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.     

Neuropsychological functions in patients with bipolar I and bipolar II disorder

Objectives:  The literature reports persistent cognitive impairments in patients with bipolar disorder even after prolonged remission. However, a majority of studies have focused only on bipolar I disorder (BP-I), primarily because bipolar II disorder (BP-II) is often underdiagnosed or misdiagnosed. More attention should be paid to the differences between BP-I and BP-II, especially the aspects of neuropsychological functioning. We examined the different neuropsychological functions in BP-I and BP-II patients and compared them with those of healthy controls.
Methods:  The study included 67 patients with interepisode bipolar disorder (BP-I: n = 30; BP-II: n = 37) and 22 healthy controls compared using a battery of neuropsychological tests that assessed memory, psychomotor speed, and certain aspects of frontal executive function.
Results:  The BP-I group performed poorly on verbal memory, psychomotor speed, and executive function compared to the BP-II and control groups. Both bipolar groups performed significantly less well than the control group on measures of working memory and psychomotor speed, while the BP-II group showed an intermediate level of performance in psychomotor speed compared to the BP-I and control groups. There was no difference between the groups on visual memory.
Conclusions:  BP-I was characterized by reduced performance in verbal memory, working memory, psychomotor speed, and executive function, while BP-II patients showed a reduction only in working memory and psychomotor speed. Cognitive impairment existed in both subtypes of bipolar disorder, and was greater in BP-I patients. Rehabilitation interventions should take into account potential cognitive differences between these bipolar subtypes.     

The Maudsley bipolar disorder project. Clinical characteristics of bipolar disorder I in a Catchment area treatment sample.

The clinical characteristics of bipolar I disorder (BD1) have prognostic and therapeutic importance. The aim of this study was to examine the effect of demographic and clinical variables on the course of BD1. We reviewed the case notes of all BD1 patients (n = 63) receiving treatment in a London psychiatric service during a 1-month period. Depressive and manic onsets were equally likely without any gender difference. The earlier the age of onset, the more likely it was for patients to experience psychotic features. Only depressive onsets predicted a higher number of episodes of the same polarity. Male gender and substance abuse were associated with younger age at first presentation, while women with co-morbid substance abuse had more manic episodes. Male patients were more likely than females to be unemployed or single.     

Gabapentin in the acute treatment of refractory bipolar disorder

Background: Gabapentin, a new anti-epileptic agent, has been anecdotally reported to be effective in the treatment of mania. We systematically assessed the response rate in bipolar patients being treated adjunctively with gabapentin for manic symptoms, depressive symptoms, or rapid cycling not responsive to standard treatments.
Method: Twenty-eight bipolar patients experiencing manic (n=18), depressive (n=5), or rapid-cycling (n=5) symptoms inadequately responsive to at least one mood stabilizer were treated in an open fashion with adjunctive gabapentin. Illness response was assessed using the Clinical Global Impression Scale modified for bipolar disorder (CGI-BP). A 'positive response' was operationalized as a CGI response of much or very much improved.
Results: Fourteen of the 18 (78%) treated for hypomania or mania had a positive response to a dosage range of 600–3600 mg/day. Patients with hypomania responded fastest, with a positive response achieved in 12.7±7.2 days. Patients with classic mania had a mean time to positive response of 25±12 days, and in patients with mixed mania it was 31.8±20.9 days. All of the five patients treated for depression had a positive response within 21±13.9 days. Only one of five patients with rapid cycling had a positive response. Gabapentin was well tolerated by all patients, with the most common side-effect being sedation.
Conclusions: Gabapentin appears to have acute anti-manic and anti-depressant properties as an adjunctive agent for refractory bipolar illness. Prospective double-blind studies are needed to further delineate its acute efficacy when used as monotherapy and its prophylactic efficacy as monotherapy or in conjuction with other mood stabilizers.     

Pharmacotherapy patterns in the treatment of bipolar disorder

Objectives:  To assess medication use patterns of patients with bipolar disorder, and, through multivariate analysis, to elucidate the role of selected demographic and clinical factors on medication choice and use patterns.
Methods:  Patients were privately insured individuals aged 18–64, continuously enrolled in a health plan for 15 months or longer during the years 1994–1998, and either diagnosed with bipolar disorder or prescribed lithium or valproate at least 90 days after the start of the study period. Medical and pharmacy claims data were used to analyze medication therapy over a 12-month period.
Results:  First-generation antipsychotics were used by 16.4% of patients and second-generation agents by 12.4%. Patients starting on antipsychotics tended to stay with them for 12 months or longer, while patients starting on anticonvulsants or antidepressants were more likely to stop therapy or to switch to another medication class. Patients treated with olanzapine appeared to have more psychiatric comorbidities and more psychiatric hospitalizations than users of first-generation agents.
Conclusions:  Although mood stabilizers and anticonvulsant agents are widely used to treat bipolar disorder, antipsychotic agents are also present in the treatment regimens of bipolar patients. Demographic and clinical factors were significant predictors of the choice of initial medication therapy and subsequent use patterns. In particular, patient gender and the number of psychiatric and physical comorbidities were significantly related to the course of medication therapy.     

