Controversies regarding lithium-associated weight gain: case-control study of real-world drug safety data.

BACKGROUND: The impact of long-term lithium treatment on weight gain has been a controversial topic with conflicting evidence. We aim to assess reporting of weight gain associated with lithium and other mood stabilizers compared to lamotrigine which is considered free of metabolic adverse drug reactions (ADRs). METHODS: We conducted a case/non-case pharmacovigilance study using data from the AMSP project (German: "Arzneimittelsicherheit in der Psychiatrie"; i.e., Drug Safety in Psychiatry), which collects data on ADRs from patients treated in psychiatric hospitals in Germany, Austria, and Switzerland. We performed a disproportionality analysis of reports of weight gain (> 10% of baseline body weight) calculating reporting odds ratio (ROR). We compared aripiprazole, carbamazepine, lithium, olanzapine, quetiapine, risperidone, and valproate to lamotrigine. Additional analyses related to different mood stabilizers as reference medication were performed. We also assessed sex and age distributions of weight-gain reports. RESULTS: We identified a total of 527 cases of severe drug-induced weight gain representing 7.4% of all severe ADRs. The ROR for lithium was 2.1 (95%CI 0.9-5.1, p > 0.05), which did not reach statistical significance. Statistically significant disproportionate reporting of weight gain was reported for olanzapine (ROR: 11.5, 95%CI 4.7-28.3, p < 0.001), quetiapine (ROR: 3.4, 95%CI 1.3-8.4, p < 0.01), and valproate (ROR: 2.4, 95%CI 1.1-5.0, p = 0.03) compared to lamotrigine. Severe weight gain was more prevalent in non-elderly (< 65 years) than in elderly patients, with an ROR of 7.6 (p < 0.01) in those treated with lithium, and an ROR of 14.7 (p < 0.01) in those not treated with lithium. CONCLUSIONS: Our findings suggest that lithium is associated with more reports of severe weight gain than lamotrigine, although this difference did not reach statistical significance. However, lithium use led to fewer reports of severe weight gain than some alternative drugs for long-term medication (olanzapine, quetiapine, and valproate), which is consistent with recent studies. Monitoring of weight gain and metabolic parameters remains essential with lithium and its alternatives.

A two-center pilot study on the effects of clinical ethics support on coercive measures in psychiatry.

BACKGROUND: The use of formal coercion such as seclusion, mechanical restraint, and forced medication is one of the most challenging and complex issues in mental health care, on the clinical, the legal, and the ethical level. Clinical ethics support aims at assisting healthcare practitioners in determining the morally most justifiable course of action in these situations. However, the effectiveness of clinical ethics support has hardly been studied so far. METHODS: Monthly moral case deliberation (MCD) was implemented in two acute wards of two different psychiatric hospitals in Switzerland. Frequency and intensity of coercion was measured on ward level (npatients = 405), and the Moral Attentiveness Scale, Knowledge on Coercion Scale, and Staff Attitudes towards Coercion Scale were applied on healthcare practitioner level (nHP = 46). Pre-post-comparisons were conducted using multi-level modeling where appropriate. RESULTS: After implementation of MCD, formal coercion was less frequent (particularly seclusion, small effect size; 9.6 vs. 16.7%, p = .034, Cramér's V = .105) and less intense (particularly mechanical restraint, large effect size; 86.8 ± 45.3 vs. 14.5 ± 12.1 h, exact p = .019, r = -.74), and approval for coercive measures among healthcare practitioners was lower when controlling for the number of MCD sessions attended. CONCLUSIONS: Clinical ethics support such as MCD may be a hitherto underutilized service for the reduction of coercion, complementing existing strategies and programs. Implementing clinical ethics support may help improve quality of care for persons suffering from severe mental illness.

Treatment of depression: Are psychotropic drugs appropriately dosed in women and in the elderly? Dosages of psychotropic drugs by sex and age in routine clinical practice.

