Biomedical subjects

Christopher Baethge

Publications and source records attributed to Christopher Baethge.

At least 19 recordsLinked to original sources

PubMed2006

Self-reported data from patients with bipolar disorder: impact on minimum episode length for hypomania.

OBJECTIVE: Some investigators have suggested decreasing the minimum hypomania episode length criterion from 4 days, as in the DSM-IV, to 2 days. Using daily self-reported mood ratings, we studied the impact of changing the length requirement on the number of hypomanic episodes in patients with bipolar disorder. METHOD: 203 patients (135 bipolar I and 68 bipolar II by DSM-IV criteria) recorded mood daily using ChronoRecord software (30,348 total days, mean 150 days). Episodes of hypomania and days of hypomania outside of episodes were determined. RESULTS: Decreasing the minimum duration criterion for an episode of hypomania from 4 to 2 days doubled the mean percent of days in a hypomanic episode for each patient (4% to 8%), doubled the number of patients with a hypomanic episode (44 to 96) and increased the number of hypomanic episodes for all patients about three-fold (129 to 404). With a minimum episode length of 4 days, bipolar I patients were more likely to report hypomania outside episodes than bipolar II patients (p=0.010), but with a length of 2 or 3 days there was no significant difference in the distribution of hypomania outside of episodes by diagnosis. With a 2-day length, about one-third (36%) of hypomania remained outside of an episode. LIMITATIONS: Self-reported data, computer access, relatively short length, fewer bipolar II than bipolar I patients. CONCLUSION: As the minimum length for an episode of hypomania decreases, there was a large increase in both the number of episodes and number of patients with episodes. One-day hypomania outside of episodes occurs frequently in both bipolar I and bipolar II disorder.

Adult↗

PubMed2006

Approximate entropy of self-reported mood prior to episodes in bipolar disorder.

BACKGROUND: Approximate entropy (ApEn) measures regularity in time series data, while traditional linear statistics measure variability. Using self-reported mood data from patients with bipolar disorder, this preliminary study addressed whether ApEn could distinguish (i) the 60 days prior to the start of a manic or depressed episode from the 60 days prior to a month of euthymia, and (ii) the 60 days prior to a manic episode from the 60 days prior to a depressed episode. METHODS: Self-reported mood data from 49 outpatients with bipolar disorder receiving standard treatment were analysed. The data contained 27 episodes (12 manic and 15 depressed), and 43 periods of 1 month of euthymia. For the 60 days prior to episode or euthymia, the ApEn, linear statistics and the correlation between linear and non-linear measures were calculated. RESULTS: ApEn was significantly greater in the 60 days prior to a manic or depressive episode than the 60 days prior to a month of euthymia. The onset of an episode was associated with greater irregularity in mood. Variability was also significantly larger and correlated with ApEn. ApEn was significantly greater in the 60 days prior to a manic episode than in the 60 days prior to a depressed episode, whereas measures of variability were not significantly different. Mood in the 60 days prior to mania was more irregular than prior to depression. CONCLUSIONS: Non-linear measures may complement traditional linear measures in the analysis of longitudinal data in bipolar disorder. A larger study is indicated.

Adult↗

PubMed2005

Secular trends in first hospitalizations for major mood disorders with comorbid substance use.

In the past half-century, the incidence of major mood disorders reportedly has risen, and onset age, diminished. Substance-use disorders (SUDs) are commonly comorbid with mood disorders and may influence their course and outcome. Since secular relationships of these disorders remain unknown, we evaluated medical records of 421 patients (233 men, 188 women) at first-lifetime admissions for major depression, mania or mixed bipolar episodes at a public hospital in Italy during 1978-2002, updated diagnoses to DSM-IV criteria, and compared selected factors between subjects with vs. without SUDs, seeking evidence of secular trends in SUDs in association with early mood disorders. SUD was diagnosed in 122 patients (29.0%). SUD risk was greatest in young males. Relative risk (RR) of diagnostic association with SUDs ranked: mixed states (RR 1.80), mania (RR 1.06), depression (RR 0.55). Annual rates of comorbid SUD and mood disorders increased continuously over the 25-yr epoch for all substances (r=0.640, p<0.001). Age at onset of illness and at first hospitalization (averaging 36 yr and 38 yr) were unrelated to year of hospitalization in this relatively brief sampling, but patients with SUD were younger at onset and admission, overall. Clinical Global Impression (CGI) ratings of illness severity at hospitalization and discharge were stable across years. These findings indicate a secular increase of comorbid SUD among first admissions for mood disorder, especially in young males, with a parallel increase in the proportion of bipolar disorder diagnoses over the past quarter of a century.

