The impact of response to previous mood stabilizer therapy on response to olanzapine versus placebo for acute mania

Objectives: A clinically important question for any new treatment for bipolar disorder is whether its efficacy extends to patients who have both responded and failed to respond to other mood stabilizers. In this secondary analysis of a placebo-controlled trial demonstrating olanzapine's efficacy for acute mania, we explore whether its usefulness extends to those patients with a history of poor response to other mood stabilizers.

Methods: This 4-week, double-blind, placebo-controlled trial studied olanzapine monotherapy 5–20 mg/day for hospitalized patients in acute manic or mixed bipolar episodes. The primary outcome variable was beginning to endpoint change in the Young-Mania Rating Scale (Y-MRS) total score. We investigated whether prospectively identified history of recent failure to respond to other mood stabilizers predicted response to olanzapine.

Results: As previously reported, olanzapine-treated patients experienced significantly greater improvement in Y-MRS total score and higher remission rates relative to placebo-treated patients. The current analysis compared these outcome parameters in patients with known poor prior response to lithium and/or valproate with all other patients and found no significant group by treatment interactions, i.e., treatment effects were not significantly diminished in non-responders to older mood stabilizing agents.

Conclusions: Olanzapine has been shown to be superior to placebo for the treatment of mania. This secondary analysis suggests that olanzapine monotherapy is similarly effective for patients whether or not they previously have failed to respond to another mood stabilizer for mania. A study limitation is that response to lithium or valproate was determined retrospectively.     

The treatment of bipolar depression

Objectives: The treatment of the depressed phase of bipolar disorder is understudied and remains a common clinical dilemma for clinicians. Compared to the manic phases, episodes of bipolar depression are more frequent and of longer duration, yet the literature on this problem is minimal. The few methodologically sound studies find that treatment effective for unipolar depression are also efficacious for bipolar depression. However, standard antidepressant agents may cause acute mania or a long-term worsening of bipolar illness. This paper reviews the available literature on the treatment of bipolar depression and offers recommendations for clinical management.

Methods: A literature search was conducted using keywords 'bipolar disorder', 'depression', 'drug therapy', 'antidepressants', 'lithium', and 'anticonvulsants'.

Results: If effectively treated by lithium, patients are spared the risk of antidepressant-induced mania. If lithium is not sufficient treatment for acute depression, the combination of lithium and a standard antidepressant appears to reduce the risk of affective switch, as well as the induction of a long-term rapid-cycling course. Additionally, tapering antidepressant medication after periods of sustained remission can be beneficial in limiting the risk of affective switch and acceleration of the cycle rate.

Conclusions: Doctors must be cautious in prescribing antidepressants for bipolar depression. Use of antidepressants alone should be avoided.     

Response to placebo among bipolar I disorder patients experiencing their first manic episode

Background: The first episode of an illness may respond differently to any treatment compared to multiple episodes of the same illness. This study details the treatment response of six first-episode manic patients who participated in a previously reported study of 139 subjects comparing olanzapine to placebo in bipolar I mania (Tohen M, Sanger TM, McElroy SL, Tollefson GD, Chengappa KNR, Daniel DG. Olanzapine versus placebo in the treatment of acute mania. Am J Psychiatry 1999; 156: 702–709).

Methods: Six first-episode subjects participated in a 3-week double-blind, random assignment, parallel group, placebo-controlled study of olanzapine for bipolar mania. The Young Mania Rating Scale (Y-MRS), Clinical Global Impression, and Hamilton Depression ratings were administered weekly. Lorazepam as rescue medication was permitted for the first 10 days.

Results: Five subjects were randomized to placebo and one to olanzapine. Two subjects (40%) with psychotic mania (who also had their first-illness episode) were assigned to placebo and responded with greater than 50% reduction in the Y-MRS score and also remitted in 3 weeks. Another placebo-assigned subject had a 46% reduction in the Y-MRS scores, and two placebo-assigned subjects worsened. The olanzapine-assigned subject had a 44% reduction in the Y-MRS score. In contrast, 34 of 69 (48.6%) multiple-episode olanzapine subjects responded and 14 of 61 (23.0%) of placebo-treated subjects did.

