Bipolar Disorder: Grunze H

Grunze H, Vieta E, Goodwin GM, Bowden C, Licht RW, Moller HJ, Kasper S. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · World J Biol Psychiatry. · Pubmed #19347775 No free full text.

Abstract: These updated guidelines are based on a first edition that was published in 2003, and have been edited and updated with the available scientific evidence until end of 2008. Their purpose is to supply a systematic overview of all scientific evidence pertaining to the treatment of acute mania in adults. The data used for these guidelines have been extracted from a MEDLINE and EMBASE search, from the clinical trial database clinicaltrials.gov, from recent proceedings of key conferences, and from various national and international treatment guidelines. Their scientific rigor was categorised into six levels of evidence (A-F). As these guidelines are intended for clinical use, the scientific evidence was finally asigned different grades of recommendation to ensure practicability.

Krüger S, Bräunig P, Grunze H. · Klinik und Poliklinik für Psychiatrie und Psychotherapie der Universitätsklinik Carl-Gustav Carus, Dresden. · Psychiatr Prax. · Pubmed #16511724 No free full text.

Abstract: There are several national and international practice guidelines on the treatment of acute mania. Their purpose is to assess the available evidence of efficacy for medication used in the treatment of bipolar mania and to grade it according to the quality of studies available. The World Federation of Societies of Biological Psychiatry (WFSBP) has developed such guidelines in 2003. They categorize the scientific quality of the studies into four levels of evidence (A-D) and provide an algorithm based on the degree of severity of the acute manic episode.

Grunze H, Kasper S, Goodwin G, Bowden C, Möller HJ, Anonymous00338. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich, Germany. · World J Biol Psychiatry. · Pubmed #15346536 No free full text.

Abstract: As with the two preceding guidelines of this series, these practice guidelines for the pharmacological maintenance treatment of bipolar disorder were developed by an international task force of the World Federation of Societies of Biological Psychiatry (WFSBP). Their purpose is to supply a systematic overview of all scientific evidence relating to maintenance treatment. The data used for these guidelines were extracted from a MEDLINE and EMBASE search, from recent proceedings from key conferences and various national and international treatment guidelines. The scientific justification of support for particular treatments was categorised into four levels of evidence (A-D). As these guidelines are intended for clinical use, the scientific evidence was not only graded, but also reviewed by the experts of the task force to ensure practicality.

Grunze H, Kasper S, Goodwin G, Bowden C, Baldwin D, Licht RW, Vieta E, Möller HJ, Anonymous00027. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich, Germany. · World J Biol Psychiatry. · Pubmed #12582971 No free full text.

Abstract: Identical to the preceding guidelines of this series, these practice guidelines for the biological, mainly pharmacological treatment of acute bipolar mania were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). Their purpose is to supply a systematic overview of all scientific evidence pertaining to the treatment of acute mania. The data used for these guidelines have been extracted from a MEDLINE and EMBASE search, from recent proceedings of key conferences, and from various national and international treatment guidelines. Their scientific rigor was categorised into four levels of evidence (A-D). As these guidelines are intended for clinical use, the scientific evidence was finally not only graded, but has also been commented by the experts of the task force to ensure practicability. Key words: bipolar disorder, mania, acute treatment, evidence-based guidelines, pharmacotherapy, antipsychotics, mood stabiliser, electroconvulsive therapy.

Grunze H, Kasper S, Goodwin G, Bowden C, Baldwin D, Licht R, Vieta E, Möller HJ, Anonymous00265. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich, Germany. · World J Biol Psychiatry. · Pubmed #12478876 No free full text.

Abstract: These practice guidelines for the biological, mainly pharmacological treatment of bipolar depression were developed by an international task force of the World Federation of Societies of Biological Psychiatry (WFSBP). Their purpose is to supply a systematic overview of all scientific evidence pertaining to the treatment of bipolar depression. The data used for these guidelines have been extracted from a MEDLINE and EMBASE search, and from recent proceedings of key conferences and various national and international treatment guidelines. Their scientific rigor was categorised into four levels of evidence (A-D). As these guidelines are intended for clinical use, the scientific evidence was not only graded, but also commented on by the experts of the task force to ensure practicability.

