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Most Recent Articles Published on Bipolar Disorder:

Latent class analysis of manic and depressive symptoms in a population-based sample in São Paulo, Brazil.

J Affect Disord. 2010 Jun;123(1-3):208-15

Authors: Moreno DH, Andrade LH

BACKGROUND: Current diagnostic criteria cannot capture the full range of bipolar spectrum. This study aims to clarify the natural co-segregation of manic-depressive symptoms occurring in the general population. METHODS: Using data from the Sao Paulo Catchment Area Study, latent class analysis (LCA) was applied to eleven manic and fourteen depressive symptoms assessed through CIDI 1.1 in 1464 subjects from a community-based study in Sao Paulo, Brazil. All manic symptoms were assessed, regardless of presence of euphoria or irritability, and demographics, services used, suicidality and CIDI/DSM-IIIR mood disorders used to external validate the classes. RESULTS: The four obtained classes were labeled Euthymics (EU; 49.1%), Mild Affectives (MA; 31.1%), Bipolars (BIP; 10.7%), and Depressives (DEP; 9%). BIP and DEP classes represented bipolar and depressive spectra, respectively. Compared to DEP class, BIP exhibited more atypical depressive characteristics (hypersomnia and increase in appetite and/or weight gain), risk of suicide, and use of services. Depressives had rates of atypical symptoms and suicidality comparable to oligosymptomatic MA class subjects. LIMITATIONS: The use of lay interviewers and DSM-IIIR diagnostic criteria, which are more restrictive than the currently used DSM-IV TR. CONCLUSIONS: Findings of high prevalence of bipolar spectrum and of atypical symptoms and suicidality as indicators of bipolarity are of great clinical importance, due to different treatment needs, and higher severity. Lifetime sub-affective and syndromic manic symptoms are clinically significant, arguing for the need of revising DSM bipolar spectrum categories.

PMID: 19896205 [PubMed - indexed for MEDLINE]

The possible antianxiety and mood-stabilizing effects of rufinamide.

Psychother Psychosom. 2010;79(3):194-5

Authors: Fava M

PMID: 20234151 [PubMed - indexed for MEDLINE]

Influence of medications and diagnoses on fall risk in psychiatric inpatients.

Am J Health Syst Pharm. 2010 Aug 1;67(15):1274-80

Authors: Lavsa SM, Fabian TJ, Saul MI, Corman SL, Coley KC

Purpose The influence of medications and diagnoses on fall risk in psychiatric inpatients was evaluated. Methods In this retrospective case-control study, psychiatric inpatients age 18 years or older with a documented fall that was reported served as study cases. These patients were matched to control patients from the same hospital (1:1) by admission year, sex, and age. Psychiatric diagnoses evaluated included major depressive disorder, schizophrenia or schizoaffective disorder, bipolar disorder, Alzheimer's disease and dementia, anxiety or neurosis, delirium, personality disorder, and obsessive-compulsive disorder. Medications assessed as independent variables were conventional antipsychotics, atypical antipsychotics, selective serotonin-reuptake inhibitors, tricyclic antidepressants, atypical antidepressants, monoamine oxidase inhibitors, lithium, anticonvulsants, benzodiazepines, nonbenzodiazepine sleep aids, Alzheimer's disease medications, antihistamines, antiarrhythmics, antihypertensives, benign prostatic hyperplasia medications, oral hypoglycemic agents, histamine H(2)-receptor blockers, laxatives and stool softeners, muscle relaxants, nonsteroidal antiinflammatory drugs, opioids, Parkinson's disease medications, and overactive bladder medications. Univariate logistic regression models were developed for each risk factor to determine its impact on fall risk. Results A total of 774 patient cases were matched with controls. Most falls occurred on the second day of hospitalization. Medications associated with a higher risk of falls were alpha-blockers, nonbenzodiazepine sleep aids, benzodiazepines, H(2)-blockers, lithium, antipsychotics, atypical antidepressants, anticonvulsants, and laxatives and stool softeners. Patients with a diagnosis of dementia and Alzheimer's disease also had an increased risk of falling. Conclusion Alpha-blockers, nonbenzodiazepine sleep aids, benzodiazepines, H(2)-blockers, lithium, atypical antipsychotics, atypical antidepressants, anticonvulsants and mood stabilizers, conventional anti-psychotics, laxatives and stool softeners, and dementia and Alzheimer's disease were significant predictors of inpatient falls in a psychiatric population.

