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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    • "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.
    Neuron 06/2015; 86(5):1131-1144. DOI:10.1016/j.neuron.2015.05.028 · 15.05 Impact Factor
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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.
    Journal of Affective Disorders 09/2014; 166:343-346. DOI:10.1016/j.jad.2014.05.034 · 3.38 Impact Factor
    • "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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    ABSTRACT: Animals subjected to maternal separation display behavioural and endocrine disturbances, as well as structural and functional changes in the prefrontal cortex and limbic areas. The aim of the present study was to determine the effect of maternal separation and treatment with either chronic constant light exposure or anti-depressant (escitalopram) on proteins in the prefrontal cortex. Four experimental groups of male Sprague-Dawley rats were subjected to (1) normal rearing, (2) maternal separation (3 h per day from postnatal day 2 (P2) to P14), (3) maternal separation followed by chronic light exposure (P42-P63) or (4) maternal separation followed by treatment with the anti-depressant drug, escitalopram (P68-P100). Groups 1-3 were treated with saline as vehicle control for the escitalopram-treated group. At P101, all rats were decapitated, and the prefrontal cortex was collected and stored at -80 °C. Tissue from three rats per group was pooled and proteins determined by isobaric tagging for relative and absolute quantification using matrix-assisted laser desorption/ionisation tandem mass spectrometry. Maternal separation led to disruptions in the prefrontal cortex that included hypometabolism by decreasing energy-related proteins (creatine kinase B, aconitate hydratase), decreased cell signalling (synapsin I, calmodulin, 14-3-3 protein epsilon) and impaired plasticity (spectrin, microtubule-associated protein). Maternal separation also increased dihydropyrimidinase-related protein/collapsin response mediator protein (CRMP) and myelin proteolipid protein. Exposure of maternally separated animals to constant light during adolescence reversed the hypometabolic state by increasing energy-related proteins in the prefrontal cortex and increasing cell signalling and cytoskeletal proteins and decreasing the expression of CRMP. Escitalopram had similar effects to light by increasing ATP synthase in maternally separated rats and dissimilar effects by increasing 2',3'-cyclic-nucleotide 3'-phosphodiesterase and myelin proteolipid protein. Constant light exposure during adolescence reversed a range of protein changes in the prefrontal cortex of rats exposed to early maternal separation. The most prominent reversal by light treatment of maternal separation-induced protein increases in the prefrontal cortex was the expression of CRMP which impairs plasticity and neuronal signalling. The effects of light treatment overlapped partially with the effects of escitalopram.
    Journal of Molecular Neuroscience 07/2013; 51(3). DOI:10.1007/s12031-013-0071-z · 2.34 Impact Factor
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