Sasse J, Pilhatsch M, Forsthoff A, Grunze H, Neutze J, Pfennig A, Schmitz B, Schwenkhagen A, Bauer M. · Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Carl Gustav Carus, Technische Universität, Fetscherstrasse 74, 01307, Dresden, Deutschland. · Nervenarzt. · Pubmed #19229511 No free full text.

Abstract: This manuscript summarizes specific issues in the disease course and pharmacological treatment of women with bipolar disorders. Gender differences relevant to the female biology manifest in symptoms, outcome, and course. The preponderance of depressive symptoms is typical, and the risk of rapid cycling is estimated to be eight times higher for women than for men. Comorbid anxiety and eating disorders occur more frequently in female patients. In planning treatment it is important to take fertility, contraception, and pregnancy into consideration and adjust the pharmacotherapy to harmonize with the patient's current phase of life. Little is known about potential sexual dysfunctions of bipolar women. Further research should include clinical and observational studies focusing on gender-specific differences in symptomatology, treatment, and long-term outcome of bipolar disorders.

Fountoulakis KN, Grunze H, Panagiotidis P, Kaprinis G. · 3rd Department of Psychiatry, Aristotle University of Thessaloniki, Greece. · J Affect Disord. · Pubmed #18037498 No free full text.

Abstract: This article attempts to summarize the current status of our knowledge and practice in the acute treatment and prophylaxis of bipolar depression. For prophylactic treatment, our knowledge about lithium firmly supports its usefulness against bipolar depression and its specific effectiveness for suicidal prevention. Valproic acid and carbamazepine could be effective, too, while lamotrigine which seems to be preferably effective against depression but not mania. The FDA has approved the olanzapine-fluoxetine combination and quetiapine monotherapy for the treatment of acute bipolar depression. The usefulness of antidepressants in bipolar depression is controversial both for acute and prophylactic treatment; guidelines suggest their cautious use and always in combination with an antimanic and mood stabilizer agent, because in some patients they may induce switching to mania or hypomania, mixed episodes and rapid cycling. Data on psychosocial intervention are restricted to the maintenance phase. Electroconvulsive therapy and transcranial magnetic stimulation are additional options for refractory patients. Bipolar depression seems to be a more difficult condition to treat than mania. Most patients need complex combination treatment although the published evidence on this type of treatment is limited.

Grunze H. · Klinik und Poliklinik für Psychiatrie, Ludwig-Maximilians-Universität. · Neuropsychiatr. · Pubmed #17640497 No free full text.

Abstract: Starting with carbamazepine and valproate in the eighties, several anticonvulsant have been established as a treatment option in bipolar disorder. They may constitute an alternative to lithium for prophylactic treatment as well as to classical and atypical antipsychotics for the treatment of acute mania. Only for the acute treatment of bipolar depression they could not demonstrate convincing results so far. However, not every anticonvulsant is at the same time a mood stabilizer; there are clear differences in efficacy and tolerability also within the group of anticonvulsants used in bipolar disorder. Nevertheless, and in contrast to epilepsy, combination treatment with several anticonvulsants is still rare in bipolar disorder, whereas combined treatment with lithium, antidepressants or antipsychotics is more common. This article is intended to give a comprehensive overview of the spectrum of efficacy, important side effects and clinical utility in bipolar disorder both for the older and new anticonvulsants, and refers the reader to the relevant literature.

Amann B, Grunze H, Vieta E, Trimble M. · Hospital Benito Menni, Dr. Antoni Pujadas 38, 08830 Sant Boi, Barcelona, Spain. · Clin EEG Neurosci. · Pubmed #17515177 No free full text.

