Bipolar Disorder Clinical Synthesis: Where Does the Evidence Lead?

Psychotherapy, Symptom Outcomes, and Role Functioning Over One Year Among Patients With Bipolar Disorder

A Simple Question Answered: Adding Moderate-Dosage Lithium Does Not Help Patients With Bipolar Disorder

Factors Associated With Stigma Among Caregivers of Patients With Bipolar Disorder in the STEP-BD Study

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.

A number of recent studies have questioned whether, despite modern treatment, the natural course of bipolar illness today still involves multiple relapses and impaired psychosocial functioning. This prospective follow-up study examined longitudinal outcome in a large group of inpatients with affective disorders. Fifty-one bipolar manic patients and 49 unipolar depressed patients were interviewed three times: 1) during hospitalization, 2) approximately 2 years after discharge, and 3) approximately 4.5 years after discharge. Subjects were treated under routine conditions and assessed for global adjustment, rehospitalization, and work and social functioning. Only 41% of the bipolar group had a good overall outcome by the time of the 4.5-year follow-up. The bipolar patients had more severe work impairment than the unipolar group. More than one-half of the bipolar patients were rehospitalized at least once during the 4.5-year follow-up period. Outcome for both diagnostic groups improved significantly over time. Many contemporary bipolar patients demonstrate gradual improvement in the first several years after hospitalization. However, a subgroup approaching 60% still experience poor posthospital adjustment in one or more areas of functioning.

Back to table of contents Previous article Next article Clinical & Research NewsFull Access`Treat to Remission' Is Message of STEP-BD StudyJim RosackJim RosackSearch for more papers by this authorPublished Online:3 Mar 2006https://doi.org/10.1176/pn.41.5.0032The first of many analyses to come from the National Institute of Mental Health's (NIMH) Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) provides much-needed, long-term data on the potential for recovery from manic and depressive episodes and predictors of relapse into subsequent mood episodes.“In spite of really optimized treatment with guideline-based pharmacotherapy, combined with psychoeducation provided by clinicians specifically trained in the management of bipolar disorder, nearly half of our patients suffered a recurrence within two years,” said Roy Perlis, M.D., an assistant professor of psychiatry at Harvard Medical School and one of several STEP-BD investigators at Massachusetts General Hospital in Boston. Perlis and his co-investigators published their report in the February American Journal of Psychiatry.“I think [these data] indicate the severity [of bipolar disorder] overall, and while we have some wonderful, newer treatments and some very effective older treatments,” Perlis told Psychiatric News,“ we still have a lot of work to do.”STEP-BD is the largest national research program aimed at determining the best treatment practices for bipolar disorder. Begun in 1998 and concluded in September 2005, researchers treated 4,360 patients with bipolar disorder (I, II, or NOS) who were followed long term to determine the most effective treatment or combination of treatments to combat depressive and manic episodes and to prevent relapse.“We also found that one of the strongest predictors of recurrence in our sample was the presence of residual mood symptoms following recovery,” Perlis said. “Even when patients were largely well, if they continued to be somewhat symptomatic, they were more likely to have a relapse. In short, those residual symptoms matter.”For the predictors of recurrence analysis, Perlis and his team looked at a subset of the full patient sample, focusing on 1,469 patients who had at least two years of participation in the STEP-BD program. The researchers found that slightly more than half (858 patients, or 58 percent) of this group achieved recovery, defined as having no more than two symptoms of the disorder for a period of at least eight weeks during the two-year follow-up period.Within that two-year window, nearly half of those who achieved recovery (416 patients, or 48.5 percent) relapsed; almost twice as many patients who relapsed suffered a depressive episode (298 patients, or 34.7 percent) than those relapsing to a manic, hypomanic, or mixed episode (118 patients, or 13.8 percent).Perlis and his co-authors concluded in their article that “taken together, these results demonstrate that mood episodes in bipolar disorder, and particularly depressive episodes, are prevalent and likely to recur in spite of guideline-based treatments.”Patients in STEP-BD, they noted, “received evidence-based care from specialized clinicians with training in the use of standardized assessments, combination pharmacotherapy, and psychosocial treatments where appropriate. In addition, participants received at minimum a core psychosocial educational intervention.”As such, the co-authors wrote, “the finding that nearly half of the study participants nonetheless suffered at least one recurrence during follow-up highlights the need for development of new interventions [for] bipolar disorder.”“I think [the importance of residual symptoms] parallels the major depression literature, where we've come to see that full remission is really the goal of treatment,” Perlis told Psychiatric News.“ Improvement is great, but remission is really critical. I think [these results] suggest that we need to take the same kind of focus in bipolar disorder—which many clinicians already do—and that is to treat to remission, not simply recovery. It emphasizes the importance of those residual symptoms and their association with risk of recurrence.”Interestingly, somewhat different factors appeared to be associated with relapse to a depressive episode versus relapse to a manic/hypomanic/mixed episode (see chart). For example, a current substance use disorder increased the risk of manic relapse, but not depressive relapse, while a current anxiety diagnosis was associated with increased risk of a depressive relapse but not manic relapse.The STEP-BD protocols were intended to represent an effectiveness study, and patients in the STEP-BD's Standard Care Pathway could receive any intervention believed to be clinically indicated by their clinician. In addition to rigorous guidelines for monitoring the progress of individual patients, clinicians adhered to pharmacotherapy guidelines based on published treatment guidelines (APA's revised Practice Guideline for the Treatment of Patients With Bipolar Disorder, the Expert Consensus Guideline Series: Medication Treatment of Bipolar Disorder, and the Department of Veterans Affairs' Clinical Practice Guidelines for Bipolar Disorder).STEP-BD also incorporated a “core psychosocial intervention.” All patients received a workbook and videotape describing the intervention, which emphasized alliance-building and provided techniques for recognizing and managing stress, negative thought patterns, problems in interpersonal interactions, and sleep disturbances.Perlis expressed some level of discomfort with the STEP-BD protocols being described as “state of the art.”“We didn't do anything that can't be done by any physician in the community,” Perlis explained, “and that was an important principle [in designing the study]—we wanted this to very specifically be generalizable across the country.” Perlis also emphasized that“ there will be much more to come from STEP-BD that will focus more on specific treatment questions. There are several studies embedded within the larger STEP-BD design looking more closely at psychosocial interventions and providing a head-to-head comparison of different pharmacotherapies.”“Predictors of Recurrence in Bipolar Disorder: Primary Outcomes From the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)” is posted at<http://ajp.psychiatryonline.org/cgi/content/abstract/163/2/217>.▪ Am J Psychiatry 2005 163 217 ISSUES NewArchived

