Anxiety Disorders: Baldessarini RJ

Salvatore P, Tohen M, Khalsa HM, Baethge C, Tondo L, Baldessarini RJ. · No affiliation provided · Epidemiol Psichiatr Soc. · Pubmed #17619540 No free full text.

Abstract: Longitudinal assessment of the course of major psychiatric disorders has been advanced by studies from onset, but only rarely have large numbers of patients with a range of psychotic and major affective disorders been studied simultaneously and systematically from illness-onset. The decade-long McLean-Harvard First Episode Project & International Consortium for Bipolar Disorder Research has systematically followed-up large numbers of patients with DSM-IV bipolar or psychotic disorders from first-hospitalization. Major findings among patients with bipolar I disorder include: [a] full functional recovery from initial episodes was uncommon, and full symptomatic recovery, much slower than early syndromal recovery; [b] risks of relapse, recurrence, and switching were very high in the first two years; [c] most early morbidity was depressive-dysphoric, as reported in mid-course; [d] initial depression or mixed-states predicted more later depressive and overall morbidity, whereas initial mania or psychosis predicted later mania and a better prognosis; [e] based on within-subject modeling, most patients did not show progressive cycling over time, and illness-course was rather chaotic within and among patients; [f] treatment-latency or episode-counts were unassociated with responsiveness to long-term mood-stabilizing treatment; [g] very high rates of suicidal behavior and accidents occurred early; [h] early substance-use comorbidity associated with anxiety; [i] factor-analysis of prodromal symptoms predicted bipolar disorder much better than non-affective psychotic disorders. Project findings indicate that the course of bipolar I disorder is much less favorable than had been believed formerly, despite clinical treatment with modern mood-stabilizing and other treatments.

Salvatore P, Bhuvaneswar C, Ebert D, Maggini C, Baldessarini RJ. · Department of Psychiatry, Harvard Medical School, Massachusetts, USA. · Harv Rev Psychiatry. · Pubmed #18569038 No free full text.

Abstract: Emil Kraepelin proposed to separate psychiatric disorders with psychotic features into two major categories, dementia praecox (later schizophrenia) and manic-depressive insanity (later bipolar disorder and major depression). Over the past century, there have been many efforts to categorize conditions that do not fit readily in either group. These conditions include many cases of acute psychotic illnesses of limited duration, with recovery between recurrences. For some of these conditions, Karl Kleist proposed the term cycloid psychosis: acute features were psychotic, as in schizophrenia, but the course was episodic, as in manic-depression. His concept was later elaborated by Karl Leonhard and Carlo Perris, and validated by modern studies. Leonhard described three overlapping cycloid subtypes (anxiety-beatific, excited-inhibited confusional, and hyperkinetic-akinetic motility dysfunction forms); Perris proposed a more unitary syndrome with operational diagnostic criteria; and recent investigators have considered relatively affective versus thought-disordered subtypes. The cycloid concept is not explicitly included in standard international diagnostic schemes, but both DSM-IV and ICD-10 have broad categories for acute, recurrent psychotic disorders, whose validity remains insecure. We present two cases of probable cycloid psychosis, review the history of the concept, and propose that it be reconsidered as a clinically useful category whose validity and utility for prognosis and treatment can be further tested.

Nykiel SA, Baldessarini RJ, Bower MC, Goodwin J, Salvatore P. · Harvard Medical School and McLean Hospital, Belmont, MA 02478, USA. · Harv Rev Psychiatry. · Pubmed #18306099 No free full text.

This publication has no abstract.

Baldessarini RJ, Perry R, Pike J. · Department of Psychiatry & Neuroscience Program, Harvard Medical School, Boston, Massachusetts, USA. · Hum Psychopharmacol. · Pubmed #18058849 No free full text.

Abstract: OBJECTIVE: Since sustained treatment-adherence is often problematic and may limit clinical outcomes among bipolar disorder (BPD) patients, we sought risk factors to guide clinical prediction of nonadherence. METHODS: Data were from a 2005 US national sample providing questionnaire responses by 131 randomly selected prescribing psychiatrists and their adult BPD patients. We contrasted demographic and clinical factors in treatment-adherent versus nonadherent patients (strictly defined as missing > or =1 dose within 10 days) in univariate analyses followed by multivariate logistic-regression modeling. RESULTS: Of 429 DSM-IV BPD patients (79% type-I; 62% women; 17% minorities), 34% reported missing > or = 1 dose of psychotropic medication within 10 days, 20% missed entire daily doses at least once, and only 2.5% missed all doses for 10 days. However, their prescribing psychiatrists considered only 6% as treatment-nonadherent. Factors significantly associated with nonadherence in multivariate modeling ranked: alcohol-dependence > youth > greater affective morbidity > various side effects > or = comorbid obsessive-compulsive disorder > or = recovering from mania-hypomania. Unrelated were sex, diagnostic subtype, and other comorbidities. Since most patients received > or = 2 psychotropics, potential relationships between treatment-complexity and adherence were obscured. CONCLUSIONS: Prevalent treatment-nonadherence among American BPD patients, and striking underestimation of the problem by prescribing clinicians may encourage increasingly complex treatment-regimens of untested value, but added expense, risk of adverse effects, and uncertain impact on treatment-adherence itself.