Abstract: This paper will discuss different definitions of the term "mood stabilizer" and highlight in detail the antiepileptic drugs carbamazepine, valproate and lamotrigine with respect to their relative strengths in stabilizing mood in bipolar patients. These drugs are heterogeneous in their mechanisms of action and in their efficacy to stabilize patients with epilepsy and the various mood states in bipolar disorder. Lamotrigine has obtained approval in several countries for the indication of preventing bipolar depressive episodes, which raises the question of differential efficacy of other antiepileptic drugs as mood stabilizers in the prevention of either depressive or hypo-/manic episodes. A Medline Search to 2006 was conducted for controlled acute and maintenance studies of the three scientifically and clinically most established antiepileptic drugs carbamazepine, valproate and lamotrigine. The medications discussed in this review only partly fulfill definitions of a mood stabilizer, and we suggest that future research should focus on combined treatment strategies.

Grunze H, Adli M, Bauer M, Berger M, Bergmann A, Bräunig P, Bschor T, Falkai P, Gastpar M, Greil W, Kasper S, Krüger S, Laux G, Müller WE, Naber D, Walden J. · Psychiatrische Klinik LMU, München. · Fortschr Neurol Psychiatr. · Pubmed #17427043 No free full text.

Abstract: During recent years valproate has been established as a cornerstone for the drug-treatment of bipolar disorder. In Germany, valproate was licensed both for the treatment of acute mania and for maintenance treatment in summer 2005. At this occasion, this review summarises the scientific evidence and clinical experience of well-known experts with valproate-treatment. It was concluded that valproate will continue to be of high clinical significance despite the recent increase of treatment alternatives, both in monotherapy and combination treatment of acute mania, mixed states and maintenance treatment.

Post RM, Altshuler LL, Frye MA, Suppes T, McElroy S, Keck PE, Leverich GS, Kupka R, Nolen WA, Grunze H. · Penn State College of Medicine, Hershey, PA, USA. · Curr Psychiatry Rep. · Pubmed #17162830 No free full text.

Abstract: In this article, we highlight recent Bipolar Collaborative Network data. We found that childhood-onset bipolar illness is common, often goes untreated for more than a decade, and carries a poor prognosis. During randomized studies of adjunctive medications in depression: 1) Venlafaxine showed higher switch rates than bupropion or sertraline; 2) Tranylcypromine was as well tolerated as lamotrigine; and 3) Modafinil was more effective than placebo. Finally, in treatment of overweight and obesity, topiramate and sibutramine showed equal efficacy but poor tolerability, and zonisamide data showed that it may be useful for mood and weight loss.

Sterr A, Amann B, Grunze H. · Psychiatrische Universitätsklinik der LMU München. · Psychiatr Prax. · Pubmed #16511731 No free full text.

Abstract: Until recently, the psychopharmacological treatment alternatives for bipolar maintenance treatment were limited to lithium, which seems of special usefulness in a classical manifestation of the illness with mood-stabilising and anti-suicidal properties. With atypical features like psychotic symptoms or rapid cycling, lithium seems to be less useful. This led to further research into alternative options as carbamazepine, valproate or lamotrigine as well as atypical neuroleptics, thyroid hormones or innovative substances like omega fatty acids. This article summarises the current state of knowledge on treatment options for maintenance therapy.

Severus WE, Grunze H, Kleindienst N, Frangou S, Moeller HJ. · Department of Psychiatry, University of Munich, Germany. · J Clin Psychopharmacol. · Pubmed #16160621 No free full text.