Bipolar Disorder and a History of Suicide Attempts With a Duplication in 5HTR1A

Differentiating Recurrent Unipolar Depressive Disorder from Bipolar Affective Disorder as a diagnostic code within the Coventry IPU 3-8 (Affective Disorders).

The course of bipolar disorder progressively worsens in some patients. Although responses to pharmacotherapy appear to diminish with greater chronicity, less is known about whether patients' prior courses of illness are related to responses to psychotherapy. Embedded in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was a randomized controlled trial of psychotherapy for bipolar depression comparing the efficacy of intensive psychotherapy with collaborative care (a three-session psycho-educational intervention). We assessed whether the number of previous mood episodes, age of illness onset, and illness duration predicted or moderated the likelihood of recovery and time until recovery from a depressive episode in patients in the two treatments. Independently of treatment condition, participants with one to nine prior depressive episodes were more likely to recover and had faster time to recovery than those with 20 or more prior depressive episodes. Participants with fewer than 20 prior manic episodes had faster time to recovery than those with 20 or more episodes. Longer illness duration predicted a longer time to recovery. Participants were more likely to recover in intensive psychotherapy than collaborative care if they had 10-20 prior episodes of depression [number needed to treat (NNT) = 2.0], but equally likely to respond to psychotherapy and collaborative care if they had one to nine (NNT = 32.0) or >20 (NNT = 9.0) depressive episodes. Number of previous mood episodes and illness duration are associated with the likelihood and speed of recovery among bipolar patients receiving psychosocial treatments for depression.