Adult↗

PubMed2005

Is dose escalation of antidepressants a rational strategy after a medium-dose treatment has failed? A systematic review.

BACKGROUND: Maximizing the dose of antidepressants is widely recommended in cases of non-response to medium-dose treatment. However, scientific evidence supporting high-dose treatment is scarce. Systematic studies comparing dose escalation with alternative strategies for refractory depression (i. e. augmentation or change of compound) are lacking. The aim of this publication is to review available direct and indirect evidence concerning dose increase of antidepressants after a medium-dose trial has failed. METHOD: We performed a systematic literature search of Medline (1966-2003) and reviewed studies and publication references for available evidence. DATA SOURCES AND STUDY SELECTION: Studies of the following types were included: 1) dose increase studies in treatment refractory patients, 2) comparative dose studies, 3) therapeutic drug monitoring studies. RESULTS: Available data suggest differential efficacy of various pharmacological classes at more than medium-dosage. Direct evidence shows no increase of efficacy with high-dose selective serotonin reuptake inhibitor (SSRI) treatment; however, indirect evidence suggests enhanced therapeutic efficacy with high-dose tricyclic antidepressants. Few clinical data show ultra-high-dose treatment with the irreversible monoamine-oxidase-(MAO-) inhibitor tranylcypromine to be effective for refractory depression. Data concerning other selective compounds are insufficient to allow any definitive conclusion on the benefit of high-dose treatment. CONCLUSIONS: Based on available data highdose antidepressant treatment of patients refractory to medium-dose treatment is recommended for tricyclic compounds but not for SSRI. Some data suggest beneficial efficacy of ultra-high doses of the irreversible MAOI tranylcypromine. Research on other substance groups is limited and inconclusive. Prospective studies comparing dose escalation with alternative strategies for treatment of non-responding patients are needed.

Antidepressive Agents↗

PubMed2005

Hallucinations in bipolar disorder: characteristics and comparison to unipolar depression and schizophrenia.

OBJECTIVE: As there is very little research on the topic, we compared the frequency and the type hallucinations among hospitalized patients diagnosed with bipolar disorder (BPD) versus other major psychiatric illnesses. METHODS: At admission, all patients hospitalized at the Department of Psychiatry at the Freie Universität Berlin (1981-2001) underwent comprehensive assessments using the standardized Association for Methodology and Documentation in Psychiatry (AMDP) system. We used these data to compare risks and types of hallucinations and associated factors by bivariate and multivariate testing in patients diagnosed with BPD, major depression, or schizophrenia. RESULTS: At admission, the cross-sectional prevalence of current hallucinations among 4972 hospitalized subjects ranked: schizophrenia (61.1%), bipolar mixed (22.9%), bipolar manic (11.2%), bipolar depressed (10.5%), unipolar depressed (5.9%). The most frequent hallucinations across all patients were auditory, followed by somatic and visual hallucinations. There were only minor age or sex differences in risk of hallucinations. Compared with patients diagnosed with schizophrenia, hallucinations among patients with BPD were less severe, more visual and less often auditory. Characteristics of hallucinations were similar among manic and both bipolar- and unipolar-depressed subjects. Among patients with major affective disorders, those with hallucinations were less well-educated, had higher anxiety scores, less insight into the illness, and their hospitalizations averaged 17% longer. Across all diagnoses, hallucinations, particularly olfactory, were significantly associated with delusions. Hallucinations in BPD were most often accompanied by persecutory delusions; delusions of grandeur were least associated with hallucinations. CONCLUSIONS: This study provides detailed descriptive data regarding the frequency (cross-sectional) and characteristics of hallucinations in a large sample of patients with BPD, major depression or schizophrenia. Our results suggest a link of lower education and the presence of hallucinations in major affective disorders. The significance of this finding, as well as the role of anxiety in hallucinating patients, requires further study.