PMID: 20651318 [PubMed - in process]

Methods for combining multiple genome-wide linkage studies.

Methods Mol Biol. 2010;620:541-60

Authors: Kippola TA, Santorico SA

Cardiovascular disease, metabolic syndrome, schizophrenia, diabetes, bipolar disorder, and autism are a few of the numerous complex diseases for which researchers are trying to decipher the genetic composition. One interest of geneticists is to determine the quantitative trait loci (QTLs) that underlie the genetic portion of these diseases and their risk factors. The difficulty for researchers is that the QTLs underlying these diseases are likely to have small to medium effects which will necessitate having large studies in order to have adequate power. Combining information across multiple studies provides a way for researchers to potentially increase power while making the most of existing studies.Here, we will explore some of the methods that are currently being used by geneticists to combine information across multiple genome-wide linkage studies. There are two main types of meta-analyses: (1) those that yield a measure of significance, such as Fisher's p-value method along with its extensions/modifications and the genome search meta-analysis (GSMA) method, and (2) those that yield a measure of a common effect size and the corresponding standard error, such as model-based methods and Bayesian methods. Some of these methods allow for the assessment of heterogeneity. This chapter will conclude with a recommendation for usage.

PMID: 20652521 [PubMed - in process]

Characteristics and Clinical Changes during Hospitalization in Bipolar and Psychotic Disorder Patients with versus without Substance-Use Disorders.

Pharmacopsychiatry. 2010 Jul 22;

Authors: Vincenti A, Ventriglio A, Baldessarini RJ, Talamo A, Fitzmaurice G, Centorrino F

BACKGROUND: Co-morbid substance-use disorders (SUDs) are prevalent among patients with severe psychiatric disorders, but the characteristics of such patients remain incompletely defined, and their current treatments and responses, poorly documented. METHODS: We evaluated the records of 481 consecutive inpatients diagnosed with DSM-IV bipolar or schizoaffective disorders, or schizophrenia, admitted to McLean Hospital in 2004 or 2009. Demographic and clinical characteristics, and treatments, were extracted from hospital and pharmacy records for bivariate and multivariate analyses. RESULTS: SUD prevalence increased 1.84-times from 2004 (31.3%) to 2009 (57.6%). Patients with (n=204) versus without co-morbid SUDs (n=277) were similar in many respects, but in multivariate modeling, the following factors were more likely with SUD, in rank-order: co-morbid anxiety disorders > men more than women > greater prevalence in 2009 vs. 2004 > younger age > greater doses of mood-stabilizers > shorter hospitalization. CONCLUSIONS: Hospitalized patients with severe primary psychiatric disorders, and comorbid SUD were more likely to be young and have anxiety disorders, to receive more combinations and higher doses of mood-stabilizers, and show more improvement in impulsivity and hostility, but otherwise differed little in treatment-responses. Prevalence of SUD rose substantially in the past five years, with increased but largely unproved use of mood-stabilizers.

PMID: 20652858 [PubMed - as supplied by publisher]

Patient characteristics associated with oral anticoagulation control: results of the veterans affairs study to improve anticoagulation.

