Predictors of medication adherence in patients with schizophrenia and bipolar disorder

Objective: To investigate potential risk factors for medication non‐adherence in patients with schizophrenia and bipolar disorder. Method: A total of 255 patients underwent clinical assessments, neurocognitive testing and blood sampling. The patients were divided into groups of ‘No’, ‘Partial’ or ‘Full’ adherence. Relationships to different risk factors were analyzed. Results: In schizophrenia, use of illicit substances, alcohol and poor insight were related to worse adherence. Schizophrenia patients with No adherence did better on tests of executive functioning, verbal learning and memory and had higher IQ than patients with better adherence. There were higher levels of autonomic side effects in the non‐adherence group, but body mass index was lower in the Partial adherence group than in the Full adherence group. In the bipolar disorder patients, there was an association between the use of illicit substances and alcohol and poor adherence. We found no relationship between adherence behavior and neurocognition in the bipolar disorder group. Conclusion: Substance use is an important risk factor for non‐adherence in patients with schizophrenia and bipolar disorder. Poor insight is also a risk factor in schizophrenia. The results suggest that cognitive dysfunction is not a risk factor for non‐adherence in these diagnostic groups.     

Medication Adherence,Ethnicity, and the Influence of Multiple Psychosocial and Financial Barriers

Medication adherence is critical for patients with bipolar disorder to avoid symptom exacerbation and diminished quality of life. Most analyses consider adherence barriers individually rather than conjointly, while neglecting potential ethnic differences. 435 patients in the Continuous Improvement for Veterans in Care––Mood Disorders study reported multiple financial and psychosocial factors influencing adherence. Logistic regression modeled adherence as a function of perceived barriers, including cost burden, access, binge drinking, poor therapeutic alliance, and medication beliefs. Nearly half the cohort experienced adherence difficulty, averaging 2.8 barriers, with minority veterans reporting lower adherence than white patients, particularly financial burden and treatment access. Total barriers were significantly associated with worse adherence (OR = 1.24 per barrier), notably poor medication beliefs, binge drinking, and difficulty accessing psychiatric specialists (ORs of 2.41, 1.95 and 1.73, respectively). Veterans with bipolar disorder experience numerous adherence barriers, with certain obstacles proving especially pernicious. Fortunately tailored clinical interventions can improve adherence, particularly by addressing modifiable risk factors.     

Treatment adherence with antipsychotic medications in bipolar disorder

OBJECTIVES: Atypical antipsychotic medications are a relatively new, increasingly prominent component of the treatment armamentarium for bipolar disorder. Information on adherence with antipsychotics among individuals with bipolar disorder in general, and atypical antipsychotics in particular, is currently quite limited. Using data from the VA National Psychosis Registry, we examined adherence with antipsychotic medications among patients with bipolar disorder (n = 73,964). METHODS: Antipsychotic medication adherence among veterans with bipolar disorder was evaluated using the medication possession ratio and categorizing patients into three groups: fully adherent, partially adherent and non-adherent. We compared characteristics of bipolar patients who received versus those who did not receive antipsychotic medication, and also identified predictors of poor adherence with antipsychotic medications. RESULTS: Approximately 45% (n = 32,993) of all individuals with bipolar disorder were prescribed antipsychotic medication. Individuals who were prescribed antipsychotic medications were younger and more often had comorbid substance abuse or post-traumatic stress disorder compared to individuals with bipolar disorder who were not prescribed antipsychotic medication. Just over half (51.9%) of individuals appear to be fully adherent with antipsychotic medications, while 48.1% of individuals are either partially adherent or non-adherent with antipsychotic medications. Factors associated with treatment non-adherence were younger age, minority ethnicity, comorbid substance abuse and homelessness. CONCLUSIONS: Treatment non-adherence is a major issue for close to half of individuals with bipolar disorder prescribed antipsychotic medication. Additional studies are needed to better understand treatment adherence within the full range of pharmacologic therapies among individuals with bipolar disorder.     