Abstract: In the 1970s, several randomized controlled trials demonstrated significant antimanic and antidepressant properties of lithium in the prophylactic treatment of bipolar disorder. However, a recent meta-analysis of randomized, placebo-controlled trials of lithium in bipolar disorder found that its protective effect against depressive relapse/recurrence was equivocal. By examining potentially relevant parameters of recent randomized controlled trials with regard to lithium's prophylactic antidepressant efficacy, we try to identify factors which might help to explain these discrepant results across the different trials. Lithium's efficacy against manic relapse/recurrence appears rather robust at plasma levels between 0.8 and 1.2 mmol/L, whereas lithium's efficacy against depressive relapse/recurrence may be more modest and dependent on whether a response during the preceding acute episode was achieved by lithium treatment. Furthermore, it might be advisable to continue lithium without interruption at the same dose/plasma level, which yielded the initial response. A lithium level between 0.5 and 0.8 mmol/L may be equally efficacious against overall relapse and associated with equal or even superior efficacy regarding depressive relapse/recurrence. To provide evidence-based guidelines on this issue, large prospective, randomized, double-blind, placebo-controlled trials are needed comparing the efficacy of lithium at different plasma levels against manic and depressive relapse/recurrence. In these trials, factors previously associated with predicting response to lithium should also be assessed.

Seemüller F, Forsthoff A, Dittmann S, Born C, Bernhard B, Severus WE, Grunze H. · Department of Psychiatry, Ludwigs-Maximilians-University, Nussbaumstr. 7, 80336 Munich, Germany. · Expert Opin Drug Saf. · Pubmed #16111448 No free full text.

Abstract: Atypical antipsychotics (aAPs), have become a first-line treatment option, both in schizophrenia and bipolar disorders. Almost all aAPs now have proven efficacy in acute mania, some also in bipolar depression and in maintenance treatment. This provides reliable data on their safety and tolerability in this particular group of patients. This review focuses on the safety and tolerability of aAPs in the treatment of bipolar disorders. Both tolerability, for example, extrapyramidal symptoms, and safety issues, for example, occurrence of weight gain and hyperglycaemia, will be highlighted for olanzapine, quetiapine, risperidone, ziprasidone and aripiprazole.

Möller HJ, Grunze H, Broich K. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #16078087 No free full text.

Abstract: This conceptual review summarises the results of relevant studies on antidepressants, mood stabilisers such as lithium and anticonvulsants, and second generation antipsychotics in the indication of bipolar depression. Based on methodological and clinical considerations, the position of antidepressants and the possible alternatives in this indication are reviewed very carefully. In addition the regulatory requirements for licensing a drug for the indication "short-term treatment of bipolar depression" are described.

Grunze H. · Department of Psychiatry, Ludwig-Maximilians University, Munich, Germany. · J Clin Psychiatry. · Pubmed #16038598 No free full text.

Abstract: The most commonly employed pharmacotherapies for bipolar depression include antidepressants, lithium, and anticonvulsants, such as lamotrigine, valproate, and carbamazepine. A combination of these agents, usually an antidepressant and a mood stabilizer, is often required to achieve an optimal response. However, some treatment guidelines still caution that antidepressant exposure should be minimized in patients with bipolar depression, due to concern that they may trigger treatment-emergent mania or cycle acceleration. This advice prevails despite data showing that antidepressants are effective in treating bipolar depression and evidence that coadministration of a mood-stabilizing medication, at least with modern antidepressants, such as the selective serotonin reuptake inhibitors, can reduce the risk of treatment-emergent mania to levels comparable with those observed with mood stabilizer monotherapy. Although the antidepressant efficacy of most mood stabilizers has not been satisfactorily proven, first-line therapy with 1 mood stabilizer alone or a combination of 2 mood stabilizers is still recommended by many guidelines. Inappropriate treatment of bipolar depression may leave patients at high risk of suicide and increased chronicity of symptoms; effective therapy should, therefore, be provided as early as possible. The efficacy and safety of antidepressants for bipolar depression both as monotherapy and when combined with a mood stabilizer should be studied in adequately powered trials in order to revise treatment guidelines. Electroconvulsive therapy remains an option for treatment-refractory patients and those intolerant to pharmacologic treatment, as well as patients who are pregnant or at high risk of suicide.