BACKGROUND: Several researchers have shown higher concentration-dose ratios of psychotropic drugs in women and the elderly. Therefore, lower dosages of psychotropic drugs may be recommended in women and the elderly. This study describes sex- and age-related dosage of psychotropic drugs prescribed to patients with major depressive disorder (MDD) in routine clinical practice. METHOD: Influence of sex and age on dosages are analysed for the 10 most commonly prescribed drugs in our dataset consisting of 32,082 inpatients with MDD. Data stems from the European drug safety program "Arzneimittelsicherheit in der Psychiatrie". The observed sex and age differences in prescriptions are compared to differences described in literature on age- and gender-related pharmacokinetics. RESULTS: Among patients over 65 years, a statistically significant decrease in dosages with increasing age (between 0.65% and 2.83% for each increasing year of age) was observed, except for zopiclone. However, only slight or no influence of sex-related adjustment of dosage in prescriptions was found. CONCLUSION: Age appears to influence adjustment of dosage in most psychotropic drugs, but to a lower extent than data on age-related pharmacokinetics suggests. Although literature also suggests that lower dosages of psychotropic drugs may be appropriate for females, this study found women are usually prescribed the same dosage as men.

Commentary about social avoidance and its significance in adolescents and young adults.

Social avoidance in young patients is a clinically worrisome phenomenon that characterizes impending schizophrenia, but that also constitutes a core phenomenon in avoidant personality disorder (AvPD), schizoid personality disorder (ScPD), and in autism spectrum disorder (ASD). Especially in the absence of any other clinically relevant phenomena, understanding the origins of social avoidance may be one the most challenging tasks in assessing whether adolescents and young adults are at risk for developing schizophrenia. Descriptive and psychometric assessments only allow to comment on the absence or the presence of this phenomenon, but do not capture the origins and the meaning of social avoidance. Based on a narrative review, we highlight the importance of a phenomenological approach to unveil the Gestalt of social avoidance in these mental disorders, including and appraisal of the underlying mental structures and attachment styles. The phenomenological approach allows to distinguish the Gestalt of social avoidance between AvPD, ScPD, ASD, and beginning schizophrenia, to ensure correct diagnostic labelling and optimal treatment, and to avoid unwarranted stigmatization.

Exploring the effectiveness of a specialized therapy programme for burnout using subjective report and biomarkers of stress.

The increasing prevalence of stress-related disorders such as burnout urges the need for specialized treatment approaches. Programmes combining psychotherapy and regenerative interventions emerge to be the most successful. However, evaluated therapy programmes are scarce and usually involve subjective symptom quantification without consideration of physiologic parameters. The aim of the present exploratory, single-group study was the multimodal investigation of the effectiveness of a specialized holistic therapy programme by assessing symptoms and biological markers of chronic stress. Seventy-one in-patients (39 men/32 women; age 46.8 ± 9.9 years) of a specialized burnout ward with the additional diagnosis of burnout (Z73.0) in conjunction with a main diagnosis of depressive disorder (F32 or F33) according to the International Classification of Diseases (ICD)-10 were included in the study. In addition to symptomatology, the stress-responsive biomarkers heart rate variability (HRV) and serum brain-derived neurotrophic factor (BDNF) were measured in patients at admittance to and discharge from the burnout ward applying a 6-week specialized treatment programme. At discharge, patients showed a significant reduction of symptom burden and a significant increase in serum BDNF, while HRV remained unchanged. The findings implicate that the therapy programme may have beneficial effects on symptomatology and neuroplasticity of patients with burnout. As therapy was often supplemented by psychopharmacological treatment, a relevant influence of antidepressant medication especially on BDNF has to be considered.

[Acceptance of Psychiatric and Somatic Advance Directives: A Comparison in Psychiatric Patients and Professionals]. / Akzeptanz von psychiatrischen und somatischen Patientenverfügungen: ein Vergleich unter psychiatrischen Patienten und Fachpersonen.

OBJECTIVE: Assessment of the attitudes towards somatic and psychiatric advance directives in the German speaking part of Switzerland. METHODS: Questionnaire for psychiatric patients, psychiatrists, psychologists, psychiatric nurses and peers assessing the attitudes towards three exemplary advance directives. RESULTS: The attitudes were mainly positive in all participating groups. Compared to professionals (79-100 %), the somatic advance directive found approval in significantly less patients (46 %). There were no significant group differences regarding the psychiatric advance directives, but patients (58 % and 84 %) were slightly more agreeing compared to professionals (31-50 % and 62-70 %). CONCLUSION: Psychiatric advance directives seem to be broadly accepted. The development of campaigns might help to raise the awareness about these instruments and increase their usage in clinical practice.