Relationships between insight and medication adherence in subjects with psychosis

BACKGROUND: Poor medication adherence in subjects with psychosis has a high prevalence and a negative impact on clinical outcome. Several studies have reported that a poor level of insight was a strong predictor of poor medi-cation adherence. However, few studies have investigated whether insight was associated with medication adherence, independently from other clinical and treatment characteristics. OBJECTIVE: To explore the link between insight and medi-cation adherence in subjects with psychosis, and to assess the impact of potential confounding factors on this association. METHOD: Subjects included in the study were patients aged 60 or less, consecutively admitted in a psychiatric ward, and presenting with at least one psychotic symptom (delusion or hallucination). Medication adherence was assessed using: 1) history of total discontinuation of treatment against medical advice over the 2 weeks before admission; 2) the 7-point rating scale developed by Kemp et al.; 3) the self-report questionnaire Drug Attitude Inventory (DAI). The Scale to assess Unawareness of Mental Disorder (SUMD) was used to measure level of insight. Assessment of symptoms was performed using the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Calgary Depression Scale (CDS). DSM IV diagnoses were assessed using the Diagnostic Interview for Psychosis (DIP). The associations between level of insight (SUMD scores) and the three measures of medication adherence were explored using the non-parametric Mann-Whitney and Spearman's tests. Logistic regression models giving Odds Ratios (ORs) and 95% confidence intervals (95% CI) were used to examine the impact of potential confounding variables on the associations between level of insight and medication adherence. RESULTS: 42 patients presenting with schizophrenia broadly defined (n=25) or psychotic mood disorder (n=17) were assessed. Significant associations were found between higher SUMD scores (ie poorer insight) and discontinuation of treatment before admission (z=- 2.6, p=0.009), poor medication adherence rated using the Kemp et al.'s scale (r=- 0.64; p=0.0001), and negative perception of treatment assessed using the DAI (r=- 0.405; p=0.009). The Kemp'scale score and the DAI score were categorised into poor vs. good according to the median for logistic regression analyses. Subjects were 1.7 times more likely (OR=1.7, 95% CI 1.1-2.5, p=0.01) to have discontinued their treatment, 1.9 times more likely (OR=1.9, 95% CI 1.3-2.8), p=0.0003) to have poor medication adherence rated with the Kemp's scale, and 1.8 times (OR=1.8, 95% CI 1.2-2.6, p=0.005) more likely to have a negative perception of the treatment for one point increase at the SUMD score (ie lower level of insight). The associations between SUMD score and the three measures of medication adherence were not modified after adjustment for demographic characteristics (age, gender, educational level, occupational status, marital status) and categorical diagnosis (schizophrenia broadly defined vs. psychotic mood disorder), severity of symptoms (SANS, SAPS, CDS scores), characteristics of the psychotropic treatment, diagnosis of substance or alcohol use disorder, age at onset, and number of previous admissions. CONCLUSION: The study demonstrates that medication adherence is associated with the level of insight, independently from other patient's demographic and clinical characteristics. The association between low level of insight and poor medication adherence should be confirmed using prospective studies carried out in ambulatory patients. These findings suggest that psycho-educational programs aimed at improving insight should be developed in order to improve medication adherence.     

Relationships between insight and medication adherence in outpatients with schizophrenia and bipolar disorder: prospective study

The aim of the present study was to explore the associations between insight and medication adherence at index interview and at 1-year follow-up interview in bipolar and schizophrenic outpatients. The Schedule for Assessment of Insight (SAI) and its expanded version (SAI-E) were used to provide a baseline insight score for 65 bipolar subjects and 74 schizophrenic subjects considered to be in remission or to have minimal psychopathology. Medication adherence of subjects was assessed at index interview and at 1-year follow-up interview, and the association between insight and medication adherence was analyzed cross-sectionally and prospectively. The results of the analysis reveal that in bipolar subjects, the index SAI scores for insight into treatment, mental-health status and psychotic experiences, and total SAI-E were positively correlated with medication adherence at both index and 1-year follow-up interviews. However, in schizophrenic subjects, insight into treatment and total SAI-E correlated positively with medication adherence at index interview but not at 1-year follow-up interview. Medication adherence at index interview could predict medication adherence 1 year later in both bipolar and schizophrenic subjects. These results indicate that the predictive value of insight for medication adherence differs between bipolar and schizophrenic patients, and building insight is an important step for establishing medication adherence in bipolar patients.     

