Prescription patterns of psychotropics in patients receiving synthetic glucocorticoids.

OBJECTIVE: Synthetic glucocorticoids cause various psychiatric symptoms. Prescription of psychotropic drugs could be considered to be a proxy for manifestation of psychiatric symptoms. The aim of this study was to investigate the prescriptions of psychotropics in outpatients receiving synthetic glucocorticoids. METHODS: We used the claims sampling data during January 2015 from the National Database of Health Insurance Claims and Specific Health Checkups of Japan made by the Ministry of Health, Labor, and Welfare in Japan. We compared the prescription rates of psychotropics between outpatients receiving oral synthetic glucocorticoids and age- and sex-matched controls and the prescription rates of psychotropics among the eight dosage groups of synthetic glucocorticoids by chi-squared test, and chlorpromazine/imipramine/diazepam equivalent doses (or daily defined doses) of respective psychotropics among these groups using Welch's t-test. RESULTS: Synthetic glucocorticoids were prescribed to 3.1% (n = 18 122) of 581 990 patients. The prescription rates of psychotropics were significantly higher among the synthetic glucocorticoid recipients than among the non-recipients: antipsychotics, 1.8% (n = 321) vs. 1.1% (n = 201) (P = 1.4 × 10-7 ); antidepressants, 4.0% (n = 724) vs. 2.0% (n = 359) (P = 8.7 × 10-30 ); anxiolytics/hypnotics, 16.7% (n = 3029) vs. 10.2% (n = 1841) (P = 2.7 × 10-75 ); and mood stabilizers, 1.3% (n = 238) vs. 0.7% (n = 120) (P = 3.6 × 10-10 ) respectively. There was no significant difference in the prescription rates of any psychotropic drugs, other than anxiolytics/hypnotics, among the eight synthetic glucocorticoid dosage groups. CONCLUSION: Prescriptions of oral synthetic glucocorticoids were found to be associated with the use of any of the types of psychotropic drugs, other than anxiolytics/hypnotics, although a causal relationship could not be confirmed due to the retrospective and cross-sectional nature of this study.

Placebo effects in adult and adolescent patients with schizophrenia: combined analysis of nine RCTs.

OBJECTIVE: To examine characteristics of placebo responders and seek optimal criteria of early improvement with placebo for predicting subsequent placebo response in patients with schizophrenia. METHOD: Data of 672 patients with schizophrenia randomized to placebo in nine double-blind antipsychotic trials were analyzed. Multiple logistic regression analyses were conducted to examine associations between placebo response at week 6 (i.e., a ≥ 25% reduction in the Positive and Negative Syndrome Scale [PANSS] score) and gender, age, study locations, baseline PANSS total or Marder 5-Factor scores, and per cent PANSS score reduction at week 1. Predictive power of improvement at week 1 for subsequent response was investigated; sensitivity and specificity of incremental 5% cutoff points between 5% and 25% reduction in the PANSS total score at week 1 were calculated. RESULTS: Per cent PANSS total score reduction at week 1 and lower PANSS Marder disorganized thought scores at baseline were significantly associated with subsequent placebo response. A 10% reduction in a per-protocol analysis or a 15% reduction in last-observation-carried-forward analysis in the PANSS total score at week 1 showed the highest predictive power. CONCLUSION: These findings are informative to identify potential placebo responders at the earliest opportunity for optimal trial design for schizophrenia.

Spreading Waves in a Farmers and Hunter-Gatherers Model of the Neolithic Transition in Europe.