Conclusions: This preliminary data set suggest there may be differences in treatment response between first-illness episode versus multi-episode bipolar manic subjects. Larger numbers of subjects with these illness characteristics are needed to either confirm or refute this suggestion.     

Comparative efficacy of typical and atypical antipsychotics as add-on therapy to mood stabilizers in the treatment of acute mania.

BACKGROUND: Typical antipsychotics are commonly used in combination with mood stabilizers for acute mania. Although typical antipsychotics are effective, they have undesirable side effects such as induction of depressive symptoms and tardive dyskinesia. Atypical antipsychotics have more favorable side effect profiles, and recent evidence shows their efficacy in treating mania. Apart from a previous small study that compared risperidone with typical neuroleptics as add-on therapy to mood stabilizers, no studies to date have directly compared atypical antipsychotics with typical antipsychotics as add-on therapy to mood stabilizers in a clinically relevant, naturalistic setting. METHOD: This study is a chart review of all patients with DSM-IV-defined bipolar disorder, current episode mania (N = 204), admitted to the University of British Columbia Hospital during a 30-month period. Patients were separated into 3 groups according to the medications used: (1) mood stabilizer and typical antipsychotic, (2) mood stabilizer and atypical antipsychotic, and (3) combination: mood stabilizer plus a typical antipsychotic, then switched to mood stabilizer plus risperidone or olanzapine within I week. The atypical group was further subdivided into risperidone and olanzapine subgroups. Outcome was measured using Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) ratings generated by review of clinical information in the chart. RESULTS: Patients treated with typical antipsychotics were more severely ill at admission and at discharge than those treated with atypical antipsychotics. Patients in the atypical (p < .005) and combination (p < .05) groups showed significantly greater clinical improvement at discharge than patients treated with typical antipsychotics. This difference was also significant in the subset of patients with psychotic features (p < .03). Risperidone and olanzapine were associated with fewer extrapyramidal side effects than were typical antipsychotics (risperidone vs. typical antipsychotics, chi2 = 8.72, p < .01; olanzapine vs. typical antipsychotics, chi2 = 16.9, p < .001). CONCLUSION: Due to their superior effectiveness and side effect profile when compared with typical antipsychotics. atypical antipsychotics are an excellent choice as add-on therapy to mood stabilizers for the treatment of patients with mania.     

Atypical antipsychotics in the treatment of mania: a meta-analysis of randomized, placebo-controlled trials

BACKGROUND: Randomized, controlled trials have demonstrated efficacy for atypical antipsychotics in the treatment of mania in bipolar disorder, either as monotherapy or adjunctive treatment. However, there are no published comparisons of individual atypical antipsychotics for mania. DATA SOURCES AND STUDY SELECTION: We conducted a systematic review and meta-analysis of randomized, placebo-controlled monotherapy and adjunctive therapy trials of atypical antipsychotics for acute bipolar mania. Studies published through 2004 were identified using searches of PubMed/MEDLINE with the search terms mania, placebo, and each of the atypical antipsychotics, limited to randomized, controlled clinical trials; review of abstracts from the 2003 meetings of the American College of Neuropsychiatry, American Psychiatric Association, and International Conference on Bipolar Disorder; and consultations with study investigators and representatives of pharmaceutical companies that market atypical antipsychotics. DATA EXTRACTION: Analyses were performed on the changes in Young Mania Rating Scale or Mania Rating Scale total scores from baseline to endpoint, using last observation carried forward and computing the difference in change scores between each drug and its corresponding placebo arm. A random-effects model with fixed drug effects was used to combine the studies and make comparisons of the antipsychotics to each other and to placebo. DATA SYNTHESIS: Data from 12 placebo-controlled monotherapy and 6 placebo-controlled adjunctive therapy trials involving a total of 4304 subjects (including 1750 placebo-treated subjects) with bipolar mania were obtained. Aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone all demonstrated significant efficacy in monotherapy (i.e., all confidence intervals exclude zero). However, after adjusting for multiple comparisons, pairwise comparisons of individual effects identified no significant differences in efficacy among antipsychotics. Magnitude of improvement was similar whether the antipsychotic was utilized as monotherapy or adjunctive therapy. CONCLUSIONS: The 5 newer atypical antipsychotics were all superior to placebo in the treatment of bipolar mania. For monotherapy and add-on therapy, cross-trial comparisons suggest that differences in acute efficacy between the drugs, if any, are likely to be small.     