Correlation between drug treatment adherence and lithium treatment attitudes and knowledge by bipolar patients

BACKGROUND: Non-adherence should always be investigated when there is a failure in bipolar treatments, since it is known that reported non-adherence rates in bipolar disorder treatment for long-term prophylactic pharmacotherapy range from 18% to 52%, with a median prevalence of 44.7%. Several factors are related to the poor adherence and reduction of medication efficiency, such as the different types of bipolar disorder, the presence of side effects, medication interactions, level of patient's knowledge about the disorder and their attitude towards treatment, complexity of medical regimens and the doctor-patient relationship. METHODS: Bipolar disorder outpatients under lithium treatment from the Hospital de Clínicas and Materno Infantil Presidente Vargas of Porto Alegre were recruited. All the patients had bipolar disorder and gave informed consent to participate in a clinical interview (106), answered the Lithium Attitudes Questionnaire (LAQ), Lithium Knowledge Test (LKT), Medication Adherence Rating Scale (MARS) and had plasma and red blood cells lithium measurements to assess their medication adherence and the factors that influenced it. RESULTS: 85.6% of bipolar disorder were adherent to lithium treatment showing plasma lithium between 0.6 and 1.2 mmol/L. There was an inverted correlation between the total LAQ score with plasma and red blood cells, a positive correlation between LKT and MARS with plasma and red blood cell lithium. CONCLUSION: These results confirmed that knowledge level is directly correlated to treatment adherence and patients' attitudes, lower adherence, general opposition to prophylaxis, fear of side effects, denial of therapeutic effectiveness and illness severity.     

Self-reported adherence versus pill count in Parkinson's disease: the NET-PD experience.

PURPOSE: To compare the Morisky medication adherence questionnaire to pill counts as measures of adherence in the NET-PD futility clinical trials. Background: Like in other chronic diseases, non-adherence with medications occurs in Parkinson's disease (PD), although nonadherence has not been of significant concern in most PD clinical trials. The most common approach to assessment is to do a pill count at each visit. The simple, 4-question Morisky medication adherence questionnaire may provide an alternative approach to monitoring treatment adherence in PD. METHODS: Adherence data from two NET-PD Phase II clinical trials enrolling a total of 413 participants were analyzed. The association between demographic and clinical characteristics and adherence was explored. RESULTS: Ninety-percent of participants took 80% or more of the study drug. However, the Morisky medication adherence questionnaires showed 56% report high and 44% report medium adherence. Agreement between the two measures is fair (ICC = 0.40). CONCLUSIONS: Overall adherence as assessed by pill count appears high. The Morisky medication adherence questionnaire may be useful in PD clinical trials, since it is moderately correlated to pill count and may be more sensitive to nonadherence.     

Why do patients with schizophrenia who have poor insight still take antipsychotics? Memory deficits as moderators between adherence belief and behavior

While lack of insight is often predictive of antipsychotic nonadherence, some inconsistency in the literature remains unexplained. Verbal memory deficits may moderate the association between insight and adherence. Based on cross-sectional data, outpatients treated with antipsychotics for a psychotic disorder were divided into those with good (n=53) and poor (n=59) memory. Poor insight predicted nonadherence only among the subgroup with relatively good memory (r=0.43; P<0.01), but had no effect in the subgroup with worse memory (r=0.08; ns). Structural equation modelling revealed significant moderation (χ=4.72; df=1; P<0.05), which means that a significantly better model fit was found by allowing the analysis to differentiate between the two memory groups. Thus, poor insight was only associated with poor medication adherence among patients with relatively good memory. We speculate that memory deficits commonly associated with schizophrenia may partly explain why poor insight does not always lead to poor medication adherence.     

