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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by jrbecker on October 19, 2004, at 9:10:49
http://www.medscape.com/viewarticle/491504?rssLight Therapy as Effective as Fluoxetine for Seasonal Affective Disorder
Oct. 18, 2004 (Montreal) — Light therapy is as safe and effective as fluoxetine for the treatment of seasonal affective disorder (SAD), according to a Canadian randomized trial. Clinicians, therefore, should consider light therapy for patients who may prefer this modality, researchers report.
"It's always a struggle to bring nonpharmacological treatments into mainstream medicine," Raymond W. Lam, MD, FRCPC, FAPA, told Medscape. "...so, we try to stress that there's a very effective [nonpharmacologic] treatment out there for winter depression — light therapy, and it's a shame that more patients aren't getting access to it because physicians aren't aware of it."
Dr. Lam is a professor and head of the Division of Clinical Neuroscience, Department of Psychiatry at the University of British Columbia (UBC) and director of the Mood Disorders Clinic at UBC Hospital in Vancouver, Canada. He presented the results of his latest trial on the use of light therapy in SAD here at the 54th annual meeting of the Canadian Psychiatric Association.
The currently accepted light therapy for this condition is use of a 10,000 lux white fluorescent lightbox 30 minutes daily in the early morning, usually between 7 and 8 am. Previous randomized controlled trials have demonstrated the benefits of light therapy and selective serotonin reuptake inhibitor (SSRIs) such as fluoxetine in the treatment of SAD. The question remains, said Dr. Lam, if one is superior to the other with respect to efficacy and adverse effects.
"Because of the lack of data and the importance of the clinical question, we embarked on a large, randomized clinical trial to directly compare light treatment with fluoxetine," Dr. Lam said during his talk.
For this multicenter trial, 96 patients with moderate to severe SAD were randomized to receive eight weeks of treatment with either 20 mg of fluoxetine daily plus 30 minutes daily of placebo 100 lux white fluorescent light in the early morning or a placebo pill plus 30 minutes daily of active 10,000 lux white fluorescent light in the early morning. Patients were studied over three winter seasons. "This is the longest light treatment study in the field," Dr. Lam said.
Patients were diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for SAD, and their depressive symptoms were measured using Hamilton Rating Scales (HAM) for Depression: HAM-17 and HAM-24. Participants in the trial had HAM-17 scores greater than 20 or HAM-24 scores greater than 22 to ensure they had moderate to severe SAD. Adverse effects were assessed using a structured questionnaire that included specific questions about individual adverse events.
During eight weeks of treatment, the mean change in HAM-24 scores was similar for both groups of patients, except for a significantly superior improvement in the light therapy group at week 1 (P </= .01).
After eight weeks, 67% of patients in both groups had responded to therapy, defined as a greater than 50% improvement in HAM-24 score. Also, 50% of patients in the light therapy group and 54% in the fluoxetine group experienced remission, defined as having a HAM-24 score less than 9. Results were similar when the most severely depressed patients were examined separately, which refutes suggestions in the literature that light therapy is only effective for more mild cases of SAD.
"Based on the primary outcome measures, there was no difference in the effect between light treatment and fluoxetine over the course of the eight weeks," said Dr. Lam.
Patients in both groups tolerated their therapies well. The only statistically significant differences were slightly higher incidences of agitation, chest tightness, palpitations, sleep disturbance, and nausea in the fluoxetine group. Overall, similar numbers of patients experienced at least one treatment-emergent adverse effect in each group.
Given their similar efficacy and tolerability, Dr. Lam suggested that factors to consider when selecting light vs drug therapy for patients with SAD include patient preference, convenience, and cost.
A free downloadable resource package for physicians on how to use light therapy in clinical practice is available at Dr. Lam's institution's Web site at http://www.ubcsad.ca. It includes information on how to obtain and use a lightbox, as well as patient education and assessment materials and additional information about the effectiveness of light therapy.
The study was funded by the Canadian Institutes of Health Research.
CPA 54th Annual Meeting: Paper PS7D. Presented Oct. 16, 2004.
