Depression and pain: An appraisal of cost effectiveness and cost utility of antidepressants

BackgroundAlthough depression and chronic pain frequently co-occur, there is a lack of clarity in the literature regarding the cost-effectiveness and cost-utility of antidepressants in the presence of these two conditions. From the perspective of healthcare provider, the current study aims to compare the cost-effectiveness and cost-utility of antidepressants in a national cohort of depressed patients with and without comorbid pain conditions.MethodsAdult patients prescribed with antidepressants for depression were identified from the National Health Insurance Research Database in Taiwan (n = 96,501). By using remission as effectiveness measure and quality-adjusted life years (QALYs) as utility measure, the cost-effectiveness and cost-utility were compared across selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs), as well as by the presence of comorbid painful physical symptoms (PPS).ResultsSSRIs dominated SNRIs in both the cost-effectiveness and cost-utility regardless of comorbid PPS. In comparison with TCAs, SSRIs were likely to be the cost-effective option for patients without PPS. In patients with PPS, the cost-utility advantage for SSRIs over TCAs varied with threshold willingness-to-pay levels. Comorbid PPS may be considered an effect modifier of the cost-utility comparisons between SSRIs and TCAs.ConclusionsFor depressed patients without PPS, SSRIs are likely to be cost-effective in improving remission rates and QALYs compared to TCAs and SNRIs. However, to improve cost-utility in those with comorbid PPS, people need to choose between SSRIs and TCAs according to threshold willingness-to-pay levels. Future research is warranted to clarify the impacts of different pain conditions on the economic evaluations of pharmacological treatments in patients with depression.     

Childhood narcolepsy with cataplexy: comparison between post-H1N1 vaccination and sporadic cases

ObjectivesWe aimed to compare post-Pandemrix® vaccination (postvaccine) childhood narcolepsy with cataplexy (NC) vs sporadic pre-H1N1 pandemic (pre-H1N1) cases.MethodsClinical, anthropometric, polysomnographic, and cerebrospinal hypocretin 1 (hcrt-1) measurements were collected together with the video recordings of cataplexy in 27 Finnish patients with NC onset after H1N1 Pandemrix® vaccination (mean age, 12 ± 4 years; 52% boys) and 42 Italian NC patients with NC onset before the H1N1 pandemic (mean age, 11 ± 3 years; 48% boys). All subjects carried the HLA-DQB1*0602 allele.ResultsPostvaccine subjects were older at NC onset (12 ± 3 vs 9 ± 3 years; P = .008) and displayed a shorter mean sleep latency in multiple sleep latency tests (MSLT) (2.3 ± 2.2 vs 3.7 ± 2.9 min; P = .026) compared to pre-H1N1 cases. Anthropometric, clinical (core NC symptoms), hcrt-1 deficiency, and polysomnographic data did not differ among groups, but higher disrupted nocturnal sleep was observed in postvaccine subjects. Comparison of cataplexy features at video assessment showed an overlapping picture with the exception for hyperkinetic movements which appeared to be more evident in pre-H1N1 subjects.ConclusionsThe clinical picture of childhood NC was similar in postvaccine and pre-H1N1 children.     

Olfactory dysfunction in narcolepsy with and without cataplexy

BackgroundNot only patients in whom REM behavior disorder (RBD) is associated with narcolepsy, but also those with narcolepsy alone are reported to have olfactory dysfunction. We investigated if hyposmia is specific to narcolepsy with cataplexy (N–C) or if narcolepsy without cataplexy (NwC) is also associated with olfactory dysfunction.MethodsWe studied olfactory function in two groups of patients: N–C group (n = 66, 26 men and 40 women; mean age 41 ± 18 years), and NwC group (n = 17, 7 men and 10 women; mean age 46 ± 20 years). As a control group we used published normative data for particular smell tests.ResultsBoth patients with N–C and patients suffering from NwC had a significantly higher olfactory threshold (N–C group, p < 0.0001; NwC group, p < 0.0001) and impaired odor identification (N–C group, p < 0.0001; NwC group, p < 0.0001). Our results show for the first time that narcolepsy without cataplexy, where the majority of cases have normal CSF hypocretin levels, is associated with olfactory dysfunction.ConclusionsIt appears that also a partial loss of hypothalamic hypocretin neurons without a clear CSF level decrease can affect smell projection.     

