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Biomedical subjects

Trisha Suppes

Publications and source records attributed to Trisha Suppes.

At least 55 records · Page 3Linked to original sources
PubMed2004

Relapse prevention in bipolar I disorder: 18-month comparison of olanzapine plus mood stabiliser v. mood stabiliser alone.

BACKGROUND: Few controlled studies have examined the use of atypical antipsychotic drugs for prevention of relapse in patients with bipolar I disorder. Aims To evaluate whether olanzapine plus either lithium or valproate reduces the rate of relapse, compared with lithium or valproate alone. METHOD: Patients achieving syndromic remission after 6 weeks'treatment with olanzapine plus either lithium (0.6-1.2 mmol/l) or valproate (50-125 microg/ml) received lithium or valproate plus either olanzapine 5-20 mg/day (combination therapy) or placebo (monotherapy), and were followed in a double-masked trial for 18 months. RESULTS: The treatment difference in time to relapse into either mania or depression was not significant for syndromic relapse (median time to relapse: combination therapy 94 days, monotherapy 40.5 days; P=0.742), but was significant for symptomatic relapse (combination therapy 163 days, monotherapy 42 days; P=0.023). CONCLUSIONS: Patients taking olanzapine added to lithium or valproate experienced sustained symptomatic remission, but not syndromic remission, for longer than those receiving lithium or valproate monotherapy.

Adult↗
PubMed2004

Treatment of bipolar mania with atypical antipsychotics.

Acute manic episodes in bipolar disorder require rapid and effective relief. Pharmacotherapy has traditionally involved mood stabilizers such as lithium or divalproex. Evidence for the efficacy of atypical antipsychotics to treat bipolar mania, either as monotherapy or in combination with traditional mood-stabilizing agents, has increased in recent years. Since the combination of an atypical agent and a traditional mood stabilizer is generally well tolerated, it represents a first-line approach for the treatment of severe and treatment-resistant mania. Atypical antipsychotics have a superior neurological tolerability profile compared with typical antipsychotics and are preferentially recommended in most treatment guidelines. The atypical agents, olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole, have demonstrated efficacy in bipolar mania in large randomized, controlled studies, and offer efficacy across a broader range of symptoms than typical antipsychotics, and may even have mood-stabilizing properties traditionally associated with lithium and divalproex. Olanzapine, risperidone and quetiapine have been shown to be effective for manic episodes both as monotherapy and in combination with other agents such as lithium and divalproex. Although the tolerability profiles of atypicals as a class are superior to those of conventional antipsychotics, there are differences among the atypical agents in their propensity to cause certain adverse events such as extrapyramidal symptoms (EPS) and weight gain, particularly in the long-term. The ultimate choice of the atypical agent will depend on the patient's individual needs, but atypical antipsychotics are clinically effective options for achieving mood stabilization in the treatment of acute bipolar mania.

Antipsychotic Agents↗
PubMed2004

A 52-week, open-label continuation study of lamotrigine in the treatment of bipolar depression.

BACKGROUND: Lamotrigine has demonstrated efficacy for the acute treatment of depression in bipolar I patients in a placebo-controlled, monotherapy study. We describe the results of a 52-week, open-label continuation of that trial. METHOD: Patients meeting DSM-IV criteria for bipolar I disorder with a current major depressive episode who completed a 7-week, double-blind study of bipolar depression were offered 1 year of open-label lamotrigine therapy (flexible doses of 100-500 mg/day) in a continuation study. To maintain the acute study blind, the first 3 weeks of the continuation study remained blinded while patients previously randomly assigned to placebo were titrated to a lamotrigine dose of 50 mg/day. Patients who had been randomly assigned to lamotrigine continued at their fixed doses. Beginning at week 4, all patients received open-label lamotrigine for up to 49 additional weeks. Concomitant psychotropic medications were permitted during the open-label phase. Effectiveness (Montgomery-Asberg Depression Rating Scale [MADRS], Clinical Global Impressions-Improvement scale) and safety assessments were administered at weeks 4, 12, 24, 36, and 52. The study was conducted from June 1996 to December 1998. RESULTS: Of 135 patients completing the acute study, 124 (92%) entered the continuation study: 77 had received lamotrigine and 47 had received placebo in the acute study. The mean duration of lamotrigine exposure was 10.4 months, with a mean modal dose of 187 mg/day. Sixty-nine patients (56%) completed 1 year of treatment. Significant and sustained improvement from baseline was seen in mean observed MADRS scores (p <.05). The proportion of patients achieving remission (MADRS score < or = 11) by week 4 of the study was 81.4%, and episodes of mania/hypomania occurred less frequently than in the preceding year. Headache was the most common drug-related adverse event. CONCLUSION: During 1 year of open-label therapy with lamotrigine as adjunctive therapy or monotherapy, bipolar I patients experienced sustained improvement in depressive symptoms without evidence of mood destabilization.

