Biomedical subjects

John Hennen

Publications and source records attributed to John Hennen.

At least 37 records · Page 2Linked to original sources

PubMed2005

Mild traumatic brain injury in psychiatric inpatients.

The purpose of this study was to compare psychiatric inpatients with and without mild traumatic brain injury (MTBI) on the variables of length of stay (LOS), number of psychiatric admissions, and change from admission to discharge on Global Assessment of Functioning (GAF). The study sample included 54 psychiatric inpatients, 18 to 65 years old, with a history of MTBI and 52 comparison psychiatric inpatients absent histories of MTBI, matched on age, sex and diagnostic category. LOS was longer for those with MTBI than for those without MTBI. This difference was statistically significant, after adjustment for matching. When adjusted for baseline GAF, this LOS difference remained statistically significant. The number of prior psychiatric admissions was 19% higher for participants with MTBI than for comparison participants, and when the LOS analysis was adjusted for this factor, it remained statistically significant. GAF change-from-baseline did not differ between the MTBI and comparison groups. Data from this study suggest that psychiatric inpatients with a history of MTBI may differ in frequency and length of hospitalization from otherwise similar inpatients without MTBI history.

Adolescent↗

PubMed2005

Recovery and functional outcomes following olanzapine treatment for bipolar I mania.

BACKGROUND: Typical experimental categorizations of treatment responses in bipolar disorder (BPD) patients may have limited relationship to clinical recovery or functional status, and there is inadequate research on such clinically important outcomes. METHODS: We analyzed data from a study of open continuation of olanzapine treatment following a 3-week placebo-controlled trial involving initially hospitalized adult subjects with DSM-IV BP-I mania to estimate rates and times to symptomatic remission (low scores on standardized symptomatic assessments) and clinical recovery (remission sustained>or=8 weeks), associated clinical factors, and functional outcomes. RESULTS: During treatment with olanzapine for 27.9+/-20.1 weeks, symptomatic remission was attained by 70% of subjects, half by 8 weeks (95% CI 6-10) weeks, and later lost by 82% of remitted subjects; remitted (versus non-remitted) subjects had slightly lower baseline clinical global impression scores and greater trial-completion. Sustained clinical recovery was attained by only 40 of 113 (35%) of subjects, half by 36 (95% CI 20-40) weeks, and later lost by 45%. Subjects with above-median (>12) initial Hamilton-Depression rating scale depression scores were half as likely to recover (p=0.016) and did so much later (36 versus 12 weeks) than those with lower scores. At final assessment, self-rated well being (SF-36 psychosocial functioning scores) improved substantially more among recovered versus non-recovered subjects (mean changes: 87% versus 23%), and two-thirds of recovered subjects remained unemployed-for-pay while half received disability-compensation. CONCLUSIONS: Clinically meaningful symptomatic remission and recovery in relatively severely ill adult bipolar I manic patients were achieved slowly and sustained by only some patients within an average of 7 months of continuous treatment. These clinically relevant outcomes were worse with relatively high initial dysphoria ratings. Well-being was rated higher by recovered subjects, but their ability to work and live independently were markedly impaired. These findings underscore the emerging view that BPD can often be severe, slow to remit, and disabling, particularly in association with prominent depression-dysphoria symptoms. Improved treatments for BPD are needed, guided by longitudinal assessments of clinically meaningful measures of symptomatic recovery and functional outcome.

Adult↗

PubMed2005

Double-blind, placebo-controlled, multicenter trial of selegiline augmentation of antipsychotic medication to treat negative symptoms in outpatients with schizophrenia.

OBJECTIVE: The authors' goal was to test the efficacy of selegiline augmentation of antipsychotic medication in outpatients with schizophrenia who had negative symptoms of moderate or greater severity. METHOD: A 12-week, double-blind, placebo-controlled, multicenter trial of oral selegiline augmentation of antipsychotic medication was carried out. Outpatients were chosen who did not manifest severe positive symptoms at baseline, who did not meet criteria for coexisting major depression, and who had been maintained on a stable regimen of antipsychotic medication. RESULTS: Negative symptoms were found to be significantly more improved in the patients who received selegiline, and global improvement scores reinforced the impression that selegiline augmentation was beneficial. CONCLUSIONS: These findings support further investigation of low-dose selegiline augmentation of antipsychotic medication in outpatients with schizophrenia who have at least a moderate burden of negative symptoms.

Administration, Oral↗

PubMed2005

Substance abuse in first-episode bipolar I disorder: indications for early intervention.

