Treatments for bipolar disorder: can number needed to treat/harm help inform clinical decisions?
ACTA PSYCHIATRICA SCANDINAVICA
2011; 123 (3): 175-189
Lamotrigine plus quetiapine combination therapy in treatment-resistant bipolar depression
ANNALS OF CLINICAL PSYCHIATRY
2011; 23 (1): 17-24
To compare bipolar treatment interventions, using number needed to treat (NNT) and number needed to harm (NNH).Results of randomized controlled clinical trials were used to assess efficacy (NNT for response and relapse/recurrence prevention vs. placebo) and tolerability (e.g. NNH for weight gain and sedation vs. placebo).United States Food and Drug Administration-approved bipolar disorder pharmacotherapies all have single-digit NNTs (i.e. > 10% advantage over placebo), but NNHs for adverse effects that vary widely. Some highly efficacious agents are as likely to yield adverse effects as therapeutic benefit, but may be interventions of choice in more acute severe illness. In contrast, some less efficacious agents with better tolerability may be interventions of choice in more chronic mild-moderate illness.Clinical trials can help inform clinical decision making by quantifying the likelihood of benefit vs. harm. Integrating such data with individual patient circumstances, values, and preferences can help optimize treatment choices.
View details for DOI 10.1111/j.1600-0447.2010.01645.x
View details for Web of Science ID 000286890300002
View details for PubMedID 21133854
Divalproex extended-release in acute bipolar II depression
JOURNAL OF AFFECTIVE DISORDERS
2010; 124 (1-2): 170-173
Lamotrigine and quetiapine are commonly used in bipolar disorder, but there are no published systematic studies of their use in combination for treatment-resistant bipolar depression.We studied 39 trials in outpatients (15 with bipolar I disorder, 22 with bipolar II disorder, and 1 with bipolar disorder not otherwise specified; 1 patient had 2 trials) with depression resistant to quetiapine or lamotrigine who were taking a mean of 1.7 other prescription psychotropic medications. Patients were given either open-label lamotrigine or quetiapine naturalistically, for up to 12 weeks of combination therapy.Lamotrigine (mean dose, 204.2 mg/d) plus quetiapine (mean dose, 188.5 mg/d) increased the euthymia rate (0.0% to 46.2%), decreased syndromal (79.5% to 30.8%) and subsyndromal (20.5% to 15.4%) depression rates, and improved Clinical Global Impression-Severity (mean change, -1.0) and Global Assessment of Functioning (mean change, +5.9) scores. Approximately one-fifth of patients discontinued therapy (20.5%) or required subsequent additional pharmacotherapy (20.5%). Only 10.3% discontinued due to adverse effects, and there was no significant change in mean body weight.The findings of this uncontrolled open pilot study must be viewed with caution. However, randomized, double-blind, placebo-controlled studies are warranted to confirm the possibility that combination therapy with lamotrigine and quetiapine is effective and well tolerated in patients with treatment-resistant bipolar depression.
View details for Web of Science ID 000287616500004
View details for PubMedID 21318192
Effectiveness of lamotrigine in bipolar disorder in a clinical setting
JOURNAL OF PSYCHIATRIC RESEARCH
2008; 43 (1): 13-23
Divalproex extended-release (divalproex-ER) is effective in acute mania, and limited data suggest divalproex may have efficacy in acute bipolar depression.A 7-week, open-label trial of divalproex-ER monotherapy or adjunctive therapy was conducted in 28 outpatients (15 female, mean age 36.7+/-9.1, and mean duration of illness 22.1+/-11.1 years) with bipolar II depression (39% with rapid cycling course of illness within the prior year). Divalproex-ER was generally given as a single dose at bedtime, starting at 250mg and increased by 250mg every 4 days to symptom relief or adverse effects. Efficacy was assessed using weekly prospective Montgomery Asberg Depression Rating Scale (MADRS) scores.Overall, mean divalproex-ER final doses and serum concentrations were 1469mg/day and 80.1microg/mL, respectively. Mean MADRS scores (last observation carried forward) decreased significantly from baseline in patients in the overall group (from 30.1 to 15.2, p<.00001). The overall response rate was 54%. Divalproex-ER therapy was generally well tolerated, with no early discontinuations due to adverse events.This study is limited by a small sample size and an open-label study design with no placebo control.Divalproex-ER as monotherapy and adjunctive therapy was well tolerated and yielded an overall response rate of 54% in bipolar II depression. Based on the results of this pilot study, randomized, double-blind, placebo-controlled studies of divalproex-ER in bipolar II depression are warranted.