Three times more days depressed than manic or hypomanic in both bipolar I and bipolar II disorder

OBJECTIVES: To assess the proportion of time spent in mania, depression and euthymia in a large cohort of bipolar subjects studied longitudinally, and to investigate depression/mania ratios in patients with bipolar I versus bipolar II disorder. METHODS: Clinician-adjusted self-ratings of mood were completed daily for one year for naturalistically treated outpatients with bipolar I (n = 405) or bipolar II (n = 102) disorder. Ratings were analyzed for mean time spent euthymic, depressed, manic, hypomanic, and cycling, and the percentages of time spent ill were compared between the two groups. RESULTS: Percentages of time spent ill for bipolar I versus II patients were: euthymia 47.7% versus 50.2%; depression 36.0% versus 37.0%; hypomania 11.5% versus 9.8%; mania 1.0% versus 0.2%; and cycling 3.7% versus 2.8%. The depression/mania ratio was 2.9 in the bipolar I and 3.8 in bipolar II sub-groups. CONCLUSIONS: Depression represents the predominant abnormal mood state for treated outpatients with bipolar I and II disorder. In contrast to other studies, we found that depression/mania ratios were of a similar magnitude, suggesting the same tendency towards mood instability in both sub-groups.     

Acute treatment outcomes in patients with bipolar I disorder and co-morbid borderline personality disorder receiving medication and psychotherapy

OBJECTIVE: Patients suffering from both bipolar I disorder and borderline personality disorder (BPD) pose unique treatment challenges. The purpose of this matched case-control study was to compare acute treatment outcomes of a sample of patients who met standardized diagnostic criteria for both bipolar I disorder and BPD (n = 12) to those who met criteria for bipolar I disorder only (n = 58). METHOD: Subjects meeting criteria for an acute affective episode were treated with a combination of algorithm-driven pharmacotherapy and weekly psychotherapy until stabilization (defined as four consecutive weeks with a calculated average of the 17-item version of the Hamilton Rating Scale for Depression and Bech-Rafaelsen Mania scale totaling < or = 7). RESULTS: Only three of 12 (25%) bipolar-BPD patients achieved stabilization, compared with 43 of 58 (74%) bipolar-only patients. Two of the three bipolar-BPD patients who did stabilize took over 95 weeks to do so, compared with a median time-to-stabilization of 35 weeks in the bipolar-only group. The bipolar-BPD group received significantly more atypical mood-stabilizing medications per year than the bipolar-only group (Z = 4.3, p < 0.0001). Dropout rates in the comorbid group were high. CONCLUSIONS: This quasi-experimental study suggests that treatment course may be longer in patients suffering from both bipolar I disorder and BPD. Some patients improved substantially with pharmacotherapy and psychotherapy, suggesting that this approach is worthy of further investigation.     

Long-term prognosis of bipolar I disorder

This study examined the contribution of demographic, syndromal and longitudinal course variables to the long-term prognosis of 165 bipolar patients prospectively observed over 10 years as part of the National Institute of Mental Health Collaborative Study of Depression. Although most baseline clinical and demographic variables were not strong prognostic indicators, switching polarity within episodes was. Most episodes among the poor-prognosis patients were polyphasic, while most episodes among the comparison group with a better prognosis were monophasic. There was no evidence of shortening of cycle lengths over follow-up for either the poor-prognosis group or the entire sample. The relevance of these findings to the 'kindling' model is discussed.     

重性抑郁障碍与双相障碍患者躯体疾病共病调查

目的:了解重性抑郁障碍(MDD)与双相障碍(BD)患者躯体疾病共病情况。方法:对141例MDD和52例BD患者进行一般情况、躯体疾病调查及精神疾病评估。结果:MDD和BD患者躯体疾病的共病率分别为68.1%、46.2%,共病的躯体疾病以慢性病为主,依次为高血压、慢性胃炎、腰椎间盘突出、糖尿病。与非共病患者比较,共病患者年龄及起病年龄大,精神疾病复发次数多(P0.05或P0.01)。MDD共病患者自杀意念风险明显增加(P0.01)。结论:较高龄及较高龄起病的MDD、BD患者更易共病慢性躯体疾病。     