Adult↗

PubMed2005

Substance abuse in first-episode bipolar I disorder: indications for early intervention.

OBJECTIVE: This study clarified the early characteristics of substance use disorders in patients with first-episode bipolar I disorder. METHOD: The authors evaluated substance use disorders, associated factors, and clinical course, prospectively, in the first 2 years of DSM-IV bipolar I disorder with standardized methods. RESULTS: Baseline substance use disorder was found in 33% (37 of 112) of the patients at baseline and in 39% at 24 months. Anxiety disorders were more frequent in the patients with than without substance use disorder (30% and 13%, respectively). Associations of alcohol dependence with depressive symptoms and cannabis dependence with manic symptoms were suggested. Patients using two or more substances had worse outcomes. CONCLUSIONS: Since substance use disorders were frequent from the beginning of bipolar I disorder and were associated with anxiety disorders and poor outcome, early interventions for substance use disorder and anxiety might improve later outcome.

Adult↗

PubMed2005

Long-term combination therapy versus monotherapy with lithium and carbamazepine in 46 bipolar I patients.

BACKGROUND: Despite wide clinical use of mood-stabilizer combinations for long-term treatment of patients with bipolar disorder, research on risks and benefits of this practice is limited. We found 14 small, usually brief, clinical trials of maintenance treatment with lithium plus carbamazepine. These trials suggest added benefit of combination treatment over use of either agent alone but also indicate the need for further studies. METHOD: In a post hoc analysis, we reviewed the course of 46 patients with DSM-IV-diagnosed bipolar I disorder identified as not improving during long-term monotherapy in a mood disorders clinic, comparing days per year hospitalized in 3 consecutive time periods: before prophylactic treatment, during monotherapy with lithium (N = 31) or carbamazepine (N = 15), and during their combined use (N = 46). Secondary outcome measures were rates of hospitalization, time to first recurrence of an affective episode, use of adjunctive treatments, and adverse effects. We compared outcomes with nonparametric bivariate methods and tested predictive factors by multiple regression. RESULTS: Subjects showed significant reductions in hospitalized days per year during combination therapy, averaging a decrease of 55.9% (p = .004). Among secondary outcomes, hospitalizations per year fell by 36.1%, and median time to recurrence nearly doubled during combination therapy. Rates of adverse effects increased 2.5-fold, compared with monotherapy, and use of adjunctive psychotropic agents increased by 21.9%. CONCLUSION: Combining lithium with carbamazepine yielded substantial benefit but more adverse effects.

Adult↗

PubMed2005

Long-term lithium treatment and thyroid antibodies: a controlled study.

OBJECTIVE: Because the role of thyroid autoimmunity in the development of lithium-induced thyroid dysfunction remains controversial, we compared the prevalence of thyroid autoantibodies in patients with affective disorders receiving long-term lithium maintenance therapy with that of age- and sex-matched controls. METHODS: We conducted a cross-sectional study with 100 adult patients with major affective disorders diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, revised (DSM-III-R), who were undergoing lithium therapy for 6 months or more at a specialized lithium university clinic and 100 age- and sex-matched controls with no history of an axis I psychiatric disorder. Serum autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb) and TSH receptors (TRAb) were measured. RESULTS: TPOAb were found in 7 patients and 11 controls, and TgAb were found in 8 patients and 15 controls. TRAb were not found in either group. CONCLUSIONS: In this sample of patients with affective disorders, long-term lithium treatment did not increase the prevalence of thyroid autoimmunity.

Adult↗

PubMed2004

Bone mineral density during maintenance treatment with supraphysiological doses of levothyroxine in affective disorders: a longitudinal study.