Medication prescribing patterns for patients with bipolar I disorder in hospital settings: adherence to published practice guidelines

Objective: The purposes of this paper were to examine the medication prescribing patterns for bipolar I disorder in hospital settings and to compare them to recently published expert consensus guidelines for medication treatment of bipolar disorder.

Methods: Data were obtained from the 1996–2000 CQI+^SM Outcomes Measurement System, on patients age 18 or older admitted to psychiatric inpatient units from over 100 medical–surgical hospitals. A total of 1864 patients with a primary discharge diagnosis of bipolar I or II disorder were identified from a large cohort of hospitalized patients. Patient characteristics were assessed at hospital admission and medication usage, at discharge. The medication analysis focused on the 1471 individuals with bipolar I mania or bipolar I depression (with or without psychotic features), representing 54% and 25% of admitted bipolar patients, respectively.

Results: At admission, the typical bipolar patient (mean age 57) had experienced a relatively severe and chronic course of illness. The array of psychotropic agents used was broad, with no single prescribing pattern predominant. Only one in three bipolar I ( manic or depressed ) patients with psychotic features was discharged on medications recommended by expert guidelines as preferred or alternate recommended treatment. Absent psychotic features, this dropped to one in six patients. Surprising was the relatively high use of antidepressants for patients with mania, particularly those without psychotic symptoms.

Conclusions: Results suggest that a substantial proportion of patients with bipolar I disorder are discharged from hospitals on medications not generally recommended by current practice guidelines.     

Antipsychotics in the treatment of mood disorders and risk of tardive dyskinesia

Psychosis occurs commonly in patients with mood disorders and has traditionally been treated with typical antipsychotics. Exposure to typical antipsychotics poses a risk for the emergence of tardive dyskinesia. Atypical antipsychotics may have advantages over typical agents in the treatment of patients with mood disorders complicated by psychotic features. The studies of typical and atypical antipsychotics in the treatment of mood disorders were reviewed. Similarly, studies regarding the risk of tardive dyskinesia from typical and atypical agents in patients with mood disorders were surveyed. Typical and atypical antipsychotics appear to be comparably effective in the treatment of acute mania. Limited data regarding these medications in psychotic depression are available. Advantages of atypical antipsychotics include, for most agents, minimal extrapyramidal and prolactin effects, inherent thymoleptic activity, and lower rates of tardive dyskinesia. Atypical antipsychotics appear to have a number of advantages over typical agents in the treatment of patients with psychotic mood disorders.     

Acute and maintenance treatment of bipolar mania: the role of atypical antipsychotics

Abstract:  Bipolar disorder is a complex condition including depression, mania, and in many cases associated with comorbid anxiety symptoms and substance abuse. Mood stabilizers including lithium and divalproex have been considered standard therapy for the treatment of patients with bipolar disorder, but remission rates remain inadequate. Conventional antipsychotics have demonstrated efficacy for acute mania, but they appear to have little role in the maintenance treatment of bipolar disorder. Despite substantial evidence of efficacy and recent guideline recommendations, atypical antipsychotics remain underused for the treatment of bipolar disorder. Data from double-blind, controlled trials are available for a number of clinically meaningful efficacy measures, including improvement in manic symptoms, onset of action, response rates, remission rates, improvement in comorbid depressive symptoms, and induction/worsening of mania or depression. Atypical antipsychotics are effective both as alternatives to lithium or divalproex as monotherapy, or in combination with these mood stabilizers, in the acute and likely the maintenance treatment of mania. The atypical antipsychotics represent an effective and relatively safe addition to our armamentarium for the treatment of bipolar disorder.     

