Jinichi Hirano

Is switching antidepressants following early nonresponse more beneficial in acute-phase treatment of depression?: a randomized open-label trial.

RATIONALE Treatment guidelines for major depressive disorder (MDD) recommend a continuous use of antidepressants for several weeks, while recent meta-analyses indicate that antidepressant efficacy starts to appear within 2 weeks and early treatment nonresponse is a predictor of subsequent nonresponse. OBJECTIVES We prospectively compared 8-week outcomes between switching antidepressants and maintaining the same antidepressant in early nonresponders, to generate a hypothesis on possible benefits of early switching strategy. METHOD Patients with MDD without any treatment history for the current episode were included. When subjects failed to show an early response (i.e., ≥20% improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS)) to the initial treatment with sertraline 50mg at week 2, they were randomly divided into two groups; in the Continuing group, sertraline was titrated at 50-100mg, whereas sertraline was switched to paroxetine 20-40 mg in the Switching group. A primary outcome measure was a response rate (i.e., ≥50% improvement in the MADRS) at week 8. RESULTS Among 132 subjects, 41 subjects showed early nonresponse. The Switching group (n=20) showed a higher rate of responders than the Continuing group (n=21) (75% vs. 19%: p=0.002). Further, the Switching group was also superior in the rate of remitters (total score of ≤10 in the MADRS) (60% vs. 14%: p=0.004) and continuous changes in the MADRS (19.0 vs. 7.5: p<0.001). CONCLUSIONS Our preliminary findings suggest that patients with MDD who fail to show early response to an initial antidepressant may derive benefits from the early switching antidepressants in the acute-phase treatment of depression.

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

BackgroundClinical 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.MethodsInpatients 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.Results523 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.ConclusionsGiven 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.

A Longitudinal Functional Neuroimaging Study in Medication-Naïve Depression after Antidepressant Treatment

Recent studies have indicated the potential clinical use of near infrared spectroscopy (NIRS) as a tool in assisting the diagnosis of major depressive disorder (MDD); however, it is still unclear whether NIRS signal changes during cognitive task are state- or trait-dependent, and whether NIRS could be a neural predictor of treatment response. Therefore, we conducted a longitudinal study to explore frontal haemodynamic changes following antidepressant treatment in medication-naïve MDD using 52-channel NIRS. This study included 25 medication-naïve individuals with MDD and 62 healthy controls (HC). We performed NIRS scans before and after antidepressant treatment and measured changes of [oxy-Hb] activation during a verbal fluency task (VFT) following treatment. Individuals with MDD showed significantly decreased [oxy-Hb] values during a VFT compared with HC in the bilateral frontal and temporal cortices at baseline. There were no [oxy-Hb] changes between pre- and post-antidepressant treatment time points in the MDD cohort despite significant improvement in depressive symptoms. There was a significant association between mean [oxy-Hb] values during a VFT at baseline and improvement in depressive symptoms following treatment in the bilateral inferior frontal and middle temporal gyri in MDD. These findings suggest that hypofrontality response to a VFT may represent a potential trait marker for depression rather than a state marker. Moreover, the correlation analysis indicates that the NIRS signals before the initiation of treatment may be a biological marker to predict patient’s clinical response to antidepressant treatment. The present study provides further evidence to support a potential application of NIRS for the diagnosis and treatment of depression.

The impact of prolactin-raising antipsychotics on bone mineral density in patients with schizophrenia: findings from a longitudinal observational cohort.

To examine the effect of prolactin-raising antipsychotics on bone mineral density (BMD), data of 164 schizophrenia patients who received ≥2 dual-energy x-ray absorptiometry scans were analyzed (49.3% men; mean ± SD age: 58.5 ± 11.0 years; duration of treatment: 26.7 ± 13.8 years). Patients were divided into a prolactin-raising antipsychotic (n=141) or prolactin-sparing (n=23) group, and time x group interaction was examined using mixed effect model. Although the BMD difference did not reach significance over 3.4 ± 1.6 years, a significant antipsychotic-class vs. time interaction was found (p=0.011), indicating a negative impact of prolactin-raising antipsychotics on BMD. Large-scale, randomized-controlled data are required to replicate and extend these findings.

A review on schizophrenia and relapse—a quest for user-friendly psychopharmacotherapy

Schizophrenia in general is notoriously associated with relapses rendering the illness progressive to worse outcomes, a concept of which is compatible with neurotoxicity. Therefore, relapse prevention is of utmost clinical relevance.

Clinical and demographic characteristics associated with postural instability in patients with schizophrenia.