BACKGROUND: This prospective study was designed to determine whether patients with prophylaxis-resistant affective disorders, receiving adjunctive maintenance therapy with supraphysiological doses of levothyroxine (L-T4), show evidence of accelerated bone loss compared to the reference population database. METHODS: In 21 patients, bone mineral density (BMD) of the spine (lumbar vertebrae L1-L4) and femur (femoral neck, trochanter, and Ward's triangle) was measured by dual energy X-ray absorptiometry (DXA). BMD measurement was performed first after patients had been on thyroid-stimulating hormone (TSH)-suppressive therapy with L-T4 (mean dose=411 mcg/d) for an average of 16.4 months and again after 33.6 months of L-T4 (mean dose=416 mcg/d) therapy. RESULTS: There was no statistically significant difference between the actual percentage decline in bone mineral density and the expected percentage decline in any of the measured bone regions. In a stepwise linear regression analysis, age was identified as a predictor of percentage change in BMD. After controlling for age, the only other variable that showed a consistent trend was the dose of L-T4, with higher doses being positively correlated with the percentage decline of BMD. LIMITATIONS: Relatively small sample size, no bone density assessment prior to treatment with L-T4, no patient control group with mood disorders who did not receive L-T4 treatment, and bone density follow-up intervals were variable. CONCLUSIONS: This study did not demonstrate evidence that long-term treatment of affectively ill patients with supraphysiological doses of L-T4 significantly accelerates loss of bone mineral density compared to the age-matched reference population. However, the decline of BMD in one individual patient underscores that caution is indicated and that regular assessment of BMD during longer-term supraphysiological thyroid hormone treatment is needed.

Absorptiometry, Photon↗

PubMed2004

Prophylaxis of schizoaffective disorder with lithium or carbamazepine: outcome after long-term follow-up.

OBJECTIVES: This study was conducted (1) to assess the prophylactic efficacy of lithium and carbamazepine in the maintenance treatment of schizoaffective disorder (SAD) with long-term follow-up, (2) to find predictors of the success or failure of prophylaxis, and (3) to search for differences in outcome between schizoaffective patients diagnosed according to either ICD-10 or DSM-IV. METHODS: Participating patients met the ICD-10 and/or DSM-IV criteria for schizoaffective disorder. Outcome was assessed using the Morbidity Index and time elapsed until the first recurrence during prophylaxis. Predictor variables were age at onset of illness, gender, and family history, as well as the following parameters prior to prophylaxis: time between onset of illness and start of prophylactic treatment (latency), severity of illness (hospitalization rate), number of hospital admissions and polarity of schizoaffective disorder (schizobipolar vs. schizounipolar). The time spent in the hospital per year was used to compare the course of illness before maintenance therapy to the time during maintenance therapy. Co-medication was taken into account. The clinical data during prophylaxis were ascertained prospectively. RESULTS: Forty-nine patients met the ICD-10 criteria for schizoaffective disorder, 34 of whom also met the DSM-IV criteria. All 49 patients underwent prophylactic therapy with either lithium (n=41) or carbamazepine (n=8) for an average of 6.8 years. After initiating prophylaxis, the number of days spent in the hospital declined dramatically from an average of 71 days to 11 days per year. No independent variable proved to be a consistent predictor of the course of treatment. In regard to the subgroup of patients diagnosed according to DSM-IV, no significant differences were observed when this subgroup was compared to the whole sample. LIMITATIONS: As this is a naturalistic study it does not allow for exact quantitative measures of effectiveness. CONCLUSIONS: This study is the first of its kind to investigate the efficacy of maintenance therapy in SAD over such an extended period of time. The results of the study show that lithium and carbamazepine appear to be highly effective in treating patients with schizoaffective disorder. However, it remains unclear how many schizoaffective patients will respond to mood stabilizer treatment and whether predictors of clinical relevance exist. In our sample, differences in the ICD-10 and DSM-IV diagnostic criteria for schizoaffective disorder were not related to significant differences in clinical outcome.

Adult↗

PubMed2004

A survival analysis for recurrent events in psychiatric research.

OBJECTIVES: Time to first recurrence, as analyzed by the Kaplan-Meier (KM) survival analysis, is a commonly applied statistical method in psychiatric research. However, many psychiatric disorders are characterized not by a single event, but rather by recurrent events, such as multiple affective episodes. This study aims to demonstrate a method of survival analysis that takes multiple recurrences into account. METHODS: We examined data on sex differences in a sample of 181 patients undergoing prophylactic treatment with lithium or carbamazepine (serum level assayed) for bipolar disorder (ICD-10). The classical KM method was compared with an approach developed by Peña, Strawderman and Hollander (PSH) that uses recurrent event data to estimate survival function. RESULTS: The results obtained with the multiple events method differed considerably from those acquired using the standard KM analysis. When taking recurrent event data into account, the probability of remaining well was lower and survival times were longer. In addition, whereas the standard KM analysis indicated that male patients had a higher likelihood of remaining well, the alternative method revealed that both sexes were similarly likely to remain well. CONCLUSIONS: Survival analysis techniques that take recurrent events into account are potentially important instruments for the study of psychiatric conditions characterized by multiple recurrences. In many cases, the standard KM analysis appears to provide only a rough approximation of the course of illness.

