Interventions to improve adherence to antipsychotic medication in patients with schizophrenia–A review of the past decade

ObjectiveNonadherence to antipsychotic medication is highly prevalent in patients with schizophrenia and has a deleterious impact on the course of the illness. This review seeks to determine the interventions that were examined in the past decade to improve adherence rates.MethodThe literature between 2000 and 2009 was searched for randomized controlled trials which compared a psychosocial intervention with another intervention or with treatment as usual in patients with schizophrenia.ResultsFifteen studies were identified, with a large heterogeneity in design, adherence measures and outcome variables. Interventions that offered more sessions during a longer period of time, and especially those with a continuous focus on adherence, seem most likely to be successful, as well as pragmatic interventions that focus on attention and memory problems. The positive effects of adapted forms of Motivational Interviewing found in earlier studies, such as compliance therapy, have not been confirmed.ConclusionNonadherence remains a challenging problem in schizophrenia. The heterogeneity of factors related to nonadherence calls for individually tailored approaches to promote adherence. More evidence is required to determine the effects of specific interventions.     

How long should patients with psychotic depression stay on the antipsychotic medication?

BACKGROUND: Patients who have major depression with psychotic features have greater morbidity and mortality than patients with nonpsychotic major depression. In particular, relapse and recurrence have been reported to occur more frequently in patients with psychotic depression than nonpsychotic depression. Despite the frequent relapse and recurrence in major depression with psychotic features, there are few studies of the efficacy of continuation and maintenance treatments. METHOD: Forty patients with a diagnosis of unipolar DSM-III-R major depression with psychotic features were treated with fluoxetine and perphenazine for 5 weeks after granting written informed consent. The patients who responded to treatment continued to receive the combination for an additional 3 months. If a patient was stable for 4 months on treatment with the combination, the patient was then gradually tapered off perphenazine treatment. For patients who exhibited impending relapse, perphenazine was restarted. Impending relapse was defined as any of the following: (1) symptoms meeting DSM-IV criteria for major depressive disorder (with or without psychotic features), (2) a total score of > or = 17 on the HAM-D, or (3) the presence of any psychotic symptoms. After 1 year of taking fluoxetine, patients were tapered off fluoxetine treatment. Data were gathered from 1992 to 1997. RESULTS: Thirty patients responded to the initial 5 weeks of treatment with perphenazine and fluoxetine. After taper of perphenazine following 4 months of treatment with fluoxetine and perphenazine, 22 (73%) of the 30 patients exhibited no signs of relapse over the next 11 months (8 months of fluoxetine monotherapy followed by a taper of fluoxetine and 3 additional months of assessment). Patients who showed signs of relapse after taper of the antipsychotic were more likely to have had a longer duration of the current episode and a history of more frequent past episodes and were more likely to be younger (under the age of 30 years). CONCLUSION: The data from this study suggest that a majority of patients who have major depression with psychotic features do not require treatment with antipsychotic medication for more than 4 months.     

Is antipsychotic medication stigmatizing for people with mental illness?

Antipsychotic medications are clearly identified as important in the treatment of individuals with schizophrenia and with bipolar disorder. However, negative societal reaction related to having a serious mental illness and the socially undesirable side effects associated with antipsychotic medication treatment may combine to worsen stigma associated with treatment for mental illness. Specific stigmatizing effects of antipsychotic therapy may be difficult to evaluate independently from factors such as symptoms, insight into illness and side effects. Attitudes towards antipsychotic medication may be positive in individuals who recognize therapeutic drug effects, however other individuals may view medications negatively due to a sense of stigma. Stigma among individuals with bipolar disorder in relation to treatment with antipsychotic medication has not been well addressed in the literature. An additional concern among individuals with bipolar disorder who receive antipsychotic medications may be the notion that antipsychotics are 'schizophrenia drugs', and thus an inappropriate treatment for their condition. Antipsychotic medications can be stigmatizing for patients with serious mental illness, however the roots of stigma are extensive, and efforts to minimize stigma can only be successful when addressed by the individual with illness, their families and loved ones, treatment providers and society at large.     