J Thromb Haemost. 2010 Jul 24;

Authors: Rose AJ, Hylek EM, Ozonoff A, Ash AS, Reisman JI, Berlowitz DR

Summary Background: In patients receiving oral anticoagulation, improved control can reduce adverse outcomes such as stroke and major hemorrhage. However, little is known about patient-level predictors of anticoagulation control. Objectives: To identify patient-level predictors of oral anticoagulation control in the outpatient setting. Patients/Methods: We studied 124,619 patients who received oral anticoagulation from the Veterans Health Administration (VA) from October 2006 - September 2008. The outcome was anticoagulation control, summarized using percent time in therapeutic range (TTR). Data were divided into inception (first 6 months of therapy; 39,447 patients) and experienced (anytime thereafter; 104,505 patients). Patient-level predictors of TTR were examined using multivariable regression. Results: The mean TTR was 48% for inception management and 61% for experienced management. During inception, important predictors of TTR included hospitalizations (expected TTR was 7.3% lower for those with 2+ hospitalizations, compared to the non-hospitalized), receipt of more medications (16+ medications predicted TTR 4.3% lower than for patients with 0-7 medications), alcohol abuse (-4.6%), cancer (-3.1%), and bipolar disorder (-2.9%). During the experienced period, important predictors of TTR included hospitalizations (4+ hospitalizations predicted 9.4% lower), more medications (16+ medications predicted 5.1% lower), alcohol abuse (-5.4%), female sex (-2.9%), cancer (-2.7%), dementia (-2.6%), non-alcohol substance abuse (-2.4%), and chronic liver disease (-2.3%). Conclusions: Some patients receiving oral anticoagulation therapy are more challenging to maintain within the therapeutic range than others. Our findings can be used to identify patients who require closer attention or innovative management strategies to maximize benefit and minimize harm from oral anticoagulation therapy.

PMID: 20653840 [PubMed - as supplied by publisher]

Brain-derived neurotrophic factor as a biomarker for mood disorders: An historical overview and future directions.

Psychiatry Clin Neurosci. 2010 Aug;64(4):341-57

Authors: Hashimoto K

Mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BPD), are the most prevalent psychiatric conditions, and are also among the most severe and debilitating. However, the precise neurobiology underlying these disorders is currently unknown. One way to combat these disorders is to discover novel biomarkers for them. The development of such biomarkers will aid both in the diagnosis of mood disorders and in the development of effective psychiatric medications to treat them. A number of preclinical studies have suggested that the brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of MDD. In 2003, we reported that serum levels of BDNF in antidepressant-naive patients with MDD were significantly lower than those of patients medicated with antidepressants and normal controls, and that serum BDNF levels were negatively correlated with the severity of depression. Additionally, we found that decreased serum levels of BDNF in antidepressant-naive patients recovered to normal levels associated with the recovery of depression after treatment with antidepressant medication. This review article will provide an historical overview of the role played by BDNF in the pathophysiology of mood disorders and in the mechanism of action of therapeutic agents. Particular focus will be given to the potential use of BDNF as a biomarker for mood disorders. BDNF is initially synthesized as a precursor protein proBDNF, and then proBDNF is proteolytically cleaved to the mature BDNF. Finally, future perspectives on the use of proBDNF as a novel biomarker for mood disorders will be discussed.

PMID: 20653908 [PubMed - in process]

Is unrecognized bipolar disorder a frequent contributor to apparent treatment resistant depression?

J Affect Disord. 2010 Jul 22;