Comorbidity of obsessive-compulsive disorder in recovered inpatients with bipolar disorder

Objective: To determine the frequency of obsessive-compulsive disorder (OCD) in inpatient subjects with bipolar disorder (BD) and to examine the clinical characteristics of BD subjects with OCD.

Method: The sample consisted of 143 inpatient subjects with DSM-III-R BD-I and BD-NOS (BD-II), recovered from a current episode of either depression or mania. Demographic and clinical variables were obtained on the day of admission. Current comorbid conditions including OCD were determined by the Structured Clinical Interview for DSM-III-R following recovery from the acute affective episode.

Results: The frequency of current OCD was 7% (N=10). All BD subjects with OCD were BD-II, were male, and had a diagnosis of current dysthymia. They had fewer episodes and a higher incidence of prior suicide attempts than bipolar subjects without OCD. None of the bipolar subjects with OCD fulfilled criteria for cyclothymia.

Conclusions: Our findings suggest that BD-II, OCD, dysthymia, and suicidality cluster together in some subjects with BD. We discuss the clinical implications of our findings.     

Acute treatment of mania: An update on new medications

Acute mania is frequently a medical emergency requiring hospitalization for behavioral control, rapid resolution of irritability, agitation, de-escalation of mood, and decreasing of risk-taking behavior. Lithium efficacy in the management of acute mania was reported in 1949 and approved by the US Food and Drug Administration (FDA) in 1970. Chlorpromazine, from the class of typical antipsychotics, was approved for treatment of bipolar disorder in 1973. Typical antipsychotics were frequently used alone and as adjunct for the treatment of bipolar mania for the next 2 decades. Divalproex was approved by the FDA for the treatment of acute mania in 1994. Since the approval of olanzapine in 2000, all five atypical antipsychotics, namely risperidone (2003), quetiapine (2004), ziprasidone (2004), and aripiprazole (2004), have been approved by the FDA for the management of acute mania. Clozapine is the only atypical antipsychotic not FDA approved for any phase of bipolar disorder. This article will systematically review some of the major studies published, randomized controlled monotherapy, and adjunct therapy trials involving five atypical antipsychotics and newer anticonvulsants for the treatment of acute bipolar mania.     

Serotonin in mania and in the mechanism of action of mood stabilizers: a review of clinical studies

Objectives: Serotonin (5-hydroxytryptamine, 5-HT) was implicated in the pathophysiology of manic-depressive illness as early as 1958. Although extensive evidence has accumulated since then to support 5-HT's role in depression, relatively fewer studies examined its role in mania. The purpose of this paper was to review and summarize the current state of knowledge on the role of 5-HT in mania and its treatment.

Methods: We systemically reviewed clinical studies of 1) 5-HT function in mania and 2) 5-HT in the mechanism of action of mood stabilizers, including lithium and anticonvulsants.

Results: Review showed that cerebrospinal fluid, postmortem, platelet, neuroendocrine challenge, and tryptophan depletion studies provided some evidence to support the hypothesis that a 5-HT deficit is involved in mania and that enhancement of 5-HT neurotransmission exerts a mood-stabilizing effect.

Conclusions: There is some evidence from clinical studies for the contribution of 5-HT in mania and in the mechanism of action of mood stabilizers. However, it is very likely that other neurotransmitters also play important roles. Future directions for research include 1) in vivo study of 5-HT receptor subtypes using positron emission tomography, 2) investigation of the interaction between 5-HT and other neurotransmitter systems, and 3) determination of the relationships between diagnostic subtypes of mania and 5-HT function and other neurotransmitter systems.     