Adult↗
PubMed2003

Clinician ratings vs. global ratings of symptom severity: a comparison of symptom measures in the bipolar disorder module, phase II, Texas Medication Algorithm Project.

This study compares ratings obtained with an itemized, clinician-rated, symptom severity measure--the 24-item Brief Psychiatric Rating Scale (BPRS(24))--to a Physician Global Rating Scale (PhGRS), a Patient Global Rating Scale (PtGRS) and the clinician-completed Multnomah Community Ability Scale (MCAS) in patients with bipolar disorder (BPD). A total of 69 patients (25 inpatients and 44 outpatients) with BPD were enrolled in a feasibility study of the use of medication algorithms in the treatment of BPD. Clinicians at each visit completed the BPRS(24), PhGRS and MCAS, and patients completed the PtGRS. Analyses compared the BPRS(24) and BPRS subscales with the PtGRS, PhGRS and MCAS. PtGRS scores correlated poorly with BPRS(24) and with PhGRS scores at baseline, although PtGRS change scores correlated moderately with BPRS(24) change scores. Baseline BPRS(24) and PhGRS scores correlated moderately at baseline with somewhat stronger correlations found on change scores for the two measures. MCAS scores showed moderate correlations with BPRS(24) scores both at baseline and with change over time. Global assessments by patients or physicians only moderately or poorly reflected BPRS(24) scores. Itemized symptom measures to gauge severity of illness or change over time are preferred over patient or physician global judgments.

Adult↗
PubMed2003

High numbers of circulating activated T cells and raised levels of serum IL-2 receptor in bipolar disorder.

BACKGROUND: Previously, we found an increased prevalence of thyroid autoantibodies in patients with bipolar disorder. In the present study, we investigated other signs of immune activation in bipolar patients, in particular an activation of the T cell system. METHODS: Fluorescence activated cell scanning (FACS) analysis was performed on lymphocytes of 64 outpatients with DSM-IV bipolar disorder using the T cell marker CD3 in combination with the activation markers MHC-class II, CD25, CD69 or CD71. In 34 patients, these assays were repeated after an interval of 2 years. In addition, T cell activation was determined by measuring serum soluble IL-2 receptor (sIL-2R) in 172 bipolar outpatients. Outcomes were compared with a healthy control group. RESULTS: Significantly higher numbers of circulating activated T cells and raised sIL-2R levels were found in euthymic, manic, and depressed bipolar patients when compared with healthy controls. In general, these abnormalities were stable over time. Manic patients showed significantly higher levels of sIL-2R in comparison with depressed patients. CONCLUSION: The T cell system was found to be activated in both symptomatic and euthymic patients with bipolar disorder. The pathophysiological significance of these findings remains to be explored.

Biomarkers↗
PubMed2003

A re-evaluation of the role of antidepressants in the treatment of bipolar depression: data from the Stanley Foundation Bipolar Network.