The Neolithic transition began the spread of early agriculture throughout Europe through interactions between farmers and hunter-gatherers about 10,000 years ago. Archeological evidence produced by radiocarbon dating indicates that the expanding velocity of farming is roughly constant all over Europe. Theoretical understanding of such evidence has been performed from mathematical modeling viewpoint. However, the expanding velocity determined by existing modeling approaches is faster than the observed velocity. For understanding this difference, we propose a three-component reaction-diffusion system which consists of two different types of farmers (sedentary and migratory) and hunter-gatherers from the viewpoint of the influence of farming technology. Our purpose is to study the relation between the expanding velocity of farmers and the farming technology parameter (say, [Formula: see text]). In this paper, we mainly focus on the one-dimensional traveling wave solution with minimal velocity and show that the minimal velocity decreases, as [Formula: see text] increases. This can be compatible with the observed velocity when farming technology is developed. Our results suggest that the reason for the slowdown of the Neolithic transition might be related to the increase in the development of farming technology.

Interval timing errors in a patient with thalamic chronotaraxis.

Thalamic chronotaraxis is an isolated disorientation of time caused by the damage of thalamus, especially the mediodorsal nucleus. We performed interval timing trials on a patient with this phenomenon. Based on the results of those trials and compared to the previous reports, thalamic chronotaraxis of our case might be due to the disfunction of the dorsolateral prefrontal cortex caused by the right thalamic infarction.

Religiosity and psychological resilience in patients with schizophrenia and bipolar disorder: an international cross-sectional study.

OBJECTIVE: The impact of religious/spiritual activities on clinical outcomes in patients with serious mental illnesses remains controversial, which was addressed in this international cross-sectional study. METHOD: Three-hundred sixty-nine subjects were recruited from Austria (n = 189) and Japan (n = 180), consisting of 112 outpatients with paranoid schizophrenia, 120 with bipolar I disorder (DSM-IV), and 137 healthy controls. Religiosity was assessed in terms of attendance and importance of religious/spiritual activities, while resilience was assessed using the 25-item Resilience Scale. General linear models were used to test whether higher religiosity will be associated with higher resilience, higher social functioning, and lower psychopathology. The association between levels of spiritual well-being and resilience was also examined. RESULTS: Attendance of religious services (F[4,365] = 0.827, P = 0.509) and importance of religion/spirituality (F[3,365] = 1.513, P = 0.211) did not show significant associations with resilience. Regarding clinical measures, a modest association between higher importance of religion/spirituality and residual manic symptoms was observed in bipolar patients (F[3,118] = 3.120, P = 0.029). In contrast to the findings regarding religiosity, spiritual well-being showed a strong positive correlation with resilience (r = 0.584, P < 0.001). CONCLUSION: The protective effect of religiosity in terms of resilience, social functioning, and psychopathology was not evident in our sample. Spiritual well-being appears more relevant to resilience than religiosity.

Quality of life in schizophrenia and bipolar disorder: The impact of symptomatic remission and resilience.

BACKGROUND: Health-related quality of life (HRQOL) is significantly affected in individuals with schizophrenia or bipolar I disorder (BD-I). The current study investigated whether symptomatic remission and resilience might differently impact HRQOL in these patients. METHODS: Fifty-two patients with schizophrenia and 60 patients suffering from BD-I from outpatient mental health services as well as 77 healthy control subjects from the general community were included into a cross-sectional study. HRQOL and resilience were assessed using the WHOQOL-BREF and the Resilience Scale. In patients, psychopathology was quantified by the Positive and Negative Syndrome Scale or the Montgomery Asberg Depression Rating Scale and the Young Mania Rating Scale, respectively. RESULTS: Notably, both patient groups showed lower HRQOL and resilience compared to control subjects, non-remitted patients indicated lower HRQOL than remitted ones. The effect of remission on HRQOL was significantly larger in patients with BD-I than in those with schizophrenia but did not explain the difference in HRQOL between groups. Resilience predicted HRQOL in all three groups. When accounting for the effect of resilience among remitted patients, only the difference in HRQOL between schizophrenia patients and control subjects was significant. CONCLUSION: These findings demonstrate the impact of symptomatic remission and resilience on HRQOL of both patients suffering from schizophrenia and BD-I and indicate that these factors are especially relevant for HRQOL of patients with BD-I.