Adult↗

PubMed2004

Manic-depressive illness in children: an early twentieth-century view by Theodor Ziehen (1862-1950). Introduction.

The German psychiatrist and philosopher Theodor Ziehen (1862-1950), little known in psychiatry today, wrote on of the first systematic treatises on child psychiatry in the early years of the twentieth century. This report provides the first English translation of Ziehen's chapters on major mood disorders of children and adolescents, with detailed biographical notes and commentary on his contributions to the foundation of child psychiatry and to characterizing manic-despressive illness in this age group.

Bipolar Disorder↗

PubMed2003

Lithium augmentation increases post-dexamethasone cortisol in the dexamethasone suppression test in unipolar major depression.

Although considerable evidence exists on the efficacy of lithium as an augmenting agent in refractory depression, the underlying neurobiology of this phenomenon is unknown. In patients with major depression, changes of the hypothalamic-pituitary-adrenocortical (HPA) system have been detected by means of the dexamethasone suppression test (DST), when administered during treatment with tricyclic antidepressants. We investigated whether the DST also reveals alterations of the HPA system during lithium augmentation. We also sought to identify whether response to lithium augmentation can be predicted with the DST. Twenty-five patients with unipolar major depression, who did not respond to an adequate antidepressant monotherapy of at least 4 weeks, were measured for basal (pre-dexamethasone, 0800h) cortisol and ACTH levels and were administered the DST the day before initiation of lithium augmentation treatment. The same neuroendocrine procedures were repeated after 3 to 4 weeks. Criteria of response to lithium augmentation, defined as a reduction of the Hamilton Depression Rating Scale (HDRS17) score by > or =50% and an end point score of 9 or less, were determined by weekly HDRS ratings. The DST revealed a statistically significant increase of the post-dexamethasone cortisol values (P = 0.021) and an increase in the post-dexamethasone ACTH values (P = 0.051) during lithium augmentation as compared to pre-treatment baseline evaluations. The pre-dexamethasone hormone values were unchanged. The number of non-suppressors at baseline was one and increased to three at follow-up. Results of DST did not predict response to lithium augmentation, which occurred in 40% of subjects. Results suggest that lithium augmentation increases HPA system activity, as indicated by the increase of post-dexamethasone cortisol and ACTH levels measured by the DST. This is in contrast to the established decline of HPA system activity during treatment with tricyclic antidepressants.

Adolescent↗

PubMed2003

Lithium augmentation therapy in refractory depression-update 2002.

Lithium has been used to augment the efficacy of antidepressant medications for more than 20 years. The present study examines whether evidence exists to support the clinical efficacy of lithium augmentation in refractory, treatment resistant depression. Studies were identified by searching Medline (1980 to August 2002) and by scanning the references of published reviews and standard textbooks. Studies were selected if they were open-labeled or double-blind, placebo-controlled or comparator trials that involved patients who had not responded to conventional antidepressants. 27 prospective studies were identified that included a total of 803 depressed patients displaying the following designs: 10 double-blind, placebo-controlled trials, 2 randomized, double-blind comparator trials, 2 randomized, open comparator trials, and 13 open-label trials. The majority of randomized controlled trials has demonstrated substantial efficacy of lithium augmentation in partial and non responders to antidepressant treatment. In the placebo-controlled trials, the response rate in the lithium group was 45% and in the placebo group 18% (p<0.001). Summarizing all open and controlled studies, approximately 50% of patients responded to lithium augmentation within 4 weeks. In conclusion, lithium is the foremost and most well-documented augmentation strategy in refractory depression.Therefore, it should be considered a first-line treatment strategy in patients with major depression who do not adequately respond to standard antidepressants.

Adult↗

PubMed2003

Wrist fracture in a patient undergoing electroconvulsive treatment monitored using the "cuff" method.