[Bio-Psycho-Social Therapy for Stress-Induced Chronic Pain]. / Bio-psycho-soziale Therapie bei stressinduzierten Schmerzzuständen.

Bio-Psycho-Social Therapy for Stress-Induced Chronic Pain Abstract. Against the background of latest neurobiological and epigenetic findings the bio-psycho-social model of disease is outlined often misinterpreted in the context of chronic pain. It represents the basic principle for a personalized treatment of stress-induced chronic pain. Consequences for diagnostic procedures are delineated to detect this pathogenetic subgroup of chronic pain patients (e.g. fibromyalgia, back pain, temporomandibular dysfunction, tension headache). Finally, the principles of a bio-psycho-social treatment program with high efficiency are presented.

Psychiatric advance directives in Switzerland: Knowledge and attitudes in patients compared to professionals and usage in clinical practice.

BACKGROUND: Psychiatric advance directives (PAD) were shown to be effective in the reduction of coercion and strengthening of the patients` autonomy. Therefore, the Swiss legislation was revised and stipulates that PAD must be taken into account during involuntary hospitalization. This study aimed to analyze knowledge on and attitudes towards this instrument in patients and healthcare practitioners and their usage in clinical practice. METHODS: We developed a structured questionnaire and included patients (n = 110), psychiatrists (n = 205), psychologists (n = 85), nurses (n = 268) and peers (n = 16) to rate their knowledge on and attitudes towards PAD. We registered the existing PAD in patients and peers. The response rate varied between 17% (nurses), 19% (psychologists) 21% (psychiatrists), 33% (peers) and 56% (patients). RESULTS: Only 7% of the participating patients had a PAD. Compared to the other groups, patients had the least knowledge on PAD. Psychiatrists were significantly more critical towards PAD. Concerns that PAD impede necessary and adequate treatment, restrict professionals and result in conflicts between patients and HCP were most frequently named as reason for critical attitudes. CONCLUSIONS: Although being explicitly mentioned in the Swiss legislation the usage of PAD is small. Proactive information and training of psychiatrists might be helpful for a reduction of skeptical attitudes. This might improve the attitudes and lead to active support of patients during the preparation of PAD.

Emotion introspection and regulation in depression.

Depressed patients suffer from an impairment to voluntarily influence and regulate their unpleasant emotional state. Strengthening the mental ability to interfere with dysfunctional emotion processing may be beneficial in treating depression. According to models of emotion processing this may be done by successful down-regulation of enhanced amygdala activity. We investigated short periods of intentional emotion-introspection compared with cognitive self-reflection as two domains of self-awareness in terms of effects on emotion regulation. Thirty depressed patients performed twelve second periods of emotion-introspection, self-reflection and a neutral condition during functional magnetic resonance imaging. We analyzed brain activation in the patients with depression by means of whole brain, region of interest and connectivity analyses. Amygdala activity decreased during emotion-introspection relative to self-reflection and to the neutral condition, whereby left amygdala was inversely activated relative to the left insula. Insula activity itself was correlated with medial and dorsolateral prefrontal cortex (PFC) activation. In conclusion, depressed patients are able to down-regulate amygdala activity by emotion-introspection. This may be interpreted as well-working emotion regulation supposedly induced by PFC connections mediated via insula. The finding supports the application of emotion-introspection, a mindfulness-related process, in a clinical setting as an element of psychotherapy to train and improve emotion regulation.

A biological perspective on differences and similarities between burnout and depression.

To compare and contrast burnout and depression is not only a conceptual issue, but may deliver important directions for treatment approaches and stabilize the awareness of disease which is essential for affected individuals. Because of the symptomatic overlap, it is a subject of multidimensional research and discussion to find specific signatures to differentiate between the two phenomena or to present evidence that they are different aspects of the same disorder. Both pathologies are regarded as stress-related disorders. Therefore, in this review burnout and depression are discussed on the basis of biological parameters, mainly heart rate variability (HRV) and brain-derived neurotrophic factor (BDNF), which are crucial to the stress response system. It emerges that instead of finding one specific discriminating marker, future research should rather concentrate on elaborating indices for burnout and depression which integrate combinations of parameters found in genetics, neurobiology, physiology and environment.

