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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    • "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.
    Journal of Affective Disorders 01/2016; 190:162-166. DOI:10.1016/j.jad.2015.09.076 · 3.38 Impact Factor
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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.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 07/2015; 25(10). DOI:10.1016/j.euroneuro.2015.07.013 · 4.37 Impact Factor
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    • "For bipolar depression with psychosis, a particularly difficult form of depression to combat, treatment remains elusive. Conventional antidepressant medications, as demonstrated in the systematic treatment enhancement program for bipolar disorder (STEP-BD) study, can actually worsen outcomes and induce shifts to manic/hypomanic states (6). Furthermore, as demonstrated in the clinical antipsychotic trials of intervention effectiveness (CATIE) study (7), even current effective frontline treatments for disorders such as schizophrenia come with a myriad of side effects. "
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    ABSTRACT: The progress of developing effective interventions against psychiatric disorders has been limited due to a lack of understanding of the underlying cellular and functional mechanisms. Recent research findings focused on exploring novel causes of psychiatric disorders have highlighted the importance of the axonal initial segment (AIS), a highly specialized neuronal structure critical for spike initiation of the action potential. In particular, the role of voltage-gated sodium channels, and their interactions with other protein partners in a tightly regulated macromolecular complex has been emphasized as a key component in the regulation of neuronal excitability. Deficits and excesses of excitability have been linked to the pathogenesis of brain disorders. Identification of the factors and regulatory pathways involved in proper AIS function, or its disruption, can lead to the development of novel interventions that target these mechanistic interactions, increasing treatment efficacy while reducing deleterious off-target effects for psychiatric disorders.
    Frontiers in Psychiatry 08/2014; 5:109. DOI:10.3389/fpsyt.2014.00109
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