disease.24 An improved cognitive reserve is thought to increase the ability to inhibit the abnormal neural processes responsible for psychotic symptoms.24 Thus, it possibly translates into a diminished symptom burden, which by itself improves adherence.14
3.1.4. Insight level
The multidimensional concept of insight includes the awareness of being ill, the recognition of symptoms, the ability to attribute deficits to the disease and the understanding of the need for treatment.2526 The level of insight may be modulated by the presence of neurocognitive deficits or coping mechanisms.2518 In the literature, low insight has been consistently associated with non-adherence.192772829
Patients with preserved insight are more able to lable psychotic symptoms as pathological, have a greater awareness of the social consequences of the disease and are ultimately more likely to find the treatment both reasonable and necessary.71118
It is also noteworthy that, although impaired insight is a well-established predictor of non-adherence, patients taking long-acting injectable antipsychotics may be adherent despite having poor insight, making these medications a reasonable option to improve outcomes in patients whose insight is impaired.25
3.1.5. Hostility
Patients exhibiting high hostility were found to be less adherent to treatment.3025 2928 Hostility and insight are often seen as concomitant factors impacting adherence and for this reason should be assessed together.29 This is further supported by the fact that hostile patients with decreased insight showed over 90% probability of not complying with medication.25 Hence, hostility is found to be both a predictor of non-adherence and an amplifier of the correlation between insight and adherence.25
3.2. Patient-related factors
3.2.1. Socio-demographics
There are conflicting results regarding the relationship between demographic variables and compliance with treatment in schizophrenic patients.30
While some don’t find an association between the patient’s age and adherence behavior,25 27 an older age has been associated with decreased compliance with treatment.31 This latter finding has been attributed to a higher pill burden in this age group, in addition to common memory and executive functioning deficits.31 However, other studies find opposite results,32153 with increasing age having a positive influence on compliance.3 23 33 The decreased independence and mobility of older individuals seems to ease clinical monitoring, contributing to higher adherence rates.34 In the same line of thought, patients who are early in their disease course and haven’t experienced repeated relapses may be more willing to take risks in order to assess their ability to remain well without medication.9
The influence of gender in adherence is highly controversial. While some studies report female gender as a negative determinant of adherence,23 12 others found no association.925 In an homeless French population, female gender was found to be a risk factor for non-adherence mostly due to increased reported side-effects and increased negative attitudes towards medication.12 Women seem to experience more negative side-effects probably due to biological differences impacting drug metabolism, particularly because antipsychotics are mostly tested in middle-aged men to avoid the concerns with pregnancy.12
Non-adherent patients are more likely to live alone than adherent patients, which may mirror an inadequate support by relatives and caregivers.18
Full adherent patients have been shown to have a higher body mass index (BMI) in comparison to those with partial adherence.7 30 Overweight patients are unlikely to gain extra weight during treatment and/or are more likely to accept this medication’s side-effect.730 Although this is a plausible explanation, others have attributed this association to naturalistic study designs, where patients who comply with medication over time are more likely to gain weight.7 On the other hand, a strong correlation has also been reported between a higher BMI and non-adherence, which can be due to the distress caused by weight gain.35
The influence of employment and educational status in compliance with treatment has also been studied.18 23 31 Illiterate schizophrenic patients were found to be significantly less adherent to medication.31 In the same way, being employed full-time or
having a significant higher educational level (of 13 or more years) was shown to improve adherence.2318 Patients who are employed and have a higher educational level appear to have a higher level of insight and functioning, which may contribute to improved adherence.18 However, a higher educational level has also been associated with worse compliance,3 possibly due to other intervening variables such as negative attitudes toward medication.3
3.2.2. Adherence background
Previous non-adherence to medication is also an important factor impacting future compliance.30 A study has found that non-adherence in the 4 weeks prior to the start of a new medication was the strongest predictor of subsequent non-adherence.30 Moreover, patients starting antipsychotics were more frequently non-adherent than those with previous consistent use of the same drugs, implying that patients need time to adjust and become adherent to an antipsychotic.328
3.2.3. Alcohol and drug use
Past or current alcohol and drug use is common amongst schizophrenic patients and most studies have considered these risk factors for medication non-adherence.930 15 33 Patients with addictions are, in many cases, primarily concerned with short-term demands, investing less on long-term goals, including those related to their own health. Furthermore, these patients often exhibit psychiatric comorbidities and are commonly stigmatized within medical environments, generating mistrust and fueling avoidance of the system.36 There is still debate, however, on whether substance abuse is a cause or a consequence of non-adherence.28 To better answer this question, detailed prospective studies will be needed.28
