Paul E Keck

• University of Cincinnati

Objective Bipolar patients in the United States (US) compared to those from the Netherlands and Germany (here abbrev. as “Europe”) have more Axis I comorbidities and more poor prognosis factors such as early onset and psychosocial adversity in childhood. We wished to examine whether these differences also extended to Axis II personality disorders (...

Background Depending on the classification system used, 5–40% of manic subjects present with concomitant depressive symptoms. This post-hoc analysis evaluates the hypothesis that (hypo)manic subjects have a higher burden of depression than non-(hypo)manic subjects. Methods Data from 806 Bipolar I or II participants of the Stanley Foundation Bipola...

Background The Stanley Foundation Bipolar Treatment Outcome Network (SFBN) recruited more than 900 outpatients from 1995 to 2002 from 4 sites in the United States (US) and 3 in the Netherlands and Germany (abbreviated as Europe). When funding was discontinued, the international group of investigators continued to work together as the Bipolar Collab...

Background Evidence is emerging that early onset bipolar disorder and the duration of the delay to first treatment are both risk factors for poor treatment outcome. We report on the incidence and implications of these two risk factors in patients from the United States (US) versus Europe. Methods Age of onset and age at first treatment for depress...

Introduction: There is a high incidence of Axis II personality disorders (PDs) in patients with bipolar illness, but their influence on the prospectively measured course of bipolar disorder has been less well explicated. Methods; 392 outpatients with bipolar disorder gave informed consent, completed the PDQ4 99 item personality disorder rating, and...

The effect of assortative mating on offspring is often not considered. Here, we present data on illness in the spouse and the parents of patients with bipolar disorder as they affect illness in the offspring. A history of psychiatric illness (depression, bipolar disorder, suicide attempt, alcohol abuse, drug abuse, and “other” illness) was elicited...

This chapter reviews the management and treatment of feeding and eating disorders. The cornerstone of managing anorexia nervosa (AN) is refeeding, nutritional rehabilitation, and weight restoration. Evidence of efficacy is strongest for family-based psychotherapy for adolescents with AN. Other forms of psychotherapy have less evidence of efficacy....

Background: Impairments in psychosocial functioning have been demonstrated in 30-60% of adults with bipolar disorder (BD). However, the majority of studies investigating the effect of comorbid mental health disorders and age at onset outcomes in BD have focused on traditional outcome measures such as mood symptoms, mortality and treatment response...

Objective: According to DSM-IV, criterion (A) for diagnosing a hypomanic/manic episode is mood change (ie, elevated, expansive, or irritable mood). Criterion (A) was redefined in DSM-5, adding increased energy or activity in addition to mood change. We sought to investigate the effect of adding increased energy or activity to criterion (A) for the...

(Reprinted with permission from Am J Psychiatry 2006; 163:313-315).

Objective Bipolar disorder has a wide range of clinical manifestations which may progress over time. The aim of this study was to test the applicability of a clinical staging model for bipolar disorder and to gain insight into the nature of the variables influencing progression through consecutive stages. Methods Using retrospectively reported lon...

Introduction Instead of the typical assessment of risk of illness in the offspring based on a parent with bipolar disorder, we explored the potential multigenerational conveyance across several disorders of the vulnerability to illness in the offspring of a patient with bipolar disorder. Methods A total of 968 outpatients (average age 41 years) wi...

The relationship of personality disorder (PD) psychopathology to the course of bipolar disorder remains inadequately described. After giving informed consent, more than 782 outpatients with bipolar disorder rated themselves on the 99-item Personality Disorder Questionnaire, Version 4 (PDQ4) when depressed or euthymic. They also rated six poor progn...

Binge eating, eating an abnormally large amount of food in a discrete period of time with a sense of loss of control over eating, is a defining feature of the eating disorders binge eating disorder (BED) and bulimia nervosa (BN). Both BED and BN are important public health problems for which there are few medical treatments. However, almost all dru...

Objectives: A high incidence of Axis II personality disorders is described in patients with bipolar disorder; however, their relationship to mood state remains uncertain. Methods: A total of 966 outpatients with bipolar disorder gave informed consent and filled out the Personality Disorder Questionnaire, 4th edition (PDQ4) and a questionnaire on...

Background: Although bipolar disorder (BD) and borderline personality disorder (BPD) share clinical characteristics and frequently co-occur, their interrelationship is controversial. Especially, the differentiation of rapid cycling BD and BPD can be troublesome. This study investigates the relationship between borderline personality features (BPF)...

