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Seasonal affective disorder: Do non-drug interventions such as light and vitamin therapy lead to better results? IQWiG Reports – Commission No. HT18-04 [Internet] Cologne (Germany): Institute for Quality and Efficiency in Health Care (IQWiG); 2021 Apr 14.
1.1. Health policy background and commission
According to § 139b (5) of Social Code Book V, Statutory Health Insurance, statutory health insurance members and other interested people may suggest topics for the scientific assessment of medical interventions and technologies to the Institute for Quality and Efficiency in Health Care (IQWiG). The topics for these health technology assessment (HTA) reports can be submitted on the ThemenCheck Medizin (“topic check medicine”) website.
ThemenCheck Medizin aims to promote the involvement of the public in evidence-based medicine and answer questions which are particularly relevant in patient care.
Once yearly, IQWiG, in collaboration with patient representatives and members of the public, selects up to 5 topics on which HTA reports are to be prepared. IQWiG then commissions external experts to investigate the research question. The results prepared by the external experts and a publisher’s comment by IQWiG are then published in the form of an HTA report.
IQWiG disseminates HTA reports to German institutions, for instance those deciding about healthcare services and structures. The HTA report will be made available to the professional community through the ThemenCheck Medizin website (www.themencheck-medizin.iqwig.de). In addition, a lay summary of the results of the HTA report will be published under the title “HTA compact: The most important points clearly explained”. This is done to ensure that the results of HTA reports will impact patient care.
1.2. Medical background
1.2.1. Definition and epidemiology
SAD is a seasonal type of depression, typically causing symptoms in autumn and winter and subsiding in spring and summer [1]. The International Statistical Classification of Diseases and Related Health Problems (ICD-10) lists SAD under F33 as a subtype of recurrent depressive disorder with a seasonal pattern [2]. The diagnostic criteria for SAD from the U.S. classification system Diagnostic and Statistical Manual of Mental Disorders (DSM-5) require at least 2 episodes of depressive disturbance occurring in consecutive years during the same season and not being able to be explained by other circumstances, such as loss of work for seasonal workers [3]. The most common type of SAD is the winter form, in which depressive symptoms develop in autumn and winter and do not resolve until spring. In the less common summer form, depressive symptoms occur only in summer [3]. This report focuses on the winter form of SAD – also known as “autumn-winter depression”. Therefore, the terms SAD and autumn-winter depression are used synonymously in this report.
SAD patients suffer not only from typical symptoms of depression, such as a depressed, low mood, lack of drive or loss of interest, and joylessness, but often also from atypical symptoms such as a ravenous appetite for carbohydrates, increased need to sleep, or weight gain [4]. Most SAD patients experience episodes of mild to moderate depression; suicidal ideation is less common than in patients suffering from nonseasonal depression. Nevertheless, SAD patients exhibit impaired functioning in winter, and the disorder adversely impacts their private and professional lives [5,6].
The prevalence of SAD is higher in northern countries than in southern ones; in Europe and the United States, it is reported as between 1% and 10%. While no prevalence data are available for Germany, surveys from Austria and Switzerland report some 2.5% of the population being affected by SAD in these latitudes [7,8].
According to a German study, some 80% of patients diagnosed with SAD experienced a depressive episode in the subsequent year as well [9]. Long-term studies have shown that 5 to 11 years after diagnosis, 22% to 42% still suffered from SAD. In 33% to 44% of patients, SAD developed into nonseasonal depression, while in 14% to 18%, symptoms disappeared completely [9,10].
1.2.2. Treatment
Since the depressive episodes start in autumn or winter, SAD development is thought to be associated with fewer hours of sunlight. Lack of sunlight might affect the circadian rhythm as well as the hormone and neurotransmitter balance [11]. Since north of 40 degrees latitude, no vitamin D is synthesised from sunlight in winter, vitamin D deficiency might be a potential cause of the development of SAD [12]. Germany is located north of 40 degrees latitude: Munich, for instance, is at 48 degrees and Hamburg at 53 degrees latitude.