3.2.4. Social functioning
In the context of schizophrenia, being socially active relates to better adherence to treatment.30 This is thought to be mediated by the severity of patients’ positive symptoms, which highly impact their social skills.30 A good psychosocial function, especially in the areas of self-care and social networks, was also shown to be one of the two best predictors of compliance.19 The engagement in activities such as art therapy, social skills training and cognitive behavioral therapy also had a positive impact on adherence.18
3.2.5. Religion
Religion can provide support for patients whose social life and individual identity has been hindered by the disease, fostering feelings of hope and purpose.6 However, religious beliefs can also lead to the replacement or delay of medical treatment, since some groups focus solely on spiritual healing and perceive suffering as salutary.6
Christianity was found to be a predictive factor of adherence.4 Christian patients were found to be 3,23 times more likely to commit to treatment than Buddhists, Muslims, Hindus and free thinkers.4 Authors attribute this to the fact that Christians tend to be less stigmatized by their religious peers,4 and that Christianity is more receptive to science-based and less supportive of superstition-science-based treatments.4
In a study conducted in the United Arab Emirates, the involvement of patients with faith healers was significantly associated with non-adherence,27 and recommendations were made to educate patients and families on the consequences of such practices.27
3.2.6. Attitudes toward medication
It is known that the patient’s attitudes toward medication may not translate directly into behaviors of adherence and non-adherence.20 A patient may forget to take the medication even though he understands its benefits.20 The same happens with someone who, although believing the medication is unnatural, harmful, lenghty or unnecessary, takes it for other reasons, such as pressure from others.20
Other studies have reached different results, with a negative attitude towards medication predicting non-adherence directly.1931 These patients have also been shown to have lower levels of insight, more medication side-effects and diminished trust in the doctor-patient relationship.37 11 It seems that several variables are able to change the patient’s view and attitude towards the treatment, ultimately impacting adherence.
Concerning patients exhibiting positive attitudes, 85% were adherent to medication,20 and this pattern has been found in independent studies.113118
3.3. Environmental-related factors
3.3.1. Living area
Improved medication adherence has been observed in schizophrenic patients living in a non-metropolitan area.8 In rural areas patients are thought to have a stronger social support network and a closer relationship with their physician, as well as less assess to illicit drugs, all factors associated with improved adherence.8
3.3.2. Poverty
In a study conducted in rural Ethiopia, the most common reason for non-adherence among schizophrenic patients was the lack of assess to basic livelihood, such as proper food.38 Moreover, in empoverished areas which commonly lack community mental health care, the support from family members is even more important since it is often the only one in which the patient can rely.38
In the homeless population, the estimated prevalence of schizophrenia is approximately 11%.12 Considering the unique difficulties and context of this population, it is understandable that, to these patients, medication adherence is not a primary concern. Pharmacological and non-pharmacological strategies should, in this way, be laid out to better address schizophrenia in the context of homelessness.12
3.3.3. Stigma and support from others
Because of the low mental health literacy among the general population, people tend to distance themselves from those exhibiting strange behaviour.4 Schizophrenic patients fear being labeled as mentally ill, since this is frequently associated with fewer marriage and job opportunities.38 Stigma is, thus, a powerful barrier to adherence.38
On the other hand, patients feel safe and understood sharing their condition with a significant other who provides support and encouragement.419 A caregiver is of great importance to these patients as it was found by a study that 44% of adherent patients had a family caregiver, contrasting with only 24,6% of non-adherent patients.18 However, significant others can also negatively impact adherence,21 as it was noted in a sample of 72 non-adherent patients, in which 20% attributed non-compliance to friends or family advice against medication intake.21
3.3.4. Doctor-patient relationship
Patients who place trust in their doctor and report good relationships with medical personnel exhibit better medication adherence.4 11 Likewise, when the psychiatrist includes the patient in the medication decision process, he tends to feel better informed and more open to discuss fears and uncertainties.39 An important thing to consider is the confounding effect of insight in the association between the quality of the therapeutic relationship and adherence.39 The extent to which the patient perceives the relationship as satisfactory depends on the concordance between doctor’s and patient’s views and goals, which is naturally increased when the patient has preserved insight.39
3.4. Hospitalizations and medication-related factors
3.4.1. Hospitalizations