Reviewed by Gary D. Vogin, MD
Alison Palkhivala is a freelance writer for Medscape
Posted by SLS on October 19, 2004, at 11:17:38
In reply to News: Light Therapy as Effective as Prozac for SAD, posted by jrbecker on October 19, 2004, at 9:10:49
It was my impression that, for properly diagnosed seasonal affective disorder, light-box therapy was substantially more effective than antidepressants. Have you ever read anything supporting this?
- Scott
Posted by ravenstorm on October 19, 2004, at 12:11:11
In reply to Re: News: Light Therapy as Effective as Prozac for SAD, posted by SLS on October 19, 2004, at 11:17:38
I have severe seasonal affective disorder. Light boxes do not help it. If I am able to get out of the midwest to the sun somewhere, I feel amazingly better within a very short period of time.
Posted by SLS on October 19, 2004, at 12:17:02
In reply to Re: News: Light Therapy as Effective as Prozac for SAD, posted by ravenstorm on October 19, 2004, at 12:11:11
> I have severe seasonal affective disorder. Light boxes do not help it. If I am able to get out of the midwest to the sun somewhere, I feel amazingly better within a very short period of time.
Do antidepressants help at all?
- Scott
Posted by jrbecker on October 19, 2004, at 14:37:25
In reply to Re: News: Light Therapy as Effective as Prozac for SAD, posted by SLS on October 19, 2004, at 11:17:38
> It was my impression that, for properly diagnosed seasonal affective disorder, light-box therapy was substantially more effective than antidepressants. Have you ever read anything supporting this?
>
>
> - ScottUnfortunately I'm not well educacted on the condition of SAD, but I wouldn't be surprised to know that most antidepressants aren't as effective for SAD as light therapy.
But I guess the big question is what drugs [besides fluoxetine] did past trials actually compare to light therapy. Considering that seasonal affective disorder's core symptomology is increased eating and lethargy, I'm not surprised to hear that most antidepressants aren't really that efficacious. However, I wonder how Wellbutrin or more stimulating meds stack up to light therapy. Wellbutrin is actually undergoing clinical trials for SAD, so I'm sure there will be some data that comes out of that.
I guess I should note that light therapy modestly helps my own atypical symptoms during the darker/colder months.
But getting outside rather than sitting in front of the light box seems to do me a lot more good [probably b/c of the exercise as well]. One study found that two-and-a-half hours under a lightbox is equal to one hour outside in the winter sun. So get outside!!
http://www.nmha.org/infoctr/factsheets/27.cfm
Of note, I also read that SAD symptoms aren't just brought on by lack of light, but also by the brain's reduced temperature in the area of the brain responsible for the circadian rhythym [the SCN]. So it's important to bundle up -- especially your head.
Posted by yznhymer on October 19, 2004, at 16:01:32
In reply to Re: News: Light Therapy as Effective as Prozac for SAD, posted by ravenstorm on October 19, 2004, at 12:11:11
> I have severe seasonal affective disorder. Light boxes do not help it. If I am able to get out of the midwest to the sun somewhere, I feel amazingly better within a very short period of time.
That's interesting. For years I wasn't sure whether I had atypical depression or SAD. Living in the northeast, I'd struggle through the winters and perk up May through September. But, coincidentally, the Fall was also when many of the most depressing aspects of my life would intensify, so it was hard to sort things out.
In any case, I found no real relief with a light box or visor (meds haven't been that great a solution either) but the amount of natural sunlight I get continues to make a huge difference in how I feel on any given day. On cloudy days I am totally devoid of energy, never really wake up, symptoms of depression deepen and I feel like !$#~!. I'm driven to self-medicate with carbohydrates and want to do nothing but hybernate.
Sunny days, however, are like a mental B-12 shot. In recent years my depression stretches through every month on the calendar, so I don't think SAD is my DX. Nevertheless, exposure to sunlight remains critical to whatever snatches of normalcy I can grab onto.
