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Background. Many patients with major depression are non-adherent to antidepressant medication and do not receive care according to current guidelines. There is increasing evidence that treatment of depression in primary care can be improved. Comparison between effective interventions may help to establish the active ingredients of such interventions.Method. In a randomized trial two interventions to improve treatment of major depression in primary care were compared (1) a depression care programme, targeting general practitioners (GPs), patients, and systematic follow-up, and (2) a systematic follow-up programme. Thirty GPs were randomized and 211 primary-care patients with current major depression were included. All patients were prescribed a selective serotonin reuptake inhibitor. Outcome measures included adherence to antidepressant medication, and depression outcome.Results. No significant differences in adherence rates and treatment outcome measures were demonstrated between interventions at week 10 or week 26. Adherence rates were high and treatment outcome was favourable.Conclusions. The depression care programme was not superior to the systematic follow-up programme. Systematic follow-up in depression treatment in primary care seems to be an intervention per se, having the potential to improve adherence and treatment outcome. [ABSTRACT FROM AUTHOR]

Background: Prevalence of psychological distress (i.e. depressive and anxiety symptoms) in medically ill patients is high. Research in the general population shows a higher prevalence of psychological distress among immigrants compared to natives. Our aim was to examine the prevalence of psychological distress in the hospital setting comparing immigrant and native Dutch patients and first and second generation immigrant patients., Methods: Prevalence of psychological distress was assessed using the extended Kessler-10 (EK-10) in 904 patients in a Dutch general teaching hospital. Logistic regression was used to calculate odds ratios to determine differences between native and immigrant patients and first and second generation immigrants in the prevalence of psychological distress. We adjusted for demographic and social variables, socio-economic status, physical quality of life, history of psychiatric disease and health care use., Results: Of 904 patients, 585 were native Dutch patients and 319 were immigrant patients. The prevalence of psychological distress in native compared to immigrant patients was 54% and 66% respectively, with especially high prevalences among Turkish and Moroccan immigrant patients. The crude OR for prevalence of psychological distress for immigrant patients versus native patients was 1.7 (95% CI 1.2-2.2) and for first versus second generation immigrant patients 2.1 (95% CI 1.2-3.5). After full adjustment ORs were 1.7 (95% CI 1.2-2.3) and 2.2 (95% CI 1.2-4.1) respectively., Conclusion: Immigrant patients and first generation immigrant patients were more likely to have psychological distress compared to native patients and second generation immigrant patients respectively. We found a particularly high prevalence of psychological distress in Turkish and Moroccan immigrants.

Background: Although job-related burnout and its core feature emotional exhaustion are common among medical professionals and compromise job satisfaction and professional performance, they have never been systematically studied in medical professors, who have central positions in academic medicine., Methods: We performed an online nationwide survey inviting all 1206 medical professors in The Netherlands to participate. They were asked to fill out the Maslach Burnout Inventory, a 'professional engagement' inventory, and to provide demographic and job-specific data., Results: A total of 437 Professors completed the questionnaire. Nearly one quarter (23.8%) scored above the cut-off used for the definition of emotional exhaustion. Factors related to being in an early career stage (i.e. lower age, fewer years since appointment, having homeliving children, having a relatively low Hirsch index) were significantly associated with higher emotional exhaustion scores. There was a significant inverse correlation between emotional exhaustion and the level of professional engagement., Conclusions: Early career medical professors have higher scores on emotional exhaustion and may be prone for developing burnout. Based upon this finding, preventive strategies to prevent burnout could be targeted to young professors.

