Bipolar symptoms, somatic burden and functioning in older-age bipolar disorder: A replication study from the global aging & geriatric experiments in bipolar disorder database (GAGE-BD) project.

OBJECTIVES: The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project pools archival datasets on older age bipolar disorder (OABD). An initial Wave 1 (W1; n = 1369) analysis found both manic and depressive symptoms reduced among older patients. To replicate this finding, we gathered an independent Wave 2 (W2; n = 1232, mean ± standard deviation age 47.2 ± 13.5, 65% women, 49% aged over 50) dataset. DESIGN/METHODS: Using mixed models with random effects for cohort, we examined associations between BD symptoms, somatic burden and age and the contribution of these to functioning in W2 and the combined W1 + W2 sample (n = 2601). RESULTS: Compared to W1, the W2 sample was younger (p < 0.001), less educated (p < 0.001), more symptomatic (p < 0.001), lower functioning (p < 0.001) and had fewer somatic conditions (p < 0.001). In the full W2, older individuals had reduced manic symptom severity, but age was not associated with depression severity. Age was not associated with functioning in W2. More severe BD symptoms (mania p ≤ 0.001, depression p ≤ 0.001) were associated with worse functioning. Older age was significantly associated with higher somatic burden in the W2 and the W1 + W2 samples, but this burden was not associated with poorer functioning. CONCLUSIONS: In a large, independent sample, older age was associated with less severe mania and more somatic burden (consistent with previous findings), but there was no association of depression with age (different from previous findings). Similar to previous findings, worse BD symptom severity was associated with worse functioning, emphasizing the need for symptom relief in OABD to promote better functioning.

Essential data dimensions for prospective international data collection in older age bipolar disorder (OABD): Recommendations from the GAGE-BD group.

BACKGROUND: By 2030, over 50% of individuals living with bipolar disorder (BD) are expected to be aged ≥50 years. However, older age bipolar disorder (OABD) remains understudied. There are limited large-scale prospectively collected data organized in key dimensions capable of addressing several fundamental questions about BD affecting this subgroup of patients. METHODS: We developed initial recommendations for the essential dimensions for OABD data collection, based on (1) a systematic review of measures used in OABD studies, (2) a Delphi consensus of international OABD experts, (3) experience with harmonizing OABD data in the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD, n ≥ 4500 participants), and (4) critical feedback from 34 global experts in geriatric mental health. RESULTS: We identified 15 key dimensions and variables within each that are relevant for the investigation of OABD: (1) demographics, (2) core symptoms of depression and (3) mania, (4) cognition screening and subjective cognitive function, (5) elements for BD diagnosis, (6) descriptors of course of illness, (7) treatment, (8) suicidality, (9) current medication, (10) psychiatric comorbidity, (11) psychotic symptoms, (12) general medical comorbidities, (13) functioning, (14) family history, and (15) other. We also recommend particular instruments for capturing some of the dimensions and variables. CONCLUSION: The essential data dimensions we present should be of use to guide future international data collection in OABD and clinical practice. In the longer term, we aim to establish a prospective consortium using this core set of dimensions and associated variables to answer research questions relevant to OABD.

The big five model in bipolar disorder: a latent profile analysis and its impact on longterm illness severity.

BACKGROUND: Using a personality typing approach, we investigated the relationship between personality profiles and the prediction of longterm illness severity in patients with bipolar disorder (BD). While previous research suggests associations between BD and traits from the NEO-FFI profiles, the current study firstly aimed to identify latent classes of NEO-FFI profiles, and, secondly, to examine their impact on the longterm prognosis of BD. METHODS: Based on the NEO-FFI profiles of 134 euthymic patients diagnosed with BD (64.2% female, mean age = 44.3 years), successive latent profile analyses were conducted. Subsequently, a subsample (n = 80) was examined prospectively by performing multiple regression analysis of the latent classes to evaluate the longitudinal course of the disease (mean: 54.7 weeks) measured using a modified Morbidity Index. RESULTS: The latent profile analyses suggested a 3-class model typifying in a resilient (n = 68, 51%), vulnerable (n = 55, 41%) and highly vulnerable (n = 11, 8%) class. In the regression analysis, higher vulnerability predicted a higher longterm Morbidity Index (R2 = 0.28). CONCLUSIONS: Subgroups of patients with BD share a number of discrete personality features and their illness is characterized by a similar clinical course. This knowledge is valuable in a variety of clinical contexts including early detection, intervention planning and treatment process.

