Published November 17, 2017 MENTAL HEALTH Seasonal Affective Disorder: Focus on the Winter Blues Maria Macchiarulo, PharmD Candidate 2018St. John’s University, College of Pharmacy & Health SciencesQueens, New YorkErica Dimitropoulos, PharmDClinical Pharmacy Specialist, Mental HealthMinneapolis Veterans Affairs Health Care SystemMinneapolis, MinnesotaEmily M. Ambizas, PharmD, MPH, CGPAssociate Clinical ProfessorSt. John’s University, College of Pharmacy & Health SciencesQueens, New YorkClinical Specialist, Rite Aid PharmacyWhitestone, New York US Pharm. 2017:42(11):8-14. As the winter months approach, healthcare providers should be aware of a mental health condition that commonly appears at this time of year, known as seasonal affective disorder (SAD). Pharmacists in particular may be helpful in detecting this disorder, which can affect up to 10% of the population in a given year.1-3 SAD is a combination of biological and mood disturbances associated with seasonal patterns of depressive symptoms that usually occur during the fall and winter months (fall-onset SAD), with full remission of symptoms seen in the spring and summer months. SAD can also appear during the spring and summer months (spring-onset SAD), though this is less common.2,3 ETIOLOGYThe exact cause of SAD is still unknown. Primary hypotheses include disturbances of circadian rhythms, decreased sensitivity of the retina, and an imbalance of serotonin.4 The photoperiod hypothesis and phase-shift hypothesis are two theories based upon changes of the body’s circadian rhythms. Photoperiod refers to the dark/light cycle. The photoperiod hypothesis proposes that the shorter days in winter can result in depressive symptoms. Melatonin secretion acts as a signal for the photoperiod.4 Active secretion of melatonin occurs with decreased light; therefore, the shorter days can result in a longer duration of melatonin secretion during the winter, inducing SAD.4-6 The phase-shift hypothesis proposes that there is an optimal relationship between the timing of circadian rhythms, including melatonin production, body temperature and cortisol rhythms, and the timing of sleep.3,4 It is theorized that circadian rhythms drift with the later dawn of winter days, leading to a misalignment that may result in the depressive symptoms experienced by many people during this time of year.7 Retinal subsensitivity is another hypothesis for the occurrence of SAD; it is proposed that patients with SAD have an impaired retinal response. Normally, sensitivity of the retina increases during winter in response to lower levels of light. Patients with SAD who have diminished retinal sensitivity to light may experience dysfunction in their circadian rhythm. Retinal sensitivity anomalies have been reported in patients affected by SAD, and light therapy has been shown to normalize this dysfunction.8 Lastly, abnormal serotonin levels have also been shown to have a role in SAD. Increased serotonin transporter activity and subsequent decreased levels of serotonin have been found in patients with winter depression.9 DIAGNOSIS AND CLINICAL PRESENTATIONSAD is diagnosed according to the criteria in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5).10 A diagnosis of SAD is made by determining that the depressive symptoms have occurred for at least 2 years during the same season, that the symptoms disappear when the season is over, and that there is no other mental or physical health problem that could be the cause. SAD is not identified as a separate mood disorder but rather a subtype of major depressive disorder and bipolar disorder. Under the DSM-5, SAD is defined as recurrent mood changes with seasonal onset and remission. The challenge in identifying SAD patients is to differentiate them from patients who have nonseasonal depression. SAD and nonseasonal depression both consist of major depressive episodes involving low mood, loss of interest or pleasure in most or all activities, change in appetite or weight, low energy, insomnia or hypersomnia, poor concentration, thoughts of worthlessness or guilt, psychomotor retardation or agitation, and recurrent thoughts about death or suicide. Patients with SAD may also present with hyperphagia and carbohydrate cravings.6 SAD is distinguished from nonseasonal depression by the onset and remission of these depressive episodes at characteristic times of the year (fall-winter or spring-summer); with nonseasonal depression, there is no temporal relationship between recurrence or remission of depressive episodes. If patients present with severe depressive symptoms, including thoughts of suicide, they should be immediately referred to their physicians for appropriate treatment. TREATMENTLight TherapyThe least invasive, most natural, and most studied therapy for SAD is light therapy. Light therapy (also known as bright-light therapy or phototherapy) is defined as visible light that produces at least 2,500 lux at eye level.11 Light on a winter or rainy day is approximately ≤2,000 lux, whereas direct sunlight provides approximately 10,000 lux.11 Because increased secretion of melatonin has been associated with SAD, the mechanism behind light therapy is to diminish melatonin levels in the bloodstream when natural light is not sufficient to do so.6 Light therapy is also thought to normalize the phase-shift delay.6 Research has demonstrated that light