OBJECTIVES: The risk-to-benefit ratio of the use of unimodal antidepressants (ADs) as adjuncts to mood stabilizers continues to be an area of controversy and disagreement among experts in the field. This paper reviews new data on: (1) depression in bipolar illness, (2) switch rates on ADs and (3) risks of AD discontinuation that are pertinent to the ongoing discussion and recommendations. METHODS: In the first study reviewed, 258 outpatients with bipolar illness were assessed prospectively on a daily basis using the National Institute of Mental Health-Life Chart Method (NIMH-LCM) for 1 year. In the second study, 127 bipolar depressed patients were randomized to 10 weeks of sertraline, bupropion, or venlafaxine, as adjuncts to mood stabilizers; non-responders were re-randomized and responders were offered a year of continuation treatment. In the final study, Altshuler et al. retrospectively and prospectively assessed the risk of depressive relapses in patients who remained on ADs after 2 months of euthymia compared with those who discontinued ADs. RESULTS: Despite intensive naturalistic treatment, the 258 outpatients with bipolar illness followed prospectively for 1 year showed three times as many days depressed as days manic, re-emphasizing the considerable depressive morbidity that remains in bipolar disorder despite the number of treatment options available. In the study of bipolar depressed patients randomized to one of three ADs, a range of severities and durations of hypomanic to manic switches were discerned following 175 trials of AD augmentation of treatment with a mood stabilizer. Of the acute 10-week trials, 9.1% were associated with switches into hypomania or mania and another 9.1% with a week or more of hypomania alone (with no to minimal dysfunction). In 73 continuation phase AD trials, 16.4 and 19.2% were similarly associated with hypomanic to manic and hypomanic switches, respectively. In the Altshuler et al. studies, those who remained well on any AD for more than 2 months (only 15-20% of those initially treated) and who continued on ADs showed a lesser rate of relapse into depression over 1 year (35 and 36% in the first and second study, respectively) compared with those who discontinued their ADs (68 and 70% relapsing into depression). Surprisingly, this continuation of ADs was associated with no increase in the rate of switching into mania compared with those stopping ADs. CONCLUSIONS: These data reveal that depression and depressive cycling remain a substantial problem in some two-thirds of intensively treated bipolar outpatients. Acute AD augmentation was associated with a modest response rate and 18.2% switched into a hypomanic to manic episode, and 35.6% of the continuation trials showed these two types of switches. Two separate studies suggest that in the very small subgroup who remain well on ADs for at least 2 months, one should consider continuation of this AD augmentation treatment, because AD discontinuation appears associated with a substantially increased risk of depression relapse over the subsequent year with no reduced risk of switching into mania.

Adult↗
PubMed2003

The efficacy of olanzapine monotherapy for acute hypomania or mania in an outpatient setting.

Randomized controlled trials have demonstrated the efficacy of olanzapine for treating acute mania or depression symptoms in patients with bipolar disorder. We aimed to evaluate the effectiveness of this medication in more usual care outpatient settings. A consecutive series of 15 patients entered an open, uncontrolled 8-week trial of olanzapine monotherapy. Inclusion criteria included significant hypomanic or manic symptoms greater than or equal to 15 on the Young Mania Rating Scale and no psychotic symptoms. The majority of patients experienced significant decreases in mania ratings and more limited improvement on depression ratings. Most patients reported adverse events consistent with other studies, but few discontinued due to these complaints. This case series highlights the individual variation in response to a proven medication. Furthermore, it highlights that those medications effective at one end of the mood spectrum may not be equally or simultaneously effective with other symptoms, emphasizing the complexity of treating bipolar illness.

Administration, Oral↗
PubMed2003

Catching up on health outcomes: the Texas Medication Algorithm Project.

OBJECTIVE: To develop a statistic measuring the impact of algorithm-driven disease management programs on outcomes for patients with chronic mental illness that allowed for treatment-as-usual controls to "catch up" to early gains of treated patients. DATA SOURCES/STUDY SETTING: Statistical power was estimated from simulated samples representing effect sizes that grew, remained constant, or declined following an initial improvement. Estimates were based on the Texas Medication Algorithm Project on adult patients (age > or = 18) with bipolar disorder (n = 267) who received care between 1998 and 2000 at 1 of 11 clinics across Texas. STUDY DESIGN: Study patients were assessed at baseline and three-month follow-up for a minimum of one year. Program tracks were assigned by clinic. DATA COLLECTION/EXTRACTION METHODS: Hierarchical linear modeling was modified to account for declining-effects. Outcomes were based on 30-item Inventory for Depression Symptomatology-Clinician Version. PRINCIPAL FINDINGS: Declining-effect analyses had significantly greater power detecting program differences than traditional growth models in constant and declining-effects cases. Bipolar patients with severe depressive symptoms in an algorithm-driven, disease management program reported fewer symptoms after three months, with treatment-as-usual controls "catching up" within one year. CONCLUSIONS: In addition to psychometric properties, data collection design, and power, investigators should consider how outcomes unfold over time when selecting an appropriate statistic to evaluate service interventions. Declining-effect analyses may be applicable to a wide range of treatment and intervention trials.

