Interepisode Residual Depressive Symptoms Affect Course of Bipolar Disorder

Individuals with depressive residual symptoms between episodes may have more of a negative course of illness.

Major stressful life events within the past 6 months and extended current illness duration were reported to be strong predictors of interepisode residual depressive symptoms in people with euthymic bipolar disorder, according to Italian researchers who recently reported their findings in the European Archives of Psychiatry and Clinical Neuroscience. Those with such residual symptoms often experience a more disabling illness course, characterized by greater psychosocial impact, than their counterparts not reporting residual symptoms.

Despite their high frequency in people with bipolar disorder, the impact of residual depressive symptoms on disease course is not fully understood. The investigators were interested in exploring the prevalence of such symptoms and any identifiable factors associated with their appearance, as it was believed that the presence of such symptomatology might be a harbinger of poorer outcomes in this suspected at-risk patient subgroup.

There were 255 participants (mean age (SD) 52.1 (15.5) years; 62.8% females) recruited into the cross-sectional study between July 2014 and May 2017, all of whom were outpatients in euthymia who were receiving maintenance therapy. Medical records and patient/family interviews were used for data collection, along with psychometric confirmation using the Montgomery-Asberg depression rating scale and the mini international neuropsychiatric interview. Participants were divided by the presence (54.5%) or absence (45.5%) of residual depressive symptoms and the 2 groups were compared regarding clinical variables using univariate and multivariate analyses.

Individuals with residual symptoms reported substance abuse (χ2(2) = 11.937, P ≤.005) less frequently and lifetime psychotic symptoms2(2) = 10.577, P =.005) more frequently than those without. These patients also more often reported increased illness episodes (t253 = 67.282, P ≤.001), longer overall illness duration (t253 = 10.755, P ≤.001) and longer current episode duration (t253 = 7.707, P ≤.001). However, multivariate analysis showed that only current episode duration (β = 0.003, P ≤.05) and stressful life events over the prior 6 months (β = 1.094, P ≤.005) continued to demonstrate significant positive impacts on residual symptoms.

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Study limitations included small sample size and cross-sectional design that limited generalizability or causal inferences, lack of examination of residual manic symptoms, a self-reporting format that requires cautious interpretation (particularly involving substance abuse), possible referral bias, and lack of controls for additional confounding factors.

The investigators recommended further exploration of these associations and advised clinicians to remain wary of the aforementioned predictors in their patient populations. Clinicians must assess residual symptoms accurately and tailor interventions accordingly, with the hope of preventing or mitigating relapse or recurrence. In their discussion, the authors noted, “…subjects with these symptoms need to be considered at higher clinical risk when compared with individuals without residual symptoms.”

No disclosures or conflicts of interest were reported.


Serafini G, Vazquez GH, Gonda X, Pompili M, Rihmer Z, Amore M. Depressive residual symptoms are associated with illness course characteristics in a sample of outpatients with bipolar disorder. Eur Arch Psychiatry Clin Neurosci [published February 7, 2018]. doi:10.1007/s00406-018-0875-5