青少年期起病的双相障碍与强迫症共病研究

目的：探讨青少年期起病的双相障碍与强迫症共病患者的临床特征。方法：选择双相障碍和强迫症共病患者（共病组）36例及强迫症患者（OCD组）31例,完成自编调查问卷、强迫症量表（Y-BOCS）测评。结果：OCD组的男性比例高于共病组;共病组的强迫症病程、平均治疗时间长于OCD组。结论：双相障碍与强迫症共病是常见的临床现象,共病对患者的病程及疗效均有影响。     

A randomised,placebo-controlled 52-week trial of continued quetiapine treatment in recently depressed patients with bipolar I and bipolar II disorder

Objectives. To examine the longer-term efficacy of quetiapine monotherapy in bipolar depression in a preplanned pooling of data from the EMBOLDEN I and II studies. Methods. Patients (N = 584) with bipolar I or II disorder (most recent episode: depressed) who achieved remission after 8 weeks of treatment with quetiapine (300 or 600 mg/day) were randomised to the same quetiapine dose or placebo for 26–52 weeks or until mood event recurrence. Results. The risk for recurrence of a mood event was significantly lower with quetiapine than placebo (HR 0.51 (95% CI: 0.38–0.69); P < 0.001). Quetiapine was associated with a lower risk for recurrence of depressive events (HR 0.43 (95% CI: 0.30–0.62); P < 0.001) but recurrence of manic/hypomanic events was not significantly reduced (HR 0.75 (95% CI: 0.45–1.24; P = 0.263). There was a lower risk of recurrence of mood events in bipolar I (HR 0.58 (95% CI: 0.41–0.82), P = 0.002) and bipolar II patients (HR 0.33 (95% CI: 0.18–0.60), P < 0.001). Discontinuation rates due to adverse events were 4.3, 4.0 and 1.7% for quetiapine 300 mg/day, 600 mg/day and placebo, respectively. Safety data, including changes in lipid and glucose parameters, were consistent with the recognized profile of quetiapine. Conclusions. The efficacy of quetiapine monotherapy in bipolar depression is maintained during continued treatment for 26–52 weeks. Quetiapine was generally well tolerated.     

A two-illness model of bipolar disorder

The current approach to mood disorders is that bipolar disorder, comprising both mania and depression, is a discreet illness distinct from unipolar depression. This formulation has profoundly influenced the approach to understanding the biology and etiology of these disorders, as well as the manner in which the various phases of bipolar disorder are treated. Our new model suggests that bipolar disorder comprises two distinct illnesses, mania and depression, and that bipolar depression is no different from unipolar depression. Studies of clinical syndromes, course of illness, family history and genetics, biological factors, and treatment response data directly or indirectly support this new model.     

A review of aripiprazole in the treatment of patients with schizophrenia or bipolar I disorder

Aripiprazole has been approved by regulatory agencies for the treatment of schizophrenia and bipolar I disorder. Although it is a dopamine partial agonist, it also has substantial binding affinity for the serotonin 5HT2A receptor. Several double-blind randomized clinical trials have established the efficacy and tolerability of aripiprazole within the dose range of 10–30 mg/day for schizophrenia, and 15–30 mg/day for manic or mixed states associated with bipolar I disorder. Relatively few comparative trials with other second-generation antipsychotics have been published for schizophrenia, with none available for bipolar disorder. The evidence so far suggests that in terms of efficacy for schizophrenia, aripiprazole is superior to placebo and haloperidol (long term), similar to perphenazine and risperidone, and inferior to olanzapine. Its tolerability profile in patients with schizophrenia appears superior to haloperidol, perphenazine, risperidone, and olanzapine. Efficacy in treating manic or mixed states was established in placebo-controlled trials. Among some patients with bipolar disorder, akathisia and gastrointestinal (GI) complaints can emerge at the start of treatment; however, the GI symptoms were time-limited in many instances. Appropriate dosing may also be important in individualizing therapy to improve tolerability, with lower starting doses becoming more important when adding to, or switching from, another antipsychotic. Aripiprazole appears to have a low propensity for weight gain, a favorable metabolic profile, and no association with hyperprolactinemia.     

双相障碍与强迫症的共病

概述

在双相障碍患者中强迫症状是常见的。因为双相障碍和强迫症的共病状态会令这两种障碍的临床治疗复杂化，所以确定这些共病的患者是很重要的。我们讨论了强迫症和双相障碍的共病，介绍了可能导致这种常见共病状态的发病机制，也讨论了该领域最新的研究进展，并提出一些管理这些患者的临床原则。

