Biomedical subjects
Publications and source records attributed to H Grunze.
The Internet has a powerful effect on society and thereby also on psychiatric patients. It offers suicide prevention services but also is a source of information and exchange of thoughts on how to commit suicide. This paper describes an 18-year-old female who learned about methods of suicide in the Internet and then ordered barbiturates. She survived because of early intervention.
BACKGROUND: Few studies have examined the relative risks of switching into hypomania or mania associated with second-generation antidepressant drugs in bipolar depression. AIMS: To examine the relative acute effects of bupropion, sertraline and venlafaxine as adjuncts to mood stabilisers. METHOD: In a 10-week trial, participants receiving out-patient treatment for bipolar disorder (stratified for rapid cycling) were randomly treated with a flexible dose of one of the antidepressants, or their respective matching placebos, as adjuncts to mood stabilisers. RESULTS: A total of 174 adults with bipolar disorder I, II or not otherwise specified, currently in the depressed phase, were included. All three antidepressants were associated with a similar range of acute response (49-53%) and remission (34-41%). There was a significantly increased risk of switches into hypomania or mania in participants treated with venlafaxine compared with bupropion or sertraline. CONCLUSIONS: More caution appears indicated in the use of venlafaxine rather than bupropion or sertraline in the adjunctive treatment of bipolar depression, especially if there is a prior history of rapid cycling.
Despite many advances in making the diagnosis of bipolar disorder, five to twelve years lie between the first affective episode and the introduction of an effective treatment. However, it is estimated that approximately only one-fourth of the patients with bipolar disorder are recognized as such at all. Clinical experience plays an important role in the diagnosis. Manias are often the cause for the first treatment with drugs, but the daily lives of patients with bipolar depression are often clearly more negatively affected. The acute therapy of bipolar depression is more complicated than that of mania and the difficult long-term treatment is always associated with a high suicide risk. A long-term therapy of bipolar disorders is not only meaningful for the prevention of new disease episodes, but also because it has a positive effect on comorbidities.
Bipolar disorders are often diagnosed too late with an average of ten years elapsing between the first disease episode and the correct diagnosis and treatment. The most common misdiagnoses are unipolar depression, schizophrenia and ADHD (Attention Deficit Hyperactivity Disorder). The suicide rate associated with bipolar disease is very high. Treatment consists in the administration of mood stabilizers, in the first instance lithium, but also atypical neuroleptics or lamotrigine. In the depressive phase, additional antidepressants or lamotrigine, in the manic phase valproate or an antipsychotic agent may be needed. Medication must be continued unchanged for several months beyond acute treatment. The subsequent relapse prophylaxis depends on effectiveness, tolerability, comorbidity, suicidal risk and compliance. Pharmacotherapy is supplemented by psychotherapy and psycho-education.
The new curriculum for medical licensure in Germany focuses on interdisciplinary and problem-based learning. In recent years, first experiences with this learning model were gathered in several German medical schools conducting courses supplementing the traditional curriculum. This article describes the course "Nervous system and behavior" at Ludwig Maximilian University in Munich. This course was established in cooperation with Harvard University in Boston, USA (The Munich-Harvard Alliance) together with three other clinical courses and has run every semester since the winter of 1999. As this course integrates neuroscience disciplines with special emphasis on neurology and psychiatry, it may serve as a role model for the implementation of these subjects in a new curriculum. This article introduces the reader to its structure and elements as well as feedback from students.
With costs of approximately 5.8 billion EUR annually, bipolar disorders represent a substantial burden on German society. The costs are mainly due to high indirect costs caused by morbidity-related unemployment, suicide-related losses of productivity, time off from work, and early retirement. Inpatient care, with a considerable average length of stay for patients with bipolar disorders, accounts for two-thirds of direct costs. This paper refers to statistics on use of healthcare services based primarily on the International Statistical Classification of Diseases, Tenth Revision. Representing a relatively narrow definition of bipolar disorders in comparison with the clinically relevant spectrum, this classification leads to a conservative estimate of the total costs. The significant lag between first acute episode and a correct diagnosis causes a delayed onset of maintenance treatment that leads to increased costs. Increasing public awareness, destigmatizing the disease, and educating physicians are necessary steps to limit the substantial economic burden for society.