Authors: Correa R, Akiskal H, Gilmer W, Nierenberg AA, Trivedi M, Zisook S

BACKGROUND: There is widespread clinical belief that unrecognized bipolar disorder (BD) is a frequent contributor to apparent treatment resistant depression (TRD). This review attempts to assess the degree to which prevailing empirical data supports that view. METHODS: All English-language articles published between January 1998 and January 2008 that focused on adults with major depressive disorder (MDD) and BD bearing on the question "Is unrecognized BD a frequent contributor to apparent TRD in patients initially diagnosed with MDD?" were reviewed. RESULTS: 196 articles were reviewed; the preponderance of the data suggested: 1) TRD populations demonstrate high rates of hidden bipolar disorder, 2) there is not sufficient evidence to unequivocally support or reject the hypothesis that patients who relapse despite continued antidepressant treatment are likely to have bipolar spectrum disorder, 3) patients initially diagnosed with MDD do not demonstrate high rates of switching to mania or hypomania when treated with antidepressants and 4) in patients diagnosed with BD, antidepressants are not robustly effective and are poorly tolerated. LIMITATIONS: The main limitation of this review is that none of the individual studies were designed to test our primary hypothesis. CONCLUSIONS: This review provides at least moderate support to the hypothesis that BD is a contributor to apparent TRD. Thus, clinicians treating MDD are urged to search for "soft" signs of bipolarity and to be prepared to alter diagnosis and treatment strategies accordingly.

PMID: 20655113 [PubMed - as supplied by publisher]

How Psychological Symptoms Relate to Different Motivations for Gambling: An Online Study of Internet Gamblers.

Biol Psychiatry. 2010 Jul 22;

Authors: Lloyd J, Doll H, Hawton K, Dutton WH, Geddes JR, Goodwin GM, Rogers RD

BACKGROUND: Gambling can be motivated by both its hedonic value and by attempts to cope with dysphoric or stressful states. Thus, motivations constitute important mechanisms linking mood fluctuations and gambling. However, little is known about how different kinds of affective disturbance, such as mood elevation and dysphoria, motivate gambling behavior. METHODS: To estimate relationships between different mood experiences and gambling motivations, we recruited 4125 Internet gamblers via hyperlinks placed on gambling Web sites. Mean (SD) age of respondents was 35.5 (11.8) years, with 79.1% (3263) being male and 68.8% (2838) UK residents. We collected ratings for 11 gambling motivations. We used principal components analysis, followed by hierarchical linear regression, to model the relationships between motivation factor scores and gambling behavior, depressive symptoms, hypomanic experiences, deliberate self-harm, and alcohol and substance misuse. RESULTS: Gambling to regulate mood, gambling for monetary goals, and gambling for enjoyment were enhanced in individuals at heightened risk of problematic gambling, with mood regulation and enjoyment factors being enhanced in female compared with male problem gamblers. Lowered mood reduced the enjoyment motivation, whereas previous mood elevation enhanced it. Gambling problems alongside previous hypomanic experiences or current dysphoria enhanced gambling to regulate emotional states. CONCLUSIONS: Recent theorizing argues that mood disorders and pathologic gambling may share aspects of pathophysiology. Different forms of emotional disturbance, such as mood elevation and dysphoric states, which confer heightened risk for bipolar disorder and depression, are associated with divergent motivations that might represent distinct pathways into gambling behavior.

PMID: 20655512 [PubMed - as supplied by publisher]

Psychiatric diagnoses in patients who screen positive on the Mood Disorder Questionnaire: Implications for using the scale as a case-finding instrument for bipolar disorder.

Psychiatry Res. 2010 Jul 24;

Authors: Zimmerman M, Galione JN, Chelminski I, Young D, Dalrymple K

Bipolar disorder is prone to being overlooked because its diagnosis is more often based on retrospective report than cross-sectional assessment. Recommendations for improving the detection of bipolar disorder include the use of screening questionnaires. The Mood Disorder Questionnaire (MDQ) is the most widely studied self-report screening scale that has been developed to improve the detection of bipolar disorder. Although developed as a screening scale, the MDQ has also been used as a case-finding measure. However, studies of the MDQ in psychiatric patients have found high false positive rates, though no study has determined the psychiatric diagnoses associated with false positive results on the MDQ. The goal of the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project was to identify the psychiatric disorders associated with increased false positive rates on the MDQ. Four hundred eighty psychiatric outpatients were interviewed with the Structured Clinical Interview for DSM-IV (SCID) and completed the MDQ. After excluding the 52 patients diagnosed with a lifetime history of bipolar disorder we compared diagnostic frequencies in patients who did and did not screen positive on the MDQ. Based on the Hirschfeld et al. scoring guidelines of the MDQ, 15.2% (n=65) of the 428 nonbipolar patients screened positive on MDQ. Compared to patients who screened negative, the patients who screened positive were significantly more likely have a current and lifetime diagnosis of specific phobia, posttraumatic stress disorder, alcohol and drug use disorders, any eating disorder, any impulse control disorder, and attention deficit disorder. Results were similar using a less restrictive threshold to identify MDQ cases. That is, MDQ caseness was associated with significantly elevated rates of anxiety, impulse control, substance use, and attention deficit disorders. Studies using the MDQ as a stand-alone proxy for the diagnosis of bipolar disorder should consider whether the presence of these other forms of psychopathology could be responsible for differences between individuals who screen positive and negative on the scale.

