Subthreshold symptoms and time to relapse/recurrence in a community cohort of bipolar disorder outpatients

Abstract

Background

Researchers have previously found that persistent subthreshold symptoms increase the risk and shorten the time until an affective relapse in bipolar disorder (BD) patients. Research has mainly focused on patients from tertiary Care Centers in USA. We tested the hypothesis that even in a different setting, BD outpatients with subsyndromal affective symptoms would re.turn to a subsequent major affective episode significantly faster than completely asymptomatic at baseline. Secondarily, we analysed other variables related to time and risk to relapse.

Methods

A community cohort of BD outpatients from Madrid (Spain) followed-up in a systematic prospective follow-up protocol for up to five years were evaluated. Patients in clinical euthymia at baseline were included and evaluated quarterly.

Results

Initially, 225 patients were included in the survival analysis. Of them, according to predefined psychometric criteria, 163 were in euthymia (72.4%) and 62 (27.6%) suffered subsyndromal symptoms. Median follow-up was 157.6 weeks (95% CI, 78.14 to 111); 57.3% of patients experienced at least one affective episode during their follow-up. Median survival time to first affective episode was 109 weeks for patients in euthymia at baseline, versus 35 weeks for those with subsyndromal symptoms (p<0.0001). Psychosocial stress (p=0.003; HR 2.20; 95% CI 1.31-3.68) and the affective mood baseline state, subsyndromal vs. euthymic (p=0.046; HR 1.74; 95%CI 1.009-3.020), were related to time to first affective episode.

Limitations

Naturalistic study, some of the data collected were necessarily retrospective.

Conclusions

In Spanish non-tertiary psychiatric outpatients, subsyndromal BD symptoms and psychosocial stress at baseline predict earlier episode relapse/recurrence.

Introduction

Bipolar disorder (BD) is a chronic disorder, and new episodes are frequent even in regularly followed patients under standard psychiatric treatment (Perlis et al., 2006). There is now strong evidence of progressive neuropathological processes in BD, changes that could explain some of the clinical and cognitive features of this disease (Berk et al., 2010), and they seem to be more profound in patients with multiple prior episodes or longer illness duration. Therefore, recognizing factors related to increased risk of relapse of a previous affective disorder, or to the appearance of a new affective episode (recurrence), seems crucial.

In several previous studies, subthreshold (subsyndromal) symptoms have been associated with an increased risk of affective relapse/recurrence (Goodnick et al., 1987, Keller et al., 1992, Kleindienst and Greil, 2002, Perlis et al., 2006, Tohen et al., 2006, Tohen et al., 2003). In a naturalistic and prolonged study, the predictive value of subsyndromal symptoms on time to relapse/recurrence was reviewed in a systematic and prospective manner (Judd et al., 2008). That research was done mainly – although not exclusively – in tertiary care centers and has not been replicated. In that study, participants recovering with subsyndromal affective symptoms experienced subsequent major affective episodes earlier than asymptomatic recoverers, and recovery status was the strongest correlate of time to episode recurrence. But the setting of care may have an impact on course and outcome of BD patients. Recent research points to possible differences between EU and U.S. sites, with lower morbidity in EU patients (De Dios et al., 2010, Baldessarini et al., 2010); hence, the possibility of considering the two populations as heterogeneous for future pharmacological studies has been proposed (Post et al., 2011).

The primary objective of our study was to analyze the influence of subsyndromal affective symptoms on time to affective relapse/recurrence in a cohort of non-US bipolar psychiatric outpatients from the community. We tested the hypothesis that BD psychiatric outpatients who are clinically in euthymia but with residual subsyndromal affective symptoms would return to a subsequent major affective episode significantly faster than those completely asymptomatic at baseline. Secondarily, we have studied other clinical and socio-demographic variables related to time to relapse/recurrence.