Clinical use of lithium salts: guide for users and prescribers.

BACKGROUND: Lithium has been used clinically for 70 years, mainly to treat bipolar disorder. Competing treatments and exaggerated impressions about complexity and risks of lithium treatment have led to its declining use in some countries, encouraging this update about its safe clinical use. We conducted a nonsystematic review of recent research reports and developed consensus among international experts on the use of lithium to treat major mood disorders, aiming for a simple but authoritative guide for patients and prescribers. MAIN TEXT: We summarized recommendations concerning safe clinical use of lithium salts to treat major mood disorders, including indications, dosing, clinical monitoring, adverse effects and use in specific circumstances including during pregnancy and for the elderly. CONCLUSIONS: Lithium continues as the standard and most extensively evaluated treatment for bipolar disorder, especially for long-term prophylaxis.

Impulsivity predicts illness severity in long-term course of bipolar disorder: A prospective approach.

BACKGROUND: Bipolar disorder is a common, severe and chronic mental illness. Despite this, predictors of illness severity remain poorly understood. Impulsivity is reported to be associated with bipolar disorder and aggravating comorbidities. This study therefore sought to examine the predictive value of impulsivity for determining illness severity in euthymic bipolar disorder patients. METHODS: Baseline trait impulsivity of 120 bipolar euthymic patients (81 bipolar disorder I [68%], 80 female [67%]) and 51 healthy controls was assessed using Barratt Impulsiveness Scale 11. The impact of impulsivity on illness severity (measured with morbidity index) was prospectively tested in 97 patients with sufficient follow-up data (average observation time: 54.4 weeks), using linear regression analysis. RESULTS: Barratt Impulsiveness Scale 11 total (ß = 0.01; p < 0.01) and in particular Barratt Impulsiveness Scale 11 attentional subscale scores (ß = 0.04; p < 0.001) predicted illness severity in bipolar disorder, while controlling for other clinical variables. Only age at onset persisted as an additional, but less influential predictor. Barratt Impulsiveness Scale 11 total scores and Barratt Impulsiveness Scale 11 attentional subscale scores were significantly higher in euthymic patients compared to controls. This was not observed for the motor or non-planning subscale scores. LIMITATIONS: The average year-long observation time might not be long enough to account for the chronic course of bipolar disorder. CONCLUSION: Trait impulsivity and particularly attentional impulsivity in euthymic bipolar patients can be strong predictors of illness severity in bipolar disorder. Future studies should explore impulsivity as a risk assessment for morbidity and as a therapeutic target in bipolar disorder patients.

[Impact of psychoeducation on the disease concept in bipolar patients]. / Auswirkungen von Psychoedukation auf das Krankheitskonzept bei Betroffenen mit Bipolar affektiver Störung.

Aim of the investigation was the proof of influence of specific psychoeducation for bipolar disorder patients and their concept of illness. Additionally we looked in a subsample at the in literature described equal efficacy of peer to peer councelling and councelling by bipolar specialists in psychoeducationIn our investigation on 176 bipolar patients we could show in group psychoeducation that specific group psychoeducation by trained personal and by experts leads to a changed perception of the disorder concept. The participants relied more in medication and trusted doctors and agreed to suffer from a serious disorder. Our results show that the additional factor alcohol consumption abolishes the effect of psychoeducation in bipolar patients.The concept of the disease was only changed in patients without alcohol consumption. This group showed additional decrease of negetive expectancies and had a hopeful attitude regarding the further course of the disorder.In a subgroup where experts (peers) were trained for psychoeducation councelling and performed peer to peer psychoeducational groups we found the same positive changes in the attitude towards the disorder, but there was a significant higher proportion of dropouts in the peer leaded groups.

Psychiatric and physical comorbidities and their impact on the course of bipolar disorder: A prospective, naturalistic 4-year follow-up study.