Non-adherence is more frequent in patients with multiple past and short-duration hospitalizations and who required hospitalization at the onset of the disease. 8182030
Patients who are hospitalized at the onset of illness presumably exhibit more severe symptomology and that could itself explain the trend to non-adhere.20
Apart from the number of previous hospitalizations which also predicted non-adherence,1830 one study showed that patients with an hospitalization of over two weeks of duration were more likely to be adherent after discharge in comparison to patients with shorter hospitalizations.8 The latter, who more frequently self-discharge, may do so owing to a poor therapeutic alliance.8 On the other hand, longer hospitalizations enable a stronger therapeutic alliance to be established and allows time for a better decision to be made in relation to the medication discharge plan.8
3.4.2. Medication side-effects
Side-effects from medication are often referred as the most important contributor to non-adherence, 2122 although other studies don’t find such association.7 A patient who had previous negative experiences with medication, either through distressful side-effects or non-response, is likely to feel skeptical about it.39 Moreover, the weight of specific side-effects will depend upon study population.22
In general, side-effects strongly associated with non-adherence vary widely between studies and include extrapyramidal symptoms, such as tardive dyskinesia, akathisia and parkinsonism, cognitive side-effects such as sedation, sleepiness and
dizziness, autonomic side-effects such as diarrhea and nausea and diminished sexual drive and weight gain.3722
Another point worth noting is the difference between acutely ill and stable patients on chronic treatment. Acutely ill patients, in which lack of insight and delusions predominate, are likely to overestimate the improvement in positive symptoms, underestimating side-effects from medication.16 On the other hand, multiepisode schizophrenic patients report changes in appearance as a significant reason for non-adherence, in comparison to first episode patients.40 It is important to take into account that long term users of antipsychotics may underreport side-effects both because they get used to them or believe the side-effects are deeply intertwined with the benefits of treatment.18
The balance between the discomfort from side-effects and the medication’s benefits seems more relevant in terms of adherence than side-effects alone.18
3.4.3. First- and second-generation antipsychotics
The impact of the type of antipsychotic on adherence has been a matter of debate and also of controversy since studies differ widely.10 While some don’t find a relationship between the type of antipsychotic used and the level of medication adherence,11 33 19 adherence was reported to be significantly higher when using typical antipsychotics,23 although the same was found in relation to atypical antipsychotics.1815
In clinical practice, although metabolic side-effects and weight gain, potential threats to adherence, are more commonly attributed to atypical antipsychotics, these seem to have supplanted the real concern with extrapyramidal side-effects more frequently caused by typical antipsychotics.28 However, some authors don’t see this so starkly, attributing equal importance to adverse effects arising from both types of antipsychotics.3
3.4.4. Oral and long-acting injectable (LAI) antipsychotics
One of the aims in the development of LAI antipsychotics, also known as depot antipsychotics, was improving adherence in schizophrenia.41 These new drugs would also allow earlier and easier detection of relapse, clearer distinction between lack of adherence and lack of efficacy, reduced risk of self-poisoning and more stable and predictable serum concentrations.41 In face of non-adherence, LAI antipsychotics also would have the advantage of creating a window of opportunity to encourage patient’s compliance without a precipitous drop in drug levels.42
The use of LAI antipsychotics in the treatment of schizophrenia has then been proposed as an alternative to their oral counterparts when there is a concern of poor adherence but in real-life discontinuation still occurs, albeit in a smaller percentage comparing to oral antipsychotics.41 43 However, this benefit on adherence is not supported by all studies.18
One could hypothesize that LAI antipsychotics would improve adherence mainly through improved efficacy. In terms of such claim, debate on whether the clinical outcomes are improved by their use over oral antipsychotics is still ongoing.4143 A large randomized control trial concluded LAI antipsychotics were not superior to oral antipsychotics in terms of time to hospitalization, symptom relief and quality of life.44 On the contrary, they have shown to reduce hospitalization frequency in a meta-analysis of mirror-image studies.45
In the clinical setting, LAI antipsychotics still tend to have low prescribing rates, mostly ascribed to psychiatrists’ concerns.41 These include the potentially stigmatizing effect of such drugs, concerns about the loss of patient’s autonomy, beliefs that they are associated with worse side-effects in comparison to their oral counterparts and concerns related to patient’s acceptance.41 The cost of LAI antipsychotics has also been pointed as a reason for underprescription, since this drug’s availability is often restricted in certain areas by the institutions holding the medication budget.41
Although most evidence seems to support the use of LAI antipsychotics to the benefit of adherence,2 it remains questionable whether depot antipsychotics truly improve adherence or simply reveal non-adherence in patients with schizophrenia.