Gajwani P, Forsthoff A, Muzina D, Amann B, Gao K, Elhaj O, Calabrese JR, Grunze H. · NIMH Bipolar Research Center, Case Western Reserve University School of Medicine, Mood Disorders Program, University Hospitals of Cleveland, OH, USA. · Epilepsia. · Pubmed #15968808 No free full text.

Abstract: Bipolar disorder is a common, recurrent, often severe mental disorder that, without adequate treatment, is associated with high rates of morbidity and mortality. We review the evidence on the efficacy of a spectrum of antiepileptic drugs (AED) in bipolar disorder. Most studies have been carried out with carbamazepine (CBZ), valproate (VPA), and lamotrigine (LTG). All three of these AEDs have been shown to be of value in the management of patients with bipolar illnesses. VPA and CBZ seem to exert stronger antimanic effects and, to a lesser degree, acute antidepressant efficacy. LTG seems to be effective against depression and mania, with a more robust activity against depression. No firm evidence supports a role for vigabatrin, tiagabine, topiramate, or levetiracetam in these disorders.

Post RM, Leverich GS, Nolen WA, Kupka RW, Altshuler LL, Frye MA, Suppes T, McElroy S, Keck P, Grunze H, Walden J, Anonymous00102. · Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health, Biological Psychiatry Branch, Bethesda, MD 20892-1272, USA. · Bipolar Disord. · Pubmed #14636363 No free full text.

Abstract: OBJECTIVES: The risk-to-benefit ratio of the use of unimodal antidepressants (ADs) as adjuncts to mood stabilizers continues to be an area of controversy and disagreement among experts in the field. This paper reviews new data on: (1) depression in bipolar illness, (2) switch rates on ADs and (3) risks of AD discontinuation that are pertinent to the ongoing discussion and recommendations. METHODS: In the first study reviewed, 258 outpatients with bipolar illness were assessed prospectively on a daily basis using the National Institute of Mental Health-Life Chart Method (NIMH-LCM) for 1 year. In the second study, 127 bipolar depressed patients were randomized to 10 weeks of sertraline, bupropion, or venlafaxine, as adjuncts to mood stabilizers; non-responders were re-randomized and responders were offered a year of continuation treatment. In the final study, Altshuler et al. retrospectively and prospectively assessed the risk of depressive relapses in patients who remained on ADs after 2 months of euthymia compared with those who discontinued ADs. RESULTS: Despite intensive naturalistic treatment, the 258 outpatients with bipolar illness followed prospectively for 1 year showed three times as many days depressed as days manic, re-emphasizing the considerable depressive morbidity that remains in bipolar disorder despite the number of treatment options available. In the study of bipolar depressed patients randomized to one of three ADs, a range of severities and durations of hypomanic to manic switches were discerned following 175 trials of AD augmentation of treatment with a mood stabilizer. Of the acute 10-week trials, 9.1% were associated with switches into hypomania or mania and another 9.1% with a week or more of hypomania alone (with no to minimal dysfunction). In 73 continuation phase AD trials, 16.4 and 19.2% were similarly associated with hypomanic to manic and hypomanic switches, respectively. In the Altshuler et al. studies, those who remained well on any AD for more than 2 months (only 15-20% of those initially treated) and who continued on ADs showed a lesser rate of relapse into depression over 1 year (35 and 36% in the first and second study, respectively) compared with those who discontinued their ADs (68 and 70% relapsing into depression). Surprisingly, this continuation of ADs was associated with no increase in the rate of switching into mania compared with those stopping ADs. CONCLUSIONS: These data reveal that depression and depressive cycling remain a substantial problem in some two-thirds of intensively treated bipolar outpatients. Acute AD augmentation was associated with a modest response rate and 18.2% switched into a hypomanic to manic episode, and 35.6% of the continuation trials showed these two types of switches. Two separate studies suggest that in the very small subgroup who remain well on ADs for at least 2 months, one should consider continuation of this AD augmentation treatment, because AD discontinuation appears associated with a substantially increased risk of depression relapse over the subsequent year with no reduced risk of switching into mania.

