The Dutch list of essential drugs for undergraduate medical education: A modified Delphi study.

AIMS: Prescribing errors among junior doctors are common in clinical practice because many lack prescribing competence after graduation. This is in part due to inadequate education in clinical pharmacology and therapeutics (CP&T) in the undergraduate medical curriculum. To support CP&T education, it is important to determine which drugs medical undergraduates should be able to prescribe safely and effectively without direct supervision by the time they graduate. Currently, there is no such list with broad-based consensus. Therefore, the aim was to reach consensus on a list of essential drugs for undergraduate medical education in the Netherlands. METHODS: A two-round modified Delphi study was conducted among pharmacists, medical specialists, junior doctors and pharmacotherapy teachers from all eight Dutch academic hospitals. Participants were asked to indicate whether it was essential that medical graduates could prescribe specific drugs included on a preliminary list. Drugs for which ≥80% of all respondents agreed or strongly agreed were included in the final list. RESULTS: In all, 42 (65%) participants completed the two Delphi rounds. A total of 132 drugs (39%) from the preliminary list and two (3%) newly proposed drugs were included. CONCLUSIONS: This is the first Delphi consensus study to identify the drugs that Dutch junior doctors should be able to prescribe safely and effectively without direct supervision. This list can be used to harmonize and support the teaching and assessment of CP&T. Moreover, this study shows that a Delphi method is suitable to reach consensus on such a list, and could be used for a European list.

The impact of a summative national prescribing assessment and curriculum type on the development of the prescribing competence of junior doctors.

PURPOSE: The primary aim of this study was to investigate the effect of including the Dutch National Pharmacotherapy Assessment (DNPA) in the medical curriculum on the level and development of prescribing knowledge and skills of junior doctors. The secondary aim was to evaluate the relationship between the curriculum type and the prescribing competence of junior doctors. METHODS: We re-analysed the data of a longitudinal study conducted in 2016 involving recently graduated junior doctors from 11 medical schools across the Netherlands and Belgium. Participants completed three assessments during the first year after graduation (around graduation (+ / - 4 weeks), and 6 months, and 1 year after graduation), each of which contained 35 multiple choice questions (MCQs) assessing knowledge and three clinical case scenarios assessing skills. Only one medical school used the DNPA in its medical curriculum; the other medical schools used conventional means to assess prescribing knowledge and skills. Five medical schools were classified as providing solely theoretical clinical pharmacology and therapeutics (CPT) education; the others provided both theoretical and practical CPT education (mixed curriculum). RESULTS: Of the 1584 invited junior doctors, 556 (35.1%) participated, 326 (58.6%) completed the MCQs and 325 (58.5%) the clinical case scenarios in all three assessments. Junior doctors whose medical curriculum included the DNPA had higher knowledge scores than other junior doctors (76.7% [SD 12.5] vs. 67.8% [SD 12.6], 81.8% [SD 11.1] vs. 76.1% [SD 11.1], 77.0% [12.1] vs. 70.6% [SD 14.0], p < 0.05 for all three assessments, respectively). There was no difference in skills scores at the moment of graduation (p = 0.110), but after 6 and 12 months junior doctors whose medical curriculum included the DNPA had higher skills scores (both p < 0.001). Junior doctors educated with a mixed curriculum had significantly higher scores for both knowledge and skills than did junior doctors educated with a theoretical curriculum (p < 0.05 in all assessments). CONCLUSION: Our findings suggest that the inclusion of the knowledge focused DNPA in the medical curriculum improves the prescribing knowledge, but not the skills, of junior doctors at the moment of graduation. However, after 6 and 12 months, both the knowledge and skills were higher in the junior doctors whose medical curriculum included the DNPA. A curriculum that provides both theoretical and practical education seems to improve both prescribing knowledge and skills relative to a solely theoretical curriculum.

Do we become better prescribers after graduation: A 1-year international follow-up study among junior doctors.