3.4.5. Medication scheme
It has been found that a complex regimen comprised of many medications with a high frequency of administration negatively affects adherence.26 This is especially pertinent in schizophrenia, since the cognitive deficits associated with the disease further impact the ability to understand an already complex regimen.26
However, it has been found that patients taking both types of antipsychotics, instead of just one, more likely remembered to take the medication.4 Authors propose that, in these patients, one antipsychotic is not enough for symptom improvement, hence patients taking more than one showed better compliance.4 The same probably applies to patients on other psychiatric medications such as mood stabilizers, anticonvulsants, anticholinergics and anxiolytics.32
3.5. First episode psychosis (FEP) and multiepisode schizophrenia
First episode and multiepisode schizophrenia patients seem to have different motivations to adhere to antipsychotic therapy.40FEP patients are peculiar in the way that their short disease course hasn’t allowed them the time to reach a “cause and effect” conclusion about medication. Unable to perceive symptom relief deriving from antipsychotics, they are prone to deem medication unnecessary once free from symptoms.40 However, other authors have found opposite results, with FEP patients whose positive symptoms were relieved by medication being more likely to stay adherent.46 These patients consider the doctor-patient relationship as the most relevant factor driving adherence.40 Hence, in the first-episode crisis, it is essential to create a strong therapeutic alliance, within which patient’s beliefs, life goals and insight into illness are taken into account.40
Multiepisode patients have different motivations, including the desire to prevent relapse and the understanding of the treatment’s benefits.40 Non-adherence in this group is highly related to changes in appearance due to medication, since their longer treatment course allows these effects to stand out.40
The moment in which the first episode occurs is also relevant for compliance.20 In adolescent FEP patients it was found that a decreased symptom burden was predictive of non-adherence, which may seem counterintuitive.2047 However, in this age group, the tighter parental supervision leads to greater adherence if symptomology is severe.20 On the otherhand, adult FEP patients are less likely to be supervised, and their adherence more closely impacted by symptom severity.47
3.6. Persistent refusal
While most non-adherent patients may be partially non-adherent, there is an understudied group which consistently denies medication, over a long period of time.39
Persistent refusers, when compared to fully adherent patients, were found to have lower insight levelsand more frequently considered previous medications unhelpful and previous psychiatrists unsatisfactory.39 Moreover, they felt they had been less informed about medication in the past.39
Although this group of patients was thought to be more severely impaired and thus less able to make judicious decisions, they were also found to have been through relatively long periods of medication in the past, making it likely that the decision to refuse had been rational and deliberate.39
4. Discussion
Adherence is a complex topic mainly because benefits and disadvantages of pharmacological treatment vary between patients, according to different sets of goals, beliefs and circumstances.26 Thus, a personalized and dynamic approach is needed.26
Although many factors have been shown to predict non-adherence, and strategies aimed at correcting them are likely to retrieve positive results, there is a set of patients in which medication intake is the only way to improve adherence on the short and long-term. This includes decompensated patients with intense positive symptomology, low insight, disorganized thoughts and dysfunctional behavior.