Choline, myo-inositol and mood in bipolar disorder: a proton magnetic resonance spectroscopic imaging study of the anterior cingulate cortex

Objectives: Alterations in choline and myo-inositol metabolism have been noted in bipolar disorder, and the therapeutic efficacy of lithium in mania may be related to these effects. We wished to determine the relationship between anterior cingulate cortex choline and myo-inositol levels, assessed using proton magnetic resonance spectroscopic imaging (MRSI), and mood state in subjects with bipolar disorder.

Methods: Serial assessments of anterior cingulate cortex choline and myo-inositol metabolism were performed in nine subjects with bipolar disorder, taking either lithium or valproate, and 14 controls. Each bipolar subject was examined between one and four times (3.1±1.3). On the occasion of each examination, standardized ratings of both depression and mania were recorded.

Results: In the left cingulate cortex, the bipolar subjects' depression ratings correlated positively with MRSI measures of Cho/Cr-PCr. In the right cingulate cortex, the Cho/Cr-PCr ratio was significantly higher in subjects with bipolar disorder compared with control subjects. In addition, bipolar subjects not taking antidepressants had a significantly higher right cingulate cortex Cho/Cr-PCr ratio compared with patients taking antidepressants or controls. No clinical or drug-related changes were observed for the Ino/Cr-PCr ratio.

Conclusions: The results of this study suggest that bipolar disorder is associated with alterations in the metabolism of cytosolic, choline-containing compounds in the anterior cingulate cortex. As this resonance arises primarily from phosphocholine and glycerophosphocholine, both of which are metabolites of phosphatidylcholine, these results are consistent with impaired intraneuronal signaling mechanisms.     

The Internal State Scale: replication of its discriminating abilities in a multisite, public sector sample

Objective: The Internal State Scale (ISS) is a self-report instrument that has been validated for discriminating mood states in patients with bipolar disorder. This study a) extends investigation to a multisite public sector sample and b) tests a revised scoring algorithm that formally identifies patients in mixed states.

Methods: Eighty-six patients with bipolar disorder from four Veterans Affairs medical centers were assessed in a cross-sectional design. Physician-conducted semi-structured interviews used DSM-IV criteria to identify subjects as meeting criteria for euthymia, mania or hypomania, depression, or mixed state (mania or hypomania plus depression). A revised ISS scoring algorithm independently assigned mood state. Mean subscale scores were analyzed across groups. Receiver-operating characteristic (ROC) curve analysis was conducted to determine optimal algorithm structure.

Results: Analysis of mean scores for the ISS subscales replicated original results for Activation, Well-Being, and Perceived Conflict, but indicated differences from the original results for the Depression Index. The ROC curve analysis identified optimal cut-off scores for the revised algorithm. The overall kappa score indicated moderate agreement between ISS and physician ratings of mood state, including mixed states.

Limitations: The study used a sample consisting primarily of male veterans. Mood state was assigned by experts using expert clinician diagnosis, not structured interviews.

Conclusion: The performance of the ISS in this multisite, public sector sample was similar to the performance in the initial research clinic sample. This finding confirms the validity of the ISS as a discriminator of mood states in bipolar disorder. The development of a revised scoring algorithm makes feasible formal identification of mixed episodes with the ISS.     

Rapid, continuous cycling and psychiatric co-morbidity in pediatric bipolar I disorder

Objectives: The primary purpose of this study was to describe the clinical presentation of bipolar I disorder (BP-I) as it occurs in children and adolescents and to assess whether the manifestations of BP-I were similar in both age groups.

Method: Ninety youths between the ages of 5 and 17 years meeting full diagnostic symptom criteria for BP-I were included in this study. The diagnosis of BP-I was established for these youths based on the results of a semi-structured diagnostic interview and a clinical assessment by a child and adolescent psychiatrist. The course of a subset of these youngsters' illnesses was assessed using the Life Charting Method (LCM). Data regarding the clinical presentation, longitudinal history, psychiatric co-morbidities and parental psychopathology were also obtained.