Purpose: To gain further understanding of the general medical comorbidity of binge eating disorder (BED) beyond its association with obesity. Method: We reviewed studies of general medical comorbidity in people with BED or clinically significant binge eating behavior beyond obesity. We also reviewed studies of BED in specific medical conditions....

A significant minority of people presenting with a major depressive episode (MDE) experience co-occurring subsyndromal hypo/manic symptoms. As this presentation may have important prognostic and treatment implications, the DSM–5 codified a new nosological entity, the “mixed features specifier,” referring to individuals meeting threshold criteria fo...

Objective: The authors compared medication-induced mood switch risk (primary outcome), as well as treatment response and side effects (secondary outcomes) with three acute-phase treatments for bipolar II depression. Method: In a 16-week, double-blind, multisite comparison study, 142 participants with bipolar II depression were randomly assigned...

Evidence of a high or increasing incidence of childhood onset bipolar disorder in the United States (US) has been viewed skeptically. Here we review evidence that childhood onsets of bipolar disorder are more common in the US than in Europe, treatment delays are longer, and illness course is more adverse and difficult. Epidemiological data and stud...

Various terms have been used to describe mania when it is accompanied by depressive symptoms. In this article, we attempt to define and discuss 3 of these terms: dysphoric mania, mixed state, and mania with mixed features specifier. We conclude that whatever term is used, it is important to be aware that mania is more often unpleasant than pleasant...

Background: Patients with bipolar disorder from the US have more early-onset illness and a greater familial loading for psychiatric problems than those from the Netherlands or Germany (abbreviated here as Europe). We hypothesized that these regional differences in illness burden would extend to the patients siblings. Methods: Outpatients with bi...

Objective: The age at onset of bipolar disorder varies greatly in different countries and continents. The association between load of family history of psychiatric illness and age at onset has not been adequately explored. Methods: 979 outpatients with bipolar disorder (from 4 sites in the United States and 3 in the Netherlands and Germany) gave...

Objective To evaluate lisdexamfetamine dimesylate (LDX) in the treatment of binge eating disorder (BED). Method Fifty participants with BED received LDX (20-70mg/day) (n=25) or placebo (n=25) for up to 12weeks in a single-center, randomized, double-blind, and flexible-dose trial. The primary outcome measure was binge eating (BE) days/week. ResultsI...

Background: Family history and adversity in childhood are two replicated risk factors for early onset bipolar disorder. However, their combined impact has not been adequately studied. Methods: Based on questionnaire data from 968 outpatients with bipolar disorder who gave informed consent, the relationship and interaction of: 1) parental and gra...

Objective: To report use and treatment success rates of medications for bipolar disorder as a function of patients' clinical characteristics. Method: Outpatients with bipolar illness diagnosed by SCID were rated by research assistants on the NIMH-LCM and those who had an good response for at least 6months (much or very much improved on the CGI-B...

We performed a qualitative review of treatment studies of binge eating disorder (BED), focusing on randomized clinical trials (RCTs). Limited effectiveness has been demonstrated for self-help strategies, and substantial effectiveness has been shown for cognitive behavioral therapy (CBT) and interpersonal therapy (IPT). CBT and IPT may each be more...

Background: Evidence suggests that patients with bipolar disorder from the United States have an earlier age of onset and a more difficult course of illness than those from Germany and the Netherlands. These characteristics were related to a greater family burden of psychiatric illness and the experience of more psychosocial adversity in childhood...

The authors assessed how family history loading affected the course of illness in patients from the United States. A total of 676 outpatients with bipolar disorder from the United States rated their illness and provided a parental and grandparental history of mood disorder, substance abuse, and other clinical conditions. A positive family history f...

We previously found that compared with Europe more parents of the USA patients were positive for a mood disorder, and that this was associated with early onset bipolar disorder. Here we examine family history of psychiatric illness in more detail across several generations. A total of 968 outpatients (average age 41) with bipolar disorder from four...

Objective: DSM-5 introduced the "with mixed features" specifier for major depressive episodes. The authors assessed the prevalence and phenomenology of mixed depression among bipolar disorder patients and qualitatively compared a range of diagnostic thresholds for mixed depression. Method: In a naturalistic study, 907 adult outpatients with bipo...