Mark
Posted by Dave001 on October 19, 2004, at 20:43:16
In reply to Re: News: Light Therapy as Effective as Prozac for SAD » ravenstorm, posted by yznhymer on October 19, 2004, at 16:01:32
> > I have severe seasonal affective disorder. Light boxes do not help it. If I am able to get out of the midwest to the sun somewhere, I feel amazingly better within a very short period of time.
>
> That's interesting. For years I wasn't sure whether I had atypical depression or SAD. LivingI don't think that SAD and depression are mutually exclusive. There is evidence that everyone responds similarly to the seasonal changes. Most likely, those with "SAD" are just more sensitive to the changes, and/or more susceptible to depression.
in the northeast, I'd struggle through the winters and perk up May through September. But, coincidentally, the Fall was also when many of the most depressing aspects of my life would intensify, so it was hard to sort things out.
>I am the same way. Living in the Boston area doesn't help, either. It sure *feels* like there is a lot more too it than just light, too. However, it is important to remember that not only are the daylight hours fewer during winter, but the *intensity* of the sunlight is also much weaker.
> In any case, I found no real relief with a light box or visor (meds haven't been that great a solution either) but the amount of natural
Yeah, I haven't noticed anything from light boxes either. One reason I question the efficacy of light boxes, is that the typical amount of light exposure "prescribed" probably isn't equivalent to much more than half an hour or so outside on a cloudy winter day. OK, it's probably more than that, but not a lot.
> sunlight I get continues to make a huge difference in how I feel on any given day. On cloudy days I am totally devoid of energy, never really wake up, symptoms of depression deepen and I feel like !$#~!. I'm driven to self-medicate with carbohydrates and want to do nothing but hybernate.
>
> Sunny days, however, are like a mental B-12 shot. In recent years my depression stretchesDamn. That's the first time I've seen such analogy with vitamin B-12 before. :-)
> through every month on the calendar, so I don't think SAD is my DX. Nevertheless, exposure to
One thing you have to realize is that most psychiatric diagnoses only describe symptoms, and say nothing of the etiology behind those symptoms.
The only distinction between SAD and "normal" depression is that the former occurs in a circumscribed pattern dependent upon seasonal changes. But it is entirely plausible and probably not at all uncommon for one to experience depression year-round with a worsening of symptoms during the dark and cold months.There is some evidence showing a link between (increased) melatonin levels and SAD, so you probably should avoid supplemental melatonin.
Dave
Posted by jrbecker on October 20, 2004, at 14:43:39
In reply to Re: News: Light Therapy as Effective as Prozac for, posted by Dave001 on October 19, 2004, at 20:43:16
here's one for provigil that looked somewhat promising...
Journal of Affective Disorders
Volume 81, Issue 2 , August 2004, Pages 173-178
doi:10.1016/S0165-0327(03)00162-9
Copyright © 2003 Elsevier B.V. All rights reserved.Modafinil treatment in patients with seasonal affective disorder/winter depression: an open-label pilot study
Leslie Lundt,
Foothills Psychiatry, 223 West State Street, Boise, ID 83702, USA
Received 7 February 2003; accepted 21 April 2003. Available online 14 August 2003.
