First episode psychosis: register-based study of comorbid psychiatric disorders and medications before and after.

Comorbid psychiatric disorders are common in first episode psychosis. We investigated comorbid disorders before, at, and after a first hospital-treated psychosis in a naturalistic nation-wide cohort (n = 2091) with a first psychosis hospitalization between 2007 and 2011, and at ages between 16 and 25. Swedish population registers were used to identify the cohort and to collect data on diagnoses at hospitalizations and medications. The proportions of cases with hospitalizations or medications increased year by year before and decreased in the years after the first psychosis hospitalization. In the 2 years before, 30% had hospitalizations with other psychiatric diagnoses and 60% had psychiatric medications. At the first psychosis hospitalization, 46% had other comorbid psychiatric diagnoses or self-harm. In the 2 years before or at the first psychosis hospitalization, 17% had anxiety or stress disorders at hospitalizations, 12% depressive disorders, 5.4% manic or bipolar disorders, 8.6% personality disorders, 26% substance use disorders, and 15% neurodevelopmental disorders. 8.2% had hospitalizations for self-harm. At most, around 30% of the cases were estimated not to have had any comorbid psychiatric disorders before or at the first psychosis presentation. Early comorbid affective, anxiety or personality disorders or self-harm were associated with a worse outcome, as measured by new psychiatric hospitalizations. The outcome was worst for personality disorders with 73% re-hospitalizations within 1 year and for patients with self-harm with 70% re-hospitalizations. In conclusion, most cases with a first psychosis hospitalization had clinical presentations indicating comorbid psychiatric disorders. Cases with comorbidity had a higher risk for re-hospitalizations.

Substance use disorders before, at and after first episode psychosis hospitalizations in a young national Swedish cohort.

BACKGROUND: Comorbidity between Substance use disorders (SUD) and psychotic disorders is common but the temporal relation of the first episodes of SUD and psychosis and how it affects the disorders has not been extensively investigated. METHODS: A nation-wide cohort (n = 2494) with a first hospitalization for psychosis at ages between 16 and 25 was identified. Psychiatric hospitalizations were followed from birth until up to 5 years after the first psychosis hospitalization. Risk factors for new SUD or psychosis hospitalization after the index hospitalization were analyzed by Cox regression. RESULTS: 30 % of the cases had SUD hospitalizations in the 5 years before or as a comorbid diagnosis at the first psychosis hospitalization. An additional 9% had a first SUD hospitalization in the five years after. The incidence of SUD hospitalizations increased year by year before and decrease year by year after the index hospitalization. The hazard ratio for a new SUD hospitalizations after the index hospitalization was significantly higher (hazard ratio 6.7, p-value<0.001) in cases with SUD before or at the index hospitalization compared to in cases without previous SUD. In cases with previous SUD, there was a strong association (p < 0.001) between a new psychosis hospitalization and a new SUD hospitalization the year after the index hospitalization, indicating that SUD may continue to aggravate the psychotic disorder in this group. CONCLUSIONS: SUD is very common before a first hospital treated psychosis. The SUD likely aggravates early psychotic disorders in many cases.

Medication, hospitalizations and mortality in 5 years after first-episode psychosis in a Swedish nation-wide cohort.

AIM: To investigate medication, rehospitalizations and mortality after first-episode hospital-treated psychosis. METHODS: A population-based nation-wide cohort (n = 2488) with a first hospitalization for psychosis at ages between 16 and 25 was identified. Cases were followed for up to 5 years after the first psychosis hospitalization with regard to mortality, hospitalizations and dispensations of antipsychotics and benzodiazepines. RESULTS: The proportion of patients dispensing antipsychotics decreased from 80% year 1 after first discharge to 55% year 5. The proportion of patients having episodes of inpatient care also decreased year by year from 46% year 1 to 27% year 5. Of 863 cases with 5 years of observation time 41% had dispensations of antipsychotics every year; 21% had no dispensation of antipsychotics or hospitalization after the first year. The cumulative 5-year mortality was 3.9%. Cumulative suicide mortality was 2.4%. Incidence of suicide was highest in the first year. Male gender, benzodiazepines, recent hospital-discharge and self-harm were identified as risk factors for suicide. CONCLUSIONS: The proportion of cases dispensing antipsychotics decreases year by year after first discharge. Mortality and rates of rehospitalization also decrease year by year from high levels the first year.