Are attitudes towards medication adherence associated with medication adherence behaviours among patients with psychosis? A systematic review and meta analysis

Background

Studies have shown patient attitudes to be an important predictor for health related behaviours including medication adherence. It is less clear whether patient attitudes are also associated with medication adherence among patients with psychoses.

Method

We conducted a systematic review and meta analysis of the data of studies that tested the association of attitude measures with medication adherence among patients with psychoses. 14 studies conducted between 1980 and 2010 were included.

Results

Results show a small to moderate mean weighted effect size (r ⁺ = 0.25 and 0.26 for Pearson and Spearman correlations, respectively).

Conclusions

Theory based interventions that target potentially modifiable attitude components are needed to assess the relationship between positive patient attitudes and adherence behaviours among patients with psychoses.     

What is the scientific evidence for the use of antipsychotic medication in anorexia nervosa?

This systematic review assesses the effectiveness of antipsychotic medication for improving core psychopathology and behavioral symptoms of anorexia nervosa. The Cochrane Depression, Anxiety and Neurosis Group Trials Register, reference lists of retrieved studies and conference abstracts were searched. Four randomized controlled trials comparing typical or atypical antipsychotic medication to other interventions were included. Clinical heterogeneity precluded meta-analysis. Overall, there is insufficient evidence to either support or refute the use of antipsychotic medication in anorexia nervosa. Further trials may be justified but should be designed with a clear theoretical framework to guide use of antipsychotic medication.     

Do treatment and illness beliefs influence adherence to medication in patients with bipolar affective disorder? A preliminary cross-sectional study

Adherence to medication is essential for achieving good outcomes for patients with bipolar affective disorder. This study tested whether treatment and illness beliefs are important predictors of adherence to medication. Results indicate that beliefs are predictive, and may be a suitable target for modification in efforts to change behaviour.     

Does neurotensin mediate the effects of antipsychotic drugs?

The possibility that the neuropeptide neurotensin (NT) may function as an endogenous antipsychotic compound was first hypothesized almost two decades ago. Since that time, considerable effort has been directed towards determining whether NT neurons mediate the effects of antipsychotic drugs (APDs). The anatomic, biochemical, behavioral, and clinical relevance of this hypothesis is reviewed. Although the majority of the available evidence is indirect, the availability of several NT receptor (NTR) antagonists have now made possible the direct examination of the involvement of the NT system in the mechanism of action of APDs. Preliminary studies in our laboratory demonstrate the ability of a selective NTR antagonist to block the effects of APDs in two models of sensory motor gating deficits characteristic of schizophrenia. These data, taken together with a compelling series of studies demonstrating that increases of NT/neuromedin N mRNA expression and NT content in the nucleus accumbens and striatum after chronic administration of APDs are predictive of clinical efficacy and extrapyramidal side effects, respectively, provide direct preclinical evidence for a role of the NT system in the clinical efficacy of APDs. Although effects of selective NTR antagonists in normal volunteers or schizophrenic patients have not been studied, and nonpeptidergic NTR agonists have not yet been identified, these cumulative results provide the groundwork for the use of NT-ergic compounds in the treatment of schizophrenia.     

Which side effects really matter? Screening for common and distressing side effects of antipsychotic medications

As a class, the newer antipsychotics are less likely to cause EPS but continue to have a range of other, non-EPS, side effects. Most standardized scales for side effects of antipsychotics emphasize the physical findings of the motor abnormalities of extrapyramidal symptoms (EPS). There is a need for screening instruments that include both EPS and non-EPS side effects. This article discusses the development of a screening instrument called the Approaches to Schizophrenia Communication (ASC). Initially derived from other subjective screening measures, the ASC was specifically designed to address the following issues pertaining to side effect evaluation of antipsychotics: 1) to cover all common and distressing side effects from antipsychotics, not just EPS, and 2) to screen for perceived distress, rather than the objective severity of the side effect. These two characteristics of the ASC make it possible for it to be given directly to the patient (the ASC Self-Report Version) or to be administered by mental health clinicians who do not have to be extensively trained in side-effect assessments (the ASC Clinician Interview version).     