Abstract
Background: Hypersomnia is a cardinal symptom of seasonal affective disorder/winter depression. This open-label pilot study assessed modafinil, a novel wake-promoting agent, as treatment for seasonal affective disorder/winter depression. Methods: Total daily modafinil dose was 100 mg (all patients week 1), and 100 mg or 200 mg split dose (weeks 2–8). Efficacy assessments (weeks 1, 2, 5, and 8) included the Structured Interview Guide for the Hamilton Depression (HAM-D) Rating Scale, Seasonal Affective Disorder Version (SIGH-SAD), Montgomery–Asberg Depression Rating Scale (MADRS), Clinical Global Impression of Change (CGI-C), Fatigue Severity Scale (FSS), and Epworth Sleepiness Scale (ESS). Results: Thirteen patients (11 women; mean age, 41 years) were enrolled, 12 were evaluable for efficacy (100 mg dose, five patients; 200 mg dose, seven patients), and nine completed treatment. Modafinil significantly improved winter depression as shown by reductions from baseline in mean SIGH-SAD at week 1 (P<0.01) through week 8 (P<0.001 weeks 2–8) and MADRS total scores from week 2 through week 8 (P<0.01 for all). At week 8, mean SIGH-SAD total score was 17.1 (versus 37.2 at baseline, P<0.001), and mean MADRS total score was 13.3 (versus 26.9 at baseline, P<0.01). Modafinil significantly improved overall clinical condition at all time points (P<0.001). The response rate was 67% on the SIGH-SAD (29 item), HAM-D (21 item), and MADRS, and 100% on eight atypical SIGH-SAD items. Modafinil significantly reduced fatigue (FSS) and improved wakefulness (ESS) from weeks 2 through 8 (P<0.01). Modafinil was well tolerated. Limitations: This was an open-label, single site study. Conclusions: Modafinil may be an effective and well-tolerated treatment in patients with seasonal affective disorder/winter depression.Author Keywords: Modafinil; Seasonal affective disorder; Winter depression; Fatigue; Wakefulness
Article Outline
1. Introduction
2. Methods
2.1. Patient selection
2.2. Study design and treatment
2.3. Assessments
2.4. Statistical analysis
3. Results
3.1. Patients and drug treatment
3.2. Efficacy
3.3. Safety
4. Discussion
Acknowledgements
References
1. Introduction
Seasonal affective disorder is a clinical subtype of Major Depressive Disorder or the depressive phase of Bipolar Disorder in which the onset and remission of depressive episodes recur at certain times of the year (DSM-IV; American Psychiatric Association, 1994).The prevalence rates reported for seasonal affective disorder vary widely, ranging from <1 to 9.7% ( Magnusson, 2000). Seasonal affective disorder is typically manifested as winter depression, in which patients experience depressive episodes during the fall and winter, with full remission during the spring and summer. Cardinal symptoms of seasonal affective disorder include depressed mood, profound lack of energy, hypersomnia, and weight gain ( Partonen and Lonnqvist, 1998 and Rosenthal et al., 1984).Patients with seasonal affective disorder experience an exacerbation of symptoms as hours of daylight decrease. This may be associated with inadequate morning light exposure, eventually leading to misalignment of the internal circadian rhythms responsible for promoting sleep and wakefulness and the habitual sleep–wake schedule. Daily bright-light treatment sessions are utilized as a first-line treatment for seasonal affective disorder (Terman and Terman, 1999). While a positive clinical response can appear within 1 week of initiation of phototherapy, this treatment has limitations associated with inconvenience and need for optimization to maintain effect. Side effects associated with bright-light treatment (>5%) include nausea, jitteriness, headache, and eye irritation ( Terman and Terman, 1999).
Antidepressant therapy is an alternative treatment that affords logistical advantages over phototherapy, with apparently comparable therapeutic benefit (Ruhrmann et al., 1998). Fluoxetine, moclobemide, and reboxetine have shown efficacy in patients with winter depression ( Lam et al., 1995; Partonen and Lonnqvist, 1996 and Hilger et al., 2001). Although antidepressants present an effective alternative to bright light treatment, no pharmacotherapy targeting the cardinal symptoms of seasonal affective disorder has emerged as a first-line treatment.
The novel wake-promoting agent modafinil may represent an alternative to both bright light and antidepressant therapy. Based on data from animal models, modafinil is thought to work selectively through the sleep–wake centers of the brain to promote wakefulness (Scammell et al., 2000). Modafinil has been shown to significantly improve wakefulness without adversely affecting nighttime sleep in a number of clinical models, including narcolepsy ( US Modafinil in Narcolepsy Multicenter Study Group, 2000), and to improve wakefulness or reduce fatigue in major depressive disorder ( DeBattista et al., 2001; DeBattista et al., 2003 and Menza et al., 2000).
The wake-promoting and fatigue-reducing effects of modafinil in patients with major depressive disorder and residual fatigue or sleepiness suggest that modafinil may be useful in managing the hypersomnolence, fatigue, and perhaps other atypical symptoms that characterize seasonal affective disorder. The objective of the present study was to evaluate the efficacy and safety of modafinil in patients with seasonal affective disorder/winter depression.