AIM: The aim of this study was to investigate how the prescribing knowledge and skills of junior doctors in the Netherlands and Belgium develop in the year after graduation. We also analysed differences in knowledge and skills between surgical and nonsurgical junior doctors. METHODS: This international, multicentre (n = 11), longitudinal study analysed the learning curves of junior doctors working in various specialties via three validated assessments at about the time of graduation, and 6 months and 1 year after graduation. Each assessment contained 35 multiple choice questions (MCQs) on medication safety (passing grade ≥85%) and three clinical scenarios. RESULTS: In total, 556 junior doctors participated, 326 (58.6%) of whom completed the MCQs and 325 (58.5%) the clinical case scenarios of all three assessments. Mean prescribing knowledge was stable in the year after graduation, with 69% (SD 13) correctly answering questions at assessment 1 and 71% (SD 14) at assessment 3, whereas prescribing skills decreased: 63% of treatment plans were considered adequate at assessment 1 but only 40% at assessment 3 (P < .001). While nonsurgical doctors had similar learning curves for knowledge and skills as surgical doctors (P = .53 and P = .56 respectively), their overall level was higher at all three assessments (all P < .05). CONCLUSION: These results show that junior doctors' prescribing knowledge and skills did not improve while they were working in clinical practice. Moreover, their level was under the predefined passing grade. As this might adversely affect patient safety, educational interventions should be introduced to improve the prescribing competence of junior doctors.

Impaired Sensorimotor Adaption in Schizophrenia in Comparison to Age-Matched and Elderly Controls.

BACKGROUND: The "cognitive dysmetria hypothesis" of schizophrenia proposes a disrupted communication between the cerebellum and cerebral cortex, resulting in sensorimotor and cognitive symptoms. Sensorimotor adaptation relies strongly on the function of the cerebellum. OBJECTIVES: This study investigated whether sensorimotor adaptation is reduced in schizophrenia compared with age-matched and elderly healthy controls. METHODS: Twenty-nine stably treated patients with schizophrenia, 30 age-matched, and 30 elderly controls were tested in three motor adaptation tasks in which visual movement feedback was unexpectedly altered. In the "rotation adaptation task" the perturbation consisted of a rotation (30° clockwise), in the "gain adaptation task" the extent of the movement feedback was reduced (by a factor of 0.7) and in the "vertical reversal task," up- and downward pen movements were reversed by 180°. RESULTS: Patients with schizophrenia adapted to the perturbations, but their movement times and errors were substantially larger than controls. Unexpectedly, the magnitude of adaptation was significantly smaller in schizophrenia than elderly participants. The impairment already occurred during the first adaptation trials, pointing to a decline in explicit strategy use. Additionally, post-adaptation aftereffects provided strong evidence for impaired implicit adaptation learning. Both negative and positive schizophrenia symptom severities were correlated with indices of the amount of adaptation and its aftereffects. CONCLUSIONS: Both explicit and implicit components of sensorimotor adaptation learning were reduced in patients with schizophrenia, adding to the evidence for a role of the cerebellum in the pathophysiology of schizophrenia. Elderly individuals outperformed schizophrenia patients in the adaptation learning tasks.

Serotonin transporter availability, neurocognitive function and their correlation in abstinent 3,4-methylenedioxymethamphetamine users.

RATIONALE: MDMA or Ecstasy has made a resurgence in popularity and the majority of users consist of teenagers and adolescents. Therefore, it is important to determine whether MDMA causes long-term damage and what this damage entails. There is an ongoing debate about possible neurocognitive changes in 3,4-methylenedioxymethamphetamine (MDMA) users related to MDMA's neurotoxic potential. Multiple neuroimaging studies have shown that Ecstasy use leads to lower serotonin transporter (SERT) availability in multiple brain regions. This may express itself in a loss of cognitive functions like memory, attention and executive function. However, there is increasing evidence reporting that MDMA's induced serotonergic adaptations are reversible over time. The question we thus address is whether the recovery of SERT function predicts a recovery of cognitive function. OBJECTIVES: This review aims to investigate MDMA's long-term effects on SERT availability and cognitive functioning. METHODS: A literature search was performed in PubMed. Studies that investigated the effects of MDMA on both SERT availability and cognitive performance were eligible for inclusion. RESULTS: SERT availability positively correlated with time of abstinence, whereas memory performance did not show this correlation, but remained impaired in MDMA users. No significant correlation between SERT availability and memory function was found (r = 0.232, p = 0.581; r = 0.176, p = 0.677). CONCLUSIONS: The main findings of this review are that MDMA-use leads to an acute decrease in SERT availability and causes an impairment in cognitive functions, mostly memory. However, SERT availability recovers with sustained abstinence while memory function does not. This suggests that SERT availability is not a biomarker for MDMA-induced cognitive impairment and likely also not for MDMA-induced neurotoxicity.