First episode psychosis and comorbid ADHD, autism and intellectual disability.

BACKGROUND: Comorbidity between neurodevelopmental disorders and psychotic disorders is common, but little is known about how neurodevelopmental disorders influence the presentation and outcome of first episode psychosis. METHODS: A nation-wide cohort (n = 2091) with a first hospitalization for psychosis between 2007-2011 and at ages between 16-25 at intake was identified from Swedish population registries. Comorbid diagnoses of neurodevelopmental disorders were identified at first psychosis hospitalization and for ADHD also by dispensations of psychostimulants before the first psychosis hospitalization. Data from the registers on hospitalizations and dispensations of antipsychotic and psychostimulant medications during the year before and 2 years after the first psychosis hospitalization were analysed. Self-harm and substance use disorders were identified by ICD10 codes at hospitalizations. RESULTS: 2.5% of the cohort was identified with a diagnosis of intellectual disability, 5.0% with autism and 8.1% with ADHD. A larger proportion of cases with Autism (OR = 1.8, p < 0.05) and intellectual disability (OR = 3.1, p < 0.01) were using antipsychotic medication year 2 compared to the rest of the cohort. Delusional disorder was more common in the autism group (OR = 2.3, p < 0.05) at first psychosis hospitalization. ADHD was associated with higher risks for substance use disorders and self-harm both before and after the first psychosis hospitalization. Year 2 substance use disorder had a OR = 2.6 (p < 0.001) and self-harm OR = 4.1 (p < 0.001). CONCLUSIONS: Psychosis with comorbid ADHD is associated with high risks for substance use disorders and for self-harm, while psychosis with comorbid autism and intellectual disability is associated with longer treatment and higher doses of antipsychotic medication.

Criteria for self-reported quantitative sleep characteristics of individuals who sought medical help for disturbed sleep - a survey of a representative sample of the Swedish population.

BACKGROUND: The public often seeks rule-of-thumb criteria for good or poor sleep, with a particular emphasis on sleep duration, sleep latency, and the number of awakenings each night. However, very few criteria are available. AIM: The present study sought to identify such criteria. METHODS: Whether or not a person has sought medical help for sleep problems was selected as an indicator of poor sleep. The group that was studied constituted a representative sample of the general Swedish population (N=1,128), with a response rate of 72.8%. RESULTS: Logistic regression analysis, with an adjustment for age and gender, showed an increased OR for a weekday sleep duration of ≤6 hour, (OR >2, and for <5 hour: OR >6). For weekend sleep, the value was ≤6 hour (OR >2). For awakenings per night, the critical value was ≥2 (OR >2, and for ≥5 awakenings: OR >9), and for a sleep latency the critical value was ≥30 minutes (OR >2, and for ≥45 minutes: OR >6). Adding difficulties falling asleep and early morning awakening (considered qualitative because of the reflected "difficulty"), led to the elimination of all the quantitative variables, except for the number of awakenings. The addition of "negative effects on daytime functioning" and "sleep being a big problem" resulted in the elimination of all the other predictors except age. CONCLUSION: It was concluded that weekday sleep ≤6 hour, ≥2 awakenings/night, and a sleep latency of ≥30 minutes, can function as criteria for poor sleep, but that qualitative sleep variables take over the role of quantitative ones, probably because they represent the integration of quantitative indicators of sleep.

Impact of group treatment for insomnia on daytime symptomatology: Analyses from a randomized controlled trial in primary care.