Dietary fish, n-3 polyunsaturated fatty acid consumption, and depression risk in Japan: a population-based prospective cohort study.

Systematic review of observational studies has revealed that fish consumption and levels of n-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid are associated with a reduced risk of depression. A reverse J-shaped effect of n-3 PUFAs was suggested. However, there is limited evidence from populations with high fish consumption and no studies have used a standard psychiatrist-based diagnosis of major depressive disorder (MDD). Therefore, this population-based, prospective study investigated the association of dietary fish, n-3 PUFA, and n-6 PUFA consumption with risk of psychiatrist-diagnosed MDD in Japan. A total of 12 219 subjects were enrolled from the Saku area in 1990. Of these, we extracted 1181 participants aged 63-82 years who completed food frequency questionnaires in both 1995 and 2000 and also underwent a mental health examination in 2014-2015. Odds ratios (ORs) and 95% confidence intervals (CIs) for MDD according to fish intake and PUFA quartiles were calculated. Current MDD was diagnosed in 95 patients. We found a reduced risk of MDD in the third quartile for fish intake (111.1 g per day, OR=0.44, 95% CI=0.23-0.84), second quartile for EPA (307.7 mg per day, OR=0.54, 95% CI=0.30-0.99) and third quartile for docosapentaenoic acid (DPA) (123.1 mg per day, OR=0.42, 95% CI=0.22-0.85). ORs adjusted for cancer, stroke, myocardial infarction and diabetes remained significant for fish and DPA intake. Our results suggest that moderate fish intake could be recommended for the prevention of MDD in aged Japanese individuals.

High serum total cholesterol is associated with suicide mortality in Japanese women.

OBJECTIVE: To investigate the association between serum total cholesterol (TC) and suicide using a large general population cohort with long follow-up times. METHOD: Analyses included 16 341 men and 28 905 women aged 40-69 from the Japan Public Health Center-based Prospective Study followed from 1990 to 2012. TC levels were defined per clinical guidelines: low (<4.66 mmol/l [180 mg/dl]), normal (4.66-5.70 mmol/l [180-220 mg/dl]), and high (≥5.70 mmol/l [220 mg/dl]). Cox proportional hazards regression models were used to determine hazard ratios (HR) and confidence intervals (CI) for suicide according to TC level. Mean follow-up time was 19 years for men and 20 years for women. RESULTS: There were 185 suicides (men: 107; women: 78) during follow-up. Compared to women with normal TC, women with high TC had a significantly increased risk of suicide (HR = 1.90, 95% CI, 1.13-3.19). Incremental increases (0.26 mmol/l [10 mg/dl]) of low-density lipoprotein (HR = 1.11, 95% CI, 1.02-1.21) and non-high-density lipoprotein cholesterol (HR = 1.09, 95% CI, 1.01-1.18) were also associated with increased risk of suicide in women. There was no association between TC levels, or lipid fractions, and suicide in men. CONCLUSION: High TC levels may be associated with an increased risk of suicide in women.

Retrospective analysis of the survival benefit of chemotherapy for recurrent or advanced epithelial ovarian carcinoma in patients previously treated with paclitaxel plus platinum-based chemotherapy.