Adult↗
PubMed2003

Gender differences in prevalence, risk, and clinical correlates of alcoholism comorbidity in bipolar disorder.

OBJECTIVE: The prevalence of lifetime alcohol abuse and/or dependence (alcoholism) in patients with bipolar disorder has been reported to be higher than in all other axis I psychiatric diagnoses. This study examined gender-specific relationships between alcoholism and bipolar illness, which have previously received little systematic study. METHOD: The prevalence of lifetime alcoholism in 267 outpatients enrolled in the Stanley Foundation Bipolar Network was evaluated by using the Structured Clinical Interview for DSM-IV. Alcoholism and its relationship to retrospectively assessed measures of the course of bipolar illness were evaluated by patient-rated and clinician-administered questionnaires. RESULTS: As in the general population, more men (49%, 57 of 116) than women with bipolar disorder (29%, 44 of 151) met the criteria for lifetime alcoholism. However, the risk of having alcoholism was greater for women with bipolar disorder (odds ratio=7.35) than for men with bipolar disorder (odds ratio=2.77), compared with the general population. Alcoholism was associated with a history of polysubstance use in women with bipolar disorder and with a family history of alcoholism in men with bipolar disorder. CONCLUSIONS: This study suggests that there are gender differences in the prevalence, risk, and clinical correlates of alcoholism in bipolar illness. Although this study is limited by the retrospective assessment of illness variables, the magnitude of these gender-specific differences is substantial and warrants further prospective study.

Adolescent↗
PubMed2003

Impact of antidepressant discontinuation after acute bipolar depression remission on rates of depressive relapse at 1-year follow-up.

OBJECTIVE: While guidelines for treating patients with bipolar depression recommend discontinuing antidepressants within 6 months after remission, few studies have assessed the implications of this strategy on the risk for depressive relapse. This study examined the effect of antidepressant discontinuation or continuation on depressive relapse risk among bipolar subjects successfully treated for an acute depressive episode. METHOD: Eighty-four subjects with bipolar disorder who achieved remission from a depressive episode with the addition of an antidepressant to an ongoing mood stabilizer regimen were followed prospectively for 1 year. The risk of depressive relapse among 43 subjects who stopped antidepressant treatment within 6 months after remission ("discontinuation group") was compared with the risk among 41 subjects who continued taking antidepressants beyond 6 months ("continuation group"). RESULTS: A Cox proportional hazards regression analysis indicated that shorter antidepressant exposure time following successful treatment was associated with a significantly shorter time to depressive relapse. Furthermore, patients who discontinued antidepressant treatment within the first 6 months after remission experienced a significantly shorter period of euthymia before depressive relapse over the length of 1-year follow-up. One year after successful antidepressant response, 70% of the antidepressant discontinuation group experienced a depressive relapse compared with 36% of the continuation group. By the 1-year follow-up evaluation, 15 (18%) of the 84 subjects had experienced a manic relapse; only six of these subjects were taking an antidepressant at the time of manic relapse. CONCLUSIONS: The risk of depressive relapse in patients with bipolar illness was significantly associated with discontinuing antidepressants soon after remission. The risk of manic relapse was not significantly associated with continuing use of antidepressant medication and, overall, was substantially less than the risk of depressive relapse. Maintenance of antidepressant treatment in combination with a mood stabilizer may be warranted in some patients with bipolar disorder.