BACKGROUND: People typically seek primary health care for daytime symptoms and impairments they experience in association with their insomnia. However, few studies address the question of whether insomnia treatment can improve such symptomatology. OBJECTIVES: To investigate whether a nurse-led group treatment program, based on the techniques of cognitive behavioral therapy for insomnia (CBT-I), improved daytime symptomatology in primary care patients with insomnia. OUTCOMES: Fatigue (Fatigue Severity Scale [FSS]; main outcome), mood (General Health Questionnaire and Montgomery-Asberg Depression Rating Scale), health-related quality of life (Short-Form Health Survey), general daytime functioning, specific daytime symptoms (individual items from the Insomnia Severity Index and Uppsala Sleep Inventory), and dysfunctional beliefs (Dysfunctional Beliefs and Attitudes about Sleep). DESIGN: A randomized controlled trial including baseline and post-treatment assessment and a 1-year post-treatment follow-up of the intervention group. SETTINGS: Seven primary health care centers (Stockholm, Sweden). PARTICIPANTS: One hundred and sixty-five primary care patients who meet the criteria for insomnia disorder (mean age 54 years, SD 16). Most were women (73%). EXCLUSION CRITERIA: severe untreated illness, bipolar disorder, current stressful life event, night shift work, and untreated sleep disorder other than insomnia. METHODS: Data came from a randomized controlled trial of a 10-week nurse-led group treatment for insomnia based on CBT-I (n = 90). The control condition was treatment as usual (n = 75). In accordance with intention-to-treat principles, analyses included data on patients who completed baseline assessments (intervention n = 82, and control group n = 71; post-treatment dropout rate 20%). Fifty-four patients were included in the 1-year follow-up. RESULTS: Fatigue severity improved significantly more (p < 0.001) in the intervention than in the control group (intervention, total FSS score 37.2 [SD 11.9] to 31.0 [SD 13.4] vs. control 35.9 [SD 12.1] to 35.7 [SD 12.8]). This was true also for measurements on mood (psychological distress and depressive symptoms), health-related quality of life (mental functioning), general daytime functioning, specific daytime symptoms (worry about sleep, sleepiness, bodily tiredness, and difficulty concentrating) and dysfunctional beliefs. All improvements were maintained one year after group treatment. CONCLUSIONS: Many aspects of the daytime symptomatology of insomnia were improved via nurse-led group treatment based on CBT-I in primary health care.

Improving insomnia in primary care patients: A randomized controlled trial of nurse-led group treatment.

BACKGROUND: Insomnia is a common health problem, and most people who seek help for insomnia consult primary care. In primary care, insomnia treatment typically consists of hypnotic drugs, although cognitive behavioral therapy for insomnia is the recommended treatment. However, such treatment is currently available to few primary care patients. OBJECTIVES: To evaluate the effects of a group treatment program for insomnia led by nurses in primary care. OUTCOMES: were the Insomnia Severity Index, a 2-week sleep diary, and a questionnaire on frequency of hypnotic drug use. DESIGN: A randomized controlled trial with pre- and post-treatment assessment and a 1-year post-treatment follow-up of the intervention group. SETTINGS: Routine primary health care; 7 primary care centers in Stockholm, Sweden. PARTICIPANTS: Patients consulting primary care for insomnia were assessed for eligibility. To be included, patients had to have insomnia disorder and be 18 years or older. Patients were excluded if they if they worked night shifts or had severe untreated somatic and/or mental illness, bipolar disorder, or untreated sleep disorder other than insomnia. One-hundred and sixty-five patients 20 to 90 years were included. Most were women, and many had co-existing somatic and/or mental health problems. The post-treatment dropout rate was 20%. METHODS: The intervention was a nurse-led group treatment for insomnia based on the techniques of cognitive behavioral therapy for insomnia. The nurses had 2days of training in how to deliver the program. Ninety patients were randomized to the intervention and 75 to the control group (treatment as usual). Data from 82 in the intervention and 71 in the control group were analyzed in accordance with intention-to-treat principles. Fifty-four of the 72 in the intervention group who participated in the group treatment program were followed up after 1year. RESULTS: Mean Insomnia Severity Index score decreased significantly from 18.4 to 10.7 after group treatment but remained unchanged after treatment as usual (17.0 to 16.6). The effect size was large (1.23). Group treatment also resulted in significant improvements in all sleep diary variables (sleep onset latency, total sleep time, time awake after sleep onset, number of awakenings, and sleep quality). It also reduced hypnotic drug use. Improvements were maintained 1-year post-treatment. CONCLUSIONS: Patients with insomnia can be treated successfully with a nurse-led group treatment program in primary health care. The results support implementation of the treatment program, particularly given the need for increased access to non-pharmacological insomnia treatments.