AIM: The outcomes of treatment for women with recurrent or advanced epithelial ovarian carcinoma previously treated with pacli- taxel plus platinum-based chemotherapy were analyzed. MATERIALS AND METHODS: Retrospective analysis was performed in a total of 65 series of treatments provided for 35 patients with a history of paclitaxel plus platinum-based chemotherapy. The chemotherapy regimens used were classified into the following four types for analysis: conventional paclitaxel plus carboplatin therapy (TC arm), pegylated liposomal doxorubicin-containing regimens (PLD arm), CPT-11-containing regimens (CPT-11 arm), and others. Disease-control rates (DCRs) were compared and subjected to univariate analysis. Progression-free survival (PFS) was determined from the date of the first cycle of each chemotherapy with the Kaplan-Meier method, and comparisons were performed using the log-rank test. RESULTS: DCR was 80%, 71%, and 26% for the TC, PLD, and CPT-l arms, respectively. The median PFS was 286, 372, and 76 days for the TC, PLD, and CPT-11 arms, respectively. There was no discernible difference in PFS between the TC and the PLD arm. In contrast, PFS of the CPT- 11 arm was significantly shorter than that of the TC and PLD arms. In addition, three of seven (42.9%) treatments in the PLD arm maintained a progression-free period for longer than one year, while only one of 25 (4%) treatments in the TC arm maintained a progression-free period for more than one year. CONCLUSIONS: The PFS of PLD is similar to that of TC. PLD-containing regimens might have a potential benefit with a higher PFS over one year than the TC regimen.

Predicting Plasma Olanzapine Concentration Following a Change in Dosage: A Population Pharmacokinetic Study.

INTRODUCTION: Due to high inter-individual variability in peripheral pharmacokinetic parameters, dosing of antipsychotics currently relies on clinical trial-and-error, and predicting antipsychotic plasma concentrations before changing a dose has been a challenge. METHODS: Patients with schizophrenia receiving a stable dose of olanzapine were included. 2 plasma samples were collected at 2 given time points for the measurement of plasma olanzapine concentrations. At least 7 days after a dosage change of olanzapine, a third sample was collected. The plasma concentration of the third sample was predicted in a blinded fashion using a mixed-effects model with NONMEM(®), using the following information: the 2 baseline plasma concentrations, the interval between the last dose and blood draw, and clinical and demographic information. RESULTS: 31 subjects (mean±SD age=56.0±11.6; 19 men) were enrolled. The mean prediction (95% confidence interval) errors were 1.6 (-2.8 to 6.0) ng/mL. A highly significant correlation was observed between the observed and predicted concentrations of the third sample (r=0.91, p<0.001). DISCUSSION: Plasma olanzapine concentrations following an actual dosage change can be predicted in advance with a high degree of certainty.

Effects of glutamate positive modulators on cognitive deficits in schizophrenia: a systematic review and meta-analysis of double-blind randomized controlled trials.

Hypofunction of N-methyl-d-aspartate (NMDA) receptors has been proposed to have an important role in the cognitive impairments observed in schizophrenia. Although glutamate modulators may be effective in reversing such difficult-to-treat conditions, the results of individual studies thus far have been inconsistent. We conducted a systematic review and meta-analysis to examine whether glutamate positive modulators have beneficial effects on cognitive functions in patients with schizophrenia. A literature search was conducted to identify double-blind randomized placebo-controlled trials in schizophrenia or related disorders, using Embase, Medline, and PsycINFO (last search: February 2015). The effects of glutamate positive modulators on cognitive deficits were evaluated for overall cognitive function and eight cognitive domains by calculating standardized mean differences (SMDs) between active drugs and placebo added to antipsychotics. Seventeen studies (N=1391) were included. Glutamate positive modulators were not superior to placebo in terms of overall cognitive function (SMD=0.08, 95% confidence interval=-0.06 to 0.23) (11 studies, n=858) nor each of eight cognitive domains (SMDs=-0.03 to 0.11) (n=367-940) in this population. Subgroup analyses by diagnosis (schizophrenia only studies), concomitant antipsychotics, or pathway of drugs to enhance the glutamatergic neurotransmission (glycine allosteric site of NMDA receptors or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors) suggested no procognitive effect of glutamate positive modulators. Further, no effect was found in individual compounds on cognition. In conclusion, glutamate positive modulators may not be effective in reversing overall cognitive impairments in patients with schizophrenia as adjunctive therapies.

Simulation of the capacity and precision of working memory in the hypodopaminergic state: Relevance to schizophrenia.