View details for DOI 10.1016/j.jad.2009.10.021
View details for Web of Science ID 000278787400022
View details for PubMedID 19923006
Adjunctive zonisamide for weight loss in euthymic bipolar disorder patients: A pilot study
JOURNAL OF PSYCHIATRIC RESEARCH
2008; 42 (6): 451-457
To assess lamotrigine effectiveness in bipolar disorder (BD) patients in a clinical setting.Open lamotrigine was naturalistically administered to outpatients at the Stanford University BD Clinic assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and monitored longitudinally with the STEP-BD Clinical Monitoring Form.One hundred and ninety-seven patients (64 BD I, 110 BD II, 21 BD NOS, 2 Schizoaffective Bipolar Type, mean+/-SD age 42.2+/-14.4 years, 62% female) had 200 trials of lamotrigine. Lamotrigine was combined with a mean of 2.1+/-1.5 other psychotropic medications, most often during euthymia or depressive symptoms. Mean lamotrigine duration was 434+/-444 days, and mean final dose was 236+/-132mg/day without valproate, and 169+/-137mg/day with valproate. Lamotrigine was discontinued in only 26.5% of trials at 255+/-242 days, most often due to inefficacy, and seldom due to adverse effects. In 31.5% of trials lamotrigine was continued 264+/-375 days with no subsequent psychotropic added. In 42.0% of trials lamotrigine was continued 674+/-479 days, but had subsequent psychotropic added at 146+/-150 days, most often for anxiety/insomnia and depressive symptoms. In 145 trials started at Stanford, lamotrigine primarily yielded relief of depressive symptoms or maintained euthymia. In 55 trials in which lamotrigine was started prior to Stanford, lamotrigine primarily maintained euthymia. Lamotrigine was generally well tolerated, with no serious rash, and only 3.5% discontinuing due to benign rash.In a cohort of bipolar disorder outpatients commonly with comorbid conditions, and most often receiving complex combination therapy, lamotrigine had a low (26.5%, with an overall mean duration of treatment of 434 days) discontinuation rate, suggesting effectiveness in BD in a clinical setting.
View details for DOI 10.1016/j.jpsychires.2008.02.007
View details for Web of Science ID 000261276000003
View details for PubMedID 18423667
Factors associated with stigma among caregivers of patients with bipolar disorder in the STEP-BD study
2007; 58 (1): 41-48
To assess the effectiveness and tolerability of open adjunctive zonisamide in treatment of obesity in euthymic bipolar disorder (BD) patients.Zonisamide was administered to recovered, overweight BD outpatients assessed with the Systematic Treatment Enhancement Program for Bipolar Disorders (STEP-BD) Affective Disorders Evaluation and followed with the STEP-BD Clinical Monitoring Form. Weight changes (Body Mass Index (BMI) and BMI percentage changes) were assessed prospectively at four weekly visits, one bi-weekly visit, and then five monthly visits, for a maximal duration of six months. Weight loss was assessed with random effects modeling to maximize all available data for analysis.Twenty-five BD (10 BD-type I, 15 BD-type II) patients (mean age 41.0+/-10.4 years, 64% female, 96% Caucasian) on a mean of 2.8+/-1.5 prescription psychotropic and 1.3+/-1.4 prescription non-psychotropic medications received zonisamide for a mean duration of 14.2+/-8.5 weeks, with a mean final dose of 375+/-206 (range 75-800) mg/day. Slope of weight loss was 0.078 BMI points per week, and non-zero (p<0.0005). Mean weight loss was 1.2+/-1.9 BMI points (baseline BMI 34.2+/-3.1 to final BMI 33.0+/-3.5, p<0.003). Eighteen patients (72%) discontinued study participation early, 11/25 (44%) due to emergent mood symptoms (eight depression, two mania, one subsyndromal mixed symptoms) requiring treatment intervention, 5/25 (20%) due to adverse physical events, and 2/25 (8%) due to patient choice, but none due to weight loss inefficacy.Adjunctive zonisamide appeared effective and generally physically tolerated, but had high rates of mood adverse events, in obese BD patients. Controlled trials are warranted to systematically explore these preliminary naturalistic observations.
View details for DOI 10.1016/j.jpsychires.2007.05.005
View details for Web of Science ID 000254720300004
View details for PubMedID 17628595
Bipolar disorder: Improving diagnosis and optimizing integrated care
JOURNAL OF CLINICAL PSYCHOLOGY
2007; 63 (1): 73-92
Little is known about the factors contributing to mental illness stigma among caregivers of people with bipolar disorder.A total of 500 caregivers of patients participating in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study were interviewed in a cross-sectional design on measures of stigma, mood, burden, and coping. Relatives and friends with bipolar disorder were assessed on measures of diagnosis and clinical status, determined by a days-well measure derived from psychiatrist ratings of DSM-IV episode status. Because patients' clinical status varied widely, separate models were run for patients who were euthymic for at least three-fourths of the past year (well group) and for those who met criteria for an affective episode for at least one-fourth of the previous year (unwell group). Stepwise multiple regression was used to identify patient, illness, and caregiver characteristics associated with caregiver stigma.In the unwell group, greater mental illness stigma was associated with bipolar I (versus II) disorder, less social support for the caregiver, fewer caregiver social interactions, and being a caregiver of Hispanic descent. In the well group, greater stigma was associated with being a caregiver who is the adult child of a parent with bipolar disorder, who has a college education, who has fewer social interactions, and who cares for a female bipolar patient.Mental illness stigma was found to be prevalent among caregivers of persons with bipolar disorder who have active symptoms as well as for caregivers of those who have remitted symptoms. Stigma is typically associated with factors identifying patients as "different" during symptomatic periods. Research is needed to understand how the stigma experienced by caregivers during stable phases of illness differs from the stigma experienced during patients' illness states.