We report on a case of a 64-year-old female patient who received electroconvulsive treatment for major depression. The patient sustained a fracture to the distal radius of the arm blocked by the "cuff" method (Smith fracture). Subsequent investigations revealed that she was suffering from osteoporosis. This case report underlines the importance of special treatment procedures for osteoporotic patients and other patient groups at risk for fractures. We recommend screening for osteoporosis in routine pre-ECT evaluation, even in younger patients, and propose not attaching the cuff to the arm in those at risk for fractures. In our patient, electroconvulsive therapy was safely continued using higher doses of succinylcholine and without the cuff method.

Depression↗

PubMed2003

Lithium augmentation therapy in refractory depression: clinical evidence and neurobiological mechanisms.

OBJECTIVE: This systematic review examines the evidence and discusses the clinical relevance of lithium augmentation as a treatment strategy for refractory major depressive episodes. It also examines hypotheses on the mode of action of lithium augmentation, with a focus on serotonin (5-HT) and neuroendocrine systems, and proposes recommendations for future research. METHOD: We searched the Medline computer database and the Cochrane Library for relevant original studies published in English from January 1966 to February 2003. The key words were as follows: lithium, augmentation strategies, lithium augmentation, major depression, refractory depression, treatment-resistant depression, neuroendocrinology, and serotonin. RESULTS: Of 27 prospective clinical studies published since 1981, 10 were double-blind, placebo-controlled trials, 4 were randomized comparator trials, and 13 were open-label trials. Five of 9 acute-phase placebo-controlled trials demonstrated that lithium augmentation had substantial efficacy. In the acute-treatment trials, the average response rate in the lithium group was 45%, and in the placebo group, 18% (P < 0.001). One placebo-controlled trial showed the efficacy of lithium augmentation in the continuation-phase treatment. Summarizing the open and controlled data, approximately 50% of patients responded to lithium augmentation within 2 to 6 weeks. Animal studies offer robust evidence that lithium augmentation increases 5-HT neurotransmission, possibly by a synergistic action of lithium and the antidepressant on brain 5-HT pathways. CONCLUSIONS: Augmentation of antidepressants with lithium is the best-documented augmentation therapy in the treatment of refractory depression. Emerging data from animal studies suggest that the 5-HTergic system is involved in the augmentatory effect of lithium.

Animals↗

PubMed2003

Prophylaxis latency and outcome in bipolar disorders.

OBJECTIVE: To analyze new and reviewed findings to evaluate relations between treatment response and latency from onset of bipolar disorder (BD) to the start of mood-stabilizer prophylaxis. METHOD: We analyzed our own new data and added findings from research reports identified by computerized searching. RESULTS: We found 11 relevant studies, involving 1485 adult patients diagnosed primarily with BD. Reported latency to prophylaxis averaged 9.6 years (SD 1.3), and follow-up in treatment averaged 5.4 years (SD 3.1). Greater illness intensity and shorter treatment latency were closely associated, resulting in a greater apparent reduction in morbidity with earlier treatment. However, this finding was not sustained after correction for pretreatment morbidity, and treatment latency did not predict morbidity during treatment. Therefore, assessments based on improvement with treatment, or without correction for pretreatment morbidity, can be misleading. CONCLUSIONS: Available evidence does not support the proposal that delayed prophylaxis may limit response to prophylactic treatment in BD and related disorders.

Anticonvulsants↗

PubMed2003

Cyclothymia, a circular mood disorder.

Ewald Hecker (1843-1909) was a collaborator of Karl Ludwig Kahlbaum (1828-1899). Both worked outside the university and public mental institutions of Germany. By meticulously observing clinical signs and illness-course, they laid the groundwork for modern descriptive psychiatry. Their clinical approach influenced Kraepelin and continues to dominate psychiatric classification. Hecker popularized several of Kahlbaum's syndromal concepts, including hebephrenia. Another was cyclothymia, a relatively benigh form of manic-depressive illness, introduced by Kahlbaum, in 1882. It included depressive (dysthymia), hypomanic (hyperthymia), and mixed hypomanic-depressive phases. The Kahlbaum-Hecker syndrome of cyclothymia survives in DSM-IV bipolar II disorder and cyclothymia. An annotated English translation of Hecker's 1898 paper is provided, with historical notes on Hecker and the significance of his work.

Cyclothymic Disorder↗