OBJECTIVES: The aim of the present study was to increase the available evidence on how physical and psychiatric comorbidities influence the long-term outcome in bipolar I and II disorder. METHODS: We examined the prevalence of comorbid physical (metabolic, cardiovascular, thyroid, and neurological) diseases and psychiatric (neurotic, stress-related, somatoform, and personality) disorders and their impact on the risk of relapse in bipolar disorder. A total of 284 consecutively admitted patients with ICD-10 bipolar I (n=161) and II (n=123) disorder were followed up naturalistically over a period of 4 years. RESULTS: Globally, 22.0% patients had metabolic, 18.8% cardiovascular, 18.8% thyroid, and 7.6% neurological diseases; 15.5% had neurotic, stress-related, and somatoform disorders; 12.0% had personality disorders; and 52.9% had nicotine dependence. We did not find any effect of comorbid metabolic, cardiovascular or neurological diseases or psychiatric disorders on the relapse risk. However, the presence of thyroid diseases, and especially hypothyroidism, was associated with an increased risk of manic relapse in bipolar disorder I (thyroid disease: hazard ratio [HR]=2.7; P=.003; hypothyroidism: HR=3.7;, P<.001). Among patients with hypothyroidism, higher blood levels of baseline thyroid-stimulating hormone (bTSH) were also associated with an increased risk of manic relapse (HR=1.07 per milli-international units per liter; P=.011), whereas blood levels of free triiodothyronine (fT3 ) or free thyroxine (fT4 ) were not found to have an influence. CONCLUSIONS: Our data underline the negative long-term impact of thyroid diseases, and especially hypothyroidism with high blood levels of bTSH, on bipolar disorder with more manic episodes, and the importance of its detection and treatment.

Prevalence and impact of comorbid alcohol use disorder in bipolar disorder: A prospective follow-up study.

OBJECTIVE: Alcohol use disorder may very well increase the likelihood of affective episodes in bipolar disorder, but prospective data on survival are inconsistent. METHOD: The authors examined the prevalence of alcohol use disorders and their impact on the risk of relapse. A total of 284 consecutively admitted International Classification of Diseases-10 bipolar I (n = 161) and II (n = 123) patients were followed up naturalistically over a period of 4 years. RESULTS: The prevalence of alcohol use disorders was higher in bipolar II disorder than in bipolar I disorder (26.8% vs 14.9%; χ(2) = 5.46, p = 0.019), with a global prevalence of alcohol use disorders of 20.1% in the whole sample. A total of 8.7% of bipolar I patients suffered from alcohol abuse and 6.2% from alcohol dependency, whereas 13% bipolar II patients had alcohol abuse and 13.8% alcohol dependency. Male bipolar subjects had a higher prevalence of alcohol use disorders than female patients (38.3% vs 12.8%; χ(2) = 21.84, p-value < 0.001). The presence of alcohol use disorders was associated with an increased risk of depressive relapse in bipolar I patients (Cox regression analysis hazard ratio = 2.7, p = 0.005). The increased risk was not modulated by medication. CONCLUSION: Our data underline the negative long-term impact of alcohol use disorders on bipolar disorder with more depressive bipolar I episodes and the importance of its detection and treatment.

The prevalence and effect of life events in 222 bipolar I and II patients: a prospective, naturalistic 4 year follow-up study.

BACKGROUND: Life events may very well increase the likelihood of affective episodes in bipolar disorder, but prospective data on survival are inconsistent. METHODS: The authors examined the prevalence of negative and goal-attainment life events within 6 months prior to the index episode and after the index episode and their impact on the risk of relapse. Two hundred twenty-two consecutively admitted ICD-10 bipolar I (n=126) and II (n=96) patients were followed-up naturalistically over a period of 4 years. RESULTS: One-hundred thirty-eight (62.2%) of the patients had at least one life event 6 month before the index episode. Seventy patients (31.5%) experienced one, 48 (21.6%) two, and 20 (9.0%) three (or more) life events. Regarding life events after the index episode, 110 (49.5%) patients had at least one life event. Fifty-four patients (24.3%) experienced one, 31 (14.0%) two, and 25 (11.3%) three (or more) life events. The number of life events was larger in patients with bipolar II disorder than in patients with bipolar I disorder (p=0.004). Using a Cox regression analysis, the risk of a depressive relapse in bipolar I patients was associated with the number of life events after the index episode (p=0.002). This was independent of the quality of the life event. LIMITATIONS: Standardized life event scales, defined dosages of drugs or blood sampling during all visits were not performed. CONCLUSIONS: Our data suggest a high and continuous number of life events prior to affective episodes. Life events after the index episode worsened the course of bipolar I patients with more depressive episodes. This underlines the importance of detection and treatment of emerging life events.