View details for Web of Science ID 000243384200007
View details for PubMedID 17215411
Adjunctive aripiprazole in treatment-resistant bipolar depression.
Annals of clinical psychiatry
2006; 18 (3): 169-172
Bipolar disorder is a chronic, severe condition commonly causing substantial mortality and psychosocial morbidity. Challenges in recognition can delay the institution of appropriate management, whereas misdiagnosis may initiate pharmacologic interventions that adversely affect the condition's course. Pharmacotherapy remains the foundation of treatment. In addition to efficacy, tolerability is an important consideration in medication choice, particularly for long-term maintenance because of its impact on adherence. Mood stabilizers are the classic treatments for bipolar disorder. Newer agents such as atypical antipsychotics may offer efficacy and/or tolerability advantages compared with other medications. The role of antidepressants in bipolar disorder remains controversial. Growing evidence indicates that adjunctive psychosocial interventions improve long-term functioning; consequently, psychologists are becoming increasingly involved in the long-term care of patients with bipolar disorder. This review seeks to update psychologists and related healthcare professionals on recent advances and the current limitations in the diagnosis and treatment of bipolar disorder.
View details for DOI 10.1002/jclp.20333
View details for Web of Science ID 000243044600005
View details for PubMedID 17115430
Coping and distress among women under treatment for early stage breast cancer: Comparing African Americans, Hispanics and non-Hispanic whites
2002; 11 (6): 495-504
There are limited management options for treatment-resistant depression in bipolar disorder (BD) patients.Open adjunctive aripiprazole was administered to outpatients with treatment-resistant depression assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and followed with the STEP-BD Clinical Monitoring Form.Thirty BD (11 type I, 15 type II, 4 NOS) patients (mean age 44.4 +/- 17.0 years, 70% female) on a mean of 3.2 +/- 1.6 other psychotropic and 2.3 +/- 1.6 nonpsychotropic prescription medications received aripiprazole for a mean duration of 84 +/- 69 days, with a mean final dose of 15.3 +/- 11.2 (range 2.5-40) mg/day. Fourteen patients (47%) discontinued aripiprazole; due to inefficacy in 5/30 (17%), patient choice in 3/30 (10%), and adverse effects in 6/30 (20%). Aripiprazole yielded improvement in Clinical Global Impression-Severity (CGI-S, 4.4 +/- 1.1 to 3.8 +/- 1.2, p < 0.01), with 8/30 (27%) patients responding (CGI-S improvement > or = 2), including 4/30 (13%) who remitted (final CGI-S < or = 2). Global Assessment of Function, and depressed mood and suicidal ideation ratings also improved. Aripiprazole was generally well tolerated, with no significant change in mean adverse effect ratings or mean weight.Aripiprazole appeared effective and generally well tolerated in treatment-resistant bipolar depression. Controlled trials are warranted to systematically explore these preliminary naturalistic observations.
View details for PubMedID 16923655
Cognitive-behavioral stress management intervention decreases the prevalence of depression and enhances benefit finding among women under treatment for early-stage breast cancer
2001; 20 (1): 20-32
This study examined coping and distress in African American (n=8), Hispanic (n=53), and non-Hispanic White (n=70) women with early stage breast cancer. The participants were studied prospectively across a year beginning at the time of surgery. African American women reported the lowest levels of distress (particularly before surgery) and depression symptoms. Hispanic women reported the highest levels of self-distraction as a coping response, non-Hispanic Whites reported the highest use of humor. Hispanics reported the highest levels of venting, African Americans reported the lowest levels. African American and Hispanic women reported more religious coping than non-Hispanic Whites. The data also provided evidence of a maladaptive spiral of distress and avoidant coping over time. Although some ethnic differences were identified, findings also point to a great many similarities across groups.
View details for DOI 10.1002/pon.615
View details for Web of Science ID 000179995600004
View details for PubMedID 12476431
The authors tested effects of a 10-week group cognitive-behavioral stress management intervention among 100 women newly treated for Stage 0-II breast cancer. The intervention reduced prevalence of moderate depression (which remained relatively stable in the control condition) but did not affect other measures of emotional distress. The intervention also increased participants' reports that having breast cancer had made positive contributions to their lives, and it increased generalized optimism. Both remained significantly elevated at a 3-month follow-up of the intervention. Further analysis revealed that the intervention had its greatest impact on these 2 variables among women who were lowest in optimism at baseline. Discussion centers on the importance of examining positive responses to traumatic events--growth, appreciation of life, shift in priorities, and positive affect-as well as negative responses.
View details for Web of Science ID 000166441300004
View details for PubMedID 11199062