Grunze H, Dittmann S. · Psychiatrische Klinik, LMU München. · MMW Fortschr Med. · Pubmed #14579481 No free full text.

Abstract: 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.

Post RM, Leverich GS, Altshuler LL, Frye MA, Suppes TM, Keck PE, McElroy SL, Kupka R, Nolen WA, Grunze H, Walden J. · Stanley Foundation Bipolar Network and Biological Psychiatry Branch, NIMH, NIH, DHHS, Bethesda, MD 20892-1272, USA. · Bipolar Disord. · Pubmed #14525551 No free full text.

Abstract: AIM AND METHODS: Selected recent findings of the Stanley Foundation Bipolar Network are briefly reviewed and their clinical implications discussed. RESULTS: Daily prospective ratings on the NIMH-LCM indicate a high degree of residual depressive morbidity (three times that of hypomania or mania) despite active psychopharmacological treatment with a variety of modalities including mood stabilizers, antidepressants, and benzodiazepines, as well as antipsychotics as necessary. The rates of switching into brief to full hypomania or mania during the use of antidepressants is described, and new data suggesting the potential utility of continuing antidepressants in the small group of patients showing an initial acute and persistent response is noted. Bipolar patients with a history of major environmental adversities in childhood have a more severe course of illness and an increased incidence of suicide attempts compared with those without. Preliminary open data suggest useful antidepressant effects of the atypical antipsychotic quetiapine, while a double-blind randomized controlled study failed to show efficacy of omega-3 fatty acids (6 g of eicosapentaenoic acid compared with placebo for 4 months) in the treatment of either acute depression or rapid cycling. The high prevalence of overweight and increased incidence of antithyroid antibodies in patients with bipolar illness is highlighted. CONCLUSIONS: Together, these findings suggest a very high degree of comorbidity and treatment resistance in outpatients with bipolar illness treated in academic settings and the need to develop not only new treatment approaches, but also much earlier illness recognition, diagnosis, and intervention in an attempt to reverse or prevent this illness burden.

Grunze H. · Psychiatriche Klinik der LMU Nussbaumstr. 7 80336 München, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #12904974 No free full text.

Abstract: Before the rise of atypical antipsychotics, lithium used to be the most frequently investigated substance in the acute treatment of bipolar disorders, although studies are not always of the highest methodological standard. Due to the doubt about a sufficient efficacy of lithium expressed in recent years from various sides, and the simultaneous availability of newer treatment alternatives, this paper attempts to make a critical stocktaking of our knowledge about lithium in the acute treatment of bipolar disorders. Aspects concerning the changed disorder concept through the broadening of the bipolar spectrum, together with the available results from controlled and open studies with lithium, are presented and appraised. This shows that lithium should still be seen as an essential, but not the only corner stone in the differentiated treatment of bipolar patients. Provided that it is taken reliably and well-tolerated, lithium represents a first choice treatment, particularly for a classical course of manic-depressive illness (Bipolar I disorder), especially for mild to moderate manic syndromes.However, as antidepressive treatment, lithium should rather not be applied as a monotherapy, particularly in severe bipolar depression, since with the new generation of antidepressants and anticonvulsants well-tolerated and very effective alternatives are available. In combination treatment, lithium should be applied particularly when it has already shown good prophylactic efficacy and/or in patients for whom a high suicide risk must be presumed.

Carta MG, Hardoy MC, Hardoy MJ, Grunze H, Carpiniello B. · Division of Psychiatry, Department of Public Health, University of Cagliari, Via Liguria 13, 09127 Cagliari, Italy. · J Affect Disord. · Pubmed #12781355 No free full text.