Substance P (SP) is possibly involved in the etiopathology of affective disorders. Here we investigated the relationship of SP serum levels and response to antidepressant drug therapy. SP serum levels were determined before and during a 9-week drug trial in 40 depressed patients treated with paroxetine in combination with either lamotrigine (n = 20) or placebo (n = 20). Responders (n = 18) and non-responders (n = 22) significantly differed in SP serum levels: responders started with higher SP levels that decreased during drug therapy, whereas non-responders had lower SP levels that increased at the beginning. There were no differences between patients with adjunct lamotrigine or placebo. These preliminary data indicate that SP serum levels might be related to response to antidepressant drug therapy. Further studies have to substantiate this finding.
Quetiapine, a new atypical antipsychotic, was added to ongoing treatment of bipolar I outpatients (n=15) for symptoms of illness (mood lability, irritability, psychosis and/or difficulty sleeping). All evaluations were prospectively obtained, with the majority of patients (n=9) showing much or very much improvement on the Clinical Global Impression for Bipolar Disorder (CGI-BP). Somatic complaints were limited. Mean (SD) duration before changes in medication regimens was 134 (100) days. Studies of the use of quetiapine in maintenance treatment of bipolar disorder are warranted.
The term bipolar disorder is no longer limited to the classical manic-depressive condition, but now subsumes a wide spectrum of illnesses. As a consequence of this expansion of the classification systems, the therapeutic utility of lithium and other mood stabilizing agents has to be defined anew. The majority treatment recommendations differentiate, symptom-related, between euphoric mania, mixed conditions, mania with psychotic symptoms and rapid cycling manic episodes. Current acute treatment includes, in addition to lithium, in particular carbamazepine and valproate, but also newer antiepileptic drugs such as lamotrigine or atypical neuroleptic agents such as olanzapine and risperidone. Due to the high suicidal risk, patients with bipolar depression often need to be given an antidepressant as well. It must, however, be remembered that in patients with rapid cycling, antidepressants may re-trigger mania.
The broadening of the classification systems for manic-depressive illness towards a spectrum of bipolar disorders implicates a more differentiated use of pharmacotherapies. However, many questions still remain open. This implies that all consensus guidelines and recommendations have to be considered as preliminary. On the other hand, research in the last decade has developed many new treatment alternatives, both for mood stabilizers and antidepressants as well as antipsychotics. These recommendations, which have been developed in the process of two consensus meetings, try to consider the broadening of the concept of bipolar disorder by differentiating between subgroups according to acute symptomatology and characteristics of the long-term course, e.g., rapid cycling. In particular, the emerging role and new indications of mood stabilizing antiepileptic drugs, atypical antipsychotics, and new antidepressants will be discussed.
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We reviewed the available literature on the efficacy of a novel anticonvulsant, Tiagabine (TGB), in the treatment of bipolar disorder. Study results indicate that TGB does not represent a valid option in acute mania due its required slow, progressive titration. More rapid titration schemes may lead to severe complications. TGB may be an option as an adjunct long-term treatment approach in refractory patients, but further studies are clearly needed to support this.
Bipolar rapid cycling (RC) is defined as 4 or more affective episodes within 1 year. It has been postulated that RC is related to a poor response to lithium, to the same extent as mixed episodes or other atypical symptoms of the illness. This article reviews the current status of alternative pharmacological or otherwise supportive therapies of RC. Biological parameters and characteristics of the illness associated with RC like gender prevalence in women, hyperthyroidism, catecholamine-O-methyltransferase allele, the influence of sleep, different subtypes of bipolar disorder and the risk of antidepressant-induced cycling will be discussed in detail.
