Blue-blocking glasses as adjunctive treatment for bipolar mania - and exploration of motor activity patterns in serious mental disorders

Background: There is a need for more effective treatments of bipolar mania. Promising reports of the effects of dark therapy on bipolar disorder symptoms and the discovery of a mainly blue-light sensitive daylight-signaling retinal ganglion cells has resulted in the utility of BB glasses to create a virtual darkness condition for the brain. Changes in activation or aberrant motor activity is present in all serious mental disorders. Actigraphy is a non-invasive and simple means of assessing motor activity, but is still mostly used to assess sleep outcomes. Before the utility of actigraphy can be broadened, there is need for further exploration of daily activity pattern characteristics for the diagnostic entities. Aims: By means of the Virtual Darkness as Additive Treatment in Mania (VATMAN) trial, we aimed to test the effectiveness and feasibility of BB glasses as an adjunctive treatment for mania compared to placebo glasses. As part of the Agitation at Admittance to a Psychiatric Acute Department Study, we aimed to characterize the motor activity patterns among a new sample of patients with psychotic disorders, and compare these characteristics to the motor activity patterns of patients with affective disorders and with healthy controls. Methods: Eligible patients for the VATMAN trial (hospitalized with bipolar disorder mania and otherwise fulfilling inclusion criteria) were randomized to receive either BB-glasses or clear-lensed placebo glasses. The glasses were worn as an adjunctive treatment from 6:00 p.m. to 8:00 a.m. for seven consecutive days. Manic symptoms were rated daily using the Young Mania Rating Scale. Motor activity was measured using wrist-worn actigraphs. Feasibility was assessed using a self-report patient experience questionnaire together with the clinical observation of side-effects. Sleep was assessed using actigraphy-derived sleep parameters. In the Agitation at Admittance to a Psychiatric Acute Department study, all hospitalized patients in the acute psychiatric ward in Østmarka Hospital, Trondheim were asked to wear an actigraph for 24 h. The motor activity patterns of patients diagnosed with schizophrenia and other psychotic disorders were compared to those of patients with mania, motor-retarded unipolar depression, and healthy controls. Linear and non-linear analytical methods were used to describe and compare motor activity variability and complexity (irregularity) for a 24 h period as well as in morning and evening sequences. Results: Out of 32 randomized patients in the VATMAN trial, 12 patients in the BB-group and 11 patients in the placebo-group were included in the analyses. After seven days, the Cohen’s d effect size was 1.86. There was a significant group difference in YMRS scores after three days (p = 0.042) and the group difference increased steadily throughout the intervention. Observed side effects included headache in one patient and rapidly reversible depressive symptoms in two patients. Actigraphy-derived sleep outcomes at night five showed significantly higher sleep efficiency, lower motor activity and less minutes of wake after sleep onset in the BB group as compared to the placebo group. Several patients in both groups displayed a 48 h-like rhythm of shorter or disrupted sleep. The schizophrenia spectrum group shared the characteristic of high motor activity variability with the unipolar depressed group, but differed with respect to more irregular (complex) activity pattern in the morning sequence. The schizophrenia spectrum and the mania groups could not be separated using formal statistical analyses, being most similar with regards to high morning activity irregularity. The mania group was the only one to show a blunted morning-to-evening activity fluctuation, while the normal morning-to-evening decline was more preserved in the schizophrenia spectrum group. Conclusions: BB-glasses were found to be both effective and feasible as an adjunctive treatment for mania. The BB-group showed actigraphy-derived sleep parameters reflecting less activated sleep compared with the placebo-group. The use of actigraphy data to characterize diurnal motor activity patterns, by use of the combination of linear and non-linear analytical approaches, seems to have potential for assessment of symptoms and for diagnostic support