Treatment adherence in schizophrenia and schizoaffective disorder

Medication nonadherence is common and difficult to detect in patients with schizoaffective disorder and schizophrenia. Roughly 50% of patients take less than 70% of prescribed doses. Many factors contribute to nonadherence, including poor illness insight, a negative attitude toward medication, substance abuse, and disorganization. Interventions to improve adherence consist of advising acceptance of illness, drawing analogies with treatment for chronic medical disease, and involving the patient in decision making. Clinicians must remain nonjudgmental, encouraging patients to disclose problems with adherence and anticipating that improvement in adherence may require a prolonged effort. Selection of medication is critical to avoid side effects and to provide a sense of well-being, which can result from improvement in insomnia, anxiety, or depression. Depot antipsychotics can improve adherence and provide the clinician with reliable information about the dosage of medication received for purposes of dose adjustments or to guide response to relapse.     

Psychosocial strategies to improve concordance and adherence in bipolar disorder

Half of patients with bipolar disorder may exhibit poor medication compliance, and relapse often occurs even when patients take their medication as prescribed. Psychosocial strategies can help patients to recognize the need for treatment and, therefore, improve medication adherence. Another benefit of psychosocial strategies is that they aid patients in controlling their moods. Cognitive-behavioral therapy teaches patients to modify dysfunctional thinking and behavior. Treatment contracting allows patients to develop a plan for identifying and coping with symptoms before they become severe. Daily mood charting assists patients in quickly identifying and intervening when changes occur. Creating and following a weekly activity schedule ensures that patients will participate in enough positive activities and avoid destructive activities. Using a variety of psychosocial strategies, patients can train themselves and a support team to effectively deal with bipolar disorder.     

Predictors of poor adherence to medication among patients with first-episode schizophrenia-spectrum disorder

Aim: This study sought to identify predictors for poor adherence to medication among patients with first‐episode schizophrenia‐spectrum disorder. Methods: Medication adherence was measured 1 and 2 years after initiation of antipsychotic medication in a follow‐up study of 547 patients. Relevant variables were systematically assessed at baseline, 1‐ and 2‐year follow up. Results: Most patients have difficulties with medication adherence over time. Negative attitudes towardsmedication and lack of consistent family support are the strongest predictors for poor adherence to medication for first‐episode psychotic patients in the first 2 years. After 1 year of treatment, unawareness of the effect of medication, lack of positive attitudes towards medication, substance abuse, young age and high global functioning also predict poor adherence to medication. Conclusions: A number of variables were independently associated with poor adherence. Rating of insight and attitudes towards medication makes it possible to predict poor adherence in incident cases with schizophrenia.     

Efficacy of valproate maintenance in patients with bipolar disorder and alcoholism: a double-blind placebo-controlled study

BACKGROUND: More than half of all individuals with bipolar disorder have a substance abuse problem at some point in their lifetime. Patients with comorbid substance abuse disorders often are excluded from clinical trials. Thus, treatments targeting this high-risk clinical population are lacking. OBJECTIVE: To evaluate the efficacy of divalproex sodium (hereafter referred to as valproate) in decreasing alcohol use and stabilizing mood symptoms in acutely ill patients with bipolar disorder and alcoholism. DESIGN: A 24-week, double-blind, placebo-controlled, randomized parallel-group trial. SETTING: A university hospital serving as a primary catchment-area hospital and tertiary-care facility. PARTICIPANTS: Fifty-nine subjects with diagnoses of bipolar I disorder and alcohol dependence.Intervention All study subjects received treatment as usual, including lithium carbonate and psychosocial interventions, and were randomized to receive valproate or placebo. MAIN OUTCOME MEASURES: Primary alcohol use outcomes included changes in alcohol use as indicated by changes in proportion of heavy drinking days and number of drinks per heavy drinking day. Other alcohol use outcomes included proportion of any drinking days, number of drinks per drinking day, and relapse to sustained heavy drinking. Mood outcomes included changes in depressive and manic symptoms. We used the mixed model to analyze longitudinal data. The first model used time of assessment, bipolar subtype (mixed, manic, or depressed), and treatment group (placebo or valproate) as covariates. The second nested model included the additional covariate of medication adherence. RESULTS: The valproate group had a significantly lower proportion of heavy drinking days (P = .02) and a trend toward fewer drinks per heavy drinking day (P = .055) than the placebo group. When medication adherence was added as covariate, the valproate group had significantly fewer drinks per heavy drinking day (P = .02) and fewer drinks per drinking day (P = .02). Higher valproate serum concentration significantly correlated with improved alcohol use outcomes. Manic and depressive symptoms improved equally in both groups. Level of gamma-glutamyl transpeptidase was significantly higher in the placebo group compared with the valproate group. CONCLUSIONS: Valproate therapy decreases heavy drinking in patients with comorbid bipolar disorder and alcohol dependence. The results of this study indicate the potential clinical utility of the anticonvulsant mood stabilizer, valproate, in bipolar disorder with co-occurring alcohol dependence.     