The establishment of a therapeutic alliance seems of upmost importance and likely paves the way to address multiple non-adherence risk factors. There is a need for longer consultations within a caring environment, in which there can be an assessment of patients’ concerns, beliefs, positive and negative attitudes, symptomology, cognitive ability, social functioning and family support.26 Providers should be clear, simple, instructive and encourage patients to ask questions and be a part of the decision-making process. Treatment should be tailored to patients’ hopes and expectations,26 taking into account their economic resources.13 This should also prevent the search for alternative treatments unsupported by scientific evidence.38
Besides a good therapeutic alliance, the involvement of family members or other caregivers seems crucial, since these can better monitor and motivate the patient to follow treatment.22 For those with strong negative attitudes, psychotherapy and psychoeducation might be of particular importance, by challenging dysfunctional beliefs both about the disorder and its treatment.21 For patients who feel ambivalent towards the psychotic experience, cognitive behavioral therapy may help counter delusional assumptions without invalidating the experience of the patient.21
Side-effects from medication should be searched for in every appointment and medication switched if necessary. Drug and alcohol use should be prevented or reduced. Although the association between cognitive dysfunction in schizophrenia and poor adherence is uncertain, consensus guidelines indicate that it is a factor contributing to non-adherence.48 For patients in which memory impairment is an important factor,22 the use of memory aids, such as alarms, calendars, behavior prompts associated with everyday tasks and notes in visible places, may be a way of improving adherence.26 These patients could also benefit from LAI antipsychotics, that assure medication delivery.22 Cognitive behavioral therapy integrating cognitive remediation has also been proposed to surpass this barrier.1448
Despite the controversy surrounding the impact of LAI antipsychotics on adherence, these tend to be used to improve adherence in high risk individuals in clinical practice, their higher cost being offset by less hospitalization costs on the long term.245
Both atypical and typical antipsychotics seem to yield similar efficacy in schizophrenia’s symptoms and relapse risk.210 In this way, the choice of antipsychotic is normally guided by side-effects or patient’s specific factors, such as comorbidities and past experience with these drugs.2 Although there is conflicting evidence regarding which type of antipsychotic is better in terms of adherence, most clinicians favor the use of atypical antipsychotics, which are less likely to induce prominent extrapyramidal symptoms and endocrinal side-effects.10
Simplifying the treatment regimen, both in terms of amount of medication and frequency of administration, is a way of improving adherence. Depot antipsychotics are also an effective way of simplifying the regimen while guaranteeing administration.26
The inconsistent results often found can be ascribed to several limitations unique to adherence studies. In the first place, the definition of medication adherence varies widely between studies10 and there are no universally established cut-off points. As adherence can be evaluated in categorical, dichotomous and continuous ways,10 there should be an effort to standardize its measurement and categorization.26
Moreover, medication adherence can be generally assessed in two ways: objetively and subjetively.10 Objetive assessments, such as the measurement of urine or serum antipsychotic concentrations, seem more reliable and take into account individual pharmacokinetics, but are usually limited by financial constraints.8 10 Other examples include the direct observation of medication intake, pill counts, electronic monitoring systems (MEM) and pharmacy refill records.10 Subjective assessments are the most commonly used in research, mostly because of their time and cost effectiveness, ease of use and relative reliability.15 These include patient’s self-report, interviews, diaries or provider reports.8 49 Although self-reporting questionnaires are patient-friendly, less expensive and easier to conduct,23 they rely on patient recall, and overestimation is likely to occur.109 It has been proposed that studies should include two measurements in their adherence assessment where at least one is objetive.7
Most studies are also designed as cross-sectional.8 Limitations include failure to assess patients over time, limiting cause-effect conclusions,31 especially since adherence is a dynamic process.18
Adherence is a complex topic in schizophrenia, with current literature exhibiting vast and heterogenous findings. Since the biology of the disease is itself an intervening factor and variables strongly interplay with one another, it is often difficult to establish predictive relations.
Taking into account the importance of this topic, and since patients’ behavior is known to fluctuate over time, future research should focus on prospective study designs over long periods of time, and in large samples, under naturalistic settings.
Acknowledgements
Not applicable.Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of interest
None.References
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Agradecimentos
Ao Sr. Prof. Doutor Manuel Esteves pela orientação, disponibilidade e dedicação na realização deste trabalho, bem como por partilhar comigo o seu conhecimento e espírito criativo.
Aos meus pais, por tudo.
Aos meus amigos, pelo ânimo que me deram nos momentos certos.
ANEXOS
COMPREHENSIVE PSYCHIATRY
AUTHOR INFORMATION PACK
TABLE OF CONTENTS
.XXX
.• Description
• Impact Factor
• Abstracting and Indexing
• Editorial Board
• Guide for Authors
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ISSN: 0010-440XDESCRIPTION
.Comprehensive Psychiatry is an open access, peer-reviewed journal that publishes on all aspects of
psychiatry and mental health. The mission of this journal is to disseminate cutting edge knowledge in order to improve patient care and advance the understanding of mental illness. With the support of an expanded international team of editors and peer reviewers, we aim to publish high quality papers with a particular emphasis on the clinical implications of the work including the improved understanding of psychopathology. We encourage our authors to adopt an accessible approach to presenting their findings, to promote the fullest engagement with clinicians and other interested parties. Through our new open access policy, we expect our papers will deliver the widest global impact, opening up fruitful scientific engagement with researchers outside the immediate circle, as well as with mental health clinicians, interested policy-makers and the public.