2. Methods
2.1. Patient selection
Eligible patients, aged 18 to 65 years, were required to fulfill the criteria for seasonal affective disorder as defined in DSM-IV (American Psychiatric Association, 1994). Patients were selected from individuals responding to newspaper advertisements. Patients also had to have at least moderate fatigue (≥4 on the Fatigue Severity Scale [FSS]) ( Krupp et al., 1989). Patients’ wake time in the morning had to be within 30 min of their normal wake time when they were not depressed. Patients were required to be stimulant-free for 30 days and not have used light or melatonin therapy within 2 weeks of the screening visit.Patients were excluded from study participation if they had a diagnosis of any Axis I disorder other than seasonal affective disorder or if they were considered by the investigator to be a significant risk of suicide. Patients could not have uncontrolled medical disorders, clinically significant drug sensitivity or drug allergy to stimulants, or medical contraindications to the use of modafinil. Patients could not have a history of drug abuse, including alcohol, within the past year, and, if female, be pregnant or lactating, or received modafinil previously. Written informed consent was obtained from each patient before study entry, and an independent review board approved the protocol.
2.2. Study design and treatment
This single-center, 8-week, open-label study evaluated the efficacy and safety of oral modafinil (100 and 200 mg total daily doses) in patients with seasonal affective disorder. The study was conducted during winter months, with first and last patient treatment dates of January 11 and March 29, 2002, respectively. The modafinil dose for all patients was 100 mg/day for the first week. The modafinil dose for the remainder of the study could either remain at 100 mg/day or be increased to 200 mg/day (100 mg between 7 and 9 a.m. with breakfast and 100 mg at midday with lunch) based on the efficacy and tolerability to the 100 mg/day modafinil dose during study week 1, as determined by the patient and physician. The modafinil dose was raised to 200 mg/day if the patient was still fatigued or sleepy at the end of week 1. Antidepressants, excluding monoamine oxidase inhibitors and tricyclic antidepressants, at dosages that had been stable for at least 30 days, were allowed.2.3. Assessments
Efficacy evaluations were conducted at baseline and weeks 1, 2, 5, and 8 (or termination visit). Assessments included the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorder Version (SIGH-SAD), including its components, the 21-item Hamilton Depression Rating Scale (HAM-D) and the 8 atypical items (Williams et al., 1994), the Montgomery–Asberg Depression Rating Scale (MADRS; Montgomery and Asberg, 1979), and the Clinical Global Impression of Change (CGI-C; Guy, 1976). Changes in fatigue were assessed using the nine-item FSS. Subjective sleepiness was assessed using the eight-item Epworth Sleepiness Scale (ESS; Johns, 1991). An experienced rater in our practice performed the efficacy evaluations.Safety was assessed by observed and spontaneously reported adverse events. Physical examinations and neurological examinations were performed at the screening visit and at week 8 (or early termination). Vital signs were monitored at all visits.
2.4. Statistical analysis
Efficacy analyses include all enrolled patients who had taken at least one dose of modafinil and had at least one postbaseline efficacy measurement in addition to a baseline efficacy measurement for a given efficacy variable. These comprise the intent-to-treat population, for whom missing data were estimated by a last-observation carried forward (LOCF) technique. Response rate was calculated as the percent of patients completing the study with a ≥50% reduction in the SIGH-SAD and the MADRS scores from baseline to week 8.Efficacy variables at all scheduled visits, including last visit, were compared with the baseline values using the paired t-test for normally distributed data or Wilcoxon signed rank test for non-normal data. Additionally, we calculated the percentages of patients who had excess fatigue (FSS score ≥4) and/or moderate to severe sleepiness (ESS score ≥10) at baseline and at week 8 or last visit. The statistical comparison was two-tailed with a significance level set at 0.05.
Patients receiving at least 1 dose of study drug were included in the safety analysis. Clinical laboratory and vital signs data were summarized using descriptive statistics. Summary statistics were also calculated for the modafinil dose being taken at each visit.
