Raymond W. Lam, MD

Seasonal patterns of illness have been recognized since ancient times, but the concept of seasonality in psychiatric disorders has only gained prominence in the past two decades. This article will briefly review the diagnosis, treatment and pathophysiology of winter seasonal affective disorder (SAD). 

 diagnostic criteria classify SAD as a subtype or "course specifier" for recurrent major depressive episodes within major depressive disorder or bipolar disorder (BD). However, only a minority of patients are diagnosed as having BD (Lam, 1998b). 

The stability of the SAD diagnosis is similar to other depressive subtypes. Longitudinal studies of one to 10 years of follow-up showed that about 30% of patients continued to have seasonal episodes, about 20% were in remission (some because of treatment) and the remaining 50% had complex patterns that were not strictly seasonal (Schwartz et al., 1996; Thompson et al., 1995). Like other forms of depression, SAD is associated with significant morbidity and health service utilization (Eagles et al., 2002).

Although not included in the diagnostic criteria, SAD is also associated with so-called atypical vegetative symptoms, including carbohydrate craving, increased appetite, weight gain and hypersomnia/morning fatigue (Lam, 1998b; Oren and Rosenthal, 1992; Winkler et al., 2002) (Table). While these symptoms are also found in atypical depression, the rejection sensitivity commonly seen in atypical depression is not prominent in SAD (Tam et al., 1997). Atypical symptoms appear to be predictive of good response to light therapy (Terman et al., 1996). 

Studies using the Seasonal Pattern Assessment Questionnaire (SPAQ) estimated the prevalence of winter SAD in North America to be approximately twice that of Europe (Mersch et al., 1999). The differences between North American and European studies may be related to translation issues with the SPAQ, cultural response biases, genetic differences in seasonality, climatic variation or other factors. Regardless, studies using the SPAQ are likely to overestimate the prevalence of SAD because clinical diagnoses are not obtained. 

Community studies using diagnostic interviews estimated the prevalence of SAD by 

 criteria as 2.6% in Ontario, Canada (Levitt and Boyle, 2002), and 0.4% in the United States (Blazer et al., 1998). Seasonal affective disorder is more prevalent with higher (more northern) latitudes, but the correlation between latitude and prevalence is modest (Levitt and Boyle, 2002; Mersch et al., 1999).

Light therapy. An early meta-analysis of over two dozen studies using fluorescent light boxes found that bright light treatment was superior to control conditions (Terman et al., 1989). However, these findings were criticized for methodological limitations, including small sample sizes and use of dim light as placebo controls. 

Since then, however, two randomized, controlled trials with large sample sizes found that bright light therapy using fluorescent light boxes was superior to plausible placebo controls. 

(For clinical remission rates, please see the figure at <http://imaging.cmpmedica.com/CME/pt/content/sad.jpg>-Ed.)

 Terman et al. (1998) studied 144 patients randomly assigned to one of four treatments for two to four weeks: morning or evening bright light exposure (consisting of a 10,000 lux fluorescent light box for 30 minutes per day) or a negative ion generator that emitted either high-density or low-density negative ions (the placebo condition). Eastman and colleagues (1998) studied 96 patients randomized to four weeks of treatment with morning or evening bright light (consisting of a 6,000 lux fluorescent light box for 1.5 hours) or morning use of a deactivated negative ion generator (the placebo condition). In both studies, bright light was superior to the placebo condition in producing clinical remissions. 

Two subsequent meta-analyses have also supported the efficacy of light therapy (Lee and Chan, 1999; Thompson, 2002). This evidence resulted in the recommendation of light therapy as a first-line treatment for SAD in expert and consensus clinical guidelines (Bauer et al., 2002; Lam and Levitt, 1999). 

The recommended protocol for light treatment is 10,000 lux exposure, administered by a fluorescent light box with an ultraviolet filter, for at least 30 minutes per day in the early morning (Lam and Levitt, 1999). Less intense light usually requires greater duration of exposure for the same response, e.g., 3,000 lux for one to two hours. Naturalistic studies show a clinical response rate of about 67% using this protocol (Lam et al., 2000). Response to light therapy usually occurs rapidly, often within one week, although some patients may require two to four weeks of treatment before noticing a clear response. Patients generally relapse after light is stopped, so most patients must use the light box daily through the winter until the time of their natural spring remission. Patients then restart light therapy at the beginning of the next winter season, either prior to, or shortly after, onset of their symptoms. 

The side effects of light therapy include headache, eyestrain, nausea, agitation, sedation and dizziness (Kogan and Guilford, 1998). These are usually mild and time-limited or improve with reducing the intensity or duration of light exposure. There have been rare reports of switching to mania or hypomania, and thus patients with BD should be followed closely. Patients with bipolar I disorder should take mood stabilizers while treated with light.

Studies of chronic use of light therapy have not shown any toxicity or damage to the eyes (Gallin et al., 1995), but patients with ocular risk factors (including pre-existing retinal disease; systemic diseases that affect the retina such as diabetes mellitus or lupus; past cataract surgery; advanced age; and photosensitizing medications such as lithium, phenothiazine [Phenergan], melatonin, St. John's wort and antipsychotics such as thioridazine [Mellaril]) may have potential risks with bright light exposure. Hence, clinical guidelines suggest that these patients have a baseline ophthalmological evaluation and periodic monitoring (Lam and Levitt, 1999). 

Novel treatments for SAD include dawn simulation, in which bedroom lights are gradually turned on to simulate a summer dawn (Avery et al., 2001), high-density negative ions (Terman et al., 1998) and exercise (Pinchasov et al., 2000). Light therapy is also being investigated for nonseasonal conditions, including jet lag, shift work, circadian sleep disorders, bulimia nervosa, premenstrual depressive disorder and nonseasonal depressive disorders (including antepartum depression) (Kripke, 1998; Lam, 1998a; Oren et al., 2002). 