Description of study population and analysis of factors influencing adherence in the observational Italian study "Evaluation of Pharmacotherapy Adherence in Bipolar Disorder" (EPHAR)

Background: In patients with bipolar disorder, medication is effective in preventing relapses. Unfortunately, adherence to treatment in bipolar disorder, as in other chronic or recurrent conditions, is not optimal. Estimates of nonadherence to prescribed treatment range from 30% to 60% in epidemiological studies, and are at around 30% in clinical trials. Adherence to treatment is a potent predictor of effectiveness, both in clinical trials and cohort studies, therefore is a very relevant area of investigation. This study will try to show a picture of the real life care where adherence is influenced by a wide range of variables. Methods: Prospective, observational, multicenter study in 650 adult patients with bipolar disorder, who had to initiate or change their treatment regimen, observed for 1 year. Adherence was measured by the Simplified Medication Adherence Questionnaire (SMAQ). Additional variables: Symptom severity, Montgomery‐Åsberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS), Clinical Global Impression–Bipolar Disorder (CGI‐BD), the Drug Attitude Inventory score (DAI‐30), and quality of life (EuroQoL 5 Dimensions). The variables were recorded every 3 months for the next year. Results: Most subjects were out‐patients (77.1%), female (58.8%), aged 31–50 years (50.1%) and overweight (41.8%) or obese (28.7%); 67.4% had type I bipolar disorder and 66.8% had depressive or mixed symptoms. Adherence was 39.9% at baseline (and increased up to 67.0% at completion. The main predictors of nonadherence were alcohol consumption, severe bipolar symptoms, young age at time of first treatment, negative attitude towards treatment. Conclusions: The patient population of this observational trial was representative of the patients changing their therapy for bipolar disorder seen in clinical practice in Italy. Lack of adherence to pharmacotherapy for bipolar disorder is a serious issue, which is more likely to arise in alcohol users and patients with severe symptoms, negative attitude towards medication and/or initiation of treatment early in life. The findings could lead to a more adequate approach of adherence in patients with bipolar disorders.     

Patterns of adherence to treatment in adolescents with bipolar disorder

Despite relatively high rates of reported nonadherence in adults with bipolar disorder, no research has documented patterns of adherence in adolescents receiving treatment for this illness. This investigation sought to describe adherence in adolescents diagnosed with bipolar disorder and examine the relations between adherence, age, and chronicity of illness. Participants were 12-19 years of age and were receiving outpatient treatment for bipolar I, bipolar II, or bipolar disorder not otherwise specified (NOS). Parents were asked to estimate adherence to all prescribed treatments. Participants in this study were 38 adolescents (18 male, 20 female; mean age, 15.80 years, SD, 1.85). Parents reported an average of only 2.29 (SD, 2.90) missed medication dosages in the 1-month period prior to assessment. Full treatment adherence to a medication regimen, however, is reported in only 13 of 37 patients (34.2%) taking medication. Age is not associated with medication adherence. Participants with optimal adherence (no missed medication doses) are more recently diagnosed (M, 1.06 years; SD, 0.87) than patients who miss one or more medication doses (M, 3.12 years; SD, 3.36; t35=2.24; p=0.032). Rates of adherence in this sample of adolescents with bipolar disorder were somewhat higher than reports in adults and broadly consistent with findings in children with other psychiatric symptoms. Nonetheless, findings suggest vigilant monitoring of medication administration prior to assessing regimen effectiveness.     