Working memory (WM) impairment has received attention as a behavioral characteristic of schizophrenia. Neurobiological studies have led to the hypothesis that a deficit in dopamine transmission through D1 receptors in the prefrontal cortex (PFC) is associated with WM impairment in schizophrenia. However, empirical approaches that aim to clarify the nature of the impairment and its underlying mechanism are difficult to enact, especially in unmedicated patients. By contrast, computational approaches using biologically plausible models have formed a powerful theoretical framework for the study of WM impairment in schizophrenia. This article attempts to directly connect neurobiological findings to the neuropsychological behaviors present in patients with schizophrenia. Using a biologically plausible prefrontal cortical circuit model, we simulated sustained activity during a simultaneous, multi-target WM task. We subsequently analyzed how dopaminergic modulation via D1 receptor activation alters the capacity and precision of WM and investigated the underlying mechanism. Hypodopaminergic modulation resulted in imprecision and a reduced capacity in WM primarily due to decreased N-methyl-d-aspartate (NMDA) conductance. Increasing NMDA conductance ameliorated both impairments. These results account for the mechanism that underlies WM impairments in schizophrenia and provide a theoretical basis for combination therapy with antipsychotic drugs and drugs that enhance NMDA receptor function, which is expected to be effective for the treatment of WM impairments in these patients.

Timing of adjunctive therapy in the treatment of depression: a chart review.

INTRODUCTION: The objective of this study was to examine the evolution of antidepressant switch and adjunctive therapy. METHODS: This chart review was conducted at 6 primary psychiatric clinics or hospitals, in Tokyo, Japan. A chart review of longitudinal prescriptions was conducted regarding 633 outpatients with major depressive disorder for up to 2 years after their first visit. Patients who had already received antidepressants prior to the visit were excluded. RESULTS: 22.6% (N=143) of the patients completed or continued the outpatient treatment over the 2 years while 27 (4.3%), 23 (3.6%), and 439 (69.4%) patients discontinued it due to hospitalization, referral to another clinic, and loss to follow-up, respectively. A total of 597 episodes of antidepressant treatment were identified. Among them, 482 episodes (80.7%) were associated with the suggested dose ranges while antidepressant drugs were under-dosed in 19.3% (N=115) of the episodes. 50 patients (7.9%) received adjunctive therapy; it was employed after a median of only one antidepressant had been tried. CONCLUSION: Psychiatrists may be hasty in prescribing an adjunctive therapy in the treatment of depression.

Improved non-invasive total haemoglobin measurements after in-vivo adjustment.

We hypothesised that an in-vivo adjustment method and/or a newer sensor would increase the accuracy of non-invasive and continuous haemoglobin monitoring (SpHb) measurements. Two sensors, the R1-25 and R2-25a (the newer version), were used with laboratory total haemoglobin concentration (tHb) values simultaneously recorded. In-vivo adjusted SpHb (AdHb) was calculated by a simple formula: AdHb = SpHb - (1(st) SpHb - 1(st) tHb). The correlation coefficients between SpHb (or AdHb) and tHb were compared: SpHb in both sensors correlated strongly with tHb (p < 0.0001). In-vivo adjustment improved the correlation coefficient between SpHb and tHb from 0.86 to 0.95 for the R1-25 and from 0.83 to 0.93 for the R2-25a. There was no difference between the R1-25 and R2-25a sensors. The in vivo adjustment method improved the accuracy of SpHb measurements in both sensors.

How psychotropic polypharmacy in schizophrenia begins: a longitudinal perspective.