As a major mainstay of clinical focus and research today, bipolar disorder affects millions of individuals across the globe with its extreme and erratic shifts of mood, thinking and behavior. Edited by a team of experts in the field, this title is a testament and guide to diagnosing and treating this exceedingly complex, highly prevalent disease. F...

This study evaluated the efficacy, tolerability, and safety of armodafinil in the treatment of binge eating disorder (BED). Sixty participants with BED were randomized to receive armodafinil (150-250 mg/day) (N=30) or placebo (N=30) in a 10-week, prospective, parallel-group, double-blind, flexible-dose, single-center trial. In the primary longitudi...

Psychopharmacologic treatment is playing a greater role in the management of patients with eating disorders. In this paper, we review randomized, placebo-controlled trials (RCTs) conducted in anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and other eating disorders over the past 3 years. Fluoxetine remains the only medica...

This phase 3 trial evaluated the efficacy, safety, and tolerability of low- and high-dose cariprazine in patients meeting DSM-IV-TR criteria for acute manic or mixed episodes associated with bipolar I disorder. This multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed/flexible-dose study was conducted from February 2010...

Many patients with bipolar disorder in the United States experience a deteriorating course of illness despite naturalistic treatment in the community. We examined a variety of factors associated with this pattern of illness progression. From 1995 to 2002, we studied 634 adult outpatients with bipolar disorder (mean age of 40 years) emanating from 4...

Backgound: Binge eating disorder (BED) is the most prevalent eating disorder and it is associated with medical and psychiatric comorbidities. In contrast with anorexia nervosa and bulimia nervosa, which predominantly affect females, BED is common in both genders. This paper explores gender differences in BED using, to our knowledge, the largest sam...

This study evaluated the efficacy and tolerability of lisdexamfetamine (LDX) in the treatment of bipolar depression. Twenty-five outpatients with bipolar I or II disorder and syndromal depression despite at least 4 weeks of stable mood stabilizer and/or antipsychotic therapy were randomized to receive LDX (N=11) or placebo (N=14) in an 8-week, pros...

Objectives Physical or sexual abuse in childhood is known to have an adverse effect on the course of bipolar disorder, but the impact of verbal abuse has not been well elucidated.Methods We examined the occurrence and frequency (never to frequently) of each type of abuse in childhood in 634 US adult outpatients (average age 40 years). Patients gave...

Background Medical illnesses are highly comorbid with bipolar disorder, but their relationship to illness characteristics has not been previously delineated. Methods The incidence of 34 medical conditions and 6 poor prognosis factors (PPFs) was derived from answers to a questionnaire in over 900 outpatients with bipolar disorder who gave informed...

Medical comorbidities are common in patients with bipolar (BP) disorder but have not been previously examined for differences between United States and Europe. More than 900 outpatients with BP I and BP II disorder (mean age, 41 years) filled out a questionnaire including the occurrence of 30 listed medical conditions. The patients from the United...

The aim of this study was to gain further understanding of placebo response in binge eating disorder. We pooled participant-level data from 10 double-blind, placebo-controlled, randomized trials of medications for binge eating disorder. The primary outcomes were response (75% reduction in binge eating episodes), cessation of binge eating episodes,...

To assess preliminarily the effectiveness of zonisamide in bulimia nervosa. This was an open-label, prospective, 12-week, flexible dose study of zonisamide in bulimia nervosa. The primary outcome was binge-purge episode frequency. Twelve individuals received zonisamide, 10 completed at least one post-baseline evaluation, and six completed the study...

Early-onset bipolar (BP) disorder and other poor prognosis characteristics are more prevalent in patients from the United States than from the Netherlands and Germany (abbreviated as Europe). We explored the impact of parental loading for affective illness on onset and other characteristics of BP disorder. Parental history for unipolar (UP) and bip...

Considerable data suggest that compared to some European countries, in the U.S. there are more childhood onset bipolar disorders, more adverse courses of illness, and greater treatment resistance. Psychosocial variables related to these findings have not been adequately explored. Therefore we analyzed psychosocial stressors in three time domains: c...

BACKGROUND: The many attempts to identify genes for bipolar disorder (BD) have met with limited success, which has generally been attributed to genetic heterogeneity and small gene effects. However, it is also possible that the categorical phenotypes used in genetic studies of BD are not the most informative or biologically relevant. We have explor...

Bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) exhibit remarkably high rates of comorbidity, as well as patterns of familial co-segregation. Epidemiological data suggests that these disorders either share a common genetic architecture or that ADHD features in BD may represent an etiologically distinct subtype. We previous...