Phototherapy
According to the German National Disease Management Guideline for unipolar depression, phototherapy is a first-line therapy for SAD patients [13]. Typically, white fluorescent light similar to natural daylight is used, while filtering out ultraviolet radiation. Patients should receive phototherapy 30 to 45 minutes daily at a light intensity of 10 000 lux [14]; ideally, the sessions should be in the mornings as soon as possible after getting up [15]. Typically, phototherapy is administered with a light box placed at a distance of 50 to 80 cm from the patient. Other options are devices which are attached directly to the head – so-called head-mounted units (HMUs) [16] – or phototherapy rooms in which patients spend time. It is important for patients to keep their eyes open during phototherapy since light is processed through a nerve tract referred to as retinopituitary tract [16].
Another form of phototherapy is dawn simulation, which involves gradually brightening the bedroom in which the patient is still sleeping from 0 to 300 lux in the mornings [17,18]. Dawn simulation is easier for patients to integrate into their daily routines, but existing studies have shown it to be less effective than phototherapy with a light box [19,20].
Phototherapy takes a few days or weeks to take effect. It should be continued throughout the winter months since discontinuing phototherapy can lead to a recurrence of depressive symptoms [5].
From the perspective of the general public, the relevant question is whether phototherapy is the effective and safe for the treatment of SAD. Therefore, the present report investigates the effectiveness and safety of phototherapy in comparison with no intervention or different interventions.
Vitamin D therapy
The body’s vitamin D needs are in part met through diet, but most of the vitamin D is produced in the skin when exposed to the sun’s ultraviolet B rays. A small study with 15 SAD patients showed better preliminary results for vitamin D supplements than for phototherapy after 1 week [21]. The National Disease Management Guideline for unipolar depression does not include any recommendations for or against vitamin D therapy in SAD [13]. However, given the importance of this issue to the German public, a systematic review of randomized controlled trials (RCTs) on the efficacy and safety of vitamin D therapy in SAD might provide insights on this topic. In the present report, the efficacy and safety of therapy with vitamin D3 (cholecalciferol), i.e. the most important physiological form of vitamin D, was examined in different pharmaceutical forms (tablets, drops) and dosages.
Second-generation antidepressants
Disturbances of the neurotransmitter system are suspected as a potential cause of SAD [22]. Therefore, SAD is often treated with second-generation antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors, noradrenergic and specific serotonergic antidepressants, selective noradrenaline reuptake inhibitors, or selective noradrenaline-dopamine reuptake inhibitors. According to the German National Disease Management Guideline for unipolar depression, SSRIs and phototherapy are recommended as the first-line treatment of SAD [13]. A Cochrane review on the effectiveness of second-generation antidepressants in the treatment of SAD identified 3 RCTs with the SSRI fluoxetine and found a numerical, but not statistically significant advantage of fluoxetine when compared to placebo [23]. This report does not rely on first-generation antidepressants (tricyclics, tetracyclics, monoamine oxidase inhibitors) as comparators, because their adverse event (AE) profile is worse than that of second-generation antidepressants.
Psychotherapy
Psychological vulnerability can play a role in the development of SAD. Therefore, psychotherapeutic interventions are viewed as potential treatment methods as well [24]. Research focuses particularly on cognitive behavioural therapy [25].
According to the Federal Joint Committee (G-BA) guideline on the conduct of psychotherapy, German statutory health insurance (SHI) covers the cost of the following psychotherapeutic services because the latter are based on a comprehensive theory of pathogenesis and have been proven to be effective in studies: psychoanalytic procedures, behavioural therapy, and systemic therapy [26,27]. This HTA report therefore focuses on these forms of psychotherapy as the comparator intervention.
1.3. Utilization
A survey in psychiatric departments and hospitals in Germany, Austria, and Switzerland showed that among the 86 responding institutions, 99% prescribe SAD patients antidepressants for the treatment of acute episodes of depression, 87% prescribe phototherapy, and 85% psychotherapy. In isolated cases, vitamin D therapy was recommended as well [28]. It is unknown whether and to what extent physicians in private practice prescribe SAD patients phototherapy, vitamin D therapy, antidepressants, or psychotherapy.
1.4. Concerns of those proposing the topic
A member of the public asked about the benefit of nondrug methods like phototherapy and vitamin therapy for patients with mild depression, such as winter depression. She was particularly interested in any effective alternatives to pharmacological antidepressants as well as in their advantages and disadvantages.
The ThemenCheck Medizin staff at IQWiG developed an HTA research question on the basis of this suggestion.