Bupropion-Induced Mania and Hypomania: A Report of Two Cases

Data Question Claims That Lithium Reduces Suicide

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessPremenstrual Mood Exacerbation Linked to Severe Bipolar SymptomsMark MoranMark MoranSearch for more papers by this authorPublished Online:18 Mar 2011https://doi.org/10.1176/pn.46.6.psychnews_46_6_17_2AbstractPremenstrual mood exacerbation may be a clinical marker predicting a worse presentation and course of bipolar disorder in reproductive-age women. Women who have bipolar disorder and also experience premenstrual mood exacerbation appear to have a worse course of illness, a shorter time to relapse, and greater symptom severity than women with bipolar disorder who do not experience premenstrual mood exacerbation, according to a report that was published February 15 online in AJP in Advance."Mood exacerbation" was defined in the study as syndromal—corresponding to the DSM-IV mood states (depression, mania, hypomania, mixed)—or subsyndromal, not meeting criteria for any of these states but having three or four depression and/or mania symptoms. "Although time to relapse to a syndromal episode did not differ between women with premenstrual exacerbation and those without during follow-up, time to relapse in those with premenstrual exacerbation was half that of those without when relapse was defined more broadly as a syndromal or subsyndromal episode," wrote lead author Rodrigo Dias, M.D., and colleagues at Massachusetts General Hospital. "Women with premenstrual exacerbation also had more severe depressive and mood elevation symptoms during follow-up, reflecting greater symptom burden. Taken together, these findings suggest that premenstrual exacerbation may be a marker for a more recurrent and symptomatic course of illness among premenopausal women with bipolar disorder." In the study, 932 women aged 18 to 40 who were enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) responded to two questions about premenstrual mood changes: "Currently, do you typically experience depression symptoms around your menstrual period?" and "Currently, do you experience mood swings around your menstrual period?" Women who provided a positive response to one or both of these questions were categorized as having premenstrual exacerbation. After exclusion of women with previous unspecified gynecological surgeries and women for whom information was lacking about whether they had menstrual cycles, a total of 293 women—191 women with premenstrual exacerbation and 102 women without—were followed prospectively for one year. During follow-up, women with premenstrual exacerbation had more mood episodes overall than those without, including more depressive episodes, though the women did not have more episodes of mania or hypomania. Differences remained when episode frequency was categorized; women reporting premenstrual exacerbation were more likely to have one to three episodes a year (73.8 percent compared with 55.9 percent) and less likely to have no episodes (24.1 percent compared with 42.2 percent) during follow-up. Time to relapse was compared among 129 women (66 with premenstrual exacerbation and 63 without) who were in recovered status at baseline and had at least one additional assessment during the follow-up period. No significant difference was seen between groups in time to relapse to a syndromal episode; however, when the analysis included subsyndromal episodes as part of a broader definition of relapse, women with premenstrual exacerbation relapsed sooner on average than did those without, according to the report. Using this broader definition of relapse, the median time to relapse was 4.5 months in the group with premenstrual mood exacerbation, compared with 8.5 months in the group without it, a statistically significant difference. (No significant differences between groups were seen in the proportion of women changing medications before they relapsed.) Finally, statistical analysis of severity of symptoms as reported by women indicated that premenstrual exacerbation adversely affects the severity of both depression and mood elevation symptoms. Dias told Psychiatric News that the results suggest that clinicians treating women with bipolar disorder should follow the menstrual cycles of patients during appointments and ask them to make notes about the mood changes between appointments. "In the last five years, the scientific literature has been paying more attention to the subsyndromal mood states in depression and in bipolar disorder," he told Psychiatric News. "This kind of mood state, wherein the patient has mood symptoms but does not meet criteria for a mood episode, has been linked with poor functionality and more relapses of mood episodes. "In our study, we observed that women with premenstrual exacerbation spend more time in that kind of mood state and have more residual symptoms suggesting that they could be considered a group of patients who will have a more severe course of bipolar disorder." "Longitudinal Follow-Up of Bipolar Disorder in Women With Premenstrual Exacerbation: Findings From STEP-BD" is posted at <http://ajp.psychiatryonline.org/cgi/reprint/appi.ajp.2010.09121816v1>. ISSUES NewArchived

Treatment of Rapid-Cycling Bipolar Disorder: Are Antidepressants Mood Destabilizers?