PMID: 20656360 [PubMed - as supplied by publisher]

Etiology of Bipolar Disorder Across the Lifespan: Essential Interplay With Diagnosis, Classification, and Assessment.

Clin Psychol (New York). 2009 Jun 10;16(2):227-230

Authors: Hankin BL

Bipolar disorder has garnered increasing attention as many argue that rates of bipolar disorder are skyrocketing and the definition of the classic bipolar disorder phenotype should be expanded, especially among children and adolescents. Understanding the psychosocial etiologies of bipolar disorder across the lifespan is critically important, and Alloy and colleagues' (2009) scholarly review makes an important contribution. Given the debate and controversy surrounding the description, diagnosis, and phenotype of bipolar disorder, having an accurate, reliable, and valid classification for definition, diagnosis, and assessment is critical for explicating potential etiology. Likewise, advanced understanding of etiology, especially when grounded in basic psychological science as Alloy and colleagues' review is, can importantly inform clinical phenomenology, course, assessment, and intervention. In summary, there is an essential interplay among description, classification, assessment, etiology, and intervention, such that a deeper understanding of all these areas is necessary for advancing an empirically based practice of assessment and intervention.

PMID: 20657707 [PubMed - as supplied by publisher]

[Cannabis and mood.]

Rev Bras Psiquiatr. 2010 Jun;32(2):173-80

Authors: Sanches RF, Marques JM

OBJECTIVE: Evaluate the relationship between acute and chronic use of cannabis and mood changes. METHOD: Articles were selected by electronic search in PubMed. Chapters in books and reference lists of selected articles were also reviewed. As the research did not involve humans, there was no evaluation by a Research Ethics Committee. RESULTS: High rates of comorbidity between use/abuse/dependence of cannabis and affective disorders in longitudinal studies and in clinical samples were observed. Longitudinal studies indicate that, in long-term, the higher use of cannabis is associated with an increased risk of developing bipolar disorder, and probably, major depression in subjects initially without affective disorder, but was not found increased risk of cannabis use among those initially only with mania or depression. Another important observation is that substance abuse in bipolar patients may be associated with a number of negative characteristics, such as difficulty in recovering the affective symptoms, more hospitalizations, poor compliance with treatment, increased risk of suicide, aggression and a poor response to lithium. Psychosocial and pharmacological treatments are indicated for the management of comorbidity between cannabis and affective disorders. CONCLUSION: The relationship between cannabis use and mood changes are observed both in the epidemiological research and in the clinical settings.

PMID: 20658056 [PubMed - in process]

Lifetime history of suicide attempts is associated with poorer social skills in patients with bipolar disorder type I.

Rev Bras Psiquiatr. 2010 Jun;32(2):200-1

Authors: Rocca CC, Gerchmann L, Abreu LN, Lafer B

PMID: 20658063 [PubMed - in process]

Do the old psychostimulant drugs have a role in managing treatment-resistant depression?