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.

Adult↗

PubMed2005

A comparison of the Aberrant Behavior Checklist and the GAF among adults with mental retardation and mental illness.

Psychiatric assessment among individuals with a diagnosis of both mental retardation and mental illness presents a clinical challenge. This retrospective study compared two rating scales--the Aberrant Behavior Checklist (ABC) and the Global Assessment of Functioning (GAF)--to determine the scales' utility in a partial hospital setting. Although ABC and GAF ratings were weakly correlated, the ABC revealed symptom patterns consistent with recognizable features of psychiatric syndromes and differential improvement in symptoms within and between diagnostic subgroups. The ABC provided a more useful measure of treatment response than the GAF in this patient population.

Adult↗

PubMed2005

Psychosocial functioning of borderline patients and axis II comparison subjects followed prospectively for six years.

The purpose of this study was to determine the course of the psychosocial functioning of patients with borderline personality disorder (BPD) over 6 years of prospective follow-up. The psychosocial functioning of 290 patients meeting both DIB-R and DSM-III-R criteria for BPD and 72 patients meeting DSM-III-R criteria for another Axis II disorder (and neither criteria set for BPD) was assessed at baseline using a semistructured interview of demonstrated reliability. Over 94% of surviving patients were reinterviewed about their psychosocial functioning blind to all previously collected information at three distinct follow-up waves: 2-, 4-, and 6-year follow-up. The psychosocial functioning of borderline patients improved substantially over time, with the percentage meeting criteria for good overall psychosocial functioning increasing from 26% at baseline to 56% during the third wave of follow-up. Despite this improvement, borderline patients functioned significantly more poorly than Axis II comparison subjects, particularly in the area of vocational achievement. However, a more detailed examination revealed that borderline patients who had experienced a symptomatic remission during the course of the study functioned significantly better both socially and vocationally than never-remitted borderline patients. More specifically, they were significantly more likely to have a good relationship with a spouse/partner and at least one parent, good work/school performance, a sustained work/school history, a GAF score of 61 or higher (43% vs. 0% 6 years after their index admission), and to have good overall psychosocial functioning (66% vs. 27% at 6 year follow-up). Taken together, the results of this study suggest that psychosocial improvement is both common among borderline patients and strongly related to their symptomatic status.

Adolescent↗

PubMed2005

The McLean Study of Adult Development (MSAD): overview and implications of the first six years of prospective follow-up.

The McLean Study of Adult Development (MSAD) began 12 years ago. It is the first NIMH-funded prospective study of the course and outcome of borderline personality disorder (BPD). After careful analysis of the first six years of follow-up, 5 main findings concerning the symptomatic and psychosocial course of BPD have emerged from this study. The first finding is that remissions are far more common than previously recognized (about 74%). The second is that these remissions are quite stable and thus, recurrences are quite rare (about 6%). The third finding is that completed suicides are far more rare than anticipated (about 4% vs. 10%). The fourth finding is that a "complex" model of borderline psychopathology best describes BPD. In this model, some symptoms resolve relatively quickly, are the best markers for the disorder, and are often the immediate reason for needing costly forms of treatment, such as psychiatric hospitalizations. We termed these symptoms (e.g., self-mutilation, help-seeking suicide threats or attempts) acute symptoms. Other symptoms resolve more slowly, are not specific to BPD, and are closely associated with ongoing psychosocial impairment. We termed such symptoms (e.g., chronic feelings of intense anger, profound abandonment concerns) temperamental symptoms. Fifth, it was also found that borderline patients were improving psychosocially over time, particularly remitted borderline patients; psychosocial functioning of remitted patients continued to improve as time progressed, suggesting that they were somewhat belatedly achieving the milestones of young adulthood and not simply returning to a prodromal level of functioning. Taken together, these results suggest that the prognosis for BPD is better than previously recognized.

Adult↗

PubMed2005

Assessing the utility of atypical antipsychotic medication in adults with mild mental retardation and comorbid psychiatric disorders.