Isolating the impact of antipsychotic medication on metabolic health: Secondary analysis of a randomized controlled trial of antipsychotic medication versus placebo in antipsychotic medication naïve first-episode psychosis (the STAGES study)

Background

Cardiovascular and metabolic diseases are the leading contributors to the early mortality associated with psychotic disorders. To date, it has not been possible to disentangle the effect of medication and non-medication factors on the physical health of people with a first episode of psychosis (FEP). This study aimed to isolate the effects of antipsychotic medication on anthropometric measurements, fasting glucose and lipids.

Methods

This study utilized data from a triple-blind randomized placebo-controlled trial comparing two groups of antipsychotic-naïve young people with a FEP who were randomized to receive a second-generation antipsychotic medication (FEP-medication group) or placebo (FEP-placebo group) for 6 months. Twenty-seven control participants were also recruited.

Results

Eighty-one participants commenced the trial; 69.1% completed at least 3 months of the intervention and 33.3% completed the full 6 months. The FEP-placebo group gained a mean of 2.4 kg (±4.9) compared to 1.1 kg (±4.9) in the control participants (t = 0.76, p = .45). After controlling for multiple analyses, there was no difference in blood pressure, waist circumference or heart rate between the FEP-placebo group and controls. After 6 months, the FEP medication group had gained 4.1 kg (±4.5), higher than those receiving placebo but not statistically significant (t = 0.8, p = .44). There were no differences in fasting glucose or lipids between the FEP groups after 3 months.

Conclusions

While limited by small numbers and high attrition, these findings indicate that some of the metabolic complications observed in psychotic disorders could be attributable to factors other than medication. This emphasizes the need to deliver physical health interventions early in the course of FEP.     

Should full adherence be a necessary goal in schizophrenia? Full versus non-full adherence to antipsychotic treatment

There is solid evidence of negative consequences of non-adherence in schizophrenia, and recently adherence has been defined as taking more than 80% of prescribed medication. However, the clinical relevance of different degrees of adherence in adherent patients has not been studied. We evaluated sociodemographic, clinical, treatment-related and psychopathological variables in 78 adherent outpatients with schizophrenia, who were classified into two groups: full-adherence (100% adherence) and non-full adherence (80–99.9%). Adherence was evaluated using electronic monitoring (MEMS®), and the injection record in case of injectable antipsychotics. Non-full adherence patients showed more extensive delusions and guilt feelings, as well as trends toward greater somatic concern, disorientation, general psychopathology, and lower number of prior psychiatric hospitalizations. These finding suggest that the ‘fullness’ of adherence to antipsychotic treatment is a relevant issue, impacting the psychopathological state of adherent patients with schizophrenia. We found that a large proportion of patients can achieve full adherence, and while ‘adherence’ is an appropriate objective to be pursued with non-adherent patients, ‘full adherence’ should be the goal among adherent patients.     

Error processing in patients with Parkinson’s disease: the influence of medication state

Summary. One of the hallmarks of Parkinson’s disease (PD) is a depletion of dopamine. Error processing, as reflected in a component of the event-related potential, the so-called error (related) negativity (Ne or ERN) is likely dependent on the midbrain dopaminergic system. In case of an unfavourable event such as an error, this system is assumed to send an error signal to the mediofrontal cortex, which elicits the Ne. Hence, the Ne should be altered in patients with PD. In fact, we earlier found a reduction of the Ne in medicated patients with PD in different tasks while another group found no such reduction in “off-medication” patients in a flanker task. In the present study, we reinvestigated this issue by measuring the Ne in a large group of treated PD patients in the “on”- and “off”-parkinsonian medication state and in matched control subjects in a flanker task. The Ne was found to be the same in the “on-medication” and “off-medication” state, while the motor score in the Unified Parkinson’s Disease Rating Scale was different. In both medication states the Ne was smaller in the patients than in the controls. The results show that the Ne reduction found earlier is unaffected by short-term differences in parkinsonian medication. The question remains open whether the long-term medication could have contributed to the Ne reduction. Correspondence: Rita Willemssen, Leibniz Research Centre of Working Environment and Human Factors (IfADo), Ardeystr. 67, 44139 Dortmund, Germany     

Do antipsychotic medications decrease the risk of suicide in patients with schizophrenia?