therapy has a positive response rate of up to 70%.6 Light boxes that can emit full-spectrum light similar to natural sunlight are available for purchase. SAD symptoms may be relieved by counseling patients to use a light box the first thing in the morning, from the early fall until spring. Light therapy involves having patients position themselves 12 to 18 inches from a fluorescent light source of 2,500 to 10,000 lux for 30 minutes per day in the morning. Improvement has been shown to occur after 1 to 2 weeks of therapy.12 Treatment should be continued until remission is reached in the spring or summer; discontinuation of light boxes can lead to relapse of symptoms. Adverse effects that can be seen with light therapy include blurred vision, eye strain, or headache; however, these effects are mild and transient.13 Dawn simulation is another form of bright-light therapy. Dawn simulators slowly increase the intensity of light 30 minutes or more before awakening. Research has suggested that this type of therapy can improve sleep inertia, cognition, performance, and mood in patients suffering from SAD.11 When compared to bright-light therapy, dawn simulation reduced depression levels similarly; however, bright light may be more beneficial in patients with more severe symptoms of depression than dawn simulators.14 AntidepressantsThe use of second-generation antidepressants such as fluoxetine, paroxetine, sertraline, and bupropion have been shown to be beneficial in treating SAD. Since antidepressants take weeks to begin showing an effect, it is recommended to start therapy prior to expected onset of symptoms. Bupropion in particular has been demonstrated to be effective in preventing depressive symptoms of SAD when started early.15 The downside of antidepressant therapy is the associated side effects, including nausea, vomiting, headache, nervousness, anxiety, heart palpitations, and a risk of suicidal ideation with initiation of antidepressants in teens and young adults. Based on a Cochrane review, there is insufficient evidence to draw overall conclusions about the use of second-generation antidepressants for SAD.16 Therefore, antidepressants can be considered for patients whose symptoms severely impair social or occupational functioning.11 Natural Products/OTC SupplementsHypericum extract, better known as St. John’s wort, has been studied in patients with SAD and has been shown to provide effective antidepressant effects.6 One study evaluated the benefit of hypericum in 20 SAD patients and whether the combination with light therapy had any additional benefits.17 The results showed that hypericum alone without the use of bright-light therapy is effective for treating the symptoms of SAD. Hypericum extract in addition to light therapy demonstrated slightly greater beneficial effects; however, the effects were not significant. In a larger study evaluating hypericum alone and hypericum with light therapy, both groups showed significant improvement in depressive symptoms, especially anxiety, loss of libido, and insomnia.18 Before suggesting hypericum, it is important to gather all pertinent information about the patient, including past medical history and medication lists, as hypericum can induce the cytochrome P450 3A4 enzyme system and P-glycoprotein drug transporter. The concomitant use of hypericum can result in decreased efficacy of comedications such as HIV protease inhibitors, non-nucleoside reverse transcriptase inhibitors, cyclosporine, and hormonal contraceptives.19 Melatonin appears to be phase-delayed in SAD patients, mediating the effects of the shortening days in winter. By administering exogenous melatonin, it is thought that the winter depressive symptoms experienced by SAD patients may be reversed. One study evaluated the effect of 2 mg of a controlled-released melatonin product given for 3 weeks. Melatonin significantly improved quality of sleep and vitality in SAD patients.20 Melatonin given at bedtime may play a clinical role in mood regulation and is another option for patients suffering from SAD.21 Low levels of vitamin D have also been associated with SAD. Vitamin D levels may possibly alter serotonin levels in the brain, thereby affecting mood.22 Levels of vitamin D are affected by dietary intake and exposure to sunshine, and its synthesis exhibits cyclical variations throughout the year. Average serum vitamin D levels reach a maximum in August and a minimum in February.22 Although further studies are needed to confirm this relationship, patients can be advised to take vitamin D before winter darkness sets in to help prevent symptoms of depression.23 Adjunctive InterventionsWhen depressive symptoms are not severe, counseling patients on diet (limiting starches and sugars), exercise, managing stress, avoiding social withdrawal, and spending more time outdoors are all factors to improve depressive symptoms.24 Counseling patients on sleep hygiene and exercise is especially encouraged throughout their SAD treatment. Sleep hygiene consists of creating a regular light-dark cycle. Patients should set a time to routinely go to bed each night, the environment should be comfortable, and eating late dinners or drinking fluids prior to the desired sleep time should be avoided. As mentioned, SAD may be caused by phase-delayed circadian rhythms that, in turn, can initially cause insomnia. Counseling