OBJECTIVE: A role for childhood adversity in the development of numerous medical conditions in adults has been described in the general population, but has not been examined in patients with bipolar disorder who have multiple medical comorbidities which contribute to their premature mortality. METHODS: More than 900 outpatients (average age 41) wit...

Background: Lack of coordination between screening studies for common mental disorders in primary care and community epidemiological samples impedes progress in clinical epidemiology. Short screening scales based on the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI), the diagnostic interview used in community e...

Bipolar disorder (BD) is associated with obesity, overweight, and abdominal obesity, and BD individuals with obesity have a greater illness burden. Factors related to BD, its treatment, and the individual may all contribute to BD's association with obesity. Management strategies for the obese BD patient include use of medications with better metabo...

Objective: Antipsychotic drug therapy is the cornerstone of treatment of persons with schizophrenia. Because most antipsychotics are metabolized by the hepatic cytochrome P450 system, concomitant use of an antipsychotic and medications that are competitively metabolized by the same system may cause a potentially harmful drug-drug interaction. This...

Background: Despite a growing number of studies of patients' health values (utilities), little is known about health values of patients with mental illness, particularly bipolar (manic-depressive) disorder. Methods: We administered a computerized rating scale, time tradeoff, and standard gamble to 53 patients. Patients were asked to rate or valu...

Weight gain is commonly observed with olanzapine treatment. Zonisamide is an antiepileptic drug associated with weight loss. This study examined the effectiveness of zonisamide in preventing weight gain in 42 patients beginning olanzapine for bipolar disorder or schizophrenia. Each patient had a body mass index of 22 mg/kg or greater and was random...

The long-term impact of prior antidepressant exposure on the subsequent course of bipolar illness remains controversial. 139 outpatients (mean age, 42 years) with bipolar I disorder diagnosed by DSM-IV criteria had a detailed retrospective examination of their prior course of illness on the National Institute of Mental Health Life Chart Method. Num...

This study evaluated duloxetine in the treatment of binge eating disorder (BED) with comorbid current depressive disorders. In this 12-week, double-blind, placebo-controlled trial, 40 patients with Diagnostic and Statistical Manual of Mental Disorders-IV-TR BED and a comorbid current depressive disorder received duloxetine (N = 20) or placebo (N =...

Greenwood TA, Nievergelt CM, Sadovnick AD, Remick RA, Keck PE Jr, McElroy SL, Shekhtman T, McKinney R, Kelsoe JR. Further evidence for linkage of bipolar disorder to chromosomes 6 and 17 in a new independent pedigree series. Bipolar Disord 2012: 14: 71–79. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: We have pre...

Growing research shows that the impulse control disorders are much more common than once thought to be. The consistency of the ‘structure’ of the irresistible impulse (a core disturbance of impulsivity and compulsivity) together with increasing research showing that it responds to certain treatments, especially cognitivebehavioural psychotherapies...

Many persons with eating disorders (EDs) receive pharmacotherapy, but pharmacotherapy research for EDs has lagged behind that for other major mental disorders. In this chapter, we first provide a brief rationale for using medications in the treatment of EDs. We then review the data supporting the effectiveness of specific medications or medication...

Because of the high costs associated with ascertainment of families, most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. Although microsatellite markers spaced every 10 cM typically extract most of the genetic information cont...

Background / Purpose: The US has 11 fold more childhood (<13 yrs of age) onset bipolar illness than in the Netherlands and Germany (abbreviated as Europe (E)) so that risk factors deserve further exploration.The hypothesis is that compared to E, the US would have more stressors 1) in childhood, 2) at illness onset and 3) prior to latest episode....

LEARNING OBJECTIVES: After participating in this activity, the psychiatrist should be better able to: * Evaluate the potential benefits of asenapine, paliperidone extended release, quetiapine, and ziprasidone in the treatment of bipolar disorder from new clinical trial results. * Analyze the strengths and limitations of data regarding trials of tam...

To assess preliminarily the effectiveness of sodium oxybate in binge eating disorder. This was an open-label, prospective, 16-week, flexible dose study of sodium oxybate in binge eating disorder. The primary outcome was binge eating episode frequency. Twelve individuals received sodium oxybate, 10 completed at least one postbaseline evaluation, and...

Increased early-onset bipolar illness was seen in the US compared with the Netherlands and Germany (abbreviated here as Europe), but other clinical characteristics, medication use, and treatment response have not been systematically explored. Outpatients with bipolar disorder were treated naturalistically and followed prospectively at four sites in...