Acta Psychiatr Scand. 2010 Apr;121(4):308-14

Authors: Parker G, Brotchie H

OBJECTIVE: As the authors have observed clinical benefit from the psychostimulants methylphenidate and dexamphetamine for treating resistant melancholic and bipolar depression, those drugs were evaluated in a consecutively recruited sample of 50 such patients. METHOD: Patients (27 bipolar, 23 unipolar) received either methylphenidate (n = 44) or dexamphetamine (n = 6), with 30 having it prescribed as an augmenting drug and 20 as monotherapy. At the final review, ranging from 6 weeks to 62 months (mean 57 weeks), 52% were still receiving their psychostimulant. RESULTS: Thirty-four per cent reported the psychostimulant as distinctly improving their depression, 30% reported some level of improvement and 36% reported no improvement and/or side-effects. For improvers, the modal dose of methylphenidate was 20 mg. Significant side-effects were reported by 18% (including one manic response), switching was rare and limited to the bipolar subjects, and most side-effects were minor. Any positive response occurred rapidly and loss of efficacy was rare. Testing of tricyclic levels in some patients suggested that stimulant drugs may raise tricyclic levels in those who are rapid metabolizers. CONCLUSION: Although this study was not controlled, the high success rate in a diagnostically refined sample implies that the psychostimulants may be efficacious for patients with melancholic and bipolar depression who have failed to respond to orthodox antidepressant drugs.

PMID: 19594481 [PubMed - indexed for MEDLINE]

Bipolar depression: overview and commentary.

Harv Rev Psychiatry. 2010 Jun;18(3):143-57

Authors: Baldessarini RJ, Vieta E, Calabrese JR, Tohen M, Bowden CL

Depressive phases are the most prevalent component of bipolar disorders, even with modern treatment. Bipolar depressive morbidity is often misdiagnosed and is limited in response to available treatments. These conditions are especially debilitating and are associated with psychiatric comorbidity, substance abuse, functional disability, and increased mortality owing to early suicide and accidents, and later medical illnesses. There is growing awareness that bipolar depression is one of the greatest challenges in modern psychiatry. It is essential to differentiate various forms of depression, dysthymia, and dysphoric mixed states of bipolar disorders from the clinical features of more common, unipolar major depressive disorders. In bipolar depression, antidepressant responses often are unsatisfactory, and these agents probably are overused. Emerging treatments, including several anticonvulsant and modern antipsychotic drugs, as well as lithium-alone or in selected combinations-are partially effective for bipolar depression. Interest in recognizing bipolar depression and seeking more effective, specific, and safer treatments for it are growing.

PMID: 20415631 [PubMed - indexed for MEDLINE]

Severity (and treatment) of chronic lithium poisoning: clinical signs or lab results as a criterion?

Acta Clin Belg. 2010 Mar-Apr;65(2):127-8

Authors: Vermeire S, Vanbrabant P, Van Boxstael P, Sabbe M

A 60-year-old woman with a lithium intoxication presented initially to the emergency department with a Glasgow coma scale (GCS) of 15/15. With initial conservative treatment (hydratation) she developed coma, necessitating haemodialysis. During haemodialysis there was no clinical improvement although there was a drop in the serum lithium levels. However, neurological recovery occurred after the first haemodialysis session, while the Lithium level rose again. This case illustrates initial clinical deterioration despite decreasing lithium levels as well as consequent clinical improvement without drop in lithium levels. This case also illustrates the pharmacokinetic profile of lithium and supports the use of primarily clinical signs completed with serum levels of lithium to determine the severity of a lithium poisoning and the adequate therapy including dialysis.

PMID: 20491363 [PubMed - indexed for MEDLINE]

Is there a role for antidepressants in the treatment of bipolar II depression?

Am J Psychiatry. 2010 Jul;167(7):738-40

Authors: Suppes T

PMID: 20595424 [PubMed - indexed for MEDLINE]

The clinician's dilemma: borderline personality disorder or bipolar spectrum disorder?

Australas Psychiatry. 2010 Aug;18(4):303-8

Authors: Little J, Richardson K

Objectives: This paper aims to explore the use of science as a basis for introducing bipolar spectrum disorder to conceptualize people who may otherwise be described as having borderline personality disorder, and offer suggestions for the management of clinical dilemmas. Conclusions: Testable observations, thoughtfulness and humility are helpful in clinical practice.