Factors associated with self-reported need for treatment of sleeping difficulties: a survey of the general Swedish population.

OBJECTIVE: This study aims to investigate factors associated with the self-reported need for treatment of sleeping difficulties in the general population. METHODS: This study consisted of a cross-sectional telephone survey of 1550 people randomly selected from the total population of Sweden. The survey, conducted by the Swedish national statistics agency, Statistics Sweden, was completed by 1115 people aged 18-85 years. Participants were asked about sleep patterns, daytime symptoms, physical and mental health disorders, use of prescribed hypnotics, help-seeking behaviors, and sociodemographic characteristics. They were also asked whether they thought they needed treatment for sleeping difficulties. RESULTS: A total of 12.5% of the participants reported a need for treatment because of sleeping difficulties. Significantly more women than men reported such a need (OR 1.46, 95% CI 1.02-2.10). Additionally, in univariate analyses, older age (age 60-69), sick leave, retirement, and unemployment were associated with a self-reported need for treatment, as were several sleep complaints, daytime symptoms, and physical and mental health disorders. A logistic regression model showed that difficulty initiating sleep (OR 6.29, 95% CI 3.67-10.78) was the factor most strongly associated with a self-reported need for treatment for sleeping difficulties. Other important factors were nonrestorative sleep (OR 3.70, 95% CI 2.05-6.69), mental health disorders (OR 3.01, 95% CI 1.59-5.67), and fatigue (OR 2.95, 95% CI 1.53-5.68). CONCLUSIONS: There was considerable self-reported need for treatment for sleeping difficulties in the population. Difficulty initiating sleep was the factor most strongly associated with this need, followed by nonrestorative sleep, mental health disorders, and fatigue.

Altered circadian clock gene expression in patients with schizophrenia.

Impaired circadian rhythmicity has been reported in several psychiatric disorders. Schizophrenia is commonly associated with aberrant sleep-wake cycles and insomnia. It is not known if schizophrenia is associated with disturbances in molecular rhythmicity. We cultured fibroblasts from skin samples obtained from patients with chronic schizophrenia and from healthy controls, respectively, and analyzed the circadian expression during 48h of the clock genes CLOCK, BMAL1, PER1, PER2, CRY1, CRY2, REV-ERBα and DBP. In fibroblasts obtained from patients with chronic schizophrenia, we found a loss of rhythmic expression of CRY1 and PER2 compared to cells from healthy controls. We also estimated the sleep quality in these patients and found that most of them suffered from poor sleep in comparison with the healthy controls. In another patient sample, we analyzed mononuclear blood cells from patients with schizophrenia experiencing their first episode of psychosis, and found decreased expression of CLOCK, PER2 and CRY1 compared to blood cells from healthy controls. These novel findings show disturbances in the molecular clock in schizophrenia and have important implications in our understanding of the aberrant rhythms reported in this disease.

The effect of the work environment on future sleep disturbances: a systematic review.

Workers often attribute poor sleep to factors at work. Despite the large number of workers with sleep disturbances, there is a lack of consensus on the relationship between the work environment and sleep. The purpose of this systematic review therefore was to conduct a comprehensive evaluation. To this end, we employed standardized methods to systematically locate, review, and tabulate the results of prospective or randomized studies of the impact of work factors on sleep disturbances. From the 7981 articles located in five databases, 24 fulfilled our inclusion criteria and formed the base of the review including meta-analyses of the effect sizes. Results showed that the psychosocial work variables of social support at work, control, and organizational justice were related to fewer sleep disturbances, while high work demands, job strain, bullying, and effort-reward imbalance were related to more future sleep disturbances. Moreover, working a steady shift was associated with disturbances while exiting shift work was associated with less disturbed sleep. We conclude that psychosocial work factors and the scheduling of work have an impact on sleep disturbances and this might be utilized in the clinic as well as for planning work environments. Future research needs to employ better methodology and focus on underlying mechanisms.