OBJECTIVE: Research on psychiatric outcomes among individuals dually diagnosed with mild mental retardation and co-occurring mental illness who are treated with antipsychotic medication is markedly limited due to difficulties encountered in (1) making valid and reliable psychiatric diagnoses and (2) accurately rating and following psychiatric symptom change over time in this specialty population. METHOD: To address these issues, DSM-IV psychiatric diagnoses were made by an experienced dual-diagnosis clinician, and the Aberrant Behavior Checklist (ABC) and the Global Assessment of Functioning were used to assess behavioral and psychiatric features in a psychiatric partial hospital setting. Data were collected by chart review from 72 patients admitted consecutively from January 1998 to December 1999. Assessments were compared at admission and discharge in this retrospective study for 3 treatment groups that were defined by antipsychotic medication status at discharge: no antipsychotic (N = 15), atypical antipsychotic only (N = 41), and mixed atypical/typical antipsychotics or typical anti-psychotic only (N = 16). RESULTS: Improvement on the ABC social withdrawal subscale was greater for atypical anti-psychotic medication-treated, dually diagnosed patients than for those who received other treatment regimens. In addition, a dose-response relationship was observed for this subscale and atypical antipsychotic medication dose. CONCLUSION: For certain psychotic patients with mild mental retardation, the atypical antipsychotics may be an appropriate and effective treatment modality.

Adult↗

PubMed2005

Long-term combination therapy versus monotherapy with lithium and carbamazepine in 46 bipolar I patients.

BACKGROUND: Despite wide clinical use of mood-stabilizer combinations for long-term treatment of patients with bipolar disorder, research on risks and benefits of this practice is limited. We found 14 small, usually brief, clinical trials of maintenance treatment with lithium plus carbamazepine. These trials suggest added benefit of combination treatment over use of either agent alone but also indicate the need for further studies. METHOD: In a post hoc analysis, we reviewed the course of 46 patients with DSM-IV-diagnosed bipolar I disorder identified as not improving during long-term monotherapy in a mood disorders clinic, comparing days per year hospitalized in 3 consecutive time periods: before prophylactic treatment, during monotherapy with lithium (N = 31) or carbamazepine (N = 15), and during their combined use (N = 46). Secondary outcome measures were rates of hospitalization, time to first recurrence of an affective episode, use of adjunctive treatments, and adverse effects. We compared outcomes with nonparametric bivariate methods and tested predictive factors by multiple regression. RESULTS: Subjects showed significant reductions in hospitalized days per year during combination therapy, averaging a decrease of 55.9% (p = .004). Among secondary outcomes, hospitalizations per year fell by 36.1%, and median time to recurrence nearly doubled during combination therapy. Rates of adverse effects increased 2.5-fold, compared with monotherapy, and use of adjunctive psychotropic agents increased by 21.9%. CONCLUSION: Combining lithium with carbamazepine yielded substantial benefit but more adverse effects.

Adult↗

PubMed2004

Frontal lobe GABA levels in cocaine dependence: a two-dimensional, J-resolved magnetic resonance spectroscopy study.

Non-invasive measures of brain gamma-aminobutyric acid (GABA) concentrations may be especially useful in the identification of cocaine-related changes in brain chemistry that can be used to guide the development of future treatments for cocaine-dependent persons. This study assessed whether brain GABA levels in cocaine-dependent subjects with and without an alcohol disorder differ from GABA levels in healthy comparison subjects. Two-dimensional, proton magnetic resonance spectroscopy was used to determine GABA levels in the left prefrontal lobe of cocaine-dependent subjects (N=35) recruited from a National Institute on Drug Abuse (NIDA)-sponsored treatment trial of cocaine dependence and a comparison group (N=20). At treatment baseline, mean GABA concentrations were 0.93+/-0.27 mM/kg in cocaine-dependent subjects and 1.32+/-0.44 mM/kg in the comparison sample (t [d.f.=53]=3.65, P<0.001). Cocaine-dependent subjects with a history of a co-morbid alcohol disorder (N=23) had significantly lower baseline GABA levels (0.87 mM/kg) (t [d.f.=41]=4.31, P<0.001) than the comparison group. However, cocaine-dependent subjects without an alcohol disorder (N=12) also had lower GABA levels (1.04 mM/kg) than the comparison subjects (t [d.f.=30]=2.09, P=0.045), suggesting that cocaine dependence alone can decrease GABA levels.

Adult↗

PubMed2004

Low-field magnetic stimulation in bipolar depression using an MRI-based stimulator.