PMID: 20645894 [PubMed - in process]

Factors associated with work, social life and family life disability in bipolar disorder patients.

Psychiatry Res. 2010 Jul 18;

Authors: Gutiérrez-Rojas L, Jurado D, Gurpegui M

We analyzed the presence of work, social life and family life disability in 108 outpatients with a Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) diagnosis of bipolar disorder and their association with previous course-of-illness variables and current psychopathology. Work disability was pragmatically defined as being on a disability pension or in the process of obtaining it; social life or family life disability was defined by a score >/=7 in the respective subscales of the Sheehan Disability Scale. At least one type of disability (for work, social life or family life) affected 52-54% of the patients; and two types, 37%. By logistic regression and multiple linear regression analyses we determined the variables independently associated with each type of disability: 1) Work disability was significantly associated with previous repeated manic episodes, three or more hospitalizations, with current depressive symptoms and inversely with the educational attainment. 2) Social life disability significantly increased with the number of hospitalizations and was associated with previous repeated depressive episodes and current depressive symptoms. In alternative models, nicotine dependence and lack of social support were significantly associated with work and social life disability respectively. And 3) family life disability significantly increased with number of hospitalizations, CAGE questionnaire score and age; and was associated with previous repeated manic episodes and current depressive symptoms. In conclusion, previous course-of-illness variables, particularly a high number of manic episodes, and current psychopathology - as indicated by the presence of nicotine dependence or depressive symptoms - may be indicators of disability; previous manic episodes appear to affect disability at work or at family life whereas previous depressive episodes seem to be related with social life disability.

PMID: 20647154 [PubMed - as supplied by publisher]

Augmentation of clozapine with aripiprazole in severe psychotic bipolar and schizoaffective disorders: a pilot study.

Clin Pract Epidemiol Ment Health. 2010;6:30-5

Authors: Benedetti A, Di Paolo A, Lastella M, Casamassima F, Candiracci C, Litta A, Ciofi L, Danesi R, Lattanzi L, Del Tacca M, Cassano GB

AIM: To evaluate the efficacy and safety of the augmentation of clozapine with aripiprazole in patients with treatment-resistant schizoaffective and psychotic bipolar disorders in a retrospective manner. Pharmacodynamic and pharmacokinetic interactions between the two drugs were also investigated. PATIENTS: Three men and 4 women (median age 36 and 40 years, respectively) who had mean scores at BPRS and CGI-Severity of 59.1+/-12.0 and 5.4+/-0.5, respectively, were treated with clozapine (mean dose 292.9+/-220.7 mg/day). Patients received an adjunctive treatment with aripiprazole (mean dose 6.8 +/- 3.7 mg/day). Clozapine, norclozapine and aripiprazole plasma levels were measured by means of a high performance liquid chromatograpy with UV detection. RESULTS: Total scores at BPRS decreased significantly (from 59.1+/-12.0 to 51.1+/-15.6, p=0.007) after aripirazole augmentation. In particular, the factors "thought disorder" (from 10.4+/-4.4 to 9.0+/-4.5, p=.047) and "anergia" (from 10.0+/-2.7 to 8.0+/-2.4, p=.018) significantly improved. Concomitant administration of aripiprazole and clozapine did not result in an increase in side effects over the period of treatment. Dose-normalized plasma levels of both clozapine and norclozapine and the clozapine/norclozapine metabolic ratio in all patients did not vary as well. CONCLUSION: The augmentation of clozapine with aripirazole was safe and effective in severe psychotic schizoaffective and bipolar disorders which failed to respond to atypical antipsychotics. A possible pharmacokinetic interaction between clozapine and aripiprazole does not account for the improved clinical benefit obtained after aripiprazole augmentation.

PMID: 20648219 [PubMed - in process]