Effects of fluoxetine versus bright light in the treatment of seasonal affective disorder. The Can-SAD study: a randomized controlled trial of the effectiveness of light therapy and fluoxetine in patients with winter seasonal affective disorder. Multicenter, placebo-controlled study of fluoxetine in seasonal affective disorder. Therapeutic effects of escitalopram and reboxetine in seasonal affective disorder: a pooled analysis. Treatment of seasonal affective disorder with duloxetine: an open-label study. Escitalopram in seasonal affective disorder: results of an open trial.
Disturbances of serotonergic neurotransmission appear to be particularly important for the pathophysiology of winter depression. This study investigated whether fluoxetine has antidepressant effects comparable to bright light in the treatment of seasonal affective disorder (winter type).
                A randomized, parallel design was used with rater and patients blind to treatment conditions. One week of placebo (phase I) was followed by 5 weeks of treatment (phase II) with fluoxetine (20 mg per day) and a placebo light condition versus bright light (3000 lux, 2 h per day) and a placebo drug. There were 40 patients (20 in each treatment condition) suffering from seasonal affective disorder (SAD) according to DSM-III-R who had a total score on the Hamilton Depression Scale of at least 16.
                Forty patients entered phase II and 35 completed it (one drop-out in the fluoxetine group and four in the bright light group). Fourteen (70%) of the patients treated with bright light and 13 (65%) of those treated with fluoxetine were responders (NS). The remission rate in the bright light group tended to be superior (bright light 50%, fluoxetine 25%; P = 0.10). Light therapy improved HDRS scores significantly faster, while fluoxetine had a faster effect on atypical symptoms. Light treatment in the morning produced a significantly faster onset of improvement, but at the end of treatment the time of light application seemed not to be crucial.
                Both treatments produced a good antidepressant effect and were well tolerated. An apparently better response to bright light requires confirmation in a larger sample. 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. The authors investigated the efficacy and safety of fluoxetine in the treatment of winter seasonal affective disorder.
                Sixty-eight outpatients who met the DSM-III-R criteria for recurrent major depressive episodes, seasonal (winter) pattern, were randomly assigned to 5 weeks of treatment with fluoxetine, 20 mg/day (N = 36), or placebo (N = 32). The outcome measures included the 29-item modified Hamilton Depression Rating Scale, administered by experienced clinicians, and the self-rated Beck Depression Inventory; adverse events and safety data were also recorded. Clinical response was defined as a greater than 50% reduction in depression score between baseline and study termination.
                Both groups showed significant improvement. The fluoxetine group had lower depression scores at termination than the placebo group, but these differences did not achieve statistical significance. However, the rate of clinical response in the fluoxetine group (59%) was superior to that in the placebo group (34%). Post hoc analyses showed that the greatest fluoxetine responses were in the most markedly depressed patients and that overall response was greater for patients studied later in the season. Fluoxetine was well tolerated, and few subjects dropped out because of adverse events.
                On the basis of clinical response rate, fluoxetine appears to be an effective, well-tolerated treatment for seasonal affective disorder. Because the differences between fluoxetine and placebo in the continuous outcome measures did not reach statistical significance, further studies with larger study groups and longer treatment periods are required to conclusively demonstrate efficacy of fluoxetine for seasonal affective disorder. The monoaminergic neurotransmitters serotonin and noradrenaline have both been implicated in the pathogenesis of seasonal affective disorder (SAD). However, the differential therapeutic value of selective serotonin reuptake inhibitors (SSRI) and selective noradrenaline reuptake inhibitors (NARI) in SAD has not been assessed until now. This study compares data from two open-label trials with similar methodology investigating the SSRI escitalopram and the NARI reboxetine. 20 SAD patients were treated with escitalopram (10-20mg) and 15 patients received treatment with reboxetine (fixed dosage: 8mg) over 6 weeks. Ratings included the structured interview guide for the Hamilton depression rating scale, SAD version (SIGH-SAD), the clinical global impression of severity (CGI-S) and improvement (CGI-I) and the UKU side effect rating scale. Treatment led to a significant reduction in SIGH-SAD score, CGI-S and CGI-I after one week in the reboxetine group and after two weeks in the escitalopram group. SIGH-SAD score was significantly lower in the reboxetine group at weeks 1, 2 and 4 but not at the end of the study. The response rate (SIGH-SAD <50% of baseline value) and the remission rate (SIGH-SAD <8) were not significantly different after 6 weeks of treatment, but the time to response and to remission was significantly shorter in the reboxetine group. The number and severity of side effects were higher in patients treated with reboxetine at all time points. Thus escitalopram and reboxetine were equally effective in treating SAD on all primary and secondary outcome measures. Reboxetine displayed a faster onset of action, but was associated with more pronounced side effects. Further studies comparing SSRI and NARI in SAD are warranted. The aim of this observational study was to evaluate the effects of duloxetine in the treatment of seasonal affective disorder (SAD).
                26 SAD patients were treated with open-label duloxetine 60-120 mg per day over 8 weeks. Ratings included the Structured Interview Guide for the Hamilton Depression Rating Scale (SAD version; SIGH-SAD) and the Clinical Global Impression (CGI). To estimate treatment effects on social functioning in SAD we employed the Social Adaptation Self Evaluation Scale (SASS), the Sheehan Disability Scale (SDS), and assessments of days lost due to illness and days with reduction in productivity.
                Duloxetine led to a significant improvement (p<0.001) of SIGH-SAD, CGI severity, SASS, and SDS scores. Days lost due to illness and days with reduction in productivity were significantly diminished during treatment (p<0.001). Treatment with duloxetine over 8 weeks yielded a response rate (SIGH-SAD<50% of baseline value) of 80.8% and a remission rate (SIGH-SAD<8) of 76.9% in the intention to treat sample. The drop-out rate due to side effects was 15.4%.
                Our preliminary results indicate that duloxetine might be effective and able to ameliorate the negative social consequences of SAD. The aim of this study was to evaluate the efficacy and tolerability of escitalopram in the treatment of seasonal affective disorder (SAD, fall-winter depression).
                Twenty SAD patients were included in an 8-week drug surveillance. Patients were treated with open-label escitalopram at a dosage of 10 to 20 mg per day. Efficacy assessments included the Structured Interview Guide for the Hamilton Depression Rating Scale (SAD version; SIGH-SAD), the Clinical Global Impression (CGI) and the Social Adaptation Self Evaluation Scale (SASS). Side effects were monitored with the UKU Side Effect Rating Scale.
                From week 2 onwards, escitalopram significantly reduced SIGH-SAD score and CGI severity score (p<0.001). From week 4 onwards, the SASS score was also significantly improved (p<0.05). The response rate (SIGH-SAD<50% of baseline value) after treatment for 8 weeks was 95%, the rate of remission (SIGH-SAD < or =7) was 85%. Side effects were mild to moderate and did not lead to cessation of therapy.
                These results suggest that escitalopram is an efficacious and altogether safe treatment for seasonal depression.