The lifetime risk of suicide in persons with schizophrenia is much greater than that in the general population. The role of antipsychotic medications in decreasing suicide risk in schizophrenia has been little studied, and results often appear inconclusive and even confusing when issues such as dose-response effect are examined. Yet, evidence exists that both the traditional and newer antipsychotic medications reduce the risk of suicide and suicide attempts in schizophrenia. Because side effects are potentially significant risk factors in suicide, considerable incentive exists to examine whether newer antipsychotic agents that have a lower incidence of extrapyramidal side effects offer greater safety for this population.     

Do patients with schizophrenia distinguish between attitudes toward antipsychotic medication and pharmacotherapy in general? Validation of the Beliefs About Medication Questionnaire

Attitudes toward medication are important predictors of medication adherence in schizophrenia. However, monitoring their strength and influence in clinical settings is challenged by the absence of assessments separating them from adherence and subjective response and distinguishing between attitudes toward pharmacotherapy in general and antipsychotic medications. This study examined the applicability of the Beliefs about Medication Questionnaire (BMQ) in outpatients with schizophrenia (N = 131). Confirmatory factor analysis (CFA) could not support the original four-factor structure. A subsequent exploratory factor analysis revealed the factors Antipsychotics Necessity, Antipsychotics Concern, and Pharmacotherapy Distrust were supported by an acceptable fit of a completing CFA. These subscales have satisfactory internal reliability, test-retest reliability, and local fit indices. Modest correlations with insight and illness perception indicate construct validity. Criterion validity was supported by a significantly higher medication adherence of accepting patients compared with skeptical patients. The BMQ is a psychometrically sound and valid measure of attitudes toward medication in outpatients with schizophrenia.     

Which factors influence therapeutic decisions in Parkinson's disease?

Development of dyskinesia is a common phenomenon during the long-term course of Parkinson's disease. During the last few years, some but not all pathogenetic mechanisms causing dyskinesias in PD have become better understood. Severity of Parkinson's disease and levodopa dosing are the main clinical risk factors. Most concepts underline the significance of pulsatile D1-receptor stimulation for the development of dyskinesias. The interactions between D1- and D2-mediated STR-Gpi pathways and colocalized neuropeptides are important but not fully understood. Glutamatergic overactivity might also be a significant pathogenetic factor. According to these pathophysiological concepts, therapeutic strategies focus mainly on continuous postsynaptic DA-receptor stimulation by long-acting DA-agonists or highly selective D2-agonists. Another strategy is the use of NMDA antagonists.     

Déjà vu experiences in schizophrenia: relations with psychopathology and antipsychotic medication

To clarify why patients with schizophrenia show déjà vu experiences less frequently, we studied déjà vu experiences in 113 schizophrenic patients in relation to psychopathologies and antipsychotic medication. Déjà vu experiences were observed in 53.1% of the schizophrenic patients. Patients with increased negative symptoms (blunted affect, motor retardation, emotional withdrawal, conceptual disorganization, and mannerisms) had déjà vu experiences less frequently. The other psychopathologies were not significantly associated with presence of déjà vu experiences. The dosage of antipsychotic drugs was significantly correlated with the frequency of déjà vu experiences. This correlation was not affected by their psychopathologies at the time of examination. The decreased frequency of déjà vu experiences in patients with schizophrenia may be mainly due to the negative symptoms. The positive relation between frequency of déjà vu experiences and the dosage of neuroleptics remains uncertain.