IMPACT FACTOR
.
2018: 2.586 © Clarivate Analytics Journal Citation Reports 2019
ABSTRACTING AND INDEXING
.
PubMed Central Web of Science Scopus
Directory of Open Access Journals (DOAJ)
EDITORIAL BOARD
.
Editor-in-Chief
N. Fineberg, University of Hertfordshire, Hatfield, United Kingdom
Associate Editor
S. Chamberlain, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom E. Grünblatt, Psychiatric University Hospital Zurich, Zurich, Switzerland
Editorial Office Editors Emeriti
D.L. Dunner, Mercer Island, WA, USA
J.C. Markowitz, New York State Psychiatric Institute, New York, New York, United States R.A. O'Connell
Editorial Board
M. van Ameringen, McMaster University, Hamilton, Ontario, Canada
B. Boland, Hertfordshire Partnership University NHS Foundation Trust, St Albans, United Kingdom
C.R. Cloninger, Washington University in Saint Louis School of Medicine, Saint Louis, Missouri, United States W.H. Coryell, University of Iowa, Iowa City, Iowa, United States
J.R. DePaulo, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States B.M. Dell'Osso, University of Milan, Milano, Italy
J. Du, Shanghai Mental Health Center Drug Abuse Treatment Center, Shanghai, China E. Fernandez-Egea, University of Cambridge, Cambridge, United Kingdom
L.F. Fontenelle, Monash University, Clayton, Victoria, Australia
D.A. Geller, Massachusetts General Hospital - Harvard Medical School Center for Nervous System Repair, Boston, Massachusetts, United States
J. E. Grant, University of Chicago, Chicago, Illinois, United States G. Grassi
E. Hollander, Yeshiva University Albert Einstein College of Medicine, Bronx, New York, United States K. Ioannidis, University of Cambridge, Cambridge, United Kingdom
S. Kasper, University of Vienna, Wien, Austria
K.R. Laws, University of Hertfordshire, Hatfield, United Kingdom B. Lerer, Hadassah Medical Center, Jerusalem, Israel
M. Mohler-Kuo
S.A. Montgomery, Imperial College London, London, United Kingdom S. Morein
Z. Nemoda, Semmelweis University of Medicine, Budapest, Hungary A. Ozerdem, Dokuz Eylül University, İzmir, Turkey
S. Pallanti, Stanford University Department of Psychiatry and Behavioral Sciences, Palo Alto, California, United States
K. A. Phillips, Cornell University, New York, New York, USA
A. J. Rothschild, University of Massachusetts Medical School, Worcester, Massachusetts, United States N. Sartorius, Association for the Improvement of Mental Health Programmes, Geneva, Switzerland L. J. Siever, Icahn School of Medicine at Mount Sinai, New York, New York, United States
D. J. Stein, University of Cape Town Department of Psychiatry and Mental Health, Cape Town, South Africa J. Stochl, University of Cambridge, Cambridge, United Kingdom
GUIDE FOR AUTHORS
.
INTRODUCTION
From January 2019 Comprehensive Psychiatry will move from a subscription to a gold open access publishing model. Authors who publish in Comprehensive Psychiatry will make their work immediately, permanently, and freely accessible. Authors submitting to the journal on or after 31st October 2018 will be expected to cover the cost of the Article Publishing Charge (APC) to publish in the journal, will have a choice of license options and will retain copyright to their published work.
Comprehensive Psychiatry is an open access, peer-reviewed journal that publishes on all aspects of
psychiatry and mental health. The mission of this journal is to disseminate cutting edge knowledge in order to improve patient care and advance the understanding of mental illness.
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• Manuscript has been 'spell checked' and 'grammar checked'
• All references mentioned in the Reference List are cited in the text, and vice versa
• Permission has been obtained for use of copyrighted material from other sources (including the Internet)
• A competing interests statement is provided, even if the authors have no competing interests to declare
• Journal policies detailed in this guide have been reviewed
• Referee suggestions and contact details provided, based on journal requirements For further information, visit our Support Center.
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PREPARATION
Peer review
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