Acute Disease↗
PubMed2003

Olanzapine versus divalproex sodium for the treatment of acute mania and maintenance of remission: a 47-week study.

OBJECTIVE: Few double-blind trials have compared longer-term efficacy and safety of medications for bipolar disorder. The authors report a 47-week comparison of olanzapine and divalproex. METHOD: This 47-week, randomized, double-blind study compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day) for manic or mixed episodes of bipolar disorder (N=251). The only other psychoactive medication allowed was lorazepam for agitation. The primary efficacy instrument was the Young Mania Rating Scale; a priori protocol-defined threshold scores were > or =20 for inclusion, < or =12 for remission, and > or = 15 for relapse. Analytical techniques included mixed model repeated-measures analysis of variance for change from baseline, Fisher's exact test (two-tailed) for categorical comparisons, and Kaplan-Meier estimates of time to events of interest. RESULTS: Over 47 weeks, mean improvement in Young Mania Rating Scale score was significantly greater for the olanzapine group. Median time to symptomatic mania remission was significantly shorter for olanzapine, 14 days, than for divalproex, 62 days. There were no significant differences between treatments in the rates of symptomatic mania remission over the 47 weeks (56.8% and 45.5%, respectively) and subsequent relapse into mania or depression (42.3% and 56.5%). Treatment-emergent adverse events occurring significantly more frequently during olanzapine treatment were somnolence, dry mouth, increased appetite, weight gain, akathisia, and high alanine aminotransferase levels; those for divalproex were nausea and nervousness. CONCLUSIONS: In this 47-week study of acute bipolar mania, symptomatic remission occurred sooner and overall mania improvement was greater for olanzapine than for divalproex, but rates of bipolar relapse did not differ.

Acute Disease↗
PubMed2003

Texas Medication Algorithm Project, phase 3 (TMAP-3): rationale and study design.

BACKGROUND: Medication treatment algorithms may improve clinical outcomes, uniformity of treatment, quality of care, and efficiency. However, such benefits have never been evaluated for patients with severe, persistent mental illnesses. This study compared clinical and economic outcomes of an algorithm-driven disease management program (ALGO) with treatment-as-usual (TAU) for adults with DSM-IV schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) treated in public mental health outpatient clinics in Texas. DISCUSSION: The disorder-specific intervention ALGO included a consensually derived and feasibility-tested medication algorithm, a patient/family educational program, ongoing physician training and consultation, a uniform medical documentation system with routine assessment of symptoms and side effects at each clinic visit to guide ALGO implementation, and prompting by on-site clinical coordinators. A total of 19 clinics from 7 local authorities were matched by authority and urban status, such that 4 clinics each offered ALGO for only 1 disorder (SCZ, BD, or MDD). The remaining 7 TAU clinics offered no ALGO and thus served as controls (TAUnonALGO). To determine if ALGO for one disorder impacted care for another disorder within the same clinic ("culture effect"), additional TAU subjects were selected from 4 of the ALGO clinics offering ALGO for another disorder (TAUinALGO). Patient entry occurred over 13 months, beginning March 1998 and concluding with the final active patient visit in April 2000. Research outcomes assessed at baseline and periodically for at least 1 year included (1) symptoms, (2) functioning, (3) cognitive functioning (for SCZ), (4) medication side effects, (5) patient satisfaction, (6) physician satisfaction, (7) quality of life, (8) frequency of contacts with criminal justice and state welfare system, (9) mental health and medical service utilization and cost, and (10) alcohol and substance abuse and supplemental substance use information. Analyses were based on hierarchical linear models designed to test for initial changes and growth in differences between ALGO and TAU patients over time in this matched clinic design.

Adolescent↗
PubMed2003

Texas Medication Algorithm Project, phase 3 (TMAP-3): clinical results for patients with a history of mania.

