The Can-SAD Study: A Randomized Controlled Trial of the Effectiveness of Light Therapy and Fluoxetine in Patients With Winter Seasonal Affective Disorder

Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
American Journal of Psychiatry (Impact Factor: 12.3). 06/2006; 163(5):805-12. DOI: 10.1176/appi.ajp.163.5.805
Source: PubMed


Light therapy and antidepressants have shown comparable efficacy in separate studies of seasonal affective disorder treatment, but few studies have directly compared the two treatments. This study compared the effectiveness of light therapy and an antidepressant within a single trial.
This double-blind, randomized, controlled trial was conducted in four Canadian centers over three winter seasons. Patients met DSM-IV criteria for major depressive disorder with a seasonal (winter) pattern and had scores > or = 23 on the 24-item Hamilton Depression Rating Scale. After a baseline observation week, eligible patients were randomly assigned to 8 weeks of double-blind treatment with either 1) 10,000-lux light treatment and a placebo capsule, or 2) 100-lux light treatment (placebo light) and fluoxetine, 20 mg/day. Light treatment was applied for 30 minutes/day in the morning with a fluorescent white-light box; placebo light boxes used neutral density filters.
A total of 96 patients were randomly assigned to a treatment condition. Intent-to-treat analysis showed overall improvement with time, with no differences between treatments. There were also no differences between the light and fluoxetine treatment groups in clinical response rates (67% for each group) or remission rates (50% and 54%, respectively). Post hoc testing found that light-treated patients had greater improvement at 1 week but not at other time points. Fluoxetine was associated with greater treatment-emergent adverse events (agitation, sleep disturbance, palpitations), but both treatments were generally well-tolerated with no differences in overall number of adverse effects.
Light treatment showed earlier response onset and lower rate of some adverse events relative to fluoxetine, but there were no other significant differences in outcome between light therapy and antidepressant medication. Although limited by lack of a double-placebo condition, this study supports the effectiveness and tolerability of both treatments for seasonal affective disorder and suggests that other clinical factors, including patient preference, should guide selection of first-line treatment.

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Available from: Raymond W. Lam, Oct 27, 2015
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    • "Seasonal fluctuations in transmitter expression in the human brain have been known for decades (Karson et al., 1984; Brewerton et al., 1988; Eisenberg et al., 2010). The highly effective treatment of seasonal affective disorder (SAD) with phototherapy (Lam et al., 2006; Pail et al., 2011) suggests that the photoperiod-dependent transmitter switching and behavioral changes observed in adult rats may be relevant in this context. PET scanning dopamine receptor expression in patients both with SAD and in remission could be revealing. "
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    ABSTRACT: Among the many forms of brain plasticity, changes in synaptic strength and changes in synapse number are particularly prominent. However, evidence for neurotransmitter respecification or switching has been accumulating steadily, both in the developing nervous system and in the adult brain, with observations of transmitter addition, loss, or replacement of one transmitter with another. Natural stimuli can drive these changes in transmitter identity, with matching changes in postsynaptic transmitter receptors. Strikingly, they often convert the synapse from excitatory to inhibitory or vice versa, providing a basis for changes in behavior in those cases in which it has been examined. Progress has been made in identifying the factors that induce transmitter switching and in understanding the molecular mechanisms by which it is achieved. There are many intriguing questions to be addressed. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Jun 2015 · Neuron
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    • "The effectiveness of LT is well established; response rates are high with minor adverse events (Golden et al., 2005; Lam et al., 2006). However, there is no consensus on the duration of treatment required to be effective; treatment duration ranges from 3 days to 8 weeks (Eastman et al., 1998; Lam et al., 2006; Meesters et al., 1994; Terman and Terman, 2005). Levitt and Levitan indicate that a shorter duration of LT (2 weeks) can be as effective as a longer duration (5 weeks), suggesting a faster response rate in the group receiving shorter LT duration (Levitt and Levitan, 2003). "
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    ABSTRACT: Background: Seasonal affective disorder (SAD) is characterized by recurrent episodes of major depression with a seasonal pattern, treated with light therapy (LT). Duration of light therapy differs. This study investigates retrospectively whether a single week of LT is as effective as two weeks, whether males and Females respond differently, and whether there is an effect of expectations as assessed before treatment. Methods: 83 women, and 25 men received either one-week (n=42) or two weeks (n=66) of LT were included in three studies. Before LT, patients' expectations on therapy response were assessed. Results: Depression severity was similar in both groups before treatment (F(1,106)=0.19 ns) and decreased significantly during treatment (main effect "time" F(2,105)=176.7, p.- 0.001). The speed of therapy response differs significantly in treatment duration, in favor of 1 week (F(2,105)=3.2, p= 0.046). A significant positive correlation between expectations and therapy response was found in women (rho=0.243, p=0.027) and not in men (rho = -0.154, ns). When expectation was added as a covariate in the repeated-measures analysis it shows a positive effect of the level of expectation on the speed of therapy response (F(2,104)=4.1, p=0.018). Limitations: A limitation is the retrospective design. Conclusions: There is no difference between 1 and 2 weeks of LT in overall therapy outcome, but the speed of therapy response differed between 1 week LT and 2 weeks LT. Together with the significant correlation between expectations and therapy response in women, we hypothesize that expectations play a role in the speed of therapy response.
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    • "Similarly, reversal of depressivelike behaviour by means of light therapy has also been demonstrated in other animal models of depression (Molina-Hernandez and Tellez-Alcantara 2000; Yilmaz et al. 2004; Schultz et al. 2008; Iyilikci et al. 2009). Clinically, depressed mood as found in seasonal and nonseasonal affective disorder is improved by light exposure (Golden et al. 2005; Terman and Terman 2005; Lam et al. 2006; Even et al. 2008). Depressed mood is associated with decreased metabolic activity in the prefrontal cortex and heightened metabolic activity in limbic areas of the brain (Videbech 2000; Seminowicz et al. 2004; Fitzgerald et al. 2008; Salerian and Altar 2012). "
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