OBJECTIVE: Anecdotal reports have suggested mood improvement in patients with bipolar disorder immediately after they underwent an echo-planar magnetic resonance spectroscopic imaging (EP-MRSI) procedure that can be performed within clinical MR system limits. This study evaluated possible mood improvement associated with this procedure. METHOD: The mood states of subjects in an ongoing EP-MRSI study of bipolar disorder were assessed by using the Brief Affect Scale, a structured mood rating scale, immediately before and after an EP-MRSI session. Sham EP-MRSI was administered to a comparison group of subjects with bipolar disorder, and actual EP-MRSI was administered to a comparison group of healthy subjects. The characteristics of the electric fields generated by the EP-MRSI scan were analyzed. RESULTS: Mood improvement was reported by 23 of 30 bipolar disorder subjects who received the actual EP-MRSI examination, by three of 10 bipolar disorder subjects who received sham EP-MRSI, and by four of 14 healthy comparison subjects who received actual EP-MRSI. Significant differences in mood improvement were found between the bipolar disorder subjects who received actual EP-MRSI and those who received sham EP-MRSI, and, among subjects who received actual EP-MRSI, between the healthy subjects and the bipolar disorder subjects and to a lesser extent between the unmedicated bipolar disorder subjects and the bipolar disorder subjects who were taking medication. The electric fields generated by the EP-MRSI scan were smaller (0.7 V/m) than fields used in repetitive transcranial magnetic stimulation (rTMS) treatment of depression (1-500 V/m) and also extended uniformly throughout the head, unlike the highly nonuniform fields used in rTMS. The EP-MRSI waveform, a 1-kHz train of monophasic trapezoidal gradient pulses, differed from that used in rTMS. CONCLUSIONS: These preliminary data suggest that the EP-MRSI scan induces electric fields that are associated with reported mood improvement in subjects with bipolar disorder. The findings are similar to those for rTMS depression treatments, although the waveform used in EP-MRSI differs from that used in rTMS. Further investigation of the mechanism of EP-MRSI is warranted.

Adolescent↗

PubMed2004

Axis I comorbidity in patients with borderline personality disorder: 6-year follow-up and prediction of time to remission.

OBJECTIVE: The purpose of this study was to assess the prevalence of axis I disorders among patients with borderline personality disorder over 6 years of prospective follow-up. METHOD: A semistructured interview of demonstrated reliability was used to assess presence or absence of comorbid axis I disorders in 290 patients who met Revised Diagnostic Interview for Borderlines criteria and DSM-III-R criteria for borderline personality disorder and 72 patients who did not meet these criteria but did meet DSM-III-R criteria for another axis II disorder. Over 94% of surviving patients were reinterviewed about their axis I disorders at 2-year, 4-year, and 6-year follow-up periods. RESULTS: Although the patients with borderline personality disorder experienced declining rates of many axis I disorders over time, the rates of these disorders remained high, particularly the rates of mood and anxiety disorders. Patients whose borderline personality disorder remitted over time experienced substantial decline in all comorbid disorders assessed, but those whose borderline personality disorder did not remit over time reported stable rates of comorbid disorders. When the absence of comorbid axis I disorders was used to predict time to remission, the absence of substance use disorders was a far stronger predictor of remission from borderline personality disorder than was the absence of posttraumatic stress disorder, mood disorders, other anxiety disorders, or eating disorders, respectively. CONCLUSIONS: The results of this study suggest that axis I disorders are less common over time in patients with initially severe borderline personality disorder, particularly for patients whose borderline personality disorder remits over time. The findings also suggest that substance use disorders are most closely associated with the failure to achieve remission from borderline personality disorder.

Adult↗

PubMed2004

Multiple versus single antipsychotic agents for hospitalized psychiatric patients: case-control study of risks versus benefits.

OBJECTIVE: Since use of multiple drugs to treat psychiatric patients is increasing, and research on this practice is rare, the authors carried out a retrospective case-control study of multiple versus single antipsychotic treatment in psychiatric inpatients. METHOD: Inpatient treatment groups receiving either antipsychotic monotherapy or polytherapy were matched in terms of age, sex, diagnostic category, and admission clinical ratings (Global Assessment of Functioning [GAF] and Clinical Global Impression [CGI]), which yielded 70 subject pairs. They were compared in terms of total chlorpromazine-equivalent daily dose, changes in total daily dose, length of hospitalization, incidence of adverse effects, and changes in clinical ratings (CGI, GAF, Positive and Negative Syndrome Scale score) between admission and discharge. RESULTS: Initial doses were closely similar at admission for both treatment groups, but the median total final antipsychotic dose was 78% higher for those receiving antipsychotic polytherapy versus monotherapy. Also, median length of stay in the hospital was 55% (8.5 days) longer, and risk of adverse effects was 56% higher with polytherapy, whereas clinical improvement scores were similar (within 11%) for both treatments. CONCLUSIONS: Short-term treatment with multiple antipsychotics was associated with major increases in drug exposure, adverse events, and time in the hospital but with no apparent gain in clinical benefit. These findings require further testing in controlled prospective studies.