Results: The clinical presentation of BP-I was similar in children and adolescents. Youths meeting diagnostic criteria for BP-I developed an average of approximately 5.8 of the 7 symptoms of mania during periods of elevated or irritable mood. BP-I was found to be a cyclic disorder characterized by high rates of rapid cycling (50%) with almost no inter-episode recovery. Almost 75% of these subjects also met diagnostic symptom criteria for a disruptive behavior disorder. High rates of mood disorders were found in fathers.

Conclusions: These data suggest that the presentation of juvenile BP-I is a cyclic and valid clinical condition with manifestations on a continuum with the later-onset forms of this illness.     

The role of atypical antipsychotics in bipolar depression and anxiety disorders

Abstract:  Bipolar disorder is a complex condition that includes symptoms of mania, depression, and often anxiety. Diagnosing and treating bipolar depression is challenging, with the disorder often being diagnosed as unipolar depression. In addition, comorbid anxiety can be a significant detractor to successful outcomes, increasing symptom severity, frequency of episodes and suicide rates, and decreasing response to antidepressant therapy. Anxiety often precedes and hastens the onset of bipolar disorder, and a shared genetic etiology has been suggested. Studies have demonstrated the efficacy of atypical antipsychotics for the acute and maintenance treatment of mania. Evidence from studies in patients with treatment-resistant major depressive disorder and bipolar depression indicate that these agents may also have antidepressant effects. In open trials in patients with bipolar mania, risperidone therapy has led to significant reductions in depression scores compared with baseline. Reductions in depression scores in patients with bipolar mania have been significantly greater with olanzapine compared with placebo. In patients with bipolar depression, the combination of olanzapine and fluoxetine resulted in significant improvement in depression compared with olanzapine alone or placebo. Although little data are available on the effects of these agents on comorbid anxiety in patients with bipolar disorder, some atypical antipsychotics have demonstrated efficacy in patients with anxiety disorders, including obsessive-compulsive disorder, post-traumatic stress disorder, and generalized anxiety disorder. Thus, atypical antipsychotics represent an important therapeutic option for the treatment of bipolar disorder, providing improvements in manic, depressive, and anxiety symptoms.     

Typical and atypical antipsychotics in bipolar depression

BACKGROUND: Symptomatic bipolar patients experience more depressive than manic symptoms, but fewer studies have been designed for bipolar depression than for bipolar mania. Since the antipsychotic agents have been shown to diminish depressive symptoms during the treatment of mania, atypical agents are now being studied for use in bipolar depression. DATA SOURCES: English-language articles published from 1980 through July 2004 and cited in MEDLINE were searched using the keywords antipsychotics, typical antipsychotics, atypical antipsychotics, bipolar depression, bipolar disorder, manic-depressive illness, placebo, and clinical trial. The generic and brand names of individual antipsychotics were also entered as keywords. Peer-reviewed abstracts of placebo-controlled studies assessing acute or long-term efficacy in bipolar depression presented at major scientific meetings were also reviewed. STUDY SELECTION: Use of a depression rating scale was required for inclusion of studies of the atypical antipsychotic agents in our analysis. DATA SYNTHESIS: Twenty-one randomized trials and 13 nonrandomized prospective trials were identified. In the only 2 acute, double-blind, placebo-controlled studies of antipsychotics in bipolar depression, the effect size of olanzapine was small (0.32) compared with the effect sizes of quetiapine (0.91-1.09, depending on dose). The effect size in acute mania of olanzapine at week 4 and quetiapine at week 3 was 0.50 and 0.39, respectively. Both olanzapine and quetiapine have been shown to be superior to placebo in the acute treatment of bipolar I depression. In addition, olanzapine has been shown to be more effective than placebo in delaying relapse into bipolar depression. With the exception of a 6-month perphenazine study, there are no other randomized studies of typical antipsychotics that support the conclusion that this class of medication worsens bipolar depression. CONCLUSION: Emerging data suggest that the atypical antipsychotic agents have a role in the acute and long-term treatment of bipolar depression. No convincing data support the impression that the typical antipsychotic agents worsen bipolar depression.     