As people with schizophrenia grow older, prevention of falls in this older population has become a public health priority. It is therefore critically important to identify risk factors to effectively prevent falls. For this purpose, the degree of postural sway can serve as a convenient index of risk assessment. The objective of this study was to find clinical and demographic characteristics associated with postural instability. Inpatients and outpatients with schizophrenia or related psychosis were recruited at 2 hospitals in Japan. The clinical stabilometric platform, which measured a range of the trunk motion, and extrapyramidal side effects were evaluated between 9 and 11 a.m. Four hundred two subjects were enrolled (age: mean, 55.5 [SD, 14.4] years). A univariate general linear model showed that the use of antipsychotic drugs with a chlorpromazine equivalent of 10 or greater, being overweight, and inpatient treatment setting were associated with a greater degree of the range of postural sway. Another general linear model, including a subgroup of 300 subjects who did not present any extrapyramidal side effects, not only consolidated these findings, but also revealed a great degree of postural sway in older subjects. In addition, quetiapine was found to be associated with a greater range of postural sway among atypical antipsychotics. Schizophrenia patients generally showed a greater degree of postural instability, compared with the reference data of healthy people. These findings highlight truncal instability as a risk factor of falls in patients with schizophrenia, especially when they are overweight, old, and/or receiving antipsychotics with a chlorpromazine equivalent of 10 or greater, including quetiapine.

Self-rated cognitive functions following chemotherapy in patients with breast cancer: a 6-month prospective study

Purpose The purpose of the study was to evaluate subjective (self-rated), family-rated, and objective (researcher-rated) cognitive functions in patients with breast cancer after chemotherapy. Method We conducted a prospective study to trace self-rated cognitive functions in 30 patients with breast cancer at the completion of chemotherapy (T0) and 6 months later (T1). Subjective cognitive functions were assessed with Cognitive Failures Questionnaire (CFQ), Dysexecutive Questionnaire (DEX-S), and Everyday Memory Checklist (EMC-S) for attention, executive function, and episodic memory, respectively. Their family members also completed DEX-I and EMC-I for executive function and episodic memory, respectively. We also examined objective cognitive functions. Self-rated cognitive functions were compared with the normative data. They were compared between T0 and T1. We calculated correlation coefficients between self-rated and other cognitive functions. Results At T0, 6 (20.0%) and 2 (6.7%) participants showed higher DEX-S and EMC-S scores than the normative data, respectively, while no participant had abnormal CFQ scores. At T1, DEX-S and EMC-S scores were normalized in 3 (50.0%) and 2 (100.0%) participants, respectively. No participant showed increases in CFQ scores. No changes were found in objective cognitive functions from T0 to T1. DEX-S and DEX-I or EMC-S and EMC-I scores were correlated at both T0 and T1, which did not survive multiple corrections. There was no association between subjective and objective cognitive functions. Conclusion Impairments in subjective cognition may be transient after chemotherapy in patients with breast cancer. Furthermore, patients and their families appear to share similar prospects on their cognitive functions.

High-dose antidepressants affect near-infrared spectroscopy signals: A retrospective study

Background Recent studies have highlighted the clinical usefulness of near-infrared spectroscopy (NIRS) in psychiatry. However, the potential effects of psychotropics on NIRS signals remain unknown. Methods We conducted a systematic chart review of 40 depressed patients who underwent NIRS scans during a verbal fluency task to clarify the relationships between psychotropic dosage and NIRS signals. The dosage of psychotropic medications was calculated using defined daily dose (DDD). We investigated the associations between the DDD of psychotropic medications and oxygenated hemoglobin (oxy-Hb) in single channel levels. Limitations Retrospective study design and small sample size are the main limitations. Results Multiple regression analysis revealed that one channel in the right temporoparietal region had a significant association with antidepressant DDD controlling for age, sex, depression severity, and the DDD of antipsychotics and benzodiazepines. Moreover, high doses of antidepressants had significant effects on NIRS signals compared with low doses, in group comparisons. Conclusions The dose-dependent impact of antidepressants on NIRS signals should be taken into account when interpreting NIRS data.

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.

Aberrant Spatial and Temporal Prefrontal Activation Patterns in Medication-Naïve Adults with ADHD

Previous near-infrared spectroscopy (NIRS) studies using a verbal fluency task (VFT) have consistently reported that adults with attention-deficit hyperactivity disorder (ADHD) showed significantly smaller oxygenated-hemoglobin [oxy-Hb] activations in the prefrontal cortex (PFC) compared to those in healthy controls (HC). Despite this consistent evidence of brain dysfunction in ADHD, ADHD is currently diagnosed based only on subjective clinical and scoring measures, which are often unreliable. Hence, it is necessary to establish objective neuroimaging biomarkers for ADHD. While most NIRS studies have utilized averaged [oxy-Hb] values during the whole task period for group comparisons, we used a cluster-based non-parametric randomization test to compare the [oxy-Hb] time-course changes with a 0.1-s time resolution between drug-naïve adults with ADHD and HC, which may provide us with more details regarding abnormal prefrontal activation patterns in ADHD. A total of 101 participants, consisting of 63 drug-naïve adult individuals with ADHD and 38 HC, were included in this study. We identified that adults with ADHD showed significantly smaller [oxy-Hb] activations than those in HC at spatially and temporally connected clusters located in the bilateral PFC (more prominent on the left) and temporal brain region (more prominent on the left). We further found that aberrant [oxy-Hb] activation differs according to the time period during the task or according to brain location. Our findings indicate more detailed aberrant prefrontal and temporal activation patterns of ADHD compared with those in previous studies, possibly representing a biological marker for ADHD.