Differential Effects of Inflammatory and Psychosocial Stress on Mood, Hypothalamic-Pituitary-Adrenal Axis, and Inflammation in Remitted Depression.

BACKGROUND/AIMS: Major depressive disorder (MDD) is highly recurrent. This may be due to increased stress sensitivity after remission. Both inflammatory and psychosocial stressors are implicated in the pathogenesis of MDD, but the additive or differential effect is unclear. METHODS: We conducted a single-blind placebo-controlled study to investigate the effects of inflammatory stress (i.e., typhoid vaccination), psychosocial stress (i.e., Trier Social Stress Test [TSST]), or a combination of both in women (25-45 years old) with (partially) remitted recurrent MDD (n = 21) and healthy female controls (n = 18). We evaluated the effect on mood measured by the Profile of Mood States, markers of the hypothalamic-pituitary-adrenal (HPA) axis activity, and inflammatory system activation. The study was performed during 2 testing days, separated by a washout of 7-14 days. In a crossover design, subjects received one of the interventions on one day and placebo on the other. RESULTS: A lowering of mood was seen in patients (ß [95% CI] = -4.79 [-6.82 to -2.75], p < 0.001) only after vaccination, but not after the TSST or the combination; this effect was not observed in controls. Controls experienced a significantly different response on adrenocorticotropic hormone (ACTH) after vaccination, with a general rise in ACTH not observed in patients. In both groups, the TSST activated the HPA axis and suppressed the inflammatory parameters. CONCLUSIONS: There is a differential effect of inflammatory and psychosocial stress on mood and HPA axis activation in patients with remitted recurrent MDD. This may be an interesting treatment target in MDD.

Implicit motor sequence learning in schizophrenia and in old age: reduced performance only in the third session.

Although there still is conflicting evidence whether schizophrenia is a neurodegenerative disease, cognitive changes in schizophrenia resemble those observed during normal aging. In contrast to extensively demonstrated deficits in explicit learning, it remains unclear whether implicit sequence learning is impaired in schizophrenia and normal aging. Implicit sequence learning was investigated using a computerized drawing task, the 'implicit pattern learning task (IPLT)' in 30 stable patients with schizophrenia, 30 age-matched controls and 30 elderly subjects on two consecutive days and after 1 week (sessions 1, 2 and 3). Fixed sequence trials were intermixed with random trials, and sequence learning was assessed by subtraction of the response time in fixed sequence trials from random trials. Separate analyses of response times and movement accuracy (i.e., directional errors) were performed. Explicit sequence knowledge was assessed using three different awareness tasks. All groups learned equally during sessions 1 and 2. In session 3, control subjects showed significantly larger learning scores than patients with schizophrenia (p = .012) and elderly subjects (p = .021). This group difference is mainly expressed in movement time and directional errors. Patients with schizophrenia demonstrated less subjective sequence awareness, and both patients with schizophrenia and elderly subjects had less explicit sequence recall. Explicit recall was positively correlated with task performance in all groups. After a short 24 h interval, all subjects showed similar improvements in implicit sequence learning. However, no benefit of prior task exposure 1 week later was observed in patients with schizophrenia and elderly subjects compared to controls. As patients with schizophrenia and elderly both display less explicit sequence recall, the control group superiority after 1 week could be explained by an explicit learning component. The few patients with schizophrenia and elderly subjects who had some sequence recall could possibly utilize this explicit knowledge to improve their task performance but did this by distinct mechanisms.

Antidepressants and the risk of hyponatremia: a class-by-class review of literature.