patients to minimize light exposure 2 hours prior to bedtime will facilitate sleep and also help shift circadian rhythms counterclockwise, or back to normal. Minimizing light exposure does not only refer use of light boxes or being in a lit room; it also encompasses blue light, such as that emitted by computer monitors, televisions, and cell phones.25 Daily walks outside, even on a cloudy day, may also be beneficial in improving symptoms of SAD, together with bright-light therapy. A study showed that along with light therapy, patients who took daily walks every morning for 60 minutes had a greater improvement in symptoms compared to patients using only artificial light therapy.26 Aerobic exercise (biking, running, swimming) has also been shown helpful in the management of SAD. There was a greater improvement of depressive symptoms in patients who performed aerobic exercise compared with no exercise or relaxation exercise. Counseling patients to exercise at least three times per week for a duration of 1 hour is another way to empower SAD patients to improve their symptoms.20,24,27 ConclusionPharmacists can play an important role in identifying, managing the treatment of, and counseling patients with SAD. First-line treatment for SAD is bright-light therapy. Certain dietary supplements have also demonstrated some effectiveness, and pharmacists can make suggestions and counsel patients regarding St. John’s wort, melatonin, and vitamin D. Patients should also be counseled on the importance of sleep hygiene, exercise, and diet. What are the symptoms of fall-onset SAD?People suffering from fall-onset SAD often feel irritable, tired or have low energy, feel as though their legs are heavy, oversleep, experience appetite changes, crave foods high in carbohydrates, and gain weight. Why does SAD happen?The exact cause of SAD is still not known, but it is thought to be related to changes in our bodies’ hormones and brain chemicals that occur as the length of daylight changes. Risk factors for SAD include being female, young, living farther from the equator, and having family members with depression or mood disorders. What can help? Exercise: Exercise and other types of physical activity are known to be helpful for relieving stress and anxiety. While it’s hard to find the energy to exercise when feeling down, exercise is a great way to boost mood and break the “rut” that people who suffer from SAD often describe. Change in Environment: People with SAD can benefit from a bright, open-spaced environment. We recommend keeping blinds open and sitting closer to windows, if possible. Also, it is important to get outside as often as able, even on cold or cloudy days. Sleep Hygiene: Sleep hygiene refers to certain behaviors that maximize the quality of sleep you get each night. These include going to bed and waking up at the same time every day (even on weekends), not eating or drinking fluids right before bed, and minimizing light and use of TV, laptop, or phone screens a few hours before bed. Incorporating these changes to your nightly routine can greatly improve your sleep and mood the next morning. Light Therapy (Phototherapy): Light therapy involves daily use of special bright lamps that mimic natural outdoor light. It has been shown to restore balance to the brain chemicals that are affected by SAD, thereby improving symptoms. It often takes a few days or weeks for this treatment to work. Light boxes range in brightness (measured in “lux”), light color, recommended length of session, size, and price; talk to your doctor or pharmacist about the best one for you. Vitamin D: We typically absorb vitamin D from the sun, so it is not uncommon for our levels to drop low during the winter months. For some people, vitamin D supplementation can improve SAD symptoms. Talk to your doctor or pharmacist about the right vitamin D product for you. Other Supplements: Some OTC supplements, such as St. John’s wort and melatonin, can be helpful for people suffering from SAD. These supplements may interact with other medications you are taking, so talk to your doctor or pharmacist if you’re thinking of trying them. Medications: For some people, prescription antidepressant medications can be helpful for managing SAD symptoms. Antidepressants often take several weeks to reach full benefit; talk with your doctor sooner rather than later. When to See a Doctor: If your symptoms become severe and begin to impact your daily functioning, or if you are having thoughts of harming yourself or others, see a doctor right away. The number for the National Suicide Prevention Lifeline is 1-800-273-8255. REFERENCES 1. Kurlansik SL, Ibay AD. Seasonal affective disorder. Am Fam Physician. 2012;86(11):1037-1041.2. Meesters Y, Gordijn MC. Seasonal affective disorder, winter type: current insights and treatment options. Psychol Res Behav Manag. 2016;9:317-327.3. Roecklein KA, Rohan KJ. Seasonal affective disorder. Psychiatry (Edgmont). 2005;2(1):20-26.4. Sohn C-H, Lam RW. Update on the biology of seasonal affective disorder. CNS Spectr. 2005;10(8):635-646.5. Wehr TA, Duncan WC, Sher L, et al. A circadian signal of change of season in patients with seasonal affective disorder. Arch Gen Psychiatry. 2001;58(12):1108-1114.6. Miller AL. Epidemiology, etiology, and natural treatment of seasonal affective disorder. 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