Purpose: To determine content validity, structural validity, construct validity and reliability of an internet-based questionnaire designed for assessment of publication pressure experienced by medical scientists., Methods: The Publication Pressure Questionnaire (PPQ) was designed to assess psychological pressure to publish scientific papers. Content validity was evaluated by collecting independent comments from external experts (n = 7) on the construct, comprehensiveness and relevance of the PPQ. Structural validity was assessed by factor analysis and item response theory (IRT) using the generalized partial credit model. Pearson's correlation coefficients were calculated to assess potential correlations with the emotional exhaustion and depersonalization subscales of the Maslach Burnout Inventory (MBI). Single test reliability (lambda2) was obtained from the IRT analysis., Results: Content validity was satisfactory. Confirmatory factor analysis did not support the presence of three initially assumed separate domains of publication pressure (i.e., personally experienced publication pressure, publication pressure in general, pressure on position of scientist). After exclusion of the third domain (six items), we performed exploratory factor analysis and IRT. The goodness-of-fit statistics for the IRT assuming a single dimension were satisfactory when four items were removed, resulting in 14 items of the final PPQ. Correlations with the emotional exhaustion and depersonalization scales of the MBI were 0.34 and 0.31, respectively, supporting construct validity. Single test administration reliability lambda2 was 0.69 and 0.90 on the test scores and expected a posteriori scores, respectively., Conclusion: The PPQ seems a valid and reliable instrument to measure publication pressure among medical scientists.

Background: Publication of scientific research papers is important for professionals working in academic medical centres. Quantitative measures of scientific output determine status and prestige, and serve to rank universities as well as individuals. The pressure to generate maximum scientific output is high, and quantitative aspects may tend to dominate over qualitative ones. How this pressure influences professionals' perception of science and their personal well-being is unknown., Methods and Findings: We performed an online survey inviting all medical professors (n = 1206) of the 8 academic medical centres in The Netherlands to participate. They were asked to fill out 2 questionnaires; a validated Publication Pressure Questionnaire and the Maslach Burnout Inventory. In total, 437 professors completed the questionnaires. among them, 54% judge that publication pressure 'has become excessive', 39% believe that publication pressure 'affects the credibility of medical research' and 26% judge that publication pressure has a 'sickening effect on medical science'. The burn out questionnaire indicates that 24% of medical professors have signs of burn out. The number of years of professorship was significantly related with experiencing less publication pressure. Significant and strong associations between burn out symptoms and the level of perceived publication pressure were found. The main limitation is the possibility of response bias., Conclusion: A substantial proportion of medical professors believe that publication pressure has become excessive, and have a cynical view on the validity of medical science. These perceptions are statistically correlated to burn out symptoms. Further research should address the effects of publication pressure in more detail and identify alternative ways to stimulate the quality of medical science.

Introduction: The H-index is a frequently used scale to rank scientists on their scientific output. Whether subjective feeling of happiness is influenced by the level of the H-index on scientists has never been investigated., Objective: To investigate the relation between the level of the H index as a measure of scientific success and feelings of unhappiness among Dutch professors., Design: Descriptive; national online questionnaire., Method: All medical professors working at the Dutch university medical centres were invited to participate in an online questionnaire. Pressure to publish was measured by a questionnaire developed for this purpose and signs of burnout were measured on the Utrecht Burnout Scale. The area of emotional exhaustion on this scale was used to measure feelings of unhappiness. Every professor was asked for his or her H-index as an outcome measure., Results: A total of 437 professors completed the questionnaire. Those in the highest tertile of the H index had significantly lower scores for emotional exhaustion (p < 0.025). Younger age was correlated with an, on average, higher score for emotional exhaustion. Professors with children living at home had a 25% higher score on emotional exhaustion than those who did not (p < 0.01)., Conclusion: The H index appears to be of influence on emotional exhaustion: a lower H index is associated with higher scores on emotional exhaustion while a high H index is associated with lower scores.

Objective: In two previous manuscripts, we described the efficacy of lamotrigine versus placebo as add-on to lithium (followed by the addition of paroxetine in nonresponders) in the short-term treatment of bipolar depression. In this paper we describe the long-term (68 weeks) outcome of that study., Methods: A total of 124 bipolar depressed patients receiving lithium were randomized to addition of lamotrigine or placebo. After eight weeks, paroxetine was added to nonresponders for another eight weeks. Responders continued medication and were followed for up to 68 weeks or until a relapse or recurrence of a depressive or manic episode., Results: After eight weeks, the addition of lamotrigine to lithium was significantly more efficacious than addition of placebo, while after addition of paroxetine in nonresponders both groups further improved with no significant difference between groups at week 16. During follow-up the efficacy of lamotrigine was maintained: time to relapse or recurrence was longer for the lamotrigine group [median time 10.0 months (confidence interval: 1.1-18.8)] versus the placebo group [3.5 months (confidence interval: 0.7-7.0)]., Conclusion: In patients with bipolar depression, despite continued use of lithium, addition of lamotrigine revealed a continued benefit compared to placebo throughout the entire study., (© 2011 John Wiley and Sons A/S.)