Pharmacologic agents for the treatment of acute bipolar mania.

The knowledge base regarding the medical treatment of acute bipolar mania is rapidly expanding. Information about agents with established antimanic properties is increasing, and more agents with putative antimanic properties are being identified. We first review the controlled studies supporting the efficacy of the established antimanic agents lithium, valproate, and carbamazepine and standard antipsychotics. We then review available research on two important classes of drugs that are emerging as potential treatments for acute mania: the novel antipsychotics, which include clozapine, olanzapine, quetiapine, risperidone, and ziprasidone, and the new antiepileptics, which include gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, and zonisamide. We conclude that although controlled data are accumulating to support the efficacy of several atypical antipsychotics in the treatment of acute bipolar mania, particularly olanzapine, ziprasidone, and risperidone, the novel antiepileptics need more extensive study before it can be concluded that any of them possess specific antimanic properties. We also conclude that as the medical options for acute bipolar mania expand, treatment guidelines must remain both evidence based and flexible, so that they represent cutting edge medical science yet can be tailored to the specific needs of individual patients.     

Determinants of voluntary vs. involuntary admission in bipolar disorder and the impact of adherence

INTRODUCTION: Treatment adherence plays a pivotal role in hospitalisation in bipolar disorder (BD). We examined the impact of adherence and pharmacological variables on involuntary vs. voluntary admission on a sample of inpatients from the European Mania in Bipolar Longitudinal Evaluation of Medication study (EMBLEM). METHODS: 1374 inpatients with an acute manic or mixed episode of BD participated in this observational study on clinical, functional and economic outcomes of pharmacological treatment. We analysed data at the time of study inclusion, and the primary outcome measure was admission status (voluntary vs. involuntary admission). RESULTS: The strongest baseline factor of admission status was adherence whereby patients' adherence was significantly associated with admission when treated with atypical antipsychotics or lithium as monotherapy. Adherence with typical antipsychotics was not significantly associated with admission status. DISCUSSION: These results emphasise the crucial role of treatment adherence for admission status and, within the context of a naturalistic study, some advantage of atypical over typical antipsychotics on admission in acute mania of BD.     

Can the expression of histocompatibility antigen be changed by lithium?

Objectives : This study attempted to determine whether human leukocyte antigen (HLA) type changes would be caused by lithium.

Methods : A total of 15 patients were chosen as subjects (4 males, 11 females) and completed tests in class I. Eight of the 15 patients completed tests in class II. Their mean age was 27±7 years. For an average of 51±17 days, lithium, 600–1200 mg/day (mean daily dose: 920±211 mg) was administered for the HLA testing and then compared with the HLA type prior to the time the drug was administered. Class I type test was performed according to the Terasaki microcytotoxicity method and class II type by the Erlich polymerase chain reaction method.

Results : Of the 15 subjects, 11 had changes in HLA-A, B, C types and two of the eight subjects had changes in HLA DR type.

Conclusion : Lithium, in the therapeutic dose, is considered to bring about changes in HLA expressions in as short a time period as 2 months.     

Behandlungsmöglichkeiten der akuten Manie mit atypischen Antipsychotika

The diagnosis and treatment of bipolar mania are extremely challenging. Therapeutic intervention for mania has traditionally relied on the use of lithium or divalproex as a first-line treatment option. However, due to the limited therapeutic range of these agents, typical neuroleptics have often been used. Although these have demonstrated efficacy in mania, they are often associated with significant side effects, especially extrapyramidal symptoms. Thus, atypical antipsychotics are increasingly preferred in the treatment of bipolar mania. In this review, data from controlled studies for several of the atypical antipsychotics in the treatment of mania are surveyed and issues in the selection of an appropriate atypical agent are discussed.