Olfactory dysfunction in narcolepsy with cataplexy

BackgroundNarcolepsy–cataplexy (NC) is caused by the loss of hypocretin neurons. Several lines of evidence suggest a role for hypocretin in olfactory function. Recent data have documented that NC is associated with olfactory dysfunction but smell testing has been performed only in small studies.MethodsOne hundred thirty NC patients were recruited from two sleep disorders centers in France and Italy. They were compared to 129 age- and gender-matched healthy controls on two well standardized olfactory tests: the Sniffin’ Sticks (France) and Brief Smell Identification (Italy) tests. Olfactory dysfunction was defined as a score below the tenth centile on each smell test.ResultsAltogether, olfactory deficit was higher in NC compared to controls (23.8% vs. 13.9%, p = 0.042, OR: 1.93 CI 95%, 1.01–3.66); olfactory identification deficit was found in 35.8% of NC compared to 13.9% of controls in Italy (p = 0.03), and in 11.2% vs. 8.2% in France (NS). Using the Sniffin’ Sticks (France) we noted significant lower discrimination and global olfactory performance in NC compared to controls. Based on standardized criteria for Sniffin’ Sticks, none of the NC patients or controls presented anosmia or severe hyposmia, but 6.4% of the NC patients had moderate hyposmia and 22.2% mild, in contrast to 6.4% of controls with only mild hyposmia. Finally except tobacco smoking, clinical potential factors including age at onset and severity of the condition did not modify olfactory performances in the whole population.ConclusionOur study is the largest investigation of olfactory performance in NC showing that the disease perse is associated with mild/moderate dysfunction in a quarter of patients.     

Hippocampal volume and memory in narcoleptics with cataplexy

Background/ObjectiveThe objective of this study was to investigate the differences in hippocampal volume (HV) between narcoleptics and normal controls and determine if HV is associated with memory function in narcoleptics. Left and right HV and intracranial volumes (ICV) were manually measured and compared between two groups.MethodsThe study consisted of 36 drug-naïve narcoleptics with cataplexy and 36 age- and sex-matched controls (mean age 29.0 years). All subjects underwent 1.6-mm-thick spoiled gradient recalled magnetic resonance imaging and took the Korean California Verbal Learning Test and the Rey Complex Figure Test to assess verbal and visual memory.ResultsThe mean ICV was not different between groups (1599.2 cm³ in narcoleptics vs. 1623.5 cm³ in controls, p = .450). Bilateral mean HVs were significantly smaller in narcoleptics (left, 2907.2 mm³ in narcoleptics vs. 3092.3 mm³ in controls, p = 0.005; right, 2990.8 mm³ in narcoleptics vs. 3184.3 mm³ in controls, p = 0.004). Significance of HV differences between groups remained after corrections were made for gender, age, and ICV. In narcoleptics, bilateral HV was positively correlated with mean sleep and REM sleep latencies in Multiple Sleep Latency Tests. Absolute memory scores were not different between groups and were not correlated with HV in narcoleptics.ConclusionsNarcoleptics had smaller bilateral HVs compared to controls. HV had a significant relationship with sleep and REM sleep latencies. This study provides supportive evidence of the functional and anatomical deficits in medial temporal areas that are related to the severity of narcolepsy.     

The burden of narcolepsy with cataplexy: How disease history and clinical features influence socio-economic outcomes

