Elsevier

Medical Hypotheses

Volume 78, Issue 4, April 2012, Pages 511-515
Medical Hypotheses

Can transcranial brain-targeted bright light treatment via ear canals be effective in relieving symptoms in seasonal affective disorder? – A pilot study

https://doi.org/10.1016/j.mehy.2012.01.019Get rights and content

Abstract

Bright light therapy (BLT) is widely accepted as first-line treatment of seasonal affective disorder (SAD). However, the mechanism of action of BLT is still widely unknown. On the other hand, in mammals, light penetrates the skull bone and reaches the brain, and extra ocular transcranial phototransduction has physiological influences such as changed reproductive cycles and increased brain serotonin levels. Therefore, we challenged the existing conceptual framework that light therapy would only be mediated through the eyes. Consequently, we run a pilot study on the putative effect of transcranial bright light in the treatment of SAD. The light was produced using light-emitting diodes (LEDs), which were attached to earplugs. The amount of photic energy was 6.0–8.5 lumens in both ear canals, and the length of treatment was 8 or 12 min five times a week during a four-week study period. Subjects were recruited through advertisements in the city of Oulu, Finland (latitude 65°01′N) during 14 January 2009–03 February 2009. The final patient series consisted of 13 (aged 37.1 ± 7.2 years) physically healthy indoor workers suffering from SAD according to DSM-IV-TR criteria. Severity of depressive symptoms was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17) and Beck Depression Inventory (BDI)-21. Furthermore, severity of anxiety symptoms was measured by the 14-item Hamilton Anxiety Rating Scale (HAMA). The HAMD-17 mean sum score at screening was 23.1 ± 1.6. Ten out of 13 SAD patients (76.9%) achieved full remission (i.e., HAMD-17 sum score ⩽7), and 92.3% (12/13) at least 50% reduction in HAMD-17 sum scores at “Week 4”. By using a mixed regression model of repeated measures (AR-1) controlling for age, gender, and HAMD-17 mean sum score at screening, significant differences were found comparing the HAMD-17 mean sum scores of “Week 0” with the corresponding scores at the “Week 3” (t = −2.05, p = 0.045) and “Week 4” visit (t = −2.77, p = 0.008). Correspondingly, significant differences were found comparing the BDI-21 mean sum scores (15.2 ± 6.7) of “Week 0” with the corresponding scores at the “Week 3” (t = −2.37, p = 0.021) and “Week 4” visit (t = −3.65, p < 0.001). The HAMA mean sum score at screening was 20.5 ± 5.4. During the study period, 12 out of 13 (92.3%) patients achieved at least 50% reduction in their HAMA sum scores, and in 10 out of 13 patients (76.9%), the HAMA sum score was <7. In conclusion, it is hard to believe that our findings could be explained solely by placebo effect. Consequently, the basic assumptions underlying extraocular photoreception in humans deserve to be reconsidered. Given that a proper placebo treatment can be implemented via ear canals, further investigations with randomized placebo-controlled and/or dose-finding study designs regarding the extraocular transcranial bright light in the treatment of SAD are called for.

Introduction

The seasonal pattern of recurrent episodes of depression, either unipolar or bipolar, has become known as seasonal affective disorder (SAD) [1], [2], [3]. The precise pathogenesis of SAD is still elusive despite several explanatory theories [2], [4]. Both DSM-IV and ICD-10 are open with regard to the season during which a major depressive episode recurs [1], [2], [3], [5], although ICD-10 has only provisional diagnostic criteria for SAD [5]. Since winter SAD is far more prevalent than summer SAD, the term SAD usually refers to winter SAD [3]. It has been estimated that the prevalence of SAD is around 1.2% in general populations, but the prevalence figures differ a lot due to methodological differences in epidemiological studies [3].

Although evidence has not been fully confirmed [6], bright light therapy (BLT) is widely accepted as first-line treatment of SAD in guidelines of high repute [7], [8], [9]. In a systematic review and meta-analysis, the effect size for the reduction of depressive symptoms by BLT (eight randomized control trials (RCTs)) in the treatment of SAD was 0.84 (95% CI 0.60–1.08) [10]. However, there was significant heterogeneity among the studies. Correspondingly, the guideline of the National Institute for Health and Clinical Excellence (NICE) found that when compared with waiting list controls, bright light reduced depressive symptoms significantly [6]. However, the guideline concludes that it is unclear whether this effect is greater than placebo effect [6]. In addition, a statistically significant reduction of depressive symptoms has been found in the treatment of SAD by using dawn simulation [11], with an effect size (five RCTs) of 0.73 (0.37–1.08) in a meta-analysis [10]. However, the corresponding evidence has been questioned [6].

Section snippets

The hypothesis

The mechanism of action of BLT and dawn simulation in the treatment of SAD is still widely unknown [7], [11]. On the other hand, there is evidence that in mammals, (a) significant amount of light penetrates the skull bone and reaches the brain, and (b) extra ocular transcranial phototransduction has certain physiological influences such as changed reproductive cycles and increased brain serotonin levels (cf. Campbell et al. 2001) [12]. Therefore, we have challenged the existing conceptual

Description of the bright light device

We developed a non-invasive photon application device, a VALKEE bright light device (Valkee Ltd., Oulunsalo Finland), which was approved as a medical device in the European Union on 30 March 2010. It was specially designed to target bright light treatment transcranially towards the brain via ear canals. The light was produced by using light-emitting diodes (LEDs), which were attached to earplugs. The light intensity at the end of both light guides in the ear canals was 6.0–8.5 lumens (lm) during

Consequences of the hypothesis and discussion

We have challenged the existing conceptual framework concerning the mechanisms of action of bright light in the treatment of SAD, i.e., that light therapy would only be mediated through the eyes [13]. For example, OPN3 [19], [20], while existing in protein level in human brain [25], [26] might play a role in non-visual phototransduction. We have initiated our human brain opsin research branch by showing that OPN3 exists in several different brain areas outside the visual pathway [26].

Role of the funding source

This study was partly funded by Oulu Deaconess Institute and Valkee Ltd.

Conflict of interest statement

MT is a minor shareholder in Valkee Ltd., was reimbursed by Pfizer for attending one conference, was paid by Pfizer, BMS, Eli Lilly, Servier and Astra Zeneca for speaking on different educational occasions, and has received advisory panel payments from Pfizer and H. Lundbeck A/S for three meetings. JN is a shareholder and CSO of VALKEE Ltd. company (Oulu, Finland), which is a producer and developer of the bright light devices for SAD. MSc. AL and JJ report no financial relationships with

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    The work was conducted by the University of Oulu, Institute of Health Sciences (General Practice), P.O. Box 5000, FIN-90014 Oulu, Finland.

    1

    These authors equally contributed to this work.

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