Effects of fluoxetine versus bright light in the treatment of seasonal affective disorder

BACKGROUND: 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). METHOD: 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. RESULTS: 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. CONCLUSION: Both treatments produced a good antidepressant effect and were well tolerated. An apparently better response to bright light requires confirmation in a larger sample.     

Greater improvement in summer than with light treatment in winter in patients with seasonal affective disorder

OBJECTIVE: The authors sought to compare the degree of mood improvement after light treatment with mood improvement in the subsequent summer in patients with seasonal affective disorder. METHOD: By using the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale, the authors rated 15 patients with seasonal affective disorder on three occasions: during winter when the patients were depressed, during winter following 2 weeks of light therapy, and during the following summer. They compared the three conditions by using Friedman's analysis of variance and the Wilcoxon signed ranks test. RESULTS: The patients' scores on the depression scale were significantly higher after 2 weeks of light therapy in winter than during the following summer. CONCLUSIONS: Light treatment for 2 weeks in winter is only partially effective when compared to summer. Further studies will be necessary to assess if summer's light or other factors are the main contributors to this difference.     

Cognitive-behavioral factors in seasonal affective disorder.

To longitudinally examine cognitive-behavioral correlates of seasonal affective disorder (SAD), the authors assessed women with a history of SAD and nondepressed, matched controls across fall, winter, and summer. SAD history participants reported more automatic negative thoughts throughout the year than controls and demonstrated a progression from decreased activity enjoyment during fall to reduced activity frequency during winter. Ruminative response style, measured in fall, predicted symptom severity during the winter. Across assessments, SAD history women endorsed greater depressive affect in response to low light intensity stimuli than to bright or ambiguous intensity stimuli, but less depressed mood to bright light stimuli than controls. These results suggest that the cognitive-behavioral factors related to nonseasonal depression may play a role in SAD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Light visor treatment for seasonal affective disorder: a multicenter study

Inhibition of growth of the lymphocyte lines by iron-binding agent deferoxamine under various iron-supply conditions was studied. Three different defined culture media, representing three different iron-supply conditions, were used: (1) ferric citrate (500 microM) medium, (2) transferrin (5 micrograms/ml) medium, and (3) low-iron medium (this medium without any iron compound added contains 0.6 microM contaminative non-transferrin iron). Mouse B cell line PLV-01, human T cell line Jurkat, and human B cell lines Raji and HSCE- were employed. Raji and HSCE- cells are able to grow in low-iron medium but PLV-01 and Jurkat cells do not grow in the medium. For all cell lines tested in ferric citrate medium, a 50% growth inhibition was achieved with 440-500 microM deferoxamine. In transferrin medium, deferoxamine concentrations of 4.4-5.5 microM were required for a 50% inhibition of PLV-01, Jurkat and HSCE- cells. For the same degree of inhibition of Raji cells, 39 microM deferoxamine was required. In the case of low-iron medium, a 50% inhibition of Raji and HSCE- cells was achieved with about 1.4-2.1 microM deferoxamine. The data demonstrate that the sensitivity of the lymphocyte lines to deferoxamine depends on iron-supply conditions. Under the same iron-supply conditions, individual cell lines can exhibit different sensitivity. However, the sensitivity does not correlate with the ability of the cell lines to grow in low-iron medium.     

Effects of bright light on sleepiness, melatonin, and 25-hydroxyvitamin D(3) in winter seasonal affective disorder

Sixteen patients with winter seasonal affective disorder and 13 healthy controls were exposed to 3300 lx of cool-white fluorescent light for either 1 hour or 15 min in the morning for 2 weeks during the winter. Subjective sleepiness, melatonin concentration in saliva, and serum 25-hydroxyvitamin D(3) concentration were measured before and after the 2-week trial as well as the following summer when the patients were well. There were no significant differences in the baseline values between the patients and healthy subjects. No significant differences in the outcome measures were observed in the patients or the controls in the two groups of each after the trial. The exposure to bright light resulted in a significant decrease in subjective sleepiness early in the evening in the patients but not in the control subjects. The reduction of depressive symptoms was associated with the decrease in subjective sleepiness but not with the changes in the melatonin or vitamin D concentrations.     

