Adherence to Oral Antipsychotics Measured by Electronic Adherence Monitoring in Schizophrenia: A Systematic Review and Meta-analysis.

BACKGROUND: Poor adherence to oral antipsychotics is common in patients with schizophrenia; nonetheless, there has been no systematic review or meta-analysis on medication adherence measured by electronic adherence monitoring (EAM), considered by many as the 'gold standard' assessment. METHODS: We systematically searched MEDLINE and Embase to identify studies investigating adherence to oral antipsychotics using EAM in patients with schizophrenia spectrum disorder. There were no exclusion criteria. We looked at the methodology in each study and defined which type of adherence was used in the study. Data on medication adherence, definition of satisfactory adherence (i.e., the threshold set in terms of the percentage of times medication was taken as prescribed), and factors associated with adherence were extracted for the included studies. Further, data on the rates of medication adherence were quantitatively synthesized. RESULTS: A total of 19 studies involving 2184 patients were included. EAM-measured medication adherence was classified into three outcome types: taking adherence, regimen adherence, and timing adherence. The meta-analysis yielded oral antipsychotic adherence rates (defined as a continuous variable) of 71.1% for taking adherence [from seven studies, n = 256, 95% confidence interval (CI) 58.0-84.1], 70.0% for regimen adherence (from five studies, n = 174, 95% CI = 63.6-76.4), and 64.9% for timing adherence (from four studies, n = 212, 95% CI 53.2-76.6), respectively. The proportions of patients with oral antipsychotic adherence, when defined as a dichotomous variable, ranged from 50 to 78.3% for the 70% threshold for satisfactory adherence, 29.8-75.7% for the 75% threshold, and 47.8-75.7% for the 80% threshold. Factors associated with poor medication adherence were greater symptom severity, more frequent dosing regimen, poorer insight, and more negative drug attitude. CONCLUSIONS: Oral antipsychotic adherence rates in schizophrenia, defined as a continuous variable and measured by EAM, were in the range of 70%, lower than the 80% threshold used widely to define satisfactory adherence.

Relationship between polydipsia and antipsychotics: A systematic review of clinical studies and case reports.

OBJECTIVE: This systematic review aimed to elucidate the relationship between polydipsia and antipsychotics. METHODS: We systematically searched MEDLINE, Embase, and PsycINFO, and included clinical studies and case reports on polydipsia induced or improved by antipsychotics. RESULTS: We identified 61 articles: 1 double-blind randomized controlled trial (RCT), 4 single-arm trials, 1 cross-sectional study, 3 case series, and 52 case reports. The double-blind RCT demonstrated no significant difference in improvement in polydipsia between olanzapine and haloperidol. Two single-arm trials showed that polydipsia improved during clozapine treatment, whereas the other 2 showed that risperidone did not improve polydipsia. The cross-sectional study showed the prevalence of hyponatremia with first-generation antipsychotics (FGAs: 26.1%) and second-generation antipsychotics (SGAs: 4.9%). Two case series reported that clozapine improved polydipsia; the other one indicated that patients with polydipsia who were treated with FGAs had schizophrenia (70.4%) and mental retardation (25.9%). Of 90 cases in the case reports, 67 (75.3%) were diagnosed with schizophrenia. Of 83 cases in which antipsychotic treatment started before the onset of polydipsia, 75 (90.3%) received FGAs, particularly haloperidol (n = 24, 28.9%), and 11 (13.3%) received risperidone. Among 40 cases in which polydipsia was improved following antipsychotic treatment, 36 (90.0%) received SGAs, primarily clozapine (n = 14, 35.0%). CONCLUSIONS: Although the causal relationship between polydipsia and antipsychotics remains unclear because of the paucity of high-quality studies, antipsychotics with high affinity to dopamine D2 receptors may be associated with an increased risk of polydipsia while clozapine may be effective for treating polydipsia.

Representativeness of clinical PET study participants with schizophrenia: A systematic review.

While positron emission tomography (PET) studies have provided invaluable data on antipsychotic effects, selection bias remains a serious concern. A systematic review of PET studies that measured dopamine D2 receptor blockade with antipsychotics was conducted to examine their inclusion/exclusion criteria, using PubMed, EMBASE, and ClinicalTrials.gov (last search, September 2016). PET studies were included if they measured D2 receptor occupancy in patients with schizophrenia and included introduction of antipsychotic treatment or antipsychotic regimen change in a systematic manner. Twenty-six studies were identified. Age limit was included in 13 studies; one study solely included geriatric patients while others targeted younger adults. Eleven, 6, and 3 studies specifically targeted clinically stable patients, patients with severe psychopathology, and antipsychotic-free patients, respectively. Nineteen and 18 studies excluded patients with physical comorbidity and substance abuse, respectively. As a result, the mean age of subjects ranged from 23 to 42 years when one study that targeted geriatric patients was excluded. Mean Positive and Negative Syndrome Scale total scores ranged from 54 to 95. No comparison active-drug or placebo arm was employed in 24 studies. Blind assessment of symptomatology was performed in 5 studies. In general, subjects participating in clinical PET studies were relatively young, presented with mild symptomatology, and were free from substance abuse or physical comorbidities. These characteristics need to be taken into account when clinical PET data are interpreted. On the other hand, it should also be noted that this study was only qualitative and conservative interpretation is necessary for possibility of subjective bias.