. Antidepressant medications have not been studied as extensively as light therapy in SAD. Selective serotonin reuptake inhibitors have the best-demonstrated evidence for medication efficacy. In one study, patients (n=68) were treated with fluoxetine (Prozac) 20 mg/day for five weeks (Lam et al., 1995). The clinical response rate (>50% improvement in depression scores) of fluoxetine (59%) was significantly superior to placebo (34%). Smaller controlled studies show that other medications, including moclobemide (Aurorix, Manerix), L-tryptophan and St. John's wort, may be effective treatments for SAD (Lam and Levitt, 1999). There are also case studies suggesting that bupropion (Wellbutrin), citalopram (Celexa), reboxetine (not approved for use in the United States) and tranylcypromine (Nardil, Parnate) are beneficial. Unfortunately, only one small study has directly compared light treatment to antidepressants (Ruhrmann et al., 1998). Forty patients with SAD were randomized to five weeks of bright light (3,000 lux fluorescent light box for two hours/day) or fluoxetine (20 mg/day). There were no significant differences in response between the two conditions. 

The choice of treatment between light and medications should be individualized for each patient (Lam and Levitt, 1999). Some patients may need treatment with both antidepressants and light therapy. 

The initial focus of the pathophysiology of SAD was on circadian rhythm theories, but research interest has expanded to include hypotheses related to abnormalities in monoamine neurotransmitters, personality and genetics (Lam and Levitan, 2000; Partonen and Magnusson, 2001). It should be noted that these major theories are not necessarily mutually exclusive, and SAD is likely a heterogeneous condition. A dual vulnerability hypothesis, in which SAD arises from the interaction of separate factors associated with seasonality and with depression, has been proposed to explain this heterogeneity (Lam et al., 2001b).

. Light is the strongest synchronizer of human circadian rhythms. Recent studies indicate that patients with SAD show changes in their overnight melatonin duration (an indicator of photoperiod) between summer and winter (Wehr et al., 2001). 

Lewy and colleagues (1988) have maintained that SAD is related to a phase delay of circadian rhythms relative to the sleep-wake cycle or external time. In this hypothesis, the timing of light treatment is critical because the magnitude and direction of light-induced circadian phase change is dependent on the timing of light exposure within the circadian cycle. Bright light exposure in the early morning, which produces a corrective phase-advance of circadian rhythms, should be more therapeutic in phase-delayed SAD patients than light exposure at other times of the day. 

Supporting studies found that SAD patients have phase-delayed circadian rhythms in core body temperature (Avery et al., 1997), melatonin onset (Lewy et al., 1987) and rest-activity cycles (Teicher et al., 1997). Other studies showed that morning light was more effective than evening light in treating SAD, with some studies finding a correlation between the degree of phase-advance and clinical response (Eastman et al., 1998; Lewy et al., 1998b; Terman et al., 2001). Additionally, low-dose melatonin, given at an appropriate circadian time to produce circadian phase-advances, has therapeutic effects in SAD (Lewy et al., 1998a).

However, other studies do not support the phase-delay hypothesis. Some studies did not find phase-delayed circadian rhythms in SAD or that response to light treatment is related to corrective phase-advances (Eastman et al., 1993; Oren et al., 1996; Thompson et al., 1997; Wirz-Justice et al., 1993). Although morning light is usually statistically superior to evening light in controlled comparisons, evening light is still more effective than placebo (Terman et al., 1998). Hence, a circadian mechanism may not be the sole cause of SAD. 

. A robust body of research also supports the role of neurotransmitters such as serotonin in the pathophysiology of SAD (Neumeister et al., 2001a). For example, neuroendocrine studies have shown evidence for serotonergic dysregulation in SAD. Drugs acting at different levels of the serotonin system, such as serotonin precursors (e.g., L-tryptophan), serotonin releasing agents (e.g., d-fenfluramine) and serotonin reuptake inhibitors (e.g., fluoxetine) are beneficial in the treatment of SAD. Conversely, rapid tryptophan depletion protocols (which reduce brain serotonin synthesis) can induce relapse of depressive symptoms in patients with SAD in short-term remission after light treatment (Lam et al., 1996; Neumeister et al., 1997). 

Other neurotransmitters, such as norepinephrine and dopamine, are also likely involved in SAD (Depue et al., 1990; Schwartz et al., 1997). Lower striatal density of dopamine transporter has been reported in SAD (Neumeister et al., 2001b). Catecholamine depletion protocols also cause a temporary relapse of depressive symptoms following light therapy (Neumeister et al., 1998) and summer remission (Lam et al., 2001a). Further research regarding the contribution of these neurotransmitters to the pathophysiology of SAD is anticipated. 

Winter SAD is a validated, common subtype of depressive illness that causes significant morbidity. There are evidence-based, effective treatments for SAD, including bright light therapy and antidepressant medications. The cause of SAD remains unknown, but there is consensus that its pathophysiology involves disturbances in circadian rhythms and neurotransmitter function. Unfortunately, there is still limited recognition of SAD by primary care clinicians and psychiatrists and limited use of light treatment in clinical settings.  Physicians should inquire about the periodicity of episodes in patients with recurrent depression to correctly identify and optimally treat SAD. 

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Articles

Many patients, particularly those living in colder climates, can suffer from seasonal affective disorder (SAD). What causes SAD and what are the treatment options for these patients?

Author | Raymond W. Lam, MD

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