Treatment of seasonal affective disorder with a high-output negative ionizer

A retrospective analysis was performed to explain the decreasing incidence of postoperative arthrofibrosis of the knee in 191 consecutive patients who had anterior cruciate ligament reconstruction using the central third patellar tendon from 1987 through 1991. Follow-up data were available on 188 patients (98%). Age, sex, time interval from injury, preoperative motion, and concomitant meniscal repair or partial meniscectomy were evaluated for their significance as risk factors. Twenty-two of 188 patients (12%) developed arthrofibrosis; the incidence was lower when the acute anterior cruciate ligament reconstruction was delayed at least 3 weeks from the injury, and when preoperative extension was 10 degrees or better. Age, sex, preoperative flexion, and need for concomitant meniscal surgery were not risk factors. The postoperative motion protocol evolved during the study period. Group 1 patients were braced in 45 degrees of flexion for 1 week before passive extension was allowed. In Group 2, motion was started after 48 hours. Group 3 patients were braced in full extension, with motion starting with 24 hours. With these changes, the incidence dropped from 23% to 3%. Decreases in the incidence of arthrofibrosis with modifications in operative technique and postoperative analgesia were not statistically significant.     

Rapid tryptophan depletion in drug-free depressed patients with seasonal affective disorder

The authors of a large number of Norwegian detective stories, particularly from the first part of this century, are occupied with neurologists and neurobiological problems. A survey of this literature shows. One Norwegian neurologist has written four detective stories. Not one single neurologist can be found as a detective hero. On the other hand there are numerous examples of the neurologist as a criminal or even a murderer. Neurological symptoms and signs (mostly functional pareses and epileptic fits) are used to construct the plot in other novels. The most striking finding is a detective story where the criminal is a neurobiologist, the plot is based on neurobiology and the author discusses neurological phenomena throughout the entire book.     

Phototherapy. An alternative for seasonal affective disorders or sleep disorders

Although clinicians have observed for centuries that som depressed patients become worse in the winter, it was first in 1984 that Norman Rosenthal and co-workers described a syndrome which they called seasonal affective disorder (SAD), characterised by winter depression, lethargy and a craving for carbohydrate. Phototherapy was proved to be an effective treatment right from the start. Recently it has been reported that not only depression, but also panic disorder and obsessive compulsive disorders may exhibit a seasonal pattern and thus benefit from phototherapy. Phototherapy may also benefit patients suffering from "sun-downing", a syndrome of confusion and agitation in the evening in persons with Alzheimer's disease. Based on the observation that bright light may both elevate brain serotonin and ameliorate sleep abnormalities, the authors report the results of phototherapy for treatment of non-seasonal depressions, either alone or in combination with antidepressants or sleep deprivation.     

A randomized controlled trial of cognitive-behavioral therapy, light therapy, and their combination for seasonal affective disorder.

This first controlled psychotherapy trial for seasonal affective disorder (SAD) compared SAD-tailored cognitive-behavioral therapy (CBT), light therapy (LT), and their combination to a concurrent wait-list control. Adults (N = 61) with major depression, recurrent with seasonal pattern, were randomized to one of four 6-week conditions: CBT (1.5-hr twice-weekly group therapy), LT (10,000-lux for 90-min/day with administration time individually adjusted), combined CBT + LT, or a minimal contact/delayed LT control (MCDT; LT following 6 weeks of monitoring). CBT, LT, and CBT + LT significantly and comparably improved depression severity relative to MCDT in intent-to-treat and completer samples. CBT + LT (73%) had a significantly higher remission rate than MCDT (20%). Using prospectively measured summer mood status to estimate the "functional" population, CBT + LT also had a significantly larger proportion of participants with clinically significant change over treatment compared with MCDT. The LT condition outcomes virtually replicated results from prior trials. CBT, alone or combined with LT, holds promise as an efficacious SAD treatment and warrants further study. If replicated, CBT + LT's remission rate would represent a clinically meaningful improvement over the 53% observed across LT studies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Circadian profiles of cortisol, prolactin, and thyrotropin in seasonal affective disorder

To determine whether circadian profiles of various plasma hormones are abnormal in patients with winter seasonal affective disorder (SAD), we obtained 24-hour profiles of plasma cortisol, prolactin, and thyrotropin in subