New-onset addictions in patients with alcohol dependence: A cross-sectional study.

BACKGROUND: Individuals who are addicted to one addiction are at an increased risk for developing another new addiction. New-onset addictions among patients with alcohol dependence needs to be considered for more effective treatment of alcohol dependence. METHODS: In this cross-sectional study, Japanese outpatients with alcohol dependence were assessed using a comprehensive, originally designed questionnaire to determine whether they were addicted to substances or behaviors other than alcohol. The prevalence rates of new-onset addictions were compared between alcohol-dependent patients who had abstained from alcohol for a year or more and those who had not. Multiple regression analysis was performed to examine the association between the number of new-onset addictions and the demographic and clinical characteristics. RESULTS: One hundred and nine outpatients with alcohol dependence (54.6±11.0 years; 97 men) participated in the study. The prevalence of new-onset addictions was 41.3%. No significant differences were found in the prevalence of new-onset addictions between the patients who had abstained for a year or more and those who had not. Multiple regression analysis revealed that the number of new-onset addictions was positively associated with the presence of psychiatric comorbidity (ß = 0.24; p = 0.02) and use of benzodiazepines (ß = 0.20; p = 0.04) with a R2 of 0.153. CONCLUSION: Alcohol dependent patients with characteristics such as psychiatric comorbidity and use of benzodiazepines should be given more attention to the development of new-onset addictive behaviors. On the other hand, those behaviors could be acceptable for harm-reduction unless excessive and loss of control.

Dysconnectivity of the Agency Network in Schizophrenia: A Functional Magnetic Resonance Imaging Study.

Background: Self-disturbances in schizophrenia have recently been explained by an abnormality in the sense of agency (SoA). The cerebral structures of SoA in healthy people are considered to mainly include the insula and inferior parietal lobule. In contrast, the functional lesion of aberrant SoA in schizophrenia is not yet fully understood. Considering the recent explanation of establishing SoA from the standpoint of associative learning, the "agency network" may include not only the insula and inferior parietal lobule but also the striatum. We hypothesized that aberrant SoA in schizophrenia is based on a deficit in the "agency network." Methods: Functional magnetic resonance imaging data were acquired while patients with schizophrenia (n = 15) and matched controls (n = 15) performed our adaptation method of agency attribution task on a trial-by-trial basis to assess participants' explicit experience of the temporal causal relationship between an action and an external event with temporal biases. Analysis of functional connectivity was done using the right supramarginal gyrus and the right middle frontal gyrus as seed regions. Results: In healthy controls, analyses revealed increased activation of the right inferior parietal lobule (mainly the supramarginal gyrus), right insula, and right middle frontal gyrus as an activation of the agency condition. We defined activated Brodmann areas shown in the agency condition of healthy controls as the seed region for connectivity analysis. The connectivity analysis revealed lower connectivity between the head of the left caudate nucleus and right supramarginal gyrus in the patients compared to healthy controls. Conclusions: This dysconnectivity of the agency network in schizophrenia may lead to self-disturbance through deficits in associative learning of SoA. These findings may explain why pathological function of the striatum in schizophrenia leads to self-disturbance.

An open-label study of algorithm-based treatment versus treatment-as-usual for patients with schizophrenia.

OBJECTIVE: The use of an algorithm may facilitate measurement-based treatment and result in more rational therapy. We conducted a 1-year, open-label study to compare various outcomes of algorithm-based treatment (ALGO) for schizophrenia versus treatment-as-usual (TAU), for which evidence has been very scarce. METHODS: In ALGO, patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) were treated with an algorithm consisting of a series of antipsychotic monotherapies that was guided by the total scores in the positive and negative syndrome scale (PANSS). When posttreatment PANSS total scores were above 70% of those at baseline in the first and second stages, or above 80% in the 3rd stage, patients proceeded to the next treatment stage with different antipsychotics. In contrast, TAU represented the best clinical judgment by treating psychiatrists. RESULTS: Forty-two patients (21 females, 39.0 ± 10.9 years-old) participated in this study. The baseline PANSS total score indicated the presence of severe psychopathology and was significantly higher in the ALGO group (n = 25; 106.9 ± 20.0) than in the TAU group (n = 17; 92.2 ± 18.3) (P = 0.021). As a result of treatment, there were no significant differences in the PANSS reduction rates, premature attrition rates, as well as in a variety of other clinical measures between the groups. Despite an effort to make each group unique in pharmacologic treatment, it was found that pharmacotherapy in the TAU group eventually became similar in quality to that of the ALGO group. CONCLUSION: While the results need to be carefully interpreted in light of a hard-to-distinguish treatment manner between the two groups and more studies are necessary, algorithm-based antipsychotic treatments for schizophrenia compared well to treatment-as-usual in this study.

Ten year outcomes of outpatients with schizophrenia on conventional depot antipsychotics: a systematic chart review.

Long-term follow-up data of patients with schizophrenia on depot antipsychotics have been few and the longest follow-up period has been up to 7 years. We carried out a systematic chart review to examine 10-year outcomes for outpatients with schizophrenia who were receiving a conventional depot antipsychotic. Maintenance of outpatient status for 10 years was considered as a favorable outcome. From the initial sample of 1587 outpatients, 90 patients who were receiving a depot antipsychotic were included in this study (mean±SD, age 44.0±13.0 years; men, N=54). Haloperidol decanoate, fluphenazine decanoate, fluphenazine enanthate, and haloperidol decanoate plus fluphenazine enanthate were used in 53 (58.9%), 29 (32.2%), seven (7.8%), and one (1.1%) patients, respectively. These depot antipsychotics accounted for 36.9% of the total antipsychotic dosage on average. Seventeen patients (18.9%) successfully maintained outpatient status for 10 years. The most frequent reason for dropout was 'hospitalization' (N=49, 54.4%), followed by 'referral to another clinic/hospital' (N=9, 10.0%) and 'side effects' (N=7, 7.8%). As only 36.9% of the chlorpromazine equivalents were administered through depot antipsychotics, it is difficult to draw any firm conclusion. Still, the data suggest that even depot antipsychotics may not sufficiently prevent relapse in the treatment of schizophrenia.

A cross-sectional study of plasma risperidone levels with risperidone long-acting injectable: implications for dopamine D2 receptor occupancy during maintenance treatment in schizophrenia.

OBJECTIVE: While 65%-80% occupancy of dopamine D2 receptors with antipsychotics has been proposed to achieve optimal therapeutic response during acute treatment of schizophrenia, it remains unclear as to whether it is also necessary to maintain D2 receptor occupancy within this "safe" window for ongoing maintenance treatment. The data are especially scarce for long-acting antipsychotic formulations. METHOD: Clinically stable patients with schizophrenia (DSM-IV) receiving a stable dose of risperidone long-acting injectable (LAI) as antipsychotic monotherapy for at least 3 months and free of any psychiatric hospitalization over the past 6 months were included. Dopamine D2 receptor occupancy levels at trough were estimated from plasma concentrations of risperidone plus 9-hydroxyrisperidone immediately before the intramuscular injection of risperidone LAI, using a 1-site binding model derived from our previous positron emission tomography data. This study was conducted from October to December 2011. RESULTS: 36 patients were included in this study (mean ± SD age, 49.3 ± 14.0 years; mean ± SD dose and interval of injections, 38.2 ± 11.6 mg and 16.5 ± 14.0 days, respectively). Mean ± SD D2 receptor occupancy was 62.1% ± 15.4%; 52.8% of the subjects (n = 19) did not demonstrate an occupancy of ≥ 65%. On the other hand, 13.9% (n = 5) showed a D2 occupancy as high as over 80% at the estimated trough. CONCLUSIONS: More than half of patients taking risperidone LAI maintained clinical stability without achieving continuous blockade of dopamine D2 receptors ≥ 65% in real-world clinical settings. Results suggest that sustained dopamine D2 receptor occupancy levels of ≥ 65% may not be necessary for maintenance treatment with risperidone LAI in schizophrenia.

Dental conditions in inpatients with schizophrenia: a large-scale multi-site survey.

BACKGROUND: Clinical relevance of dental caries is often underestimated in patients with schizophrenia. The objective of this study was to examine dental caries and to identify clinical and demographic variables associated with poor dental condition in patients with schizophrenia. METHODS: Inpatients with schizophrenia received a visual oral examination of their dental caries, using the decayed-missing-filled teeth (DMFT) index. This study was conducted in multiple sites in Japan, between October and December, 2010. A univariate general linear model was used to examine the effects of the following variables on the DMFT score: age, sex, smoking status, daily intake of sweets, dry mouth, frequency of daily tooth brushing, tremor, the Clinical Global Impression-Schizophrenia Overall severity score, and the Cumulative Illness Rating Scale for Geriatrics score. RESULTS: 523 patients were included in this study (mean ± SD age = 55.6 ± 13.4 years; 297 men). A univariate general linear model showed significant effects of age group, smoking, frequency of daily tooth brushing, and tremor (all p's < 0.001) on the DMFT score (Corrected Model: F(23, 483) = 3.55, p < 0.001, R2 = 0.42) . In other words, older age, smoking, tremor burden, and less frequent tooth brushing were associated with a greater DMFT score. CONCLUSIONS: Given that poor dental condition has been related with an increased risk of physical co-morbidities, physicians should be aware of patients' dental status, especially for aged smoking patients with schizophrenia. Furthermore, for schizophrenia patients who do not regularly brush their teeth or who exhibit tremor, it may be advisable for caregivers to encourage and help them to perform tooth brushing more frequently.