Prophylactic lithium treatment and cognitive performance in patients with a long history of bipolar illness: no simple answers in complex disease-treatment interplay.

Cognitive impairment in patients with bipolar disorder (BD) is not restricted to symptomatic phases. It is also present in euthymia. There is evidence of differences in the brain's structure between bipolar patients and healthy individuals, as well as changes over time in patients. Lithium constitutes the gold standard in long-term prophylactic treatment. Appropriate therapy that prevents new episodes improves the disease's course and reduces the frequency of harmful outcomes. Interestingly, preclinical data suggest that lithium has a (additional) neuroprotective effect. There is limited data on its related effects in humans and even less on its long-term application. In this multi-center cross-sectional study from the International Group for the Study of Lithium-treated Patients (IGSLi), we compared three groups: bipolar patients without long-term lithium treatment (non-Li group; <3 months cumulative lithium exposure, ≥24 months ago), bipolar patients with long-term lithium treatment (Li group, ongoing treatment ≥24 months), and healthy subjects (controls). Strict inclusion and exclusion criteria were defined; the inclusion criteria for patients were diagnosis of BD types I or II, duration of illness ≥10 years, ≥5 episodes in patient's history and a euthymic mood state. Neurocognitive functioning was assessed using the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the California Verbal Learning Test (CVLT), and a visual backward masking (VBM) task. A total of 142 subjects were included, 31 in the non-Li and 58 in the Li group, as well as 53 healthy controls. Treated patients with long-standing BD and controls did not differ significantly in overall cognitive functioning and verbal learning, recall, and recognition; regardless of whether lithium had been part of the treatment. Patients, however, demonstrated poorer early visual information processing than healthy controls, with the lithium-treated patients performing worse than those without. Our data suggest that bipolar patients with a long illness history and effective prophylactic treatment do not reveal significantly impaired general cognitive functioning or verbal learning and memory. However, they are worse at processing early visual information. Accompanying volumetric and spectroscopic data suggest cell loss in patients not treated with lithium that may be counterbalanced by long-term lithium treatment.

A prospective 4-year naturalistic follow-up of treatment and outcome of 300 bipolar I and II patients.

BACKGROUND: Because randomized clinical trials in bipolar disorder include restricted study populations, the possibilities for generalizing to real-world bipolar patients are limited. Naturalistic long-term data can add valuable information about the diversity of treatment and outcome in bipolar disorder. METHOD: After discharge from a psychiatric community hospital, 300 consecutively admitted patients with ICD-10 bipolar I (n = 158) and II (n = 142) disorder were followed up naturalistically for 4 years. Patients were assessed with regard to time to relapse, relapse polarity in relation to index episode, prophylactic effects of prescribed medication, prescribing behaviors, and medication adherence. Drugs were chosen by the treating psychiatrists on the basis of clinical judgment. Prescribed medications included lithium, carbamazepine, valproate, lamotrigine, antidepressants, and atypical antipsychotics, all of which were compared as a single mood stabilizer or in combination with at least 2 prophylactic agents. The study was conducted from 2000 through 2008. RESULTS: 204 of 300 patients (68%) relapsed within 4 years, with a mean of 208 days (SD = 356.2) until the next affective episode. Relapses correlated in a statistically significant manner with the index episode (χ²4 = 57.48, P = .000; bipolar I: χ²4 = 20.19, P = .000; bipolar II: χ²4 = 106.82, P = .000). A Kaplan survival analysis showed that lithium in monotherapy statistically significantly delayed time to the next affective relapse (P = .002). Survival (time to relapse) was also statistically significantly reduced when prophylactic medication was changed by the psychiatrist (P = .000) or stopped by the patient (P = .001). In general, no differences in tested parameters were seen between the bipolar I and II groups. CONCLUSIONS: Our data confirm a high risk of relapse in a naturalistic setting. Lithium seems to offer some advantage over other medication over the long-term treatment of bipolar I and II disorder. Patients tend to relapse with the same polarity as their index episode; this emphasizes the importance of the polarity concept. Changing of medications by the psychiatrist and stopping of medication by the patient appear to be risk factors for an earlier affective relapse. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01792128.

[Risks for Burden among Relatives Caring for Schizophrenia Patients]. / Prädiktoren für die Belastung von Angehörigen Schizophreniekranker.