According to the cognitive neuropsychological hypothesis of antidepressant action, the onset of subjectively experienced therapeutic effects to treatment is preceded by favourable changes in psychological functioning that can be measured by implicit methods. The aim of this study was to examine additional data to explore this hypothesis in an intention-to-treat repetitive transcranial magnetic stimulation (rTMS) study targeting the right parietal cortex. Changes in depression scores from baseline and the sensitivity for recognizing emotional facial expressions were studied in 28 patients with depressive disorder receiving ten sessions of real (n=14) or sham (n=14) rTMS treatments in a double-blind, sham-controlled design. In the patient group results showed significantly higher sensitivity for recognizing angry facial expressions in response to receiving real compared to receiving sham rTMS treatment. Overall mood improvement was similar across real and sham rTMS treatments. However, the sensitivity for recognizing angry facial expressions was correlated to the percentage decrease in depression scores. These results provide the first preliminary support for the cognitive neuropsychological hypothesis of antidepressant action in rTMS treatment.

Objective: In a previous paper, we reported about the efficacy of the addition of lamotrigine to lithium in patients with bipolar depression. In the second phase of this study paroxetine was added to ongoing treatment in non-responders., Method: Bipolar depressed patients (n = 124) treated with lithium were randomized to addition of lamotrigine or placebo. In non-responders after 8 weeks, paroxetine 20 mg was added for another 8 weeks to ongoing treatment., Results: After 8 weeks the improvement in patients treated with lamotrigine vs. patients treated with placebo was significant. After addition of paroxetine this difference disappeared as a result of greater further improvement in the non-responders to placebo., Conclusion: Addition of lamotrigine to lithium was found effective in bipolar depressed patients. Further addition of paroxetine in non-responders to lithium plus lamotrigine did not appear to provide additional benefit, while it appeared to do so in non-responders to lithium plus placebo.

Gamma-hydroxybutyric acid (GHB) is a neurotransmitter that occurs naturally in the brain and is increasingly being used as a 'party drug' because of its relaxing and euphoria-inducing effects. GHB has a limited medical use in the treatment of narcolepsy. GHB-intoxications occur often in non-medical use, and generally result in a coma of short duration. GHB use several times a day can lead to tolerance and dependence. After sudden cessation or reduction of intensive GHB use, a severe withdrawal syndrome may occur with symptoms varying from tremor, anxiety and agitation to autonomic instability, hallucinations and delirium. Treatment of the GHB withdrawal syndrome consists of supportive care and benzodiazepines, often in high doses. The controlled detoxification of GHB using pharmaceutical GHB in an adjusted dose is currently being investigated in the Netherlands. There is no literature concerning the treatment of patients following GHB intoxication or after detoxification.

Objective: To review the literature on the predictive value of psychiatric comorbidity for weight loss following bariatric surgery in patients with morbid obesity., Design: Systematic review., Method: PubMed databases were searched for literature comparing weight loss following bariatric surgery in morbidly obese patients with and without preoperative psychiatric symptoms. General psychiatric disorders were distinguished from eating disorders., Results: The search yielded 204 references, 6 of which complied with inclusion criteria. 2 studies were retrospective (169 patients in total; the other 4 were prospective (1140 patients in total). The average follow-up period varied between 12 and 60 months. In 2 studies (n = 528 patients), the influence of eating disorders on the outcome of bariatric surgery was specifically studied. The quality of the studies was low. Psychiatric disorders and eating disorders did not influence the outcome of bariatric surgery. In 1 study, weight loss was less after surgery in patients diagnosed with more than 2 psychiatric disorders., Conclusion: In 5 of the 6 studies, psychiatric comorbidity was not related to the weight loss following bariatric surgery. In view of the differences in design and the poor quality of the studies, definite conclusions cannot be drawn. There is no indication that routine psychiatric screening should form part of the work-up for bariatric surgery. We advise that note should be taken of the psychiatric history and any current psychiatric treatment.