Abstract: BACKGROUND: with increasing awareness of lithium's limitations, several new anticonvulsants had been tested for their mood stabilisation during recent years. Among the innovative third generation mood stabilizing anticonvulsants, gabapentin (GBP) seems to have a broad spectrum of efficacy, although no certain data are available as to its efficacy and use in clinical practice. Accordingly, an extensive review on this subject has been carried out. METHODS: A computer-generated search of the biomedical literature and abstract books of the more important scientific psychiatric congresses until June 2000 was undertaken to identify all pertinent case reports, case series and studies of GBP as monotherapy or adjunctive therapy in mood disorders. We identified 40 open-label studies on the use of GBP in at least 600 patients with bipolar disorder (BP), manic, depressed, or mixed episodes and unipolar depression and four controlled studies. RESULTS: The 40 open-label studies and two of the controlled trials suggested that GBP may have a role as adjunctive agent in the treatment of patients with bipolar disorders particularly when complicated by co-morbid anxiety disorder or substance abuse. GBP is usually very well tolerated and has no pharmacological interference with other mood stabilisers. However, in the other two double-blind studies GBP has not been found to be efficacious in the treatment of refractory mania or refractory bipolar depression. CONCLUSIONS: Although failing to show clear antimanic efficacy in randomized trials, gabapentin still remains a clinically useful agent when it comes to combination treatment in refractory and co-morbid patients.

Grunze H, Schlösser S, Walden J. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich, Germany. · World J Biol Psychiatry. · Pubmed #12607221 No free full text.

Abstract: In contrast to mania, bipolar depression is usually characterised by longer-lasting episodes and a higher incidence of treatment refractoriness. Additionally, the risks of antidepressive standard treatment regimens are increasingly recognised, especially the risk of a switch into mania or induction of a rapid cycling course. Mood stabilisers, e.g. lithium, and some anticonvulsants, appear to have at least some antidepressant efficacy, which, however, may not be sufficient for treating severe depression. Currently, their use as a monotherapy of mild depression and at the start as a co-medication to antidepressants in severe depression is under consideration. The potential usefulness and risks of currently applied antidepressive treatment strategies as well as potential future developments will be reviewed in this article. At this stage, at least in severe depression, the use of true antidepressants still appears to be mandatory, especially because of the risk of suicide. However, initial combination with a mood stabiliser can be recommended. The treatment of depressive episodes only responsive to ECT should include combination with a mood stabiliser, in this case lithium, right from the start. In patients with lithium refractoriness, mood stabilising anticonvulsants should be initiated directly after the end of the ECT cycle. In order to reach sufficient plasma levels and thus reduce the risk of a switch, a loading therapy is recommended.

Grunze H, Walden J. · Department of Psychiatry, LMU, Nussbaumstr. 7, D-80336 Munich, Germany. · J Affect Disord. · Pubmed #12589899 No free full text.

Abstract: The so-called atypical forms of bipolar disorder are not a rarity, but instead are rather the rule. Particularly in specialized settings such as the bipolar disorder clinic, the majority of patients are characterized by atypical manifestations (). Mixed states, psychotic mania and a rapid cycling course of bipolar disorder are a challenge both to pharmacological and non-pharmacological treatment. The benefit of classical mood stabilizers such as lithium and carbamazepine is limited in monotherapy, although valproate has a broader spectrum of activity in atypical bipolar disorders and is often used in combination with other agents. Thus, new treatment alternatives are needed urgently for optimizing the treatment of atypical bipolar disorder. During the last decade, several new antiepileptic drugs have been released, e.g. lamotrigine, gabapentin, tiagabine, topiramate and levetiracetam. Others have been available for some time, but only recently have become the focus of bipolar disorder research; for example, phenytoin, and especially, oxcarbazepine. This review will consider our current knowledge of the benefit of these new and newly rediscovered anticonvulsants in treating bipolar disorders, with a special focus on their value in treating atypical manifestations.

Grunze H, Walden J, Dittmann S, Berger M, Bergmann A, Bräunig P, Dose M, Emrich HM, Gastpar M, Greil W, Krüger S, Möller HJ, Uebelhack R. · Psychiatrische Klinik der Universität München. · Nervenarzt. · Pubmed #11975062 No free full text.

Abstract: 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.