OBJECTIVE: Relatives of persons with schizophrenia have an essential role in informal caregiving. This may result in a high level of burden. Aim of the study was to investigate, if the frequency of unmet needs among relatives caring for schizophrenia patients increases the risk for burden among these relatives. METHODS: 135 relatives of patients with schizophrenia or schizoaffective disorder were investigated by means of the "Involvement Evaluation Questionnaire" (IEQ) and the "Carer's Needs Assessment for Schizophrenia" (CNA-S). RESULTS: Multiple linear regression analyses showed positive associations between the frequency of caregivers' unmet needs and the IEQ-subscores "tension" and "worrying". Further, the IEQ-subscore "worrying" was significantly lower among caregivers of outpatients than among caregivers of inpatients or day hospital patients. The IEQ-subscore "urging" was significantly associated with patient's negative symptoms. CONCLUSION: Unmet needs among caring relatives have negative effects on their burden. Further, the patients' type of treatment setting (inpatient, outpatient, day hospital) seems to predict caregivers' burden.

Impact of sunlight on the age of onset of bipolar disorder.

OBJECTIVE: Although bipolar disorder has high heritability, the onset occurs during several decades of life, suggesting that social and environmental factors may have considerable influence on disease onset. This study examined the association between the age of onset and sunlight at the location of onset. METHOD: Data were obtained from 2414 patients with a diagnosis of bipolar I disorder, according to DSM-IV criteria. Data were collected at 24 sites in 13 countries spanning latitudes 6.3 to 63.4 degrees from the equator, including data from both hemispheres. The age of onset and location of onset were obtained retrospectively, from patient records and/or direct interviews. Solar insolation data, or the amount of electromagnetic energy striking the surface of the earth, were obtained from the NASA Surface Meteorology and Solar Energy (SSE) database for each location of onset. RESULTS: The larger the maximum monthly increase in solar insolation at the location of onset, the younger the age of onset (coefficient= -4.724, 95% CI: -8.124 to -1.323, p=0.006), controlling for each country's median age. The maximum monthly increase in solar insolation occurred in springtime. No relationships were found between the age of onset and latitude, yearly total solar insolation, and the maximum monthly decrease in solar insolation. The largest maximum monthly increases in solar insolation occurred in diverse environments, including Norway, arid areas in California, and Chile. CONCLUSION: The large maximum monthly increase in sunlight in springtime may have an important influence on the onset of bipolar disorder.

[Psychiatric day hospital - one year follow up]. / Psychiatrische Tagesklinik - 1 Jahres Nachuntersuchung.

OBJECTIVE: The psychiatric day hospital of the county hospital Neunkirchen was opened in 2003. All patients of the first year were followed up after one year to review and evaluate our support proposal. RESEARCH DESIGN: The data of all patients who were admitted in the first year were collected before admission, at discharge and after a 1 year follow up period. 57,7% also did psychological questionnaires about psychiatric symptoms, existential orientation, state of health, impairment and selfmanagement ability at all 3 dates. RESULTS: Almost all the patients (93%) utilized an after care offer and were still in aftercare treatment after on year. About 40% had no psychiatric episodes, 62% had no further admission to a psychiatric unit in the follow up period. We also found that the improvement of the psychiatric symptoms, existential orientation, state of health, impairment and selfmanagement ability which was achieved during the treatment was stable over the 1 year follow up period. CONCLUSION: The results of the one year follow up show that the concept of the psychiatric day hospital at Neunkirchen with two diagnose specific treatment groups seems to be successful regarding motivation for after care treatment and the stability of psychiatric symptoms in evidence of further admissions to a psychiatric unit.

[Psychiatric day hospital - missing treatment start and early drop outs]. / Psychiatrische Tagesklinik - Fehlende Behandlungsaufnahme und Vorzeitige Behandlungsbeendigung.

OBJECTIVE: Early drop outs are a common problem in day hospital treatment. In this article special focus is given to patient description and reasons for rejecting the programme after entrance evaluation and informed consent for the program and early drop outs within 7 days. RESEARCH DESIGN: The data of all consecutive patients of the first year were collected before admission, absent treatment start and early drop out. RESULTS: There were no differences found between the group of early drop outs and rejecters and the other patients who participated to the programme as planned regarding social data, diagnostic, severity, distance or feasibility of transportation. The only difference we could find in our data was that the rejecters group had significant more somatic diagnosis. CONCLUSION: We spend lot of time and personal resources on informed consent and selection before admission, which may be one reason for the low drop out rate. The possibilities of transfer to the inpatient unit or to somatic wards are necessary. In our experience it is helpful for treatment in a day hospital to cooperate with and be nearby a psychiatric department at a general hospital.