INTRODUCTION: While patients with schizophrenia are often treated with psychotropic polypharmacy, how and when polypharmacy begins is not well documented. METHODS: A systematic chart review of 300 patients, 100 of whom were psychotropic-free prior to their first visit, was conducted to examine 2-year longitudinal prescription patterns of concomitant psychotropics, in addition to a primary antipsychotic. RESULTS: Overall polypharmacy occurred in 79% patients, with 2-year rates of the use of hypnotics, benzodiazepine derivative anxiolytics, anticholinergic drugs, antidepressants, and mood stabilizers were 56.7, 49.7, 38.3, 21.3, and 14.0%, respectively. Once polypharmacy had started, it was continued until their final visit in >70% of the patients. In a subgroup of 100 psychotropic-free patients, mood stabilizers, antidepressants, anticholinergic antiparkinsonian drugs, anxiolytics, and hypnotics were initiated after 2.3, 2.3, 2.1, 1.6, and 1.5 antipsychotics had been prescribed, respectively (mean duration before the introduction of a concomitant drug in days: 17.7, 121.6, 86.4, 32.1, and, 57.7, respectively). CONCLUSION: Routine practice deviates significantly from algorithms--with polypharmacy often being initiated early, often a without trial of other options, and once started commonly stays.

Craniospinal irradiation using helical tomotherapy: evaluation of acute toxicity and dose distribution.

The purpose of this study was to evaluate acute toxicity of craniospinal irradiation (CSI) using helical tomotherapy (HT) and compare its dose distribution with that of conventional linac-based plans. Twelve patients with various brain tumors were treated with HT-CSI. Median patient age was 14 years (range: 4-37 years). Median CSI dose was 30.6 Gy in 18 fractions (range: 23.4-40 Gy in 13-25 fractions). Toxicities were assessed according to the Common Terminology Criteria for Adverse Events version 4.0. Before CSI, 11 patients (92%) received neoadjuvant chemotherapy, so acute toxicity was evaluated by comparing patient status before and after CSI. HT-CSI plans were compared with linac-based CSI plans made using Pinnacle(3) planning system in 9 patients. All patients completed planned CSI without interruption. Grade 3 or higher toxicities were leukopenia seen in 11 patients (92%), anorexia in 6 (50%), anemia in 5 (42%), and thrombopenia in 5 (42%). Administration of granulocyte colony-stimulating factor, platelet transfusion and total parenteral nutrition were required in 8 (67%), 5 (42%) and 5 (42%) patients, respectively. HT plans were superior to linac-based plans in terms of homogeneity and conformality in planning target volume (PTV). For most organs at risk (OARs), volumes receiving more than 10 Gy (V10 Gy) or 20 Gy (V20 Gy) were lower in HT plans. However, HT plans significantly increased mean doses to the lung, kidneys and liver, and V5 Gy of 6 OARs including the lung. Despite intensive neoadjuvant chemotherapy, acute toxicity of HT-CSI was acceptable. HT provided better dose distribution in PTV than conventional linac. In most OARs, smaller volumes received >10-20 Gy in HT plans, although larger volumes received 5-10 Gy.

Local adaptation at the range peripheries of Sitka spruce.

High-dispersal rates in heterogeneous environments and historical rapid range expansion can hamper local adaptation; however, we often see clinal variation in high-dispersal tree species. To understand the mechanisms of the species' distribution, we investigated local adaptation and adaptive plasticity in a range-wide context in Sitka spruce, a wind-pollinated tree species that has recently expanded its range after glaciations. Phenotypic traits were observed using growth chamber experiments that mimicked temperature and photoperiodic regimes from the limits of the species realized niche. Bud phenology exhibited parallel reaction norms among populations; however, putatively adaptive plasticity and strong divergent selection were seen in bud burst and bud set timing respectively. Natural selection appears to have favoured genotypes that maximize growth rate during available frost-free periods in each environment. We conclude that Sitka spruce has developed local adaptation and adaptive plasticity throughout its range in response to current climatic conditions despite generally high pollen flow and recent range expansion.

Adaptive gradients and isolation-by-distance with postglacial migration in Picea sitchensis.