The aim of this treatment study was to evaluate the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) over the right parietal cortex in depression. In a double-blind, sham-controlled design ten consecutive sessions of 2 Hz rTMS (inter-pulse interval 0.5 s) at 90% motor threshold to the right parietal cortex (2400 pulses per session) were applied to 34 patients with the primary diagnosis of DSM-IV depression and a score of > or =15 on the 17-item Hamilton Rating Scale for Depression (HAMD). The primary outcome measures were the percentage change from baseline on the 17-item HAMD scores after ten sessions, and the percentage of clinical (defined as > or =50% reduction in HAMD score) and partial clinical (defined as > or =30% reduction in HAMD score) responders. Reduction of HAMD scores in the real rTMS treatment (mean real+/-S.D., -19.9+/-32.5%) was not statistically different from the sham rTMS treatment (mean sham+/-S.D., -5.6+/-28.4%), and the number of clinical responders did not differ between treatments. However, a significant greater number of partial clinical responders were observed in the real (43.8%) compared to the sham rTMS treatment (6.3%). This study provides the first evidence showing that 2 Hz rTMS over the right parietal cortex may have antidepressant properties, and warrants further research.

Objective: Lamotrigine is one of the pharmacologic options for the treatment of bipolar depression but has only been studied as monotherapy. This study compared the acute effects of lamotrigine and placebo as add-on therapy to ongoing treatment with lithium in patients with bipolar depression., Method: Outpatients (N = 124) aged 18 years and older with a DSM-IV bipolar I or II disorder and a major depressive episode (Montgomery-Asberg Depression Rating Scale [MADRS] score > or = 18 and Clinical Global Impressions-Bipolar Version [CGI-BP] severity of depression score > or = 4) while receiving lithium treatment (0.6-1.2 mmol/L) were randomly assigned to 8 weeks of double-blind treatment with lamotrigine (titrated to 200 mg/d) or placebo. The primary outcome measure was mean change from baseline in total score on the MADRS at week 8. Secondary outcome measures were response (defined as a reduction of > or = 50% on the MADRS and/or change of depression score on the CGI-BP of "much improved" or "very much improved" compared to baseline) and switch to mania or hypomania (defined as a CGI-BP severity of mania score of at least mildly ill at any visit). Patients were included in the study between August 2002 (Spain started in October 2003) and May 2005., Results: Endpoint mean change from baseline MADRS total score was -15.38 (SE = 1.32) points for lamotrigine and -11.03 (SE = 1.36) points for placebo (t = -2.29, df = 104, p = .024). Significantly more patients responded to lamotrigine than to placebo on the MADRS (51.6% vs. 31.7%, p = .030), but not on the CGI-BP change of depression (64.1% vs. 49.2%, p = .105). Switch to mania or hypomania occurred in 5 patients (7.8%) receiving lamotrigine and 2 patients (3.3%) receiving placebo (p = .441)., Conclusion: Lamotrigine was found effective and safe as add-on treatment to lithium in the acute treatment of bipolar depression., Trial Registration: clinicaltrials.gov Identifier: NCT00224510., (Copyright 2009 Physicians Postgraduate Press, Inc.)

Objective: Many depressed patients have negative beliefs about antidepressants, leading to poor adherence, unfavorable depression outcome, and low perceived well-being, role functioning, and quality of life. Interventions to ameliorate beliefs are therefore needed., Method: In a cluster-randomized controlled trial conducted from September 1999 to January 2001, 2 interventions to improve management of major depressive disorder in primary care were compared: (1) a depression care program (DCP), providing enhanced patient education, stimulation of active participation of general practitioners and patients in the treatment process, discussion of benefits and costs of taking antidepressant medication, and systematic follow-up and (2) a systematic follow-up program (SFP). Thirty general practitioners were randomly assigned, and 211 patients with current major depressive disorder (diagnosed according to DSM-IV) were included. All patients were prescribed a selective serotonin reuptake inhibitor. Beliefs were assessed at baseline, at week 10, and at week 26. Differences in change of beliefs between DCP and SFP groups were analyzed., Results: Changes in patients' beliefs were more favorable in the DCP condition at week 10 and week 26, compared with SFP only (beliefs concerning appropriate medication-taking, week 10: effect size = 0.39, p = .012; week 26: effect size = 0.55, p = .001; beliefs concerning harmfulness, week 10: effect size = 0.45, p = .011; week 26: effect size = 0.62, p = .002)., Conclusion: The depression care program ameliorates beliefs about antidepressants in primary care patients with major depressive disorder. The study results encourage the implementation of a depression care program in order to improve beliefs about antidepressant medication in primary care patients diagnosed with major depressive disorder.