中文全文

本文全文中文版从2015年10月26日起在http://dx.doi.org/10.11919/j.issn.1002-0829.215009可供免费阅览下载 Previous studies have documented high rates of comorbidity of other psychiatric conditions among individuals with bipolar disorders (BD).[1] One study estimated that obsessive-compulsive disorders (OCD) accounted for 21% of all comorbidities in BD.[2] There is continuing debate about whether (a) these are two independent conditions that can co-occur or (b) OCD is a specific subtype of BD. Regardless of the interrelationship of the two conditions, the comorbid occurrence of these two types of symptoms can cause a clinical dilemma because selective serotonin reuptake inhibitors (SSRIs)-which are quite commonly used to treat OCD-increases the risk of precipitating manic symptoms.[3,4,5,6] The OCD symptoms that occur in individuals with BD often occur during the depressive episodes or during the intervals between episodes of depressive or manic symptoms.[7,8] This timing of OCD symptoms during BD is consistent with the cyclic nature of BD and suggests shared biological mechanisms between the two disorders. In support of this hypothesis, a study using Positron Emission Tomography (PET) found that in untreated persons with BD the serotonin-transporter binding potential in the insular and dorsal cingulate cortex was higher among BD patients with pathological obsessions and compulsions than among BD patients without such symptoms.[9] Moreover, a linkage study found that compared to OCD patients without comorbid BD, patients with comorbid OCD and BD were more likely to have a family history of mood disorders but less likely to have a family history of OCD.[10] However, another study found no significant difference in the rates of a positive family history of OCD between patients with OCD alone and those with comorbid OCD and BD.[11] Further support for the hypothesized common etiology comes from a preliminary molecular genetic study which found that hyperpolarization activated cyclic nucleotide-gated channel 4 (HCN4) is a common susceptible locus for both mood disorders and OCD, but further studies with larger sample sizes are needed to replicate this finding.[12] The presence of OCD in BD complicates the clinical presentation. Compared to patients with BD without comorbid OCD, those that have comorbid BD and OCD often have a more severe form of BD, have more prolonged episodes, are less adherent to medication, and are less responsive to medication. Recent studies about comorbid BD and OCD have reported the following: (a) Temporal relationship. Some studies suggest that OCD is an antecedent of BD,[10] but others report concurrent onset of OCD and BD.[13,14] (b) Course of disease. In 44% of patients with comorbid BD and OCD the episodes are cyclic.[15] The course of disease is more chronic among BD patients with OCD compared to those without comorbid OCD.[16,17] OCD is more commonly observed in patients with Type II BD, among whom the prevalence of OCD has been reported to be as high as 75%.[18] (c) Compulsive behaviors. The most commonly reported compulsions among patients with comorbid OCD and BD are compulsive sorting,[14,19,20,21] controlling or checking, [20] repeating behaviors,[13,22] excessive washing,[20] and counting.[19] Obsessive reassurance-seeking is also commonly reported in these patients.[23] In children and adolescents with BD, compulsive hoarding, impulsiveness,[24] and sorting[25] are more common. (d) Substance and alcohol abuse. A study found a higher prevalence of sedative, nicotine, alcohol, and caffeine use among individuals with comorbid OCD and BD compared to those with BD without OCD.[14] Similarly, compared to OCD patients without comorbid mood disorders, those with a comorbid mood disorder were more likely to have a substance abuse diagnosis (OR=3.18, 95%CI=1.81-5.58) or alcohol abuse diagnosis (OR=2.21, 95%CI=1.34-3.65).[11,13,26,27,28] (e) Suicidal behaviors. Compared to BD patients without OCD, a greater proportion of patients with both disorders had a lifetime history of suicidal ideation and suicide attempts.[2,11,13,29,30] The clinical management of comorbid OCD and BD requires first focusing on stabilizing the patient’s mood, which requires the combined use of multiple medications such as the use of lithium with anticonvulsants or atypical antipsychotic medications such as quetiapine;[31,32,33] adjunctive treatment with aripiprazole may be effective for the comorbid OCD symptoms.[4] In the case of OCD comorbid with type II BD, after full treatment of the mood symptoms with mood stabilizers the clinician can, while monitoring for potential drug interactions, cautiously try adjunctive treatment with antidepressants that are effective for both depressive symptoms and OCD symptoms and that have a low risk of inducing a full manic episode, including the selective serotonin reuptake inhibitors (SSRIs): fluoxetine, fluvoxamine, paroxetine, and sertraline.[32,35] In summary, BD comorbid with OCD may be etiologically distinct from either of the disorders. Clinicians should pay attention to its complex clinical manifestations and carefully consider the treatment principles outlined above.     

Clinical evidence for genomic imprinting in bipolar I disorder

The phenotypic indicators of the genomic imprinting model were applied to clinical psychopathology data on 100 bipolar (BP) I probands and their families. The paternal transmission was associated with a significantly younger age of onset of the BP illness in probands and a higher rate of affective disorders in first- and second-degree relatives. The effect of the sex of the transmitting parent on age of onset in probands decreased but remained significant when controlling for the effect of the probands' age at investigation. Probands' sex had no significant influence on their age of onset. The severity of the BP illness in probands in terms of number of illness episodes and annual frequency was not influenced by the sex of the transmitting parent.