BACKGROUND: Antidepressant-induced hyponatremia can cause significant morbidity and mortality. It is mostly associated with the use of selective serotonin reuptake inhibitors (SSRIs), but its frequency and class specificity are uncertain. OBJECTIVES: To determine the relationship between hyponatremia and antidepressants and to define the incidence and odds ratios for antidepressant classes. METHODS: A review of the literature prior to March 2013 was performed using Web of Science and PubMed by employing combinations of search strings "antidepressants" and antidepressant class and generic drug names with "hyponatr(a)emia," "SIADH," or "inappropriate ADH." RESULTS: Overall, 21 effect studies and more than 100 case reports were considered, most concerning SSRIs. Because of variations in study designs, populations, and cutoff values, incidence rates diverged between 0.06% and 40% for SSRIs and 0.08% and 70% for venlafaxine. Although based on less solid evidence, incidence figures for mirtazapine and tricyclic antidepressants were lower. Regarding classes, odds ratios for SSRIs (1.5-21.6) were consistently higher than for tricyclic antidepressants (TCAs) (1.1-4.9). The risks associated with monoamine oxidase inhibitors, reboxetine, and bupropion could not be established owing to insufficient information. Patient risk factors included older age (odds ratios = 6.3) and concomitant use of (thiazide) diuretics (odds ratios = 11.2-13.5). CONCLUSION: Hyponatremia is a potentially dangerous side effect of antidepressants and is not exclusive to SSRIs. Current evidence suggests a relatively higher risk of hyponatremia with SSRIs and venlafaxine, especially when combined with patient risk factors, warranting clinicians to be aware of this complication. The risks associated with mirtazapine are moderate, supporting this antidepressant as an alternative treatment for patients with (an increased risk of) hyponatremia.

Absent or Hidden? Hyperactivity in Females With ADHD.

OBJECTIVE: This study aimed to objectively assess signs of hyperactivity in adults suspected of having ADHD, addressing potential sex bias in diagnosis. METHODS: About 13,179 (49% female) adults with an average age of 33 years with ADHD and 1,910 (41% female) adults with an average age of 36 years without ADHD were included. Motor activity was measured using the Quantified Behavioral Test, analyzing "provoked," and "basal" activity. Sex by group differences were analyzed using analysis of variance. RESULTS: Results showed significant ADHD effects on the basal and provoked activity measures, while sex effects were only notable for provoked activity. Males, irrespective of diagnosis, exhibited higher provoked activity than females, while both sexes with ADHD displayed approximately twice the basal activity and about three times the provoked activity compared to their respective sex controls. CONCLUSION: These findings suggest that females with ADHD suffer equally from hyperactivity compared to males, challenging the notion of a sex-dependent presentation of hyperactivity. This may lead to more accurate and timely diagnoses, reducing ADHD-related burdens and comorbidities in females.

[Oxytocin for the treatment of PTSD?] / Oxytocine voor de behandeling van PTSS?

Oxytocin is mostly known for its pro-social effects and may increase positive emotions, and as such may be a relevant treatment option for PTSD. Although oxytocin indeed showed some alleviating effects on PTSD in the study by Koch et al., effects were small and the clinical significance of these findings remains to be determined.

Digging deeper in the differential effects of inflammatory and psychosocial stressors in remitted depression: Effects on cognitive functioning.

BACKGROUND: Major Depressive Disorder (MDD) covers a wide spectrum of symptoms, including cognitive dysfunction, which can persist during remission. Both inflammatory states and psychosocial stress play a role in MDD pathogenesis. METHODS: The effects of inflammatory (i.e., Salmonella typhi vaccine) and psychosocial stressor (i.e., Trier Social Stress Test), as well as their combination were investigated on cognition in women (aged 25-45 years, n = 21) with (partially) remitted MDD and healthy controls (n = 18) in a single-blind placebo-controlled study. In a crossover design, patients received on the first day one of the aforementioned interventions and on the other day a placebo, or vice versa, with a washout period of 7-14 days. Short-term and verbal memory, working memory, attention, verbal fluency, information processing speed, psychomotor function, and measures of attentional bias to emotions were measured. Exploratory analyses were performed to assess the correlation between biomarkers of inflammation and the Hypothalamic-Pituitary-Adrenal axis and cognitive functioning. RESULTS: In patients, inflammatory stress decreased information processing speed and verbal memory, and increased working memory; after psychosocial stress, there was an increase in attention. There was also an increased negative attentional bias in patients after inflammatory stress. Neither stressor had any effect in controls. LIMITIATIONS: Limitations are the relatively small sample size and antidepressant use by a part of the participants. The effects of the stressors were also measured a relatively short period after administration. CONCULSION: Patients were sensitive to the cognitive effects of inflammation and psychosocial stress on cognition, while controls were not.