Atypical neuroleptics are increasingly used in the treatment of bipolar and schizoaffective disorders. Currently, numerous controlled short-term studies are available for clozapine, olanzapine, risperidone or quetiapine, but long-term data are still missing. Three patients (2 with bipolar disorder, 1 with schizoaffective disorder) are described who showed a marked reduction of affective symptomatology after clozapine had been added to mood stabilizer pretreatment. The patients were seen once a month before and after the introduction of clozapine for at least 6 months. Treatment response was evaluated using different rating scales (IDS, YMRS; GAF; CGI-BP) and the NIMH Life Chart Methodology. All patients showed a marked improvement after the add-on treatment with clozapine had been initiated. Clozapine was tolerated well with only transient and moderate weight gain and fatigue as only side effects. This case series underlines the safety and efficacy of clozapine as add-on medication in the treatment of bipolar and schizoaffective disorders.
The Stanley Foundation Bipolar Network (SFBN) is an international, multisite network investigating the characteristics and course of bipolar disorder. Methods (history, ratings and longitudinal follow-up) are standardized and equally applied in all 7 centres. This article describes demographics and illness characteristics of the first 152 German patients enrolled in the SFBN as well as the results of 2.5 years of follow-up. Patients in Germany were usually enrolled after hospitalisation. More than 72% of the study population suffered from bipolar I disorder and 25% from bipolar II disorder. The mean +/- SD age of the study participants was 42.08 +/- 13.5 years, and the mean +/- SD age of onset 24.44 +/- 10.9 years. More than 40% of the sample reported a rapid-cycling course in history, and even more a cycle acceleration over time. 37% attempted suicide at least once. 36% had an additional Axis I disorder, with alcohol abuse being the most common one, followed by anxiety disorders. During the follow-up period, only 27% remained stable, 56% had a recurrence, 12.8% perceived subsyndromal symptoms despite treatment and regular visits. 27% suffered from a rapid-cycling course during the follow-up period. Recurrences were significantly associated with bipolar I disorder, an additional comorbid Axis I disorder, rapid cycling in history, a higher number of mood stabilizers and the long-term use of typical antipsychotics. Rapid cycling during follow-up was only associated with a rapid-cycling course in history, a higher number of mood stabilizers and at least one suicide attempt in history.
UNLABELLED: Myelinolysis may occur as a severe complication of eating disorders, especially anorexia nervosa (AN). One of the most important reasons can be a rapid correction of hyponatremia caused by tubulopathy, water intoxication (WI), or abuse of diuretics in individuals with AN. METHOD AND RESULTS We report on a 24-year-old female patient with an 8-year history of AN. A rapid correction of severe hyponatremia and hypokalemia induced by WI led to central pontine myelinolysis, which was confirmed by magnetic resonance imaging (MRI) examination. Besides affective lability, incoherence, and an acute confusional state, surprisingly, no severe neurological symptoms emerged. CONCLUSION: Thus, physicians should be aware of the risk of pontine myelinolysis with new psychiatric symptoms emerging in the absence of obvious neurological deficits.
Pharmacotherapeutic intervention in psychiatric patients often bears the risk of drug abuse for suicide attempts. Especially intoxication with tricyclic antidepressants, e.g., amitriptyline, may cause severe complications such as cardiac arrhythmia. Even under intensive care conditions, 2-3% of intoxicated patients still die. Here, we report on a depressed female patient who, thanks to timely and intense intervention, survived a suicide attempt with amitriptyline despite highly toxic plasma levels.
Little is known about possibilities of chronic hepatitis C treatment with interferon-alpha (IFN-alpha) in psychiatric patients continuously taking antipsychotics. We report on a 28-year-old hepatitis C-positive man with paranoid psychosis. He was successfully treated with clozapine, an atypical antipsychotic drug which is known for the risk of granulocytopenia and agranulocytosis. With doses up to 200 mg/day over 3 years, he showed no remarkable changes in WBC. Because of the chronic hepatitis C with genotype 3a, additional treatment was started with IFN-alpha (s.c., 3 x 6 million IU/week). After 2 months of therapy he developed a severe agranulocytosis. Both clozapine and IFN-alpha were discontinued, and his WBC returned to normal. Results from bone marrow examination were compatible with a toxic reaction possibly caused by either or both medications. We discuss possible problems with IFN-alpha during the treatment of psychiatric patients, interactions with psychiatric medication, and hematotoxic side effects like those from clozapine. We recommend combining IFN-alpha with less "toxic" antipsychotics and weekly checks of WBC.