Insomnia in sweden: a population-based survey.

Aims. Estimate the prevalence of insomnia and examine effects of sex, age, health problems, sleep duration, need for treatment, and usage of sleep medication. Methods. A sample of 1,550 subjects aged 18-84 years was selected for a telephone interview. The interview was completed by 1,128 subjects (72.8%). Results. 24.6% reported insomnia symptoms. Insomnia disorder, that is, insomnia symptoms and daytime consequences, was reported by 10.5%. The prevalence was similar among all age groups, with the exception of women aged 40-49 years who demonstrated a significantly higher prevalence, 21.6%. Having at least one physical or psychiatric disorder was reported by 82.8% of subjects with insomnia disorder. Mean sleep duration for subjects with insomnia disorder was 5.77 hours on weeknights and 7.03 hours on days off/weekends. The corresponding figures for subjects without insomnia disorder were 7.04 hours and 7.86 hours, respectively. Among those with insomnia disorder 62.5% expressed a need for treatment, and 20.0% used prescribed sleep medication regularly. Conclusions. Insomnia disorder is highly prevalent in the population. There are significant associations between insomnia disorder and physical and psychiatric disorders. A majority of subjects with insomnia disorder expressed a need for treatment, indicating a public health problem.

Activation of kynurenine pathway in ex vivo fibroblasts from patients with bipolar disorder or schizophrenia: cytokine challenge increases production of 3-hydroxykynurenine.

Accumulating data suggest a causative link between immune stimulation, disturbed metabolism of tryptophan, and pathogenesis of bipolar disorder and schizophrenia. The goal of this study was to examine the production of kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK) and the expression of kynurenine pathway enzymes involved in their synthesis and metabolism in cultured skin fibroblasts obtained from patients with bipolar disorder, schizophrenia or from healthy control individuals. The assessment was performed under basal conditions or following treatment with interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, or their combinations, in cells exposed to exogenous kynurenine. In both groups of patients, the baseline production of KYNA and 3-HK was increased, as compared to control subjects. Case-treatment analyses revealed significant interactions between bipolar case status and IL-1ß, IL-6, IFN-γ + TNF-α, or IFN-γ + IL-1ß, as well as between schizophrenia case status and IL-1ß, IFN-γ + TNF-α, or IFN-γ + IL-1ß, in terms of higher 3-HK. Noteworthy, no case-treatment interactions in terms of KYNA production were found. Observed changes did not appear to correlate with the expression of genes encoding kynurenine aminotransferases (KATs), kynureninase (KYNU) or kynurenine-3-monooxygenase (KMO). The single nucleotide polymorphisms (SNPs), rs1053230 and rs2275163, in KMO influenced KYNA levels yet did not explain the case-treatment discrepancies. In conclusion, our present findings indicate the utility of skin-derived fibroblasts for kynurenines research and support the concept of kynurenine pathway alterations in bipolar disorder and schizophrenia. The increase in ratio between neurotoxic 3-HK and neuroinhibitory/neuroprotective KYNA following exposure to cytokines may account for altered neurogenesis and structural abnormalities characteristic for both diseases.

An item response theory evaluation of three depression assessment instruments in a clinical sample.