[Reliability and concordance validity of a German version of the Young Mania Rating Scale (YMRS-D)]. / Relabilität und Übereinstimmungsvalidität der deutschen Version der Young Mania Rating Scale (YMRS-D).

OBJECTIVE: The Young Mania Rating Scale (YMRS) is the most widely used assessment tool for severity of manic symptoms in bipolar patients. While the original English version has been translated to various different languages, a validated German translation of YMRS has not yet been available. METHODS: We translated the original English version to German (YMRS-D) and tested its use in clinical practice in 81 manic inpatients at two different psychiatric hospitals in Austria. The interviews were carried out by eight experienced and trained psychiatrists in random pairs of two interviewers. In order to assess concordance validity of YMRS-D, all patients were simultaneously rated using the Clinical Global Impression Rating Scale, Bipolar Version (CGIBP), by one of three experienced senior raters. RESULTS: Inter-Rater Reliability was assessed calculating the Intra-Class Correlation Coefficient and showed high values (between 0.79 and 0.97, all p<.001) in all items of the German Rating Scale. Internal Consistency analysis of the scale yielded a value of .74 (Cronbach's Alpha). Spearmans rank correlation coefficient for the total scores of CGI-BP and YMRS-G was high (0.91, p<.001), suggesting good concordance validity of YMRS-D. Sensitivity to change was assessed in a subgroup of 20 patients by comparing YMRS-D and CGI-BP total scores at inclusion and at an additional interview three weeks later which showed a highly significant correlation (r = -0,953; p<.0005). CONCLUSIONS: The German version of YMRS seems to be a valid, reliable and useful tool for the assessment and quantification of manic symptoms.

[Minor relatives of schizophrenia patients: burden and needs]. / Minderjährige Angehörige von Schizophrenie-Kranken: Belastungen und Unterstützungsbedarf.

OBJECTIVES: The aim of the present study was to investigate the burden of minor relatives of schizophrenia patients and of the needs for support for the relatives. METHODS: 135 relatives of patients with schizophrenia or schizoaffective disorders were assessed by using the "Involvement Evaluation Questionnaire" and the "Carers' Needs Assessment for Schizophrenia". RESULTS: 24.4% of the total sample (N=33) had minor (i.e. below 18 years) siblings (N=18) or children (N=15). If the patient had minor siblings, almost the half of the adult relatives reported moderate or severe problems. However, among those patients who had to take care for minor children, only a fifth reported moderate or severe problems. Among the patients' offsprings being under the age of 16 behavioural disturbances, reduced appetite and other consequences of the disease were reported frequently. CONCLUSIONS: These results indicate that patients with schizophrenia or schizoaffective disorders often have minor relatives in their family frequently suffering from marked burden.

[Lithium and bipolar disorder--a renaissance?]. / Lithium und bipolare Erkrankung--eine Renaissance?

OBJECTIVE: Overview and discussion regarding the use and relevance of lithium as an therapeutic agent for bipolar disorder in general, with a special focus on pregnancy, suicidality and possible side-effects. METHOD: Literature was handsearched and by searches of medline with special interest in recent results and comparative studies. RESULTS: Lithium is still of high importance in the treatment of bipolar disorder. It is unmatched regarding decades of clinical experience and scientific evidence. It has a proven efficacy in every spectrum of bipolar illness, with less profound data regarding acute bipolar depression. Especially long term treatment of bipolar patients with lithium shows clear clinical benefits i.e.: importance of a continuous setting, gain of mood stabilizing effect over time, no loss of efficacy, reduced morbidity and mortality. DISCUSSION: Lithium should be regarded as a first line treatment for bipolar disorder.

Occurrence of delirium after a short-term intake of olanzapine.

Olanzapine is an atypical antipsychotic drug, which is claimed to have fewer side effects than conventional antipsychotics. We report three cases where patients developed a classic delirium within a few days after first intake of olanzapine. The symptoms fulfilled all criteria of DSM-IV for delirium, and rapidly diminished after discontinuation of olanzapine. Additional reasons for the development of the delirias are possible, but less likely. Special awareness and future research of this phenomenon is highly indicated because of the common use of this drug.