A comparative study of two methods for attaining constant alcohol levels.

AIMS: Alcohol effects or drug-alcohol interactions are preferably studied at constant blood levels. To achieve pseudo-steady state levels, various methods are used, which usually produce adequate averages but variable individual concentration profiles. The aim was to compare two modes of alcohol administration: a 'two-step prekinetic procedure' and a 'clamping method'. METHODS: The two-step prekinetic procedure started with determination of individual pharmacokinetic (PK) parameters, during a prestudy occasion. Individual infusion regimens were calculated afterwards, based on a pseudo-steady state breath alcohol concentration (BrAC) of 0.65 g l(-1) and applied on a separate occasion. For the clamping procedure, a spreadsheet-based paradigm was developed using BrAC-guided adjustments of infusion rates, to maintain stable BrAC levels of 0.6 g l(-1). RESULTS: The mean BrAC during clamping [0.61 g l(-1), 95% confidence interval (CI) 0.58, 0.63] did not differ from its intended level of 0.6 g l(-1) (1.0% on average). In contrast, the mean BrAC during the prekinetic procedure was significantly lower than the 0.65 g l(-1) set-point (0.59 g l(-1), 95% CI 0.54, 0.63) and deviated from this target by 9.7% on average. The clamping method also showed less variation between subjects [coefficient of variation (CV) 6.2%] compared with the prekinetic procedure (CV 14.6%). CONCLUSIONS: Although the two methods differ considerably in their approach, clamping of BrAC resulted in more accurate alcohol levels than infusion based on PK modelling and does not require an extra prestudy occasion. The novel alcohol clamping paradigm can be of value in future studies of alcohol interactions or the pharmacodynamics of acute alcohol administration.

A case of dose escalation of quetiapine in persistent insomnia disorder.

Quetiapine, an atypical antipsychotic drug, is recommended for the treatment of schizophrenia and mood disorders. In addition, given its sedative effects, a low dose of the agent is also widely used in the treatment of anxiety disorders, personality disorders, substance abuse, and sleep disturbances. In this case study, quetiapine was the first effective drug in reducing chronic insomnia in a male patient with a long treatment history. Because its effect declined over time, in the course of two years, a gradual dose increase led to a posology 50 times higher than the off-label dosage used to obtain sedation, i.e. 25-100 mg quetiapine administered once daily. This case raises awareness of the ease with which dose escalation of quetiapine occurs. The risk of side effects and, possibly, dependence and abuse underlines the importance of regular and careful patient monitoring. Given the unexpected effectiveness of the agent and the absence of side effects in the described case, we argue that in treatment-resistant insomnia, a high dose of quetiapine may be justifiable in selected cases but also urge that further research on the long-term effects and potential adverse events of quetiapine for this indication is of the utmost importance.

The effect of mood-stabilizing drugs on cytokine levels in bipolar disorder: A systematic review.

OBJECTIVES: Cytokine level alterations suggest a role for the immune system in the pathophysiology of bipolar disorder (BD). Pharmacotherapy is an important confounding factor in clinical research on cytokine levels. In this systematic review we collate the evidence on blood cytokine levels in medication-free BD and the effects of single mood-stabilizing drugs on these levels. METHODS: A systematic review was conducted according to the PRISMA statement. We searched the Pubmed and Embase databases for clinical studies reporting either on cytokine levels in medication-free BD or on the effects of single mood-stabilizing drugs on cytokine levels in BD. RESULTS: Of the 564 articles screened, 17 were included. Fourteen articles report on medication-free patients with BD and indicate state-related cytokine alterations. Six articles discuss the effect of lithium. Whereas no data on short-term effects of lithium were found, ≥2 months lithium use in euthymic populations is associated with normal cytokine levels. Two studies report no effect of valproate and no studies were found on carbamazepine, lamotrigine or antipsychotics. LIMITATIONS: The available studies are characterized by a broad methodological heterogeneity and limited replication between studies. CONCLUSIONS: This systematic review suggests the presence of state-related cytokine level alterations in medication-free BD with most evidence pointing to a proinflammatory cytokine response in mania. Euthymia and long-term lithium use are associated with normal cytokine levels. To improve our understanding of the impact of mood-stabilizing drugs on cytokine levels, longitudinal studies with medication-free baseline, randomized controlled single-drug treatment protocols and close mood state monitoring are needed.

