Predictors of Recurrence in Bipolar Disorder: Primary Outcomes From the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)

Boston University, Boston, Massachusetts, United States
American Journal of Psychiatry (Impact Factor: 12.3). 03/2006; 163(2):217-24. DOI: 10.1176/appi.ajp.163.2.217
Source: PubMed


Little is known about clinical features associated with the risk of recurrence in patients with bipolar disorder receiving treatment according to contemporary practice guidelines. The authors looked for the features associated with risk of recurrence.
The authors examined prospective data from a cohort of patients with bipolar disorder participating in the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study for up to 24 months. For those who were symptomatic at study entry but subsequently achieved recovery, time to recurrence of mania, hypomania, mixed state, or a depressive episode was examined with Cox regression.
Of 1,469 participants symptomatic at study entry, 858 (58.4%) subsequently achieved recovery. During up to 2 years of follow-up, 416 (48.5%) of these individuals experienced recurrences, with more than twice as many developing depressive episodes (298, 34.7%) as those who developed manic, hypomanic, or mixed episodes (118, 13.8%). The time until 25% of the individuals experienced a depressive episode was 21.4 weeks and until 25% experienced a manic/hypomanic/mixed episode was 85.0 weeks. Residual depressive or manic symptoms at recovery and proportion of days depressed or anxious in the preceding year were significantly associated with shorter time to depressive recurrence. Residual manic symptoms at recovery and proportion of days of elevated mood in the preceding year were significantly associated with shorter time to manic, hypomanic, or mixed episode recurrence.
Recurrence was frequent and associated with the presence of residual mood symptoms at initial recovery. Targeting residual symptoms in maintenance treatment may represent an opportunity to reduce risk of recurrence.

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Available from: Noreen A Reilly-Harrington, Jan 18, 2016
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    • "Residual (subsyndromal) mood symptoms commonly persist between mood episodes, impairing function (American Psychiatric Association, 2013) and increasing mood episode recurrence risk (Perlis et al., 2006), which in turn can yield illness progression (Post et al., 1992). "
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    ABSTRACT: Background: Sleep disturbance in bipolar disorder (BD) is common during and between mood episodes. In recovered (euthymic at least two months) BD patients, we assessed sleep compared to controls and its relationships with residual mood symptoms and mood episode recurrence. Method: Recovered Stanford University BD Clinic patients diagnosed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation and monitored with the STEP-BD Clinical Monitoring Form (CMF) for > 1 year and healthy controls completed the Pittsburgh Sleep Quality Index (PSQI). PSQI parameters were compared in BD patients versus controls, and the most robustly differentiating PSQI parameter was assessed in relationship to residual mood symptoms, and time to mood episode recurrence in BD patients. Results: Eighty nine recovered BD patients compared to 56 healthy controls had significantly worse PSQI global score, more sleep medication use, longer sleep latency, and worse daytime dysfunction. PSQI global score had the greatest BD patient versus control effect size, and among BD patients, correlated significantly with residual mood symptoms and predicted earlier mood episode recurrence, even after covarying for residual mood symptoms. Limitations: Use of subjective (PSQI) rather objective (polysomnography) sleep metric. Statistical power limited by small sample size. Potential psychotropic medication confound. Northern California tertiary BD clinic referral sample. Conclusion: Further research is needed to confirm that in recovered BD patients, poor sleep quality correlates with residual mood symptoms, and independently predicts mood episode recurrence. If confirmed, these observations suggest potential mood benefit for focusing on sleep quality in interventions for recovered BD patients. Published by Elsevier B.V.
    Full-text · Article · Jan 2016 · Journal of Affective Disorders
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    • "Among the 10 naturalistic studies analyzed, overall recurrence risk (% of subjects) averaged 55.2% [CI: 49.6–60.8], and ranged from 40.4% to 66.0% (Table 1), (Perlis et al., 2006; Kulkarni et al., 2012; Silverstone et al., 1998; Dittmann et al., 2002; Tohen et al., 2003; Fekadu et al., 2006; Altamura et al., 2008; Hong et al., 2010; Li et al., 2014; Simhandl et al., 2014) annualized recurrence rates averaged 26.3 [23.6–29.0] %/year. "
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    ABSTRACT: Bipolar disorder (BD) is a recurrent, lifelong illness with high risks of disability and excess mortality. Despite many treatment options with demonstrated short-term efficacy, evidence concerning long-term treatment effectiveness in BD remains limited and the relative value of naturalistic studies versus randomized, controlled trials (RCTs) in its assessment, uncertain. Systematic computer-searching yielded 10 naturalistic studies and 15 RCTs suitable for analysis of recurrence rates and their association with treatments and selected clinical factors. In naturalistic studies (3904 BD subjects, 53.3% women, 85.8% BD-I, mean onset age 29.1, followed up to 2.1 years), the pooled recurrence rate was 55.2% (26.3%/year). In RCTs (4828 subjects, 50.9% women, 96.0% BD-I, mean onset age 23.1, followed up to 1.9 years), the pooled recurrence rate was 39.3% (21.9%/year) with mood-stabilizing drug-treatment versus 60.6% (31.3%/year) with placebo; drug-versus-placebo outcomes favored antipsychotics over lithium, and disfavor an approved anticonvulsant. Depressive episode-polarity increased from 27.7% at intake to 52.0% at first-recurrence (p<0.0001). Recurrence rate (%/year) did not differ by study-type, was greater with younger onset and rapid-cycling, and paradoxically declined with longer observation. In short, recurrences of major affective episodes up to two years during putative mood-stabilizing treatment of BD patients in prospective, naturalistic studies and RCTs were substantial and similar (26.3 vs. 21.9%/year). Episode-polarity shifted strongly toward depressive first-recurrences. These findings support the value of naturalistic studies to complement long-term RCTs, and add to indications that control of depression in BD remains particularly unsatisfactory. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.
    Full-text · Article · Jul 2015 · European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology
    • "We also tested for drug-placebo differences when available, using randomeffects meta-analysis when trial count was Z3, and fixed-effect models with only 1 or 2 trials. Analyses were based on Statview.5 s spreadsheets (SAS Institute, Cary, NC), and commercial statistical software, R.3.0.1 s (R Foundation, Vienna, Austria), SAS.9.4 s (SAS Institute), and Stata.13 s (StataCorp., College Station, TX). Figure 1A) and 15 RCTs (e-Appendix Figure 1B) involving a total of 8798 BD patients followed up to 2.1[Table 1), (Perlis et al., 2006;Kulkarni et al., 2012;Silverstone et al., 1998;Dittmann et al., 2002;Tohen et al., 2003;Fekadu et al., 2006;Altamura et al., 2008;Hong et al., 2010;Li et al., 2014;Simhandl et al., 2014) annualized recurrence rates averaged 26.3[Most subjects in these clinical trials (69.6%) presented with depressive index episodes, and a majority (55.7%) of their first recurrent episodes during two years of follow-up also were depressive (Table 1). Types of treatments used in these naturalistic studies (Table 1, footnotes) ranked: lithium or anticonvulsants with putative mood-stabilizing activity (carbamazepine , gabapentin, lamotrigine, topiramate, or valproate; 59.0%), with or without antidepressants (mainly serotonin reuptake inhibitors or bupropion; 50.6%), unspecified, or combined treatments (43.7%), or atypical antipsychotics (mostly olanzapine, quetiapine, or risperidone; 38.0%); more than one medicine was used by approximately 91% of participants. "

    No preview · Article · Jun 2015 · Bipolar Disorders
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