Objective: In depression treatment, switching treatment after lack of initial improvement, e.g., after 6 weeks, may result in a better outcome. The extent of the lack of initial improvement, as well as the timing of its assessment on the basis of which treatment change may be considered, remains unclear. This study compared the relationships of several grades of symptom improvement after 2 and 6 weeks with remission after 10 weeks in depressed patients treated with antidepressants in primary care., Method: This was a prospective cohort study, conducted between January 1999 and September 2001 in primary care practices in the Netherlands, of 172 patients starting selective serotonin reup-take inhibitor (SSRI) treatment for major depressive disorder, diagnosed according to DSM-IV criteria. At weeks 2 and 6, patients were classified as unimproved, partially improved, or improved. For each category, we calculated the proportion of remission at week 10. The primary outcome measure was the Beck Depression Inventory., Results: Of the unimproved or partially improved patients at week 6, 29% (95% CI = 18 to 43) and 27% (95% CI = 17 to 40) attained remission at week 10, respectively., Conclusion: These data suggest that, in primary care, depression treatment with an SSRI should be reconsidered in depressed patients who are unimproved or partially improved by week 6.

Background: The results of treatment for depression are frequently disappointing. The main reasons for this are inadequate treatment and non-compliance., Aim: This article attempts to deal with the question of how patient compliance and the results of treatment for depression can be improved., Method: We performed a critical analysis of the literature. We searched Medline (1966- January 2002), psycinfo (1984-January 2002), Embase (1980-January 20002) and the Cochrane Controlled Trials Register (1966-Janaury 2002) for reports of randomised controlled trials. In our search we used the terms 'patient compliance', 'adherence', patient dropout', 'depression', 'depressive disorder', and 'affective disorder'. On the basis of the results of our search we compared two interventions that could be applied in Dutch practices. results We found 11 articles, all relating to treatment in primary care settings. Usual care proved to be inadequate. The quality of the usual care currently provided can be improved by extra interventions. So far there are no indications that complex interventions benefit the patient more than simple interventions, such as regular follow-up procedures. Therefore, for the time being, simple interventions are to be preferred., Conclusion: Treatment for depression can be improved by means of relatively simple interventions.

Two schizophrenic women, aged 30 and 40 years, respectively, in whom the symptoms changed after a switch in medication from clozapine to aripiprazole and from olanzapine followed by quetiapine to risperidone, respectively, were initially thought to be experiencing a possible recurrence. After thoughtful consideration, the phenomena, such as disappearance of drowsiness and of loss of energy, in combination with cognitive improvement, could be understood as the result of a dramatic improvement, known as 'awakening'. This had significant consequences for the follow-up since the patients had to deal with new possibilities and emotions.

Four patients, two women aged 29 and 52 and two men aged 46 and 25, respectively, consulted a neurologist for attention and memory disorders. Further investigation revealed that the symptoms were caused by metachromatic leucodystrophy, Graves' disease, Huntington's disease, and a psychological background, respectively. The first patient became dependent in 1.5 years, the second recovered after treatment, the third was independent with slowly progressive symptoms after 1 year, and the fourth was advised to consult a psychologist. Disorders of attention and memory in relatively young people deserve a detailed evaluation at the very first visit, involving the elaboration of an initially extensive differential diagnosis. Too early a separation between a psychic and an organic pathogenesis should be avoided. Indications for the presence of a neurological condition include: consultation at the initiative of others, a relatively brief duration of symptoms without a clear provoking factor, the absence of a psychiatric history or life event, cognitive dysfunction in several areas, abnormal behaviour and an incriminating family history.