The effects of nicotine on cognition are dependent on baseline performance.

Since cholinergic neurotransmission plays a major role in cognition, stimulation of the nicotinic acetylcholine receptor may be a target for cognitive enhancement. While nicotine improves performance on several cognitive domains, results of individual studies vary. A possible explanation for these findings is that the effect of nicotine administration may be dependent on baseline cognitive function, where subjects with a suboptimal cognitive performance may benefit from nicotine, while subjects who already perform optimally may show a decline in performance after nicotinic stimulation. We conducted a double-blind randomised placebo-controlled crossover trial, examining the effects of placebo, 1, and 2mg of nicotine on cognition in young (n=16, age 18-30 years) and healthy elderly (n=16, age 60-75 years) subjects. We hypothesised that the elderly would benefit more from nicotine compared to young subjects, as normal ageing is associated with decreases in cognitive function. Attention, working memory, visual memory, information-processing speed, psychomotor function, stereotypy, and emotion recognition were assessed. Compared to the young volunteers, the elderly performed significantly worse on psychomotor function and emotion recognition in the placebo condition. Nicotine had no effect in the young volunteers and decreased performance on working memory and visual memory in the elderly. Contrary to our hypothesis, the effect of nicotine was dependent on baseline performance in both the groups, with subjects with lower baseline performance benefiting from nicotine administration, while those with higher baseline performance performed worse after nicotine administration. This suggests that subjects with lower cognitive performance, irrespective of age, may benefit from nicotine.

Preserved Learning during the Symbol-Digit Substitution Test in Patients with Schizophrenia, Age-Matched Controls, and Elderly.

OBJECTIVE: Speed of processing, one of the main cognitive deficits in schizophrenia is most frequently measured with a digit-symbol-coding test. Performance on this test is additionally affected by writing speed and the rate at which symbol-digit relationships are learned, two factors that may be impaired in schizophrenia. This study aims to investigate the effects of sensorimotor speed, short-term learning, and long-term learning on task performance in schizophrenia. In addition, the study aims to explore differences in learning effects between patients with schizophrenia and elderly individuals. METHODS: Patients with schizophrenia (N = 30) were compared with age-matched healthy controls (N = 30) and healthy elderly volunteers (N = 30) during the Symbol-Digit Substitution Test (SDST). The task was administered on a digitizing tablet, allowing precise measurements of the time taken to write each digit (writing time) and the time to decode symbols into their corresponding digits (matching time). The SDST was administered on three separate days (day 1, day 2, day 7). Symbol-digit repetitions during the task represented short-term learning and repeating the task on different days represented long-term learning. RESULTS: The repetition of the same symbol-digit combinations within one test and the repetition of the test over days resulted in significant decreases in matching time. Interestingly, these short-term and long-term learning effects were about equal among the three groups. Individual participants showed a large variation in the rate of short-term learning. In general, patients with schizophrenia had the longest matching time whereas the elderly had the longest writing time. Writing time remained the same over repeated testing. CONCLUSION: The rate of learning and sensorimotor speed was found to have a substantial influence on the SDST score. However, a large individual variation in learning rate should be taken into account in the interpretation of task scores for processing speed. Equal learning rates among the three groups suggest that unintentional learning in schizophrenia and in the elderly is preserved. These findings are important for the design of rehabilitation programs for schizophrenia.

Stable schizophrenia patients learn equally well as age-matched controls and better than elderly controls in two sensorimotor rotary pursuit tasks.

