What is the background of the HTA report?

For “ThemenCheck Medizin” (Topic Check Medicine), published by the Institute for Quality and Efficiency in Health Care (IQWiG), insured persons and other interested individuals are invited to propose topics for the assessment of medical procedures and technologies. The assessment is done in the form of a health technology assessment (HTA) report. HTA reports include an assessment of medical benefit and health economics as well as an investigation of ethical, social, legal, and organizational aspects of a technology.

In a 2-step selection procedure, which also involves the public, up to 5 topics are selected each year from among all submitted proposals. According to the legal mandate, these topics should be of particular relevance to patients [1]. IQWiG then commissions external teams of scientists to investigate the topics in accordance with IQWiG methods, and it publishes the HTA reports.

In 2018, IQWiG commissioned a team of scientists from Danube University Krems to investigate the selected topic “Seasonal affective disorder: Do nondrug treatments such as phototherapy and vitamin therapy lead to better results?” The team consisted of methodologists experienced in generating HTA reports, experts with knowledge and experience in health economic, ethical, social, legal and organizational topics as well as a specialist in psychiatry and psychotherapy.

Why is the HTA report important?

People with seasonal affective disorder (SAD) suffer from seasonal symptoms such as depressed mood, loss of interest, lack of drive, extreme tiredness, or sudden hunger pangs, often associated with weight gain. Most patients experience episodes of mild to moderate depression, which can nevertheless adversely impact their professional and private lives. Annually, about 2.5% of the population in German-speaking countries is affected by SAD, and in the majority of patients, the disorder recurs in the subsequent year [2–4]. SAD is often diagnosed late or not at all, in part due to the prevailing societal perception of the associated symptoms being somewhat normal and a side effect of the darker months. It is not unusual to hear people say, “I have the winter blues.”

After diagnosis, SAD is often treated with drugs (antidepressants) and/or psychotherapy. However, patients and treatment providers are also looking for alternatives: The reduced number of sunlight hours in autumn and winter is suspected to have physical effects which can be compensated by phototherapy. Since the body synthesizes less vitamin D in the winter as a result of less intensive sunlight, the administration of vitamin D represents a potential treatment option.

This HTA report therefore aims to investigate the benefits and harms of phototherapy and vitamin D therapy in comparison with each other as well as in comparison with antidepressants, psychotherapy, placebo or no treatment in adults with SAD. Of particular interest were any effects on mortality, the extent of depression symptoms, and health-related quality of life as well as adverse events.

Which questions are answered – and which are not?

For the assessment of benefit and harm of phototherapy, the team of scientists from Danube University Krems included 21 relevant studies, most of them of moderate qualitative certainty of results. Sixteen studies compared phototherapy versus placebo, 3 studies phototherapy versus cognitive behavioural therapy, and 2 studies phototherapy versus the antidepressant fluoxetine.

After an intervention period of 2 to 8 weeks, there were indications suggesting that light box-based phototherapy resulting in greater improvements in symptoms of depression than placebo. This was the case for the patient-relevant aspects of response, remission of depression, and severity of depressive symptoms. In addition, for the comparison of light box therapy with fluoxetine, there was a hint of the antidepressant therapy being more likely to lead to AEs such as sleep disorders or tachycardia. The benefit of light box therapy was, however, comparable to the benefit of fluoxetine or cognitive behavioural therapy. For phototherapy with head-mounted units, there was no hint of greater effect than placebo.

Mortality-related treatment effects were not investigated in any study, and effects on health-related quality of life and cognitive functioning were each examined by only 1 study. Further, no long-term data on phototherapy were available since, except for a survey taken immediately following the 2 to 8 weeks of therapy, patients were not followed up for a longer time period. The external team of scientists did not find any studies on SAD treatment with vitamin D.

The costs of light box phototherapy include the device price and the cost of the associated consultations with a physician or psychotherapist and are similar to the costs of vitamin D or fluoxetine therapy for the respective minimum treatment durations. Only cognitive behavioural therapy – in group or individual setting – is far more cost-intensive. The treatment costs of fluoxetine and cognitive behavioural therapy are covered by SHI, while those of phototherapy and vitamin D therapy are typically not. However, some SHIs pay some of the costs of phototherapy if a diagnosis of SAD has been medically established. Two health economic studies comparing phototherapy with cognitive behavioural therapy were identified. According to the external team of scientists, the informative value of these studies was very limited due to methodological limitations as well as lack of transferability from the U.S. to the German healthcare setting.

Generally, SAD patients represent a vulnerable group: About half of patients have a known family history of psychiatric disorders, and, alongside psychological stress some exhibit physical conditions such as excess weight or coronary heart disease. Although SAD patients are less stigmatized by society than people with different types of depression, societal acceptance of the disorder is poor. SAD is often perceived as a side effect of the darker months or as “winter fatigue”. Against this background, it comes as no surprise that both patients and physicians tend to discuss it as a disease caused by biological processes rather than a mental disorder.