Relatively little is known about the co-occurrence of bipolar and eating disorders. We therefore assessed the prevalence and clinical correlates of eating disorders in 875 patients with bipolar disorder. 875 outpatients with DSM-IV bipolar I or II disorder were evaluated with structured diagnostic interviews and clinician- and self-administered que...

This study evaluated the efficacy and tolerability of ramelteon in ambulatory bipolar I disorder with manic symptoms and insomnia. Twenty-one outpatients with bipolar I disorder by Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria with mild-to-moderate manic symptoms and sleep disturbance were randomized to receive eith...

To assess preliminarily the effectiveness of acamprosate in binge eating disorder (BED). In this 10-week, randomized, placebo-controlled, flexible dose trial, 40 outpatients with BED received acamprosate (N = 20) or placebo (N = 20). The primary outcome measure was binge eating episode frequency. While acamprosate was not associated with a signific...

Although a range of antidepressant medications are available, a substantial number of patients either do not respond adequately to these or are unable to tolerate their adverse effects. A treatment strategy that has gathered substantial empirical support is the use of second generation antipsychotic agents (SGAs) in combination with antidepressants...

To evaluate the clinical correlates of and types of naturalistic treatments associated with sustained improvement/remission for at least 6 months in outpatients with bipolar disorder. Five hundred twenty-five outpatients with bipolar disorder (77.7% bipolar I) gave informed consent, had their mood rated daily on the National Institute of Mental Hea...

IntroductionLithiumValproic acidCarbamazepineFirst-generation (typical) antipsychoticsSecond-generation (atypical) antipsychoticsElectroconvulsive therapyNew potential antimanic agentsAgents without demonstrated antimanic efficacyClinical recommendationsSummaryReferences

We examined the influence of age at onset of illness and the delay in time to first treatment on morbidity in adulthood. 529 adult outpatients with a mean age of 42 years, who entered our research network from 1996 through 2001 and who were diagnosed with bipolar disorder according to DSM-IV criteria, were rated prospectively on a daily basis with...

The authors assessed gender differences in the proportion of clinical visits spent depressed, manic, or euthymic in patients with bipolar disorder. Data were analyzed from 711 patients with bipolar I or II disorder who were followed prospectively over 7 years (13,191 visits). The main outcome measures were the presence of symptoms of depression or...

To determine whether divalproex extended release (ER) would be effective in outpatients with DSM-IV-TR-diagnosed ambulatory bipolar spectrum disorder (BSD) and moderate-to-severe hypomanic or mild manic symptoms (hypomania/mild mania). An 8-week, randomized, double-blind, placebo-controlled trial of divalproex ER oral loading (begun at 15 mg/kg/d a...

Higher rates of bipolar disorder amongst the first-degree relatives of probands with ADHD, and increased rates of ADHD in the relatives of bipolar probands have been reported in many studies. This suggests some commonality in the genetic basis for bipolar disorder and ADHD. We hypothesized that ADHD symptoms in bipolar disorder may access a quantit...

There are no randomized, placebo-controlled data for quetiapine in outpatients with bipolar spectrum disorder (ambulatory BSD) and moderate-to-severe hypomanic or mild manic symptoms (hypomania/mild mania). An 8-week, randomized, double-blind, placebo-controlled trial of quetiapine in ambulatory BSD with hypomanic/mild manic symptoms, defined opera...

Background. In spite of widespread recognition of the importance of maintenance treatment for bipolar disorder, there are relatively few available well-designed clinical trials that have provided rigorous evidence for the efficacy of specific agents. One approach used effectively in analyses of lithium studies has been the stratification of efficac...

To evaluate long-term safety and efficacy of ziprasidone. Subjects completing a 21-day placebo-controlled trial of ziprasidone in DSM-IV acute bipolar mania (N = 65) were enrolled in a 52-week open-label extension of flexibly dosed ziprasidone 40 to 160 mg/day, administered b.i.d. Three subjects had missing evaluations (N = 62) but still provided d...

Evaluate the efficacy and tolerability of memantine (20, 30, and 40 mg/d) in the acute treatment of adults with bipolar I disorder hospitalized for mania. This multicenter, open-label, pilot trial included adults with bipolar I disorder (manic or mixed episode, with and without psychotic features). Patients were assigned to 21 days of treatment: co...