BACKGROUND: This study investigates whether an analysis, based on Item Response Theory (IRT), can be used for initial evaluations of depression assessment instruments in a limited patient sample from an affective disorder outpatient clinic, with the aim to finding major advantages and deficiencies of the instruments. METHODS: Three depression assessment instruments, the depression module from the Patient Health Questionnaire (PHQ9), the depression subscale of Affective Self Rating Scale (AS-18-D) and the Montgomery-Åsberg Depression Rating Scale (MADRS) were evaluated in a sample of 61 patients with affective disorder diagnoses, mainly bipolar disorder. A '3- step IRT strategy' was used. RESULTS: In a first step, the Mokken non-parametric analysis showed that PHQ9 and AS-18-D had strong overall scalabilities of 0.510 [C.I. 0.42, 0.61] and 0,513 [C.I. 0.41, 0.63] respectively, while MADRS had a weak scalability of 0.339 [C.I. 0.25, 0.43]. In a second step, a Rasch model analysis indicated large differences concerning the item discriminating capacity and was therefore considered not suitable for the data. In third step, applying a more flexible two parameter model, all three instruments showed large differences in item information and items had a low capacity to reliably measure respondents at low levels of depression severity. CONCLUSIONS: We conclude that a stepwise IRT-approach, as performed in this study, is a suitable tool for studying assessment instruments at early stages of development. Such an analysis can give useful information, even in small samples, in order to construct more precise measurements or to evaluate existing assessment instruments. The study suggests that the PHQ9 and AS-18-D can be useful for measurement of depression severity in an outpatient clinic for affective disorder, while the MADRS shows weak measurement properties for this type of patients.

Valproic acid phase shifts the rhythmic expression of Period2::Luciferase.

Valproic acid (VPA) is an anticonvulsant used to treat bipolar disorder, a psychiatric disease associated with disturbances in circadian rhythmicity. Little is known about how VPA affects circadian rhythms. The authors cultured tissues containing the master brain pacemaker for circadian rhythmicity, the suprachiasmatic nuclei (SCN), and skin fibroblasts from transgenic PERIOD2::LUCIFERASE (PER2::LUC) mice and studied the effect of VPA on the circadian PER2::LUC rhythm by measuring bioluminescence. VPA (1 mM) significantly phase advanced the PER2::LUC rhythm when applied at a time point corresponding to the lowest (trough, ~ZT 0) PER2::LUC expression but phase delayed the PER2::LUC rhythm when the drug was administered at the time of highest (peak, ~ZT 12) protein expression. In addition, it significantly increased the overall amplitude of PER2::LUC oscillations at time points at or close to ZT 12 but had no effect on period. Real-time PCR analyses on mouse and human fibroblasts revealed that expressions of other clock genes were increased after 2 h treatment with VPA. Because VPA is known to inhibit histone deacetylation, the authors treated cultures with an established histone deacetylation inhibitor, trichostatin A (TSA; 20 ng/mL), to compare the effect of VPA and TSA on molecular rhythmicity. They found that TSA had similar effects on the PER2::LUC rhythm as VPA. Furthermore, VPA and TSA significantly increased acetylation on histone H3 but in comparison little on histone H4. Lithium is another commonly used treatment for bipolar disorder. Therefore, the authors also studied the impact of lithium chloride (LiCl; 10 mM) on the PER2::LUC rhythm. LiCl delayed the phase, but in contrast to VPA and TSA, LiCl lengthened the PER2::LUC period and had no effect on histone acetylation. These results demonstrate that VPA can delay or advance the phase, as well as increase the amplitude, of the PERIOD2::LUCIFERASE rhythm depending on the circadian time of application. Furthermore, the authors show that LiCl delays the phase and lengthens the period of the PER2::LUC rhythm, confirming previous reports on circadian lithium effects. These different molecular effects may underlie differential chronotherapeutic effects of VPA and lithium.

Persistent nightmares are associated with repeat suicide attempt: a prospective study.

The aim of this prospective study was to determine if sleep disturbances and nightmares are associated with increased risk of repeat suicide attempt. Patients (n=165) aged 18-68 years who were admitted to medical or psychiatric wards after a suicide attempt completed an initial interview; 98 of these took part in a 2-month follow-up interview. The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and two self-report instruments, the Uppsala Sleep Inventory and the Comprehensive Psychopathological Rating Scale (CPRS) Self-Rating Scale for Affective Syndromes, were administered both at baseline and follow-up. Data concerning repeat suicide attempts within 2 years were obtained from hospital records. Analyses were performed using Student's t-test, chi-square test, and logistic regression. In total 42 patients (26%) made at least one repeat suicide attempt within 2 years. While neither difficulties initiating/maintaining sleep nor early morning awakening at baseline predicted repeat attempt, having frequent nightmares did (OR=3.15). The risk was further heightened when nightmares were reported at both baseline and 2-month follow-up (OR=5.20). These associations remained after adjusting for sex, axis-I DSM-IV diagnoses, and self-reported depression and anxiety symptom intensity. Our findings suggest that nightmares might constitute a marker for increased risk of suicidal behavior.