Purpose: In the literature, noncompliance to medication in patients with schizophrenia ranges from 20 to 89%. There is an urgent need for reliable and valid techniques that measure compliance in antipsychotic drug treatment. In this study, we use pharmacy-dispensing records to assess compliance by calculating the refill rate of antipsychotic medication., Methods: Refill rates of chronic antipsychotic drug users in 1999 and in 2000 were established by dividing the number of prescribed days by the total number of calendar days that the patient was registered in a pharmacy prescription records database., Results: More than 50% of patients using an antipsychotic drug show a refill rate that is associated with medication compliance (0.9-1.1). The number of daily antipsychotic drug intakes was associated with a divergent refill rate, more than once daily dosing was associated with a significantly elevated refill rate (p < 0.015)., Conclusions: The refill rate is a valuable addition to the small arsenal of objective compliance measurement tools. It is an easy to obtain and inexpensive way to estimate (non)compliance. We recommend future studies to medication use in both mental and physical disorders, in order to further specify the actual value of refill rates in clinical practice., (Copyright 2004 John Wiley & Sons, Ltd.)

Background: Effectiveness of antidepressant medication is reduced by patients' nonadherence. Several interventions to improve adherence in patients diagnosed with unipolar depression have been tested., Objective: To systematically review the effectiveness of interventions that aimed to improve adherence to antidepressant medication in patients with unipolar depression., Method: Systematic review of English-language articles of randomized controlled trials obtained by a computerized literature search of MEDLINE (1966-January 2002) using the terms patient compliance, patient dropout, treatment refusal, patient education, adherence, clinical trial, randomized controlled trial, controlled trial, depressive disorder, and depression; PSYCINFO (1984-January 2002) using the terms random, clinical, control, trial, adherence, compliance, noncompliance, dropouts, patient education, depression, major depression, affective disorders, and dysthymic disorder; EMBASE (1980-January 2002) using the terms patient compliance, patient dropouts, illness behavior, treatment refusal, patient education, clinical trial, controlled study, randomized controlled trial, and depression; and the Cochrane Controlled Trials Register (no restrictions) using the terms random*, complian*, adheren*, pharmacotherapy, regimen*, educat*, medicat*, depression, and depressive disorder., Results: Educational interventions to enhance adherence failed to demonstrate a clear benefit on adherence and depression outcome. However, collaborative care interventions tested in primary care demonstrated significant improvements in adherence during the acute and continuation phase of treatment and were associated with clinical benefit, especially in patients suffering from major depression who were prescribed adequate dosages of antidepressant medication., Conclusion: We found evidence to support the introduction of interventions to enhance adherence with antidepressant medication in primary care, not only because of better adherence but also because of better treatment results. Because collaborative care interventions require additional resources, a better understanding of the mode of action of different programs is needed to reduce avoidable costs. The effectiveness of educational interventions needs more evidence.

A 35-year-old man with anxiety and depression who was treated with venlafaxine, 300 mg a day, developed severe withdrawal symptoms in the form of a delirium during gradual tapering of the dosage. The symptoms resolved when the dosage was kept constant and did not recur when the dosage was reduced more gradually. Withdrawal symptoms are common during discontinuation of antidepressants, particularly after prolonged use of agents with a short half-life. The symptoms are usually mild and transient, especially in the case of selective serotonin reuptake inhibitors and venlafaxine. The occurrence of delirium as a result of the withdrawal of venlafaxine has not been reported previously. Even when antidepressants are being withdrawn with care, one should remain alert to the possible development of severe withdrawal symptoms.

Two patients, a 29-year-old man and a 32-year-old woman who were being treated with paroxetine HCl hemihydrate for depression and panic disorder with agoraphobia, respectively, unexpectedly developed complaints after switching to paroxetine mesylate. The symptoms were generalised itching with relapse of the depressive disorder in the man, and nausea with diarrhoea in the woman. The symptoms disappeared after the original treatment with paroxetine HCl hemihydrate was resumed. In the first patient, a rechallenge with the mesylate form of paroxetine led to the same complaints which subsided again after using the first product. Those treating such patients, and the patients themselves, should be informed if the delivery form of paroxetine is changed.

Compliance during treatment with antidepressants is important, yet about half of the patients stop using antidepressive medication within 3 months. A structured treatment programme, in which the patient actively participates, with extensive education, surveillance of side effects and compliance, simple regimes, improving problem-solving behaviour and eventually engaging and educating family members and friends can improve compliance. This has been demonstrated in published studies. Research has shown that interventions that enhance compliance can lead to a better outcome of the depression.