Back to table of contents Previous article Next article Letter to the EditorFull AccessSubstance Abuse and Switch From Depression to Mania in Bipolar DisorderJoseph F. Goldberg, M.D.Joseph F. GoldbergSearch for more papers by this author, M.D.Published Online:1 Jul 2010https://doi.org/10.1176/appi.ajp.2010.10030367AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: The recent Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) article by Michael J. Ostacher, M.D., M.P.H., et al. (1), published in the March 2010 issue of the Journal, identified an association between current or past substance abuse or dependence in bipolar disorder patients and a greater likelihood for affective polarity switch from depression to mania, hypomania, or mixed state relative to when comorbid substance use disorders were absent (1). Consistent with this finding, previous naturalistic data from a study that I co-authored (2) demonstrated that a history of comorbid alcohol or substance use disorders conferred an approximate 7-fold increased risk in bipolar disorder patients for developing antidepressant-induced mania, regardless of cotherapy with antimanic agents. Using multiple regression, similar findings during antidepressant therapy were reported by Manwani et al. (3). In light of this prior literature, it would have been informative within the STEP-BD database to determine whether the presence or absence of antidepressant use mediated the relationship between a comorbid substance use disorder and affective polarity switch from depression. Although STEP-BD subjects with comorbid substance use disorders were less likely to receive an antidepressant than those without substance use disorders, this comparison in itself does not address the question of whether depressed bipolar subjects with a substance use disorder were more likely to experience a polarity switch in the presence rather than absence of an adjunctive antidepressant.Elsewhere, the STEP-BD randomized acute depression pathway (4) showed no increased risk for mood destabilization with antidepressants among bipolar depressed patients overall, but that investigation has not yet examined whether there may be distinct bipolar subgroups who are prone to affective polarity switch during antidepressant therapy. Insofar as Dr. Ostacher et al. identify bipolar disorder patients with comorbid substance use disorders as especially vulnerable to mood instability, yet no less likely to recover from a depressive episode as those without substance use disorder comorbidity, the potential safety versus efficacy of adjunctive antidepressants in this particular subset of individuals with bipolar depression warrants further examination.New York, N.Y.Dr. Goldberg has served on the speaker's bureaus of AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck, and Pfizer; he has received honoraria for lectures for Janssen-Cilag; and he has served as a consultant to or on the scientific advisory board for Cephalon and Eli Lilly.References1 Ostacher MJ , Perlis RH , Nierenberg AA , Calabrese J , Stange JP , Salloum I , Weiss RD , Sachs GS ; for STEP-BD Investigators: Impact of substance use disorders on recovery from episodes of depression in bipolar disorder patients: prospective data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am J Psychiatry 2010; 167:289–297 Link, Google Scholar2 Goldberg JF , Whiteside JE : The association between substance abuse and antidepressant-induced mania in bipolar disorder: a preliminary study. J Clin Psychiatry 2002; 63:791–795 Crossref, Medline, Google Scholar3 Manwani SG , Pardo TB , Albanese MJ , Zablotsky B , Goodwin FK , Ghaemi SN : Substance use disorder and other predictors of antidepressant-induced mania: a retrospective chart review. J Clin Psychiatry 2006; 67:1341–1345 Crossref, Medline, Google Scholar4 Sachs GS , Nierenberg AA , Calabrese JR , Marangell LB , Wisniewski SR , Gyulai L , Friedman ES , Bowden CL , Fossey MD , Ostacher MJ , Ketter TA , Patel J , Hauser P , Rapport D , Martinez JM , Allen MH , Miklowitz DJ , Otto MW , Dennehy EB , Thase ME : Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med 2007; 356:1711–1722 Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited byCanadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 201312 December 2012 | Bipolar Disorders, Vol. 15, No. 1 Volume 167Issue 7 July 2010Pages 868-869 Metrics PDF download History Accepted 1 April 2010 Published online 1 July 2010 Published in print 1 July 2010

Early identification and treatment of young people at high risk of recurrent mood disorders: a feasibility study