Is usage of hypnotics associated with mortality?

OBJECTIVE: To investigate the influence of hypnotic usage on all-cause and cause-specific mortality in a middle-aged population. METHODS: A cohort of 1750 men and 1773 women aged 30-65 years who responded to a postal questionnaire in 1983. The questionnaire included questions about hypnotic usage, sleep duration, sleep complaints, medical conditions, depression, demographic and life style variables. Mortality data for the period 1983-2003 were collected. RESULTS: Regular hypnotic usage was reported by 1.7% of men and 2.2% of women, and was associated with short sleep, sleeping difficulties, several health problems and depression. During the 20-year follow-up period 379 men (21.5%) and 278 women (15.5%) died. After adjustment for potential risk factors in multivariate analyses regular hypnotic usage was associated with significantly increased risk of all-cause mortality in men (Hazard ratios [HR], 4.54; 95% confidence interval [CI], 2.47-8.37) and in women 2.03 (95% CI, 1.07-3.86). With regard to cause-specific mortality, regular hypnotic usage in men was a risk factor for coronary artery disease death, cancer death, suicide and death from "all remaining causes." In women it was a risk factor for suicide. CONCLUSIONS: Our results show an increased risk of all-cause mortality and cause-specific mortality in regular users of hypnotics.

Identifying predictors for good lithium response - a retrospective analysis of 100 patients with bipolar disorder using a life-charting method.

PURPOSE: Our aim was to investigate bipolar patients in order to test the validity of various outcome measures and to identify prognostic predictors for pharmacological treatment. MATERIAL AND METHOD: One hundred patients were interviewed using a computerized life-charting program in a descriptive, retrospective analysis. The concept "Burden of illness" was defined as a combination of severity and duration of episodes. Response to treatment was defined as the difference in burden before and after treatment, a low burden during treatment, and freedom of episodes for at least 3 years after insertion of treatment. RESULTS: The absence of mixed episodes and a high initial burden predicted a good response measured as the difference in burden. If remission for 3 years or a low burden during lithium treatment was used, the absence of rapid cycling and of mixed episodes were the most important predictors. The severity of illness before treatment had no impact. DISCUSSION AND CONCLUSION: We suggest the use of absolute measures of severity during treatment as the most appropriate measure of the outcome. Furthermore, our data provide corroboration that treatment with lithium ameliorates the prognosis of the illness, but that mixed episodes and rapid cycling predict a poorer response to lithium.

Restless legs symptoms with sleepiness in relation to mortality: 20-year follow-up study of a middle-aged Swedish population.

AIM: The aim of the present study was to investigate restless legs symptoms with concomitant daytime sleepiness as a risk factor for mortality in a middle-aged population. METHODS: A cohort of 5102 subjects aged 30-65 years in mid-Sweden who responded to a postal questionnaire in 1983 was followed up. The questionnaire included questions about restless legs symptoms, daytime sleepiness, demographic and lifestyle variables, sleep habits, medical conditions and depression. Mortality data for the period 1983-2003 were collected and death certificates were available for all the 657 responders who died during the follow-up period. RESULTS: Restless legs symptoms with daytime sleepiness was reported by 10.3% and was associated with shorter night sleep time, several health problems and depression. During the follow-up period 379 men (21.6%) and 278 women (15.5%) died. A multivariate model adjusted for age, short night sleep time, lifestyle factors, medical conditions and depression showed that women reporting restless legs symptoms with daytime sleepiness had an excess mortality compared to women without restless legs symptoms and daytime sleepiness (hazard ratios, 1.85; 95% confidence interval, 1.20-2.85; P = 0.005). No influence on mortality risk was found in men reporting restless legs symptoms with daytime sleepiness. CONCLUSIONS: The occurrence of restless legs symptoms with daytime sleepiness in middle-aged women is associated with increased mortality risk.