BACKGROUND: The Texas Medication Algorithm Project (TMAP) assessed the clinical and economic impact of algorithm-driven treatment (ALGO) as compared with treatment-as-usual (TAU) in patients served in public mental health centers. This report presents clinical outcomes in patients with a history of mania (BD), including bipolar I and schizoaffective disorder, bipolar type, during 12 months of treatment beginning March 1998 and ending with the final active patient visit in April 2000. METHOD: Patients were diagnosed with bipolar I disorder or schizoaffective disorder, bipolar type, according to DSM-IV criteria. ALGO was comprised of a medication algorithm and manual to guide treatment decisions. Physicians and clinical coordinators received training and expert consultation throughout the project. ALGO also provided a disorder-specific patient and family education package. TAU clinics had no exposure to the medication algorithms. Quarterly outcome evaluations were obtained by independent raters. Hierarchical linear modeling, based on a declining effects model, was used to assess clinical outcome of ALGO versus TAU. RESULTS: ALGO and TAU patients showed significant initial decreases in symptoms (p =.03 and p <.001, respectively) measured by the 24-item Brief Psychiatric Rating Scale (BPRS-24) at the 3-month assessment interval, with significantly greater effects for the ALGO group. Limited catch-up by TAU was observed over the remaining 3 quarters. Differences were also observed in measures of mania and psychosis but not in depression, side-effect burden, or functioning. CONCLUSION: For patients with a history of mania, relative to TAU, the ALGO intervention package was associated with greater initial and sustained improvement on the primary clinical outcome measure, the BPRS-24, and the secondary outcome measure, the Clinician-Administered Rating Scale for Mania (CARS-M). Further research is planned to clarify which elements of the ALGO package contributed to this between-group difference.

Adolescent↗
PubMed2003

Factors associated with suicide attempts in 648 patients with bipolar disorder in the Stanley Foundation Bipolar Network.

BACKGROUND: Clinical factors related to suicide and suicide attempts have been studied much more extensively in unipolar depression compared with bipolar disorder. We investigated demographic and course-of-illness variables to better understand the incidence and potential clinical correlates of serious suicide attempts in 648 outpatients with bipolar disorder. METHOD: Patients with bipolar I or II disorder (DSM-IV criteria) diagnosed with structured interviews were evaluated using self-rated and clinician-rated questionnaires to assess incidence and correlates of serious suicide attempts prior to study entry. Clinician prospective ratings of illness severity were compared for patients with and without a history of suicide attempt. RESULTS: The 34% of patients with a history of suicide attempts, compared with those without such a history, had a greater positive family history of drug abuse and suicide (or attempts); a greater personal history of early traumatic stressors and more stressors both at illness onset and for the most recent episode; more hospitalizations for depression; a course of increasing severity of mania; more Axis I, II, and III comorbidities; and more time ill on prospective follow-up. In a hierarchical logistic regression, a history of sexual abuse, lack of confidant prior to illness onset, more prior hospitalizations for depression, suicidal thoughts when depressed, and cluster B personality disorder remained significantly associated with a serious suicide attempt. CONCLUSION: Our retrospective findings, supplemented by prospective follow-up, indicate that a history of suicide attempts is associated with a more difficult course of bipolar disorder and the occurrence of more psychosocial stressors at many different time domains. Greater attention to recognizing those at highest risk for suicide attempts and therapeutic efforts aimed at some of the correlates identified here could have an impact on bipolar illness-related morbidity and mortality.

Adolescent↗
PubMed2002

Developing novel treatments for mood disorders: accelerating discovery.

This review was generated from discussions by the Pharmacologic and Somatic Treatments Section of the National Institute of Mental Health Strategic Plan for Mood Disorders Committee on advancing novel pharmacologic and somatic treatments for mood disorders. The opening section of the article summarizes in broad strokes, current pharmacologic treatments, and new directions in the field. Thereafter the topics focus on specific research initiatives that could advance the current therapeutics for mood disorders including new basic and clinical research in vivo human imaging procedures, somatic therapeutics, and the vast new area of pharmacogenetics. New scientific and technical opportunities exist today based on advances in basic neuroscience, opportunities in clinical testing, industry interest in advancing central nervous system therapeutics, and on active consumer advocacy groups. The question of how to bring all of these positive forces together to accelerate discovery in mood disorder thera-peutics is the topic of this article.

Animals↗