3. Results
3.1. Patients and drug treatment
Demographic and disease-specific characteristics at baseline are presented in Table 1. Nine patients completed the study (one patient withdrew consent, and one patient withdrew from the study due to mild headache and dizziness; two patients, both taking modafinil concomitantly with antidepressants, withdrew due to insufficient efficacy, at weeks 1 and 2, respectively). The final total daily modafinil dose was 100 mg for five patients and 200 mg for seven patients.
Table 1. Demographic and baseline characteristics: all enrolled patients
CGI-S=Clinical Global Impression of Severity; FSS=Fatigue Severity Scale; ESS=Epworth Sleepiness Scale.
3.2. Efficacy
Modafinil rapidly and significantly improved seasonal affective disorder, as assessed by a significant reduction on the SIGH-SAD Total score at week 1 (P<0.01). This reduction was progressive and sustained through week 8 (P<0.001; Fig. 1). Modafinil also significantly improved scores on both the 21-item HAM-D and the eight atypical symptoms components of the SIGH-SAD from weeks 1 to 8, compared with baseline (Fig. 1). The improvement was similar in those receiving modafinil as monotherapy and modafinil adjunct therapy. Additionally, modafinil treatment significantly improved seasonal affective disorder from weeks 2 through 8 as shown by MADRS total score (P<0.01; Table 2). Two thirds of patients who completed 8 weeks of modafinil treatment were considered responders on the total SIGH-SAD (29 items), HAM-D (21 items), and MADRS. The response rate for the eight atypical items component of the Total SIGH-SAD was 100%.
(6K)Fig. 1. Clinical response to modafinil treatment of 12 patients shown as mean (±S.E.M.) scores on the Structured Interview Guide for the Hamilton Depression Rating Scale Seasonal Affective Disorder Version (SIGH-SAD). Scores for the 29-item Total SIGH-SAD (&z.cirf;) and its components, the 21-item HAM-D () and the eight atypical items (), are shown separately. Data are based on LOCF analysis. a, P<0.01; b, P<0.001, compared with baseline, for the 29-item total SIGH-SAD, the 21-item HAM-D and the eight atypical items.
Table 2. Modafinil improves seasonal affective disorder/winter depression, fatigue, and sleepiness
MADRS=Montgomery–Asberg Depression Rating Scale. FSS, Fatigue Severity Scale; ESS, Epworth Sleepiness Scale.
Modafinil significantly improved overall clinical condition as assessed by the CGI-C from weeks 1 to 8 (P<0.001). Improvement on the CGI-C was rapid; 10/12 patients improved at week 1, and 11/12 patients improved at week 2. This improvement in overall clinical condition was sustained throughout treatment.Modafinil significantly reduced fatigue and improved wakefulness at week 2; these effects were progressive and sustained through week 8 (P<0.01, see FSS and ESS; Table 2). Modafinil reduced the percentage of patients who were both excessively fatigued (FSS≥4) and excessively sleepy (ESS≥10) from 75% at baseline to 17% at week 8.
3.3. Safety
Eleven of the 13 patients enrolled in the study experienced at least one adverse event. The most common adverse event was headache (38%).The remaining adverse events reported by more than 1 patient were: dry mouth (30%), dyspepsia (23%), and eructation (15%).All adverse events were rated as mild or moderate in nature, with the exception of one patient’s headache that was rated as severe. This headache, considered possibly related to modafinil treatment, resolved in 1 day with concomitant ibuprofen treatment. No serious adverse events were reported during the course of the study. One patient experienced increased blood pressure. This was detected at the patient’s physical examination during the final study visit, and was considered at the time to be unrelated to modafinil treatment as she had previously had pregnancy-related hypertension and was taking sympathomimetics as needed for allergies.