Fossil pollen records suggest rapid migration of tree species in response to Quaternary climate warming. Long-distance dispersal and high gene flow would facilitate rapid migration, but would initially homogenize variation among populations. However, contemporary clinal variation in adaptive traits along environmental gradients shown in many tree species suggests that local adaptation can occur during rapid migration over just a few generations in interglacial periods. In this study, we compared growth performance and pollen genetic structure among populations to investigate how populations of Sitka spruce (Picea sitchensis) have responded to local selection along the historical migration route. The results suggest strong adaptive divergence among populations (average Q(ST)=0.61), corresponding to climatic gradients. The population genetic structure, determined by microsatellite markers (R(ST)=0.09; F(ST)=0.11), was higher than previous estimates from less polymorphic genetic markers. The significant correlation between geographic and pollen haplotype genetic (R(ST)) distances (r=0.73, P<0.01) indicates that the current genetic structure has been shaped by isolation-by-distance, and has developed in relatively few generations. This suggests relatively limited gene flow among populations on a recent timescale. Gene flow from neighboring populations may have provided genetic diversity to founder populations during rapid migration in the early stages of range expansion. Increased genetic diversity subsequently enhanced the efficiency of local selection, limiting gene flow primarily to among similar environments and facilitating the evolution of adaptive clinal variation along environmental gradients.

A comparative study of the efficacy and safety profiles between fluvoxamine and nortriptyline in Japanese patients with major depression.

OBJECTIVE: The aim of this study was to compare the efficacy and safety profiles between fluvoxamine and nortriptyline in Japanese patients with major depression. METHODS: The efficacy and safety profiles of fluvoxamine, a selective serotonin-reuptake inhibitor, and nortriptyline were compared under a single-blind fashion in 74 Japanese patients with major depression. The efficacy was assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D), Clinical Global Impression Scale (CGI) severity and improvement scores, while the safety profiles were assessed using the UKU Side Effect Rating Scale at baseline, and on days 7, 14, 28 and 56. Moreover, with the aim of determining the distinct efficacy profiles of each drug, the effects on each of the factor scores extracted by the principal component analysis performed for HAM-D scores were compared between drugs. RESULTS: Both drug groups showed significant amelioration of depressive symptomatology over the trial period lasting for 8 weeks. Statistical analyses revealed no significant between-group differences regarding the efficacy assessed by either HAM-D or CGI scores; however, the efficacy of nortriptyline tended to appear earlier than that of fluvoxamine. Moreover, no significant differences were obtained for the factor scores, representing 'depressed mood', 'physical symptoms' or 'sleep disturbances', although 'sleep disturbances' appeared to improve earlier in the nortriptyline group than in the fluvoxamine group. As for the safety profiles, the nortriptyline group scored a significantly higher incidence of adverse events such as dysarthria or orthostatic dizziness, as well as increased heart rate. CONCLUSIONS: These findings suggest that fluvoxamine is generally comparable to nortriptyline in its efficacy and superior in its safety profile, in accordance with findings obtained in previous comparative clinical trials conducted in Caucasian populations.

Primary malignant melanoma of the oral cavity: assessment of outcome from the clinical records of 35 patients.

Oral malignant melanoma is extremely rare and carries a poor prognosis. The treatment of choice remains controversial. We retrospectively studied 35 patients with primary malignant melanoma of the oral cavity between 1970 and 2001 to define the clinical features of this disease and evaluate treatment methods. The main variables studied were clinical findings, response to therapy, and outcome. Surgery with complete macroscopic resection was performed at the primary site in 13 patients (surgery group) and radiotherapy was done without surgery in 17 (non-surgery group). The 5-year cumulative survival rate was 15.4% in the surgery group, 35.3% in the non-surgery group, and 21.8% overall. Distant metastasis was present in 64.7% (11/17) of the non-surgery group and 76.9% (10/13) of the surgery group. Improved outcome in oral malignant melanoma requires the development of new therapies and the prevention of distant metastasis.