Sim K, Lee NB, Chua HC, Mahendran R, Fujii S, Yang SY, Chong MY, Si T, He YL, Lee MS, Sung KM, Chung EK, Chan YH, Shinfuku N, Tan CH, Sartorius N, Baldessarini RJ. · Institute of Mental Health/Woodbridge Hospital, Singapore. · Br J Clin Pharmacol. · Pubmed #17076698 links to  free full text

Abstract: AIMS: Antidepressant use in East Asia is poorly documented. We compared patients given newer and older antidepressants to test the hypothesis, suggested in the literature, that use of newer antidepressants is associated with treatment settings rather than specific diagnostic categories. METHODS: We compared rates of use of older (pre1990) vs. newer antidepressants among 1898 patients identified as antidepressant treated at 21 centres in five East Asian countries (China, Japan, Korea, Singapore, Taiwan) in 2003. Demographics, treatment setting and clinical factors associated with preferential use of newer drugs were tested in univariate and multivariate analyses. RESULTS: Newer antidepressants were included in the treatment regimens of 67.5% (N = 1282/1898) of study subjects. Prescription for newer antidepressants was significantly associated with younger age (z = -4.55, d.f. = 1888, P < 0.001), hospitalization [odds ratio (OR) 1.32, 95% confidence interval (CI) 1.07, 1.64, P < 0.01] and treatment within psychiatric hospitals (OR 1.59, 95% CI 1.27, 2.00, P < 0.001). On multivariate analyses, treatment with newer antidepressants was independently associated with younger age (P < 0.001), country (P < 0.001) and treatment within private hospitals (P < 0.001), but not with sex or diagnosis of affective or anxiety disorders (all P > 0.1). CONCLUSION: Demographic factors and treatment settings appear to influence antidepressant choice more than clinical factors such as diagnosis.

Centorrino F, Hennen J, Mallya G, Egli S, Clark T, Baldessarini RJ. · Schizophrenia and Bipolar Disorder Program, McLean Hospital, Belmont 02478, and Department of Psychiatry, Harvard Medical School, Cambridge, MA, USA. · Hum Psychopharmacol. · Pubmed #16625524 No free full text.

Abstract: BACKGROUND: Bipolar disorder (BPD) is often comorbid with obsessive-compulsive (OCD) and other anxiety disorders, but the impact of such comorbidity on long-term outcome has not been evaluated systematically. METHODS: Extensive follow-up assessments were carried out at 4.3 years after index hospitalizations in a mixed BPD-OCD group (N=20) compared to matched groups with BPD (N=22) or OCD (N=20) alone. RESULTS: At follow-up, ratings of functional status were similar across groups. Rehospitalizations were similar among BPD-OCD and BPD subjects, but 2.9-times more frequent among comorbid than OCD patients. OCD symptoms averaged 150% more severe in OCD than comorbid subjects, and were not measured in BPD subjects. CONCLUSIONS: Despite potential sampling bias with previously hospitalized subjects, the findings suggest that comorbid BPD-OCD patients may be clinically more similar to BPD than OCD patients, and that BPD-OCD comorbidity may not negatively impact the long-term clinical outcome.

Baethge C, Baldessarini RJ, Khalsa HM, Hennen J, Salvatore P, Tohen M. · Department of Psychiatry, Harvard Medical School, Boston, MA, USA. · Am J Psychiatry. · Pubmed #15863809 links to  free full text

Abstract: OBJECTIVE: This study clarified the early characteristics of substance use disorders in patients with first-episode bipolar I disorder. METHOD: The authors evaluated substance use disorders, associated factors, and clinical course, prospectively, in the first 2 years of DSM-IV bipolar I disorder with standardized methods. RESULTS: Baseline substance use disorder was found in 33% (37 of 112) of the patients at baseline and in 39% at 24 months. Anxiety disorders were more frequent in the patients with than without substance use disorder (30% and 13%, respectively). Associations of alcohol dependence with depressive symptoms and cannabis dependence with manic symptoms were suggested. Patients using two or more substances had worse outcomes. CONCLUSIONS: Since substance use disorders were frequent from the beginning of bipolar I disorder and were associated with anxiety disorders and poor outcome, early interventions for substance use disorder and anxiety might improve later outcome.

Baethge C, Baldessarini RJ, Freudenthal K, Streeruwitz A, Bauer M, Bschor T. · Department of Psychiatry, International Consortium for Bipolar Disorder Research, Harvard Medical School, McLean Division of Massachusetts General Hospital, Belmont, MA 02478-9106, USA. · Bipolar Disord. · Pubmed #15762854 No free full text.