4. Discussion
Modafinil significantly improved seasonal affective disorder/winter depression, as demonstrated on the SIGH-SAD Total Score, the MADRS, and CGI-C. The improvement in symptoms assessed by these scales was rapid, achieving statistical significance after 1 or 2 weeks, and was sustained throughout modafinil treatment. Modafinil also significantly reduced fatigue and improved wakefulness.The response rate (67%) observed on Total SIGH-SAD, the HAM-D, and the MADRS in the present study is comparable to the response rates reported for other treatments, including bright light, fluoxetine, meclobemide, and reboxetine, in patients with seasonal affective disorder (Ruhrmann et al., 1998; Lam et al., 1995; Partonen and Lonnqvist, 1996 and Hilger et al., 2001). The 100% response rate on the eight atypical items of the SIGH-SAD that we observed in patients completing 8 weeks of modafinil treatment is consistent with modafinil’s effects of improved wakefulness in narcolepsy ( US Modafinil in Narcolepsy Multicenter Study Group, 2000) and reduced fatigue in major depressive disorder ( DeBattista et al., 2001; DeBattista et al., 2003 and Menza et al., 2000).
Results found in the present study in patients with seasonal affective disorder are consistent with results previously reported in patients with major depressive disorder who have residual sleepiness or fatigue after a partial response to antidepressant therapy. In a retrospective case series, open-label adjunct modafinil resulted in a ≥50% decrease in HAM-D scores in five of seven patients (Menza et al., 2000). Preliminary results from a prospective open-label trial indicated that adjunct modafinil produced significant improvements in depression scores (HAM-D and Beck) and two fatigue scales, with eight of 11 patients reporting that fatigue was reduced and cognition improved ( DeBattista et al., 2001). In both of these reports, modafinil rapidly reduced fatigue and improved depression scores within 1 to 2 weeks. In a preliminary multi-site, double-blind, placebo-controlled trial, adjunct modafinil also rapidly and significantly improved subjective wakefulness (ESS), compared with placebo at week 1 (P <0.01), and significantly reduced fatigue (FSS), compared with placebo at week 2 (P <0.05) (DeBattista et al., 2003). The improvement in wakefulness and reduction of fatigue in patients were sustained throughout the 6-week trial, although they were not statistically significant at endpoint, compared with patients receiving placebo and antidepressant treatment. In all three of these reports, as in our study, modafinil was well tolerated.
Interpretation of the current results must consider that this study enrolled a relatively small number of patients at a single site who received open-label modafinil. Two patients withdrew early during the treatment regimen due to insufficient efficacy, suggesting that for some patients the effects of modafinil may take longer than 1 to 2 weeks to be evident. In the absence of a placebo control, we cannot exclude the occurrence of some degree of spontaneous remission, especially in those patients whose treatment began and ended later in the 11-week period over which the study took place. It is not possible to determine if modafinil improved seasonal affective disorder due to a direct effect on mood or more likely if the positive overall response was secondary to the known effects of modafinil on wakefulness and fatigue.
The results of this preliminary open-label study suggest that modafinil may be an effective and well-tolerated treatment for seasonal affective disorder/winter depression. Double-blind, placebo-controlled clinical trials of modafinil in patients with seasonal affective disorder should be conducted to confirm these findings.
Acknowledgements
This study was supported by Cephalon, Inc., West Chester, PA, USA. The author acknowledges Jana Thomas and Nancy Nadolski for their assistance with the study.
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Posted by Noa on October 20, 2004, at 19:37:15
In reply to News: Light Therapy as Effective as Prozac for SAD, posted by jrbecker on October 19, 2004, at 9:10:49
I have what you might call "triple depression"--double depression plus SAD. The dysthymia is in partial remission and the recurrent major depression seems to be in full remission. I'm on a pretty serious med cocktail for the double depression, and I use a light box seasonally for the SAD--and it works very well. The trick is dedicating the time to get enough light box time every morning. This year, I have been using the light box properly for about 2 weeks and I've seen excellent improvement so far. I usually need it from about late September through early April.
Posted by sjb on October 21, 2004, at 9:55:10
In reply to Re: more on Seasonal Affective disorder (SAD) » SLS, posted by jrbecker on October 19, 2004, at 14:37:25
Wow, I thought I've read everything on SAD, but had not heard about the brain getting cold. Hmmmm. I'll bundle more (something I generally do not do.)
This is the end of the thread.
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