OBJECTIVE: To compare sensorimotor performance and learning in stable schizophrenia patients, healthy age- and sex-matched controls and elderly controls on two variations of the rotary pursuit: circle pursuit (true motor learning) and figure pursuit (motor and sequence learning). METHOD: In the circle pursuit, a target circle, rotating with increasing speed along a predictable circular path on the computer screen, must be followed by a cursor controlled by a pen on a writing tablet. In the eight-trial figure pursuit, subjects learn to draw a complex figure by pursuing the target circle that moves along an invisible trajectory between and around several goals. Tasks were administered thrice (day 1, day 2, day 7) to 30 patients with stable schizophrenia (S), 30 healthy age- and sex-matched controls (C), and 30 elderly participants (>65 years; E) and recorded with a digitizing tablet and pressure-sensitive pen. The outcome measure accuracy (% of time that cursor is within the target) was used to assess performance. RESULTS: We observed significant group differences in accuracy, both in circle and figure pursuit tasks (E < S < C, p < 0.01). Strong learning effects were found in each group. Learning curves were similar in circle pursuit but differed between groups in figure pursuit. When corrected for group differences in starting level, the learning gains over the three sessions of schizophrenia patients and age-matched controls were equal and both were larger than those of the elderly controls. CONCLUSION: Despite the reduced sensorimotor performance that was found in the schizophrenia patients, their sensorimotor learning seems to be preserved. The relevance of this finding for the evaluation of procedural learning in schizophrenia is discussed. The better performance and learning rate of the patients compared to the elderly controls was unexpected and deserves further study.

Bupropion for the treatment of seasonal affective disorder.

INTRODUCTION: Seasonal affective disorder (SAD) is a psychiatric illness with recurring depressive episodes during particular seasons, mostly winter. Bupropion is effective in the preventive treatment of SAD and is probably also effective in the acute treatment of SAD. AREAS COVERED: This review covers the pharmacokinetics and pharmacodynamics of bupropion. The authors also evaluate bupropion's clinical efficacy as well as its safety and tolerability. EXPERT OPINION: Bupropion is available in an immediate release formulation, as well as a sustained release formulation and an extended release (XR) formulation. The XR formulation is recommended for SAD due to its ease of use and is the only formulation currently used as a therapy. Due to the predictable nature of SAD, the use of bupropion XR is considered a relevant treatment option. Bupropion's efficacy is shown in three trials that started in autumn at a time when SAD symptoms were not yet present although treatment effects were relatively small compared with a placebo. Bupropion was also shown to have efficacy in an open-label study. That being said, in order to reach definitive conclusions about its efficacy with acute treatment of SAD, more placebo-controlled trials are needed.

Acute effects of MDMA (3,4-methylenedioxymethamphetamine) on EEG oscillations: alone and in combination with ethanol or THC (delta-9-tetrahydrocannabinol).

RATIONALE: Typical users of 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") are polydrug users, combining MDMA with alcohol or cannabis [most active compound: delta-9-tetrahydrocannabinol (THC)]. OBJECTIVES: The aim of the present study was to investigate whether co-administration of alcohol or THC with MDMA differentially affects ongoing electroencephalogram (EEG) oscillations compared to the administration of each drug alone. METHODS: In two separate experiments, 16 volunteers received four different drug conditions: (1) MDMA (100 mg); (2) alcohol clamp (blood alcohol concentration = 0.6‰) or THC (inhalation of 4, 6 and 6 mg, interval of 1.5 h); (3) MDMA in combination with alcohol or THC; and (4) placebo. Before and after drug administration, electroencephalography was recorded during an eyes closed resting state. RESULTS: Theta and alpha power increased after alcohol intake compared to placebo and reduced after MDMA intake. No interaction between alcohol and MDMA was found. Significant MDMA x THC effects for theta and lower-1-alpha power indicated that the power attenuation after the combined intake of MDMA and THC was less than the sum of each drug alone. For the lower-2-alpha band, the intake of MDMA or THC alone did not significantly affect power, but the intake of combined MDMA and THC significantly decreased lower-2-alpha power. CONCLUSIONS: The present findings indicate that the combined intake of MDMA and THC, but not of MDMA and alcohol, affects ongoing EEG oscillations differently than the sum of either one drug alone. Changes in ongoing EEG oscillations may be related to the impaired task performance that has often been reported after drug intake.