Abstract: OBJECTIVE: As there is very little research on the topic, we compared the frequency and the type hallucinations among hospitalized patients diagnosed with bipolar disorder (BPD) versus other major psychiatric illnesses. METHODS: At admission, all patients hospitalized at the Department of Psychiatry at the Freie Universität Berlin (1981-2001) underwent comprehensive assessments using the standardized Association for Methodology and Documentation in Psychiatry (AMDP) system. We used these data to compare risks and types of hallucinations and associated factors by bivariate and multivariate testing in patients diagnosed with BPD, major depression, or schizophrenia. RESULTS: At admission, the cross-sectional prevalence of current hallucinations among 4972 hospitalized subjects ranked: schizophrenia (61.1%), bipolar mixed (22.9%), bipolar manic (11.2%), bipolar depressed (10.5%), unipolar depressed (5.9%). The most frequent hallucinations across all patients were auditory, followed by somatic and visual hallucinations. There were only minor age or sex differences in risk of hallucinations. Compared with patients diagnosed with schizophrenia, hallucinations among patients with BPD were less severe, more visual and less often auditory. Characteristics of hallucinations were similar among manic and both bipolar- and unipolar-depressed subjects. Among patients with major affective disorders, those with hallucinations were less well-educated, had higher anxiety scores, less insight into the illness, and their hospitalizations averaged 17% longer. Across all diagnoses, hallucinations, particularly olfactory, were significantly associated with delusions. Hallucinations in BPD were most often accompanied by persecutory delusions; delusions of grandeur were least associated with hallucinations. CONCLUSIONS: This study provides detailed descriptive data regarding the frequency (cross-sectional) and characteristics of hallucinations in a large sample of patients with BPD, major depression or schizophrenia. Our results suggest a link of lower education and the presence of hallucinations in major affective disorders. The significance of this finding, as well as the role of anxiety in hallucinating patients, requires further study.

Faedda GL, Baldessarini RJ, Glovinsky IP, Austin NB. · Lucio Bini Mood Disorders Center, New York, NY 10022, USA. <> · J Affect Disord. · Pubmed #15465590 No free full text.

Abstract: BACKGROUND: Pediatric bipolar disorder (BPD) can be misdiagnosed as a depressive, attention, conduct, or anxiety disorder and treatment with antidepressants and stimulants is common. Risk of adverse outcomes related to such treatment remains poorly defined. METHODS: We analyzed clinical records of 82 children (mean age 10.6 years) meeting modified DSM-IV diagnostic criteria for BPD to evaluate risk and timing of operationally-defined treatment-emergent mania (TEM) or increased mood-cycling following pharmacological treatment. RESULTS: Of 82 juvenile BPD patients, 57 (69%) had been given a mood-elevating agent at least once; 33/57 (58%) so-exposed met criteria for TEM, with median latency of 14 days; TEM was observed twice as often with antidepressants as stimulants (44% vs. 18%). TEM led to first-recognition of BPD in 14 cases (17%), and some drug-exposed children (4-9%) had prominent suicidal, homicidal or psychotic behavior. In addition to recent exposure to a mood-elevating agent, TEM was associated with early-onset anxiety and female gender. LIMITATIONS: Findings are retrospective in clinically diagnosed and treated outpatients, but involved otherwise unselected cases of juvenile BPD. CONCLUSIONS: TEM was reported in 58% of children with probable juvenile BPD within several weeks of new exposure to a mood-elevating agent.

Faedda GL, Baldessarini RJ, Glovinsky IP, Austin NB. · Lucio Bini Mood Disorders Center, New York, NY 10022, USA. · Bipolar Disord. · Pubmed #15225148 No free full text.

Abstract: BACKGROUND: Specific features and diagnostic boundaries of childhood bipolar disorder (BD) remain controversial, and its differentiation from other disorders challenging, owing to high comorbidity with other common childhood disorders, and frequent lack of an episodic course typical of adult BD. METHODS: We repeatedly examined children meeting DSM-IV criteria for BD (excluding episode-duration requirements) and analyzed their clinical records to evaluate age-at-onset, family history, symptoms, course, and comorbidity. RESULTS: Of 82 juveniles (aged 10.6 +/- 3.6 years) diagnosed with BD, 90% had a family history of mood or substance-use disorders, but only 10% of patients had been diagnosed with BD. In 74%, psychopathology was recognized before age 3, usually as mood and sleep disturbances, hyperactivity, aggression, and anxiety. At onset, dysphoric-manic and mixed presentations were most common (48%), euphoric mania less (35%), and depression least (17%). Subtype diagnoses were: BP-I (52%) > BP-II (40%) > cyclothymia (7%). DSM episode-duration criteria were met in 52% of cases, and frequent shifts of mood and energy were common. LIMITATIONS: Partly retrospective study of clinically diagnosed referred outpatients without a comparison group. CONCLUSIONS: Pediatric BD is often mis- or undiagnosed, although it often manifests with mood lability and sleep disturbances early in life. DSM BD criteria inconsistent with clinical findings require revision for pediatric application.