ObjectiveTo investigate in narcolepsy with cataplexy (NC) patients of working age (18–65 years) the influence of age at onset, age at diagnosis and clinical features on socio-occupational conditions, disease-related economic burden, and quality of life.MethodsOne hundred consecutive patients underwent a semistructured interview on socio-occupational aspects, NC-related direct and indirect costs, and NC history. Questionnaires were used to evaluate excessive daytime sleepiness, cataplexy, depressive symptoms, and quality of life.ResultsNC patients (51 males, mean age 37 ± 11.5 years) had educational and occupational levels similar to those of the Italian population of the same age range, but married less often, especially if NC onset occurred at a young age. Total annual NC-related costs were €9814 ± 10,372 per patient. Multivariate analyses showed that patients with NC onset before the age of 30 years had a higher educational level, married less frequently, and were less frequently unemployed or inactive (retired, housewife). Patients diagnosed before the age of 30 years were less frequently unemployed or inactive, had fewer work changes, and had a better general health perception. Irresistible sleepiness was associated with work absences and higher indirect costs. Depressive symptoms were strongly associated with lower quality-of-life scores.ConclusionsNC age at onset and at diagnosis modulates the disease-related burden. A diagnosis at a young age could improve patients’ occupational prognosis, and their general health perception.     

Association of insomnia with mania in Lebanese patients with bipolar disorder

ObjectiveTo assess: (1) the association between insomnia experienced at admission, sociodemographic and other patients’ characteristics and mania; and (2) the variation of insomnia and mania before and after treatment in bipolar patients with manic episodes (type I).MethodsSixty-two patients were interviewed shortly after their admission to the hospital (after 3 to 5 days). The current symptoms experienced by the patients were assessed upon admission and again at discharge from the hospital.ResultsA poorer quality of sleep (higher PSQI scores) (Beta = 0.590) was significantly associated with higher mania, whereas the intake of SSRIs (Beta = ?5.952) and TCAs (Beta = ?8.181) was significantly associated with lower mania. Furthermore, highly significant reductions were reported in the PSQI scores (4.96 vs. 2.75, P < 0.001), ISI scores (8.30 vs. 3.45, P < 0.001) and YMRS scores (8.60 vs. 3.06, P < 0.001) between admission to and discharge from the hospital.ConclusionInsomnia in patients with bipolar disorder type I is associated with mania, with a significant reduction of sleep problems seen during a period of approximately 20 days of hospitalization. Further longitudinal studies are needed to confirm the validity of our results and identify the causes. In the meantime, this research recommends a strategy to improve sleeplessness experienced during inter-episode phases may be helpful in preventing manic episodes in BD.     

Sodium oxybate in the treatment of childhood narcolepsy-cataplexy: a retrospective study

ObjectiveTo evaluate the efficacy and side effect profile of sodium oxybate in the treatment for narcolepsy–cataplexy in the pediatric age group.MethodsA retrospective study was conducted on 15 children and adolescents with narcolepsy–cataplexy who had been treated with sodium oxybate. The mean age at diagnosis of narcolepsy was 11 years (range 3–17 years). Subjects were followed for 3–90 months (mean 33) after starting sodium oxybate. During this period of time they were also maintained on other medications for sleepiness (n = 14) and cataplexy (n = 6). The charts were reviewed for documentation of improvement in sleepiness or cataplexy, side effects, and functioning in daily life.ResultsSubsequent to the addition of sodium oxybate, sleepiness improved in 13/15 patients. In patients who had Epworth Sleepiness Scale (ESS) assessments, the score fell from a baseline median of 18 to 12 (n = 10, p = 0.01). The number of cataplexy episodes estimated by parents decreased from a median of 38/week pre-treatment to <1/week post treatment (n = 14, p < 0.001). Cataplexy severity, measured on an arbitrary scale, fell from a median of 3 (severe) to 1 (mild) in all 15 subjects (p < 0.001).Two of the 15 patients (13%) discontinued sodium oxybate, one for insurance reasons and the other due to constipation and dissociative feelings. A third patient stopped the medication temporarily due to body aches and dizziness, but then resumed treatment without recurrence of symptoms. Side effects in four others included tremor, blurring of vision, nocturnal awakenings, and increased nightmares. Overall, side effects occurred in 6/15 (40%) individuals. Improvement in social/academic spheres was noted in 11/15 (73%) subjects after starting sodium oxybate. The median BMI before and after treatment remained unchanged at 23 (n = 14, p = 0.99). Median values of height and weight before and after treatment also did not change significantly. The mean dose of sodium oxybate was 5 ± 2 g. Dose escalation owing to development of tolerance was not encountered.ConclusionsSodium oxybate is effective in alleviating sleepiness and cataplexy in childhood onset narcolepsy–cataplexy. The therapeutic response was sustained over time, and without development of tolerance. Forty percent of the subjects experienced adverse effects.     