Medication adherence mediates the impact of sustained cannabis use on symptom levels in first-episode psychosis

Both medication non-adherence and co-morbid cannabis abuse are associated with poor clinical outcome in first episode psychosis (FEP). The nature of interaction between adherence to medication and continued cannabis use remains unexplored. The objectives of this study were to examine variation in medication adherence associated with cessation or continuation of cannabis use, and to determine the impact of interaction between cannabis use and adherence to medication on symptom outcome at 12months. From a consecutive patient cohort (N=192) with a DSM-IV diagnosis of a FEP, 62 patients who met DSM-IV criteria for a currently active cannabis abuse disorder were followed up for one year. Complete data on repeated measures of medication adherence, symptoms, and cannabis use were available for 48 of the 62 patients. Twenty-eight patients (58.7%) continued while 20 (41.2%) stopped cannabis use after entering treatment. While both groups were relatively non-adherent at six months, 25/28 (92%) of the former group became adherent compared to 8/20 (40%) of those who stopped cannabis use (p<.01). While there was no overall effect of continued cannabis use on symptom levels at 12months, after controlling for medication adherence patients with continuous cannabis use had significantly higher level of symptoms (F(1,30)=2.74, p=0.03). FEP patients with an active cannabis use disorder may make a choice of either stopping cannabis and not taking medications or continuing cannabis but becoming more adherent to medications, adherence to medication appears to help both groups but continuous users remain at higher risk of poor symptom outcome even while on medication.     

Strategies for increasing treatment adherence in bipolar disorder

Although bipolar disorder cannot be cured, effective medications are available that can shorten the duration of illness episodes and reduce the rates of relapse. Unfortunately, treatment nonadherence is common among patients with bipolar disorder. Factors contributing to nonadherence vary, and nonadherence can be deliberate or accidental. Strategies to improve medication adherence include forming a strong alliance with patients, educating patients and their caregivers about the disorder and the importance of adherence, simplifying medication regimens, monitoring tolerability and proactively addressing adverse effects, and treating comorbid illnesses.     

Morisky问卷测量重性抑郁障碍患者服药依从性的信效度分析

目的:探讨Morisky问卷测量对我国抑郁症患者服药依从性的信效和效度。方法:144例符合美国精神障碍诊断与统计手册第4版重性抑郁障碍诊断标准的住院患者,在出院后2个月使用Morisky问卷评价服药依从性,其中50例患者间隔5~7 d后重测;统计分析Morisky问卷的内部一致性、折半信度、重测信度、结构效度和效标效度。结果:信度分析结果显示,Morisky问卷的内部一致性Cronbach’sα系数为0.74,折半信度为0.77,重测信度为0.86。探索性因子分析共提取1个公共因子,可解释的总变异量为57.53%,4条目的载荷值分别为0.67、0.78、0.82和0.76。用Morisky问卷法和药片计数法对患者服药依从性评价的一致性检验:Kappa系数为0.80(P0.001),呈高度一致。结论:Morisky问卷作为我国抑郁症患者服药依从性的评估工具具有良好的信度和效度。     

A prospective 3-year longitudinal study of cognitive predictors of relapse in first-episode schizophrenic patients

BACKGROUND: Cognitive predictors of relapse have been extensively explored only in few long term longitudinal studies of first-episode schizophrenia. METHOD: This study prospectively followed 93 patients with first-episode schizophrenia, schizophreniform disorder, and schizoaffective disorder for 3 years after their first-episode illness. Cognitive domains including verbal intelligence, verbal and visual memory, verbal fluency, and Wisconsin Card Sorting Test performance were investigated as potential predictors of relapse. RESULTS: We found that by the first year 21% patients had relapsed, by the second year 33% had relapsed, and by the third year 40% had relapsed. There was a significant difference in the relapse rate between patients with good adherence and patients with poor adherence to medication regimes. A multiple logistic regression analysis revealed that after controlling for medication adherence, perseverative error in the Wisconsin Card Sorting Test was the only cognitive function that significantly predict relapse with an odds ratio of 2.4. CONCLUSIONS: Cognitive flexibility in set shifting is related to tendency towards relapse in first-episode schizophrenic patients. Other cognitive factors appear not to be related to relapse. Possible mechanisms included the link between prefrontal dysfunction and sub-cortical dopamine system stability, as well as the effects of executive dysfunction on insight impairment and adherence behavior.