Adult↗

PubMed2004

Borderline psychopathology in the first-degree relatives of borderline and axis II comparison probands.

The purpose of this study was to assess the prevalence of each of the nine DSM criteria for borderline personality disorder and the prevalence of the disorder itself in the first-degree relatives of borderline probands and Axis II comparison subjects. Four hundred and forty-five inpatients were interviewed about familial borderline psychopathology using the Revised Family History Questionnaire--a semistructured interview of demonstrated reliability. Of these 445 subjects, 341 met both DIB-R and DSM-III-R criteria for BPD and 104 met DSM-III-R criteria for another type of personality disorder (and neither criteria set for BPD). The psychopathology of 1,580 first-degree relatives of borderline probands and 472 relatives of Axis II comparison subjects was assessed. Both DSM-III-R and DSM-IV BPD were found to be more common among the relatives of borderline than Axis II comparison probands. However, five of the criteria for BPD (inappropriate anger, affective instability, paranoia/dissociation, general impulsivity, and intense, unstable relationships) and all four sectors of borderline psychopathology (affect, cognition, impulsivity, and interpersonal relationships) were found to be both more common and discriminating than the BPD diagnosis itself. Taken together, the results of this study suggest that the subsyndromal phenomenology of BPD may be more common than the borderline diagnosis itself.

Adolescent↗

PubMed2004

Mental health service utilization by borderline personality disorder patients and Axis II comparison subjects followed prospectively for 6 years.

OBJECTIVE: The purpose of this study was to describe the psychiatric treatment received by a well-defined sample of patients with borderline personality disorder and Axis II comparison subjects over 6 years of prospective follow-up. METHOD: 362 inpatients were interviewed about their treatment histories during their index admission (1992-1995). 290 patients met both Revised Diagnostic Interview for Borderlines and DSM-III-R criteria for borderline personality disorder and 72 met DSM-III-R criteria for at least 1 nonborderline Axis II disorder (and neither criteria set for borderline personality disorder). Over 94% of surviving patients were re-interviewed about their psychiatric treatment histories 2, 4, and 6 years later. RESULTS: Only 33% of borderline patients were hospitalized during the final 2 years of the 6-year follow-up, a substantial decline from the 79% who had prior hospitalizations at baseline. Much the same pattern emerged for day and/or residential treatment (from 55% to 22%). In contrast, about three quarters of borderline patients were still in psychotherapy and taking psychotropic medications after 6 years of follow-up. Additionally, over 70% of borderline patients participating in these outpatient modalities did so for at least 75% of each follow-up period. While rates of intensive psychotherapy declined significantly over time (from 36% to 16%), rates of intensive polypharmacy remained relatively stable over time, with about 40% of borderline patients taking 3 or more concurrent standing medications during each follow-up period, about 20% taking 4 or more, and about 10% taking 5 or more. CONCLUSIONS: The results of this study suggest that the majority of borderline patients continue to use outpatient treatment in a sustained manner through 6 years of follow-up, but only a declining minority use more restrictive and costly forms of treatment.

Adolescent↗

PubMed2004

Comparison of rapid-cycling and non-rapid-cycling bipolar I manic patients during treatment with olanzapine: analysis of pooled data.

INTRODUCTION: Rapid-cycling (RC) bipolar disorder patients experience high levels of morbidity, typically respond unsatisfactorily to available treatments, and, so, require additional studies of novel treatments. We report on the first controlled study comparing acute and continuous clinical outcomes in RC and non-RC manic patients treated with olanzapine. METHOD: We analyzed data pooled from 2 placebo-controlled, double-blind, 3- to 4-week trials of olanzapine in mania (N = 254), 1 with an open-label extension up to 1 year (N = 113) and controlled supplementation with lithium or fluoxetine as needed, to compare demographic, clinical, and outcome measures between RC and non-RC subgroups of 254 DSM-IV bipolar I manic subjects. RESULTS: RC (N = 90, 35%) versus non-RC subjects (N = 164, 65%) were younger at intake (p = .02), less often psychotic (p < .0001), and more likely to have familial bipolar disorder (p < .0001), abused substances (p = .01), more previous hospitalizations (p = .004), and many more illness episodes (p < .001). In initial blinded trial outcomes, relative responses (> or = 50% improvement of mania) to olanzapine/placebo were similar in RC and non-RC subjects, though early responses to olanzapine favored RC over non-RC subjects (p = .003), and long-term outcomes favored non-RC subjects (p = .05). Fewer RC subjects achieved strictly defined initial symptomatic remission (p = .014) within a year; RC subjects were more likely to experience recurrences (p = .002), especially of depressive illness (< .001), and had more rehospitalizations (p = .01) and suicide attempts (p = .03). CONCLUSIONS: RC bipolar I patients showed major initial differences and more rapid initial clinical changes, especially toward depression, with less favorable long-term outcomes than non-RC cases during treatment with olanzapine. Inclusion of RC bipolar disorder patients can complicate therapeutic trials, but these patients require further study for differential responsiveness to innovative treatments with methods of assessing clinical response that take their mood instability into account.