Utilization patterns of antidepressants between 1991 and 2011 in a population-based cohort of middle-aged and elderly

BackgroundIn middle-aged and older patients in whom antidepressant use increased in last decades, patterns of use might be of concern The objective of this study was to investigate the patterns of prevalence, incidence and duration of antidepressant use in an ageing population.MethodsAll participants (aged > 45 years) from the population-based Rotterdam Study were followed from January 1st 1991 until death, loss to follow-up, or end of the study period (December 31st 2011). Antidepressant drug dispensing, based on pharmacy records, were subdivided into Tricyclic Antidepressants (TCAs), Selective Serotonin Reuptake Inhibitors (SSRIs) and other antidepressants. One-year prevalence, 5-year incidence and duration of antidepressant use were calculated.ResultsYearly prevalence of antidepressant use increased from 3.9% in 1991 to 8.3% of the population in 2011. The increase in SSRI use was 5.8-fold, whereas use of other antidepressants doubled and TCA use remained stable over time. Incidence of all antidepressants decreased from 23.9 to 14.2 per 1000 person-years between 1992 and 2011. The duration of a first treatment episode increased over time.ConclusionDespite the prevalence of antidepressant use increased over time, incidence did not, which is most likely explained by a longer treatment duration and recurrent episodes.     

Association analysis of the major histocompatibility complex,class II,DQ β1 gene,HLA-DQB1, with narcolepsy in Han Chinese patients from Taiwan

BackgroundNarcolepsy is a rare, chronic, disabling neuropsychiatric disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and abnormal rapid eye movement sleep. It is strongly associated with the HLA-DQB1¹06:02 allele in various ethnic groups. Our study aimed to investigate the allelic spectrum of HLA-DQB1 in a sample of Han Chinese patients with narcolepsy and control subjects from Taiwan.MethodsWe determined the genotype of the major histocompatibility complex, class II, DQ β1 gene, HLA-DQB1, in 72 narcolepsy subjects (44 men, 28 women), including 52 narcolepsy subjects with cataplexy (narcolepsy + cataplexy), 20 narcolepsy subjects without cataplexy (narcolepsy–cataplexy), and 194 control subjects (94 men, 100 women) using a sequence-specific oligonucleotide-probe hybridization technique.ResultsWe found a strong HLA-DQB1¹06:02 association in narcolepsy + cataplexy subjects (odds ratio [OR], 321.4 [95% confidence interval {CI}, 70.7–1461.4]). The association was less prominent in narcolepsy–cataplexy subjects (OR, 6.9 [95% CI, 2.4–20.1]). In addition to the DQB1¹06:02, we found that ¹03:01 also was a predisposing allele (OR, 2.0 [95% CI, 1.1–3.7]) in narcolepsy + cataplexy subjects, though the ¹06:01 was a predisposing allele (OR, 2.8 [95% CI, 1.2–6.7]) in narcolepsy–cataplexy subjects. Furthermore, we found a significant overrepresentation of DQB1¹06:02 homozygotes in narcolepsy + cataplexy subjects.ConclusionsOur data add further support to the strong association of the HLA-DQB1¹06:02 allele with narcolepsy, especially in narcolepsy + cataplexy patients. Our study also indicates additional HLA-DQB1 alleles may modify the presentation of narcolepsy + cataplexy patients, such as DQB1¹03:01 and DQB1¹06:01 in our study. Our results are limited by the small sample size and can only be considered as preliminary findings.     