Psychopharmacological treatment of 2195 in-patients with borderline personality disorder: A comparison with other psychiatric disorders.

Patients with borderline personality disorder (BPD) are usually prescribed a variety of psychotropic drugs; however, none is recommended in the guidelines nor has any been approved for this indication. As data on drug prescriptions for BPD are sparse, cross-sectional data from the European Drug Safety Project AMSP were used to analyse drug prescriptions of 2195 in-patients with BPD between 2001 and 2011, and the mean values, confidence intervals and regression analyses were calculated. 70% of all BPD patients were medicated with antipsychotics and/or antidepressants, 33% with anticonvulsants, 30% with benzodiazepines, and 4% with lithium; 90% received at least one, 80%≥2, and 54%≥3 psychotropic drugs concomitantly (mean: 2.8). Prescription rates for quetiapine, the single drug most often used in BPD (22%), increased significantly over time. In view of the high percentage of young females with BPD, 18-40 year-old female patients with BPD were compared with patients of the same age but with depression (unipolar and bipolar) and schizophrenia. Typical sedative antipsychotics and anticonvulsants were prescribed more often in BPD than in the other diagnostic groups, with the exception of bipolar depression; this was true for the single substances quetiapine, levomepromazine, chlorprothixene, carbamazepine, and valproate. A limitation of the study was the use of clinical data without verifying the diagnoses by structured interviews. Contrary to the guidelines, about 90% of in-patients with BPD received psychotropic drugs. Polypharmacy was common, and antipsychotics with sedative profiles such as quetiapine and mood-stabilizing anticonvulsants such as valproate appear to be preferred.

In need of psychiatric help--leave a message after the beep.

BACKGROUND/AIM: Every day, a substantial proportion of the general population experiences the distressing and frightening signs of an upcoming psychiatric illness. The consequences can be enormous because severe psychiatric disorders typically cause the loss of the ability to work and often mean a long-term burden for both the patients and their families. Even though most developed countries have an exceptionally high density of general practitioners and psychiatrists in private practice, getting a mental health appointment and seeing a doctor is often very difficult for patients with acute psychiatric symptoms. This study aimed at quantifying the time delay involved in seeking medical attendance when psychiatric disorders begin to develop. METHODS: Two female actors with well-proven experiences of realistically simulating the clinical presentation of depression and psychotic disorders made systematic phone calls to 106 psychiatrists in private practice and 106 general practitioners (GPs) of the Zurich City area. The actors asked for an appointment at the doctor's earliest convenience due to acute psychiatric symptoms. We assessed (1) the number of phone calls it took to reach each doctor; (2) the time it took to book an appointment; (3) the time span between the first phone call and the earliest available appointment, and (4) the possibility of personal contact with a doctor prior to booking the appointment. RESULTS: A total of 383 phone calls were made by the two actors (227 to psychiatrists and 156 to GPs) which resulted in analyzable data from 102 psychiatrist and 106 GP practices. Two thirds (68%) of the phone calls to the psychiatrists in private practice were answered by voice mail, compared to 21% among the GPs. A personal contact was established with 56% of the psychiatrists and 95% of the GPs. On average, 7.3 phone calls were necessary to successfully book an appointment with a psychiatrist. Almost half of the psychiatrists (45.6%) were not accepting new patients so appointments were able to be booked in less than one third of cases (30.4%). The situation was significantly better with GPs (p < 0.002) but depended on clinical diagnosis (p < 0.01). The waiting time to seeing a psychiatrist often far exceeded 7 days. CONCLUSIONS: A high density of psychiatrists in private practice does not necessarily improve the long and troublesome circumstances of obtaining a mental health appointment in acute psychiatric situations. Under these circumstances, a considerable proportion of patients might give up prior to seeing a doctor. This has important implications--many patients could miss the potential benefits from timely therapeutic interventions which can significantly modify both the acute and long-term course of the illness. The situation might be improved if psychiatrists and GPs joined forces in the form of group practices or networks as this would readily ensure (1) a rapid mental health triage by assessing and categorizing the urgency of mental health-related problems, and (2) timely therapeutic interventions whenever indicated.