Assuming SAD is due to a physical deficiency, phototherapy and vitamin D therapy might represent potential treatment options. However, due to a lack of studies, no conclusions can be drawn on the benefits and harms of vitamin D in SAD treatment. This is reflected by current healthcare practice: Vitamin D is currently not a recommended treatment option for SAD patients and is prescribed only to treat selected disorders or vitamin deficiencies which have been confirmed by laboratory testing. Currently, guidelines recommend antidepressants, phototherapy, or cognitive behavioural therapy [5,6]. Patients’ desire for a less invasive alternative to the commonly prescribed antidepressants also leads to greater acceptance of other measures, e.g. phototherapy or vitamin D therapy. This holds true at least in the experience of the external team of scientists.

In contrast to cognitive behavioural therapy, fluoxetine or vitamin D therapy as well as phototherapy can be applied by patients at their own homes, after consultation with a physician. If the light box is purchased by the patient, it can be used again in any further depressive episodes in autumn or winter without incurring any additional costs. Since few SHIs pay for all or part of phototherapy, access requirements differ. Patients who cannot afford to pay for phototherapy themselves and do not wish to switch to another SHI are forced to rely on the reimbursable drug and psychotherapeutic therapies. Nevertheless, every physician must inform patients about all treatment options, provided the latter are equally medically indicated, are part of standard medical practice, and are suitable for replacing treatments such as antidepressant therapy. From an organizational perspective, since consultation is provided by the same care provider, the use of phototherapy does not increase resource consumption or cause any shift in services.

IQWiG confirms the assessment from the Danube University Krems team of scientists, who found that light box therapy can indeed represent an alternative in the treatment of SAD. Published studies have shown that, after 2 to 8 weeks of intervention, light box therapy improved depression symptoms to a greater extent than did placebo. In addition, it was associated with fewer adverse events than the antidepressant fluoxetine. Light boxes can be easily used at home at a convenient time and require only a one-time purchase. Due to a lack of relevant studies, no conclusions can be drawn on the benefits and harms associated with vitamin D therapy in SAD.

What’s the next step?

To obtain a more comprehensive picture, it is desirable to have additional informative studies investigating the long-term benefits and harms of light box therapy, its effects on additional patient-relevant aspects such as health-related quality of life as well as light box therapy in comparison with other established therapies. Further, there is a general need for further research on SAD treatment with vitamin D. Apart from seeking to answer the question as to which therapy is safest and most effective, this HTA report is intended to help focus public attention on SAD and hence increase awareness of a disorder which can affect patients’ social and professional functioning.

References

1.

Bundesministerium der Justiz und für Verbraucherschutz. Sozialgesetzbuch (SGB) Fünftes Buch (V): Gesetzliche Krankenversicherung; (Artikel 1 des Gesetzes v. 20. Dezember 1988, BGBl. I S. 2477) [online]. 22.03.2020 [Accessed: 14.05.2020]. URL: http://www​.gesetze-im-internet​.de/sgb_5/SGB_5.pdf.

2.

Wirz-Justice A, Graw P, Krauchi K, Wacker HR. Seasonality in affective disorders in Switzerland. Acta Psychiatr Scand Suppl 2003; (418): 92-95. [PubMed: 12956822]

3.

Pjrek E, Baldinger-Melich P, Spies M, Papageorgiou K, Kasper S, Winkler D. Epidemiology and socioeconomic impact of seasonal affective disorder in Austria. Eur Psychiatry 2016; 32: 28-33. [PubMed: 26802981]

4.

Schwartz PJ, Brown C, Wehr TA, Rosenthal NE. Winter seasonal affective disorder: a follow-up study of the first 59 patients of the National Institute of Mental Health Seasonal Studies Program. Am J Psychiatry 1996; 153(8): 1028-1036. [PubMed: 8678171]

5.

Deutsche Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde. S3-Leitlinie/Nationale VersorgungsLeitlinie Unipolare Depression: Langfassung; Version 5 [online]. 2015 [Accessed: 14.05.2020]. URL: https://www​.leitlinien​.de/mdb/downloads/nvl​/depression/depression-2aufl-vers5-lang.pdf.

6.

National Institute for Health and Care Excellence. Depression in adults: recognition and management [online]. 28.10.2009 [Accessed: 20.08.2019]. (Clinical Guidelines; Volume 90). URL: https://www​.nice.org​.uk/guidance/cg90/resources​/depression-in-adults-recognition-and-management-pdf-975742636741. [PubMed: 31990491]