Adult↗

PubMed2004

A preliminary study of risperidone in the treatment of posttraumatic stress disorder related to childhood abuse in women.

BACKGROUND: This study evaluated the effectiveness of risperidone in women for the treatment of posttraumatic stress disorder (PTSD) related to childhood physical, sexual, verbal, and emotional abuse. METHOD: Subjects were outpatient adult women, aged 18 to 64 years, with chronic PTSD related to childhood physical, sexual, verbal, or emotional abuse. Data were collected from November 18, 2001, to June 7, 2003. Subjects met DSM-III-R criteria for PTSD and criteria for PTSD on the Clinician-Administered PTSD Scale, 1-month version (CAPS-1). Subjects were randomly assigned to receive risperidone (N = 12) in flexible daily dosages in the range of 0.5 to 8 mg or placebo (N = 9) for 8 weeks. The primary outcome measures were changes in score from baseline on the CAPS-1 and the Clinician-Administered PTSD Scale, 1-week version (CAPS-2). RESULTS: Risperidone-treated patients had a significantly greater reduction in total score on the CAPS-2 (z = -2.44, p = .015). Risperidone-treated patients also had significantly greater reductions in the intrusive (z = -5.71, p < .001) and hyperarousal (z = -2.74, p = .006) subscale scores of the CAPS-2. CONCLUSION: The results of the current study indicate that low-dosage risperidone is a safe and effective treatment for intrusive and hyperarousal symptoms in adult women with chronic PTSD from childhood physical, sexual, verbal, and emotional abuse.

Adolescent↗

PubMed2004

Weight gain during treatment of bipolar I patients with olanzapine.

BACKGROUND: Body weight increase during long-term treatment with olanzapine in schizophrenia patients is well documented, but weight gain and its association with other medical measures are less well evaluated in bipolar disorder patients. METHOD: We analyzed data from a 3-week, randomized, placebo-controlled trial of olanzapine for acute mania in DSM-IV bipolar I patients, followed by open continuation treatment with olanzapine up to a year. We examined factors associated with increased body mass index (BMI), including ratings of clinical change and selected physiologic measures. RESULTS: Among 113 subjects treated with olanzapine for a mean +/- SD of 28.6 +/- 19.9 weeks, BMI increased from a baseline mean of 28.8 +/- 6.2 kg/m(2), by 7.9 +/- 10.8% (p < .001), into the obese range (31.0 +/- 6.1 kg/m(2)). Initial BMI change (first 3 weeks of drug exposure) predicted final BMI increases (Spearman rank correlation r(s) = 0.32, p < .001). History of longer illness (p = .006) and lifetime substance abuse (p = .02) were associated with below-median BMI increases. BMI increased much more among 40 subjects achieving symptomatic recovery than in the 73 who did not (by 11.9 +/- 13.2% vs. 5.3 +/- 7.7%; p = .004), with correspondingly longer olanzapine exposure (44.7 +/- 11.8 vs. 19.7 +/- 17.7 weeks; p < .001) at similar doses. On average, serum cholesterol increased 4.8 times more (17.5% vs. 3.6%) and endpoint cholesterol levels were newly 240 mg/dL or greater 3.6 (95% CI = 1.5 to 8.0) times more frequently in subjects with above-median BMI gain, who also experienced significantly larger increases in systolic and diastolic blood pressure, pulse rates, and nonfasting serum glucose than low-BMI-gain subjects. CONCLUSIONS: Weight gain associated with long-term olanzapine treatment for mania was common, substantial, time-dependent, predicted by initial increases, and temporally associated with significant changes in cardiovascular and metabolic measures in bipolar I patients with prolonged illness and already-high basal BMI. An association of weight gain with favorable clinical response probably reflects longer olanzapine treatment.

Adult↗