Mazindol in narcolepsy and idiopathic and symptomatic hypersomnia refractory to stimulants: A long-term chart review

ObjectiveMazindol is a tricyclic, anorectic, non-amphetamine stimulant used in narcolepsy and obesity since 1970. This study aimed to evaluate the long-term benefit/risk ratio in drug-resistant hypersomniacs and cataplexy sufferers.MethodsBy retrospective analysis of the patients’ files in the hospitals of Paris-Salpêtrière (n = 91), Montpellier (n = 40) and Lyon (n = 8), the benefit (Epworth Sleepiness Score (ESS), cataplexy frequency, authorization renewal) and tolerance (side-effects, vital signs, electrocardiogram and cardiac echography) of mazindol were assessed.ResultsThe 139 patients (45% men) aged 36 ± 15 years (range: 9–74) suffered narcolepsy (n = 94, 66% with cataplexy), idiopathic (n = 37) and symptomatic hypersomnia (n = 8) refractory to modafinil, methylphenidate and sodium oxybate. Under mazindol (3.4 ± 1.3 mg/day, 1–6 mg) for an average of 30 months, the ESS decreased from 17.7 ± 3.5 to 12.8 ± 5.1, with an average fall of −4.6 ± 4.7 (p < 0.0001) and the frequency of cataplexy fell from 4.6 ± 3.1 to 2 ± 2.8 episodes per week. The cataplexy was eliminated in 14.5% of patients, improved in 27.5%, and unchanged in 29% (missing data in 29%). The treatment was maintained long term in 83 (60%) patients, and stopped because of a lack of efficacy (22%) and/or secondary effects (9%). There was no pulmonary hypertension in the 45 patients who underwent a cardiac echography. The most common adverse effects were dry mouth (13%), palpitations (10%, including one with ventricular hyperexcitability), anorexia (6%), nervousness (6%) and headaches (6%).ConclusionMazindol has a long-term, favorable benefit/risk ratio in 60% of drug-resistant hypersomniacs, including a clear benefit on cataplexy.     

Salivary testosterone: associations with depression, anxiety disorders, and antidepressant use in a large cohort study

ObjectiveLow circulating levels of testosterone have been associated with major depression, but there is more limited evidence for differences in patients with anxiety disorders. The use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressants is associated with sexual side effects, warranting testing for interactions with testosterone.MethodsData are from 722 male and 1380 female participants of The Netherlands Study of Depression and Anxiety (NESDA), who were recruited from the community, general practice care, and specialized mental health care. Depressive and anxiety diagnoses were assessed using the DSM-IV Composite International Diagnostic Interview. To smooth the episodic secretion, the four morning saliva samples per participant and the two evening samples were pooled before testosterone analysis.ResultsMorning median testosterone levels were 25.2 pg/ml in men and 16.2 pg/ml in women, with lower evening levels of 18.2 and 14.1 pg/ml, respectively. Significant determinants of testosterone levels were sex, age, time of the day, use of contraceptives, and smoking status. Female patients with a current (1-month) depressive disorder (effect size 0.29; P = 0.002), generalized anxiety disorder (0.25; P = 0.01), social phobia (0.30; P < 0.001), and agoraphobia without panic disorder (0.30; P = 0.02) had lower salivary testosterone levels than female controls. Higher testosterone levels were found in male and female participants using SSRIs than in non-users (effect size 0.26; P < 0.001).ConclusionSalivary testosterone levels are lower in female patients with a depressive disorder, generalized anxiety disorder, social phobia, and agoraphobia as compared to female controls. SSRIs may increase salivary testosterone in men and women.     

The effect of modafinil on cortical excitability in patients with narcolepsy: A randomized,placebo-controlled,crossover study

ObjectiveTo investigate the effect of modafinil on cortical excitability in patients with narcolepsy using transcranial magnetic stimulation (TMS).MethodsNineteen drug-naïve narcolepsy patients with cataplexy (10 males, 9 females, and mean age 28.5 years) and 25 age- and sex-matched healthy controls were recruited. In this double-blind, randomized, crossover study, patients and controls received a single dose of 400 mg modafinil or placebo. Modafinil and placebo administrations were separated by a 2-week washout period. TMS parameters, such as resting motor thresholds (RMT), motor-evoked potential (MEP) amplitudes, cortical silent periods (CSP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF), were measured before and 3 h after administering modafinil or placebo. The differences of TMS parameters were statistically tested between patients and controls and between before and after modafinil or placebo administration.ResultsNarcolepsy patients had significantly increased CSP durations compared to controls (independent t-test, P < 0.05), indicating decreased excitability of cortical networks in human narcolepsy. In patients after modafinil administration, MEP amplitudes, SICI, and ICF increased, and CSP duration shortened significantly, meaning enhanced motor excitability, whereas in controls modafinil did not change TMS parameters significantly. Placebo administration did not affect TMS parameters both in patients or controls.ConclusionsNarcolepsy patients with cataplexy showed decreased cortical excitability than normal healthy controls. Single dose modafinil significantly increased motor excitability in narcolepsy patients but had no effect in healthy controls.     

REM sleep behavior disorder in 703 sleep-disorder patients: The importance of eliciting a comprehensive sleep history

ObjectivesThe aim of our study was to evaluate the frequency of REM sleep behavior disorder (RBD) in a mixed sleep laboratory population and to assess potential associations. Moreover, we investigated referral diagnoses of patients subsequently diagnosed with RBD and assessed the frequency of incidental RBD.MethodsCharts and polysomnographic reports of 703 consecutive patients comprising the full spectrum of ICSD-2 sleep disorders [501 males, 202 females; mean age, 51.0 ± 14.1 years (range: 10–82 years)] were carefully reviewed. The vast majority of patients were adults (98.7%). Patients were categorized into those with and without RBD. For associations, all concomitant sleep and neurological diagnoses and medications were evaluated.ResultsThirty-four patients (4.8%) were diagnosed with RBD (27 men; 7 women, mean age, 57.7 ± 12.3 years). RBD was idiopathic in 11 patients (1.6%; 9 men) and symptomatic in 23 patients (3.3%; 18 men) secondary to Parkinsonian syndromes (n = 11), use of antidepressants (n = 7), narcolepsy with cataplexy (n = 4), and pontine infarction (n = 1). Six out of 34 patients were referred for suspected RBD, 20 reported RBD symptoms only on specific questioning, and 8 patients had no history of RBD but showed typical RBD behavioral manifestations in the video-polysomnography. Logistic regression analysis revealed significant associations between RBD and the presence of Parkinsonian syndromes (odds ratio [OR] 16.8, 95%CI: 6.4–44.1; P < 0.001), narcolepsy with cataplexy (OR 10.7, 95%CI: 2.9–40.2; P < 0.001), SSRI use (OR 3.9, 95%CI: 1.6–9.8; P = 0.003), and age (OR 1.5/10-year increase, 95%CI: 1.0–2.0; P = 0.039).ConclusionIn this population of 703 consecutive sleep-disorder patients, RBD was uncommon. Its etiology was predominantly symptomatic. The majority of RBD patients reported RBD symptoms on specific questioning only, underlining the importance of eliciting a comprehensive sleep history for the diagnosis of RBD.     

Evaluating the safety and efficacy of felbamate in the context of a black box warning: A single center experience

IntroductionFelbamate was approved in 1993 to treat partial seizures with and without secondary generalization in adults and in Lennox–Gastaut Syndrome in children. Its use was later restricted when rare but fatal cases of aplastic anemia and hepatic failure were identified.MethodsThis single center analysis retrospectively evaluated the safety and efficacy of felbamate in a cohort of children, adolescents, and adults with epilepsy.ResultsA chart review identified 103 patients taking felbamate. The range of felbamate dose was 300–4500 mg (mean: 1800 ± 900 mg). The duration of therapy ranged from 1 month to 20 years (mean duration: 35 ± 45 months). Eighteen (17.5%) subjects experienced adverse events including insomnia, nausea, vomiting, decreased appetite, weight loss, gastric discomfort, diarrhea, mood and behavioral problems, high blood pressure, headache, and elevated liver enzymes. Out of these, 6 (5.9%) patients discontinued the therapy. No hepatic failure or agranulocytosis was observed. Fifty-nine (57.72%) patients achieved ≥ 50% reduction in seizure frequency, and 30 (29.12%) patients achieved seizure freedom.ConclusionsThese findings suggest that felbamate is safe, well tolerated, and effective in treatment of various types of epilepsy syndromes.     

Hypocretin (orexin) neuropeptide precursor gene,HCRT, polymorphisms in early-onset narcolepsy with cataplexy

BackgroundTo test if the hypocretin (orexin) neuropeptide precursor (HCRT) gene, HCRT, mutations are implicated in the development of narcolepsy with cataplexy deficiency in young children.MethodsThe entire HCRT gene and ∼2000 bp promoter region was first sequenced in 181 patients and 153 controls, and rare polymorphisms including three nonsynonymous amino acid changes were identified. Next the 557 bp region of exon 2 harboring the three nonsynonymous changes was sequenced in an additional 298 early-onset subjects and in 148 control samples.ResultsA previously known common polymorphism (rs760282) and nine rare novel polymorphisms were identified in subjects and controls without significant differences. Two nonsynonymous exon 2 substitutions (+977 H54A, +979 G55R) were detected in two subjects with early onset at 7 and 6 years, respectively, but were not found in any controls. These substitutions are not likely to vastly change peptide binding to hypocretin receptors. One additional exon 2 substitution (+1019, K68R) was found in two patients and one control. Additional sequencing that focused on exon 2 showed additional subjects and controls with the +1019 K68R polymorphism and without significant differences between the subjects and the control. Segregation of two of these three nonsynonymous single nucleotide polymorphisms (SNPs) were observed from unaffected parents to offspring.ConclusionsSequencing of a large number of early-onset narcolepsy subjects revealed three novel nonsynonymous substitutions within the preprohypocretin protein, two of which were only found in patients with early-onset narcolepsy but are not likely to be functionally significant, especially in heterozygote subjects.     

Sertraline and periodic limb movements during sleep: an 8-week open-label study in depressed patients with insomnia

BackgroundPrevious studies have reported that selective serotonin reuptake inhibitors (SSRIs) might induce or exacerbate periodic limb movements during sleep (PLMS). However, most of these studies were retrospective and cross-sectional studies with small sample sizes on a selective SSRI, fluoxetine. Because different SSRIs have different pharmacologic profiles, it was not certain if other SSRIs also might lead to PLMS.MethodsData were taken from an open-label 8-week trial of sertraline in depressive patients with insomnia (n = 31). Depressed patients were administered sertraline 50 mg at 8:00 am on the first day, and the dosage was subsequently titrated up to a maximum of 200 mg daily during the 8-week trial. All participants were tested by repeated polysomnography (PSG) (baseline, first day, 14th day, 28th day, and 56th day). Periodic leg movements (PLM) were visually counted and the PLM index (PLMI) was calculated. PLMS was defined as PLMI ⩾5, and significant PLMS was defined as PLMI ⩾15.ResultsCompared with baseline (PLMI, 3.6 ± 1.5), all PLMI indices increased on the immediate administration of sertraline on the first day (PLMI, 5.1 ± 3.9). From the 14th day onward, PLMI became stable and significantly higher than baseline and the first day (8.7 ± 3.1 on the 14th day, 8.3 ± 3.7 on the 28th day, and 8.5 ± 3.6 on the 56th day; F[11.81]; P = .003). The clinical responses and PSG characteristics continuously improved during the 8-week trial. The PLMS group (PLMI ⩾5) had a higher arousal index (AI) than the non-PLMS group on the 14th day (9.4 ± 5.5 vs 5.2 ± 3.7; t test, 4.22; P = .03) and the 56th day (8.1 ± 5.5 vs 4.3 ± 3.7; z score, 3.11; P = .04); albeit, there was no significant clinical disturbances in the PLMS group.ConclusionsPLMS were increased during sertraline treatment, but only a few of the PLMS reached the significant level. This effect of sertraline on PLMS might be dosage dependent. Although the sertraline-induced PLMS did not seem to cause significant clinical disturbance, the PLMS group (PLMI ⩾5) had a higher AI than the non-PLMS group. Thus clinicians should pay more attention to PLMS during SSRI antidepressant treatment.     

Evaluation of levetiracetam and valproic acid as low-dose monotherapies for children with typical benign childhood epilepsy with centrotemporal spikes (BECTS)

PurposeThis study aimed to compare the monotherapeutic efficacies of levetiracetam (LEV) and valproic acid (VPA) in a cohort of newly diagnosed children with typical benign childhood epilepsy with centrotemporal spikes (BECTS).MethodsA total of 56 children with typical BECTS were retrospectively reviewed in the analyses. Thirty-three children received LEV and 23 received VPA as initial monotherapy, and the treatments lasted for at least 18 months.ResultsThe average dosage of LEV was 22.7 ± 4.7 mg/kg/day, and that of VPA was 18.7 ± 5.7 mg/kg/day. The seizure-freedom rates were not significantly different between the two groups at 6 (57.5% vs. 60.9%), 12 (81.8% vs. 73.9%) or 18 months (100% vs. 100%). However, a greater number of the children taking VPA achieved Electroencephalography (EEG) normalization compared to those taking LEV both at 12 (78.3% vs. 45.5%) and 18 months (95.7% vs. 72.7%; p < 0.05). No children discontinued therapy due to adverse effects during the follow-up. Only one child (4.7%) in the VPA group exhibited mild weight gain (BMI increase of 2 at the end of follow-up) but did not withdraw from treatment.ConclusionLow-dosage VPA and LEV monotherapies are equally effective in controlling seizures, but VPA exhibited better efficacy than LEV in improving the electrophysiological abnormalities of children with BECTS. None of the patients discontinued therapy, which was likely due to the administration of low dosages.     

Patterns of caffeine consumption in psychiatric patients. An Italian study

PurposeThe aim of the present study was to explore and compare the caffeine intake, intoxication, withdrawal and dependence prevalence in Italian psychiatric patients and healthy subjects.Materials and methodsThree hundred and sixty-nine out- and inpatients, suffering from different psychiatric disorders, and 104 healthy subjects were included in the study. They were assessed by the SCID and by a structured interview for caffeine intoxication and withdrawal and for substance dependence applied to caffeine use.ResultsPatients and healthy subjects did not differ in terms of current caffeine intake (mg/day, mean ± SD: 281 ± 325 vs. 288 ± 148, respectively), while the maximum lifetime intake of caffeine was significantly higher in the first group (mg/day, mean SD: 630 ± 549 vs. 504 ± 344, respectively; F = 4.897, p = .03) where it was significantly related to the CGI severity item scores (rho = .107; p = .04). In both patients and healthy subjects, a lower age was related to a higher current caffeine intake, while both current and maximum lifetime caffeine intake in the healthy subjects were significantly higher in men than in women. The patients suffering from eating disorders reported higher current caffeine intake than those with anxiety or mood disorders. The prevalence of dependence and intoxication was significantly higher in the patients than in the healthy subjects, without inter-group differences. Healthy subjects showed a trend towards a higher prevalence of withdrawal.ConclusionsOur study highlights the need that a more accurate attention should be paid to the caffeine use which seems to be strongly, although generically, related to different psychiatric disorders.     

The relationship between psychotic-like experiences and sleep disturbances in adolescents

ObjectiveWe investigated the relationships between sleep disturbances and psychotic-like experiences (PLEs) among adolescents.MethodsA total of 8530 students (grades 7–11) were recruited in the Republic of Korea, and 7172 students who completed all of the relevant questionnaires participated in the current study. The survey included the Eppendorf Schizophrenia Inventory (ESI), the Youth Psychosis At Risk Questionnaire (Y-PARQ), the Beck Depression Inventory (BDI), the Epworth Sleepiness Scale and questionnaires about sleep disturbances (insomnia, cataplexy and snoring).ResultsSubjects with insomnia, excessive daytime somnolence (EDS), or probable cataplexy had higher ESI and Y-PARQ scores after controlling for age, sex and BDI scores (all p < 0.001). Insomnia (OR = 4.40), EDS (OR = 3.84) and probable cataplexy (OR = 2.97) predicted clinical high risk of psychosis. Insomnia, EDS and probable cataplexy remained as significant predictors of clinical high risk for psychosis, even after controlling for depressive symptoms or when analyses were confined to non-depressive adolescents.ConclusionsInsomnia and EDS were found to predict PLEs in adolescents, independent of depression. Our findings suggest that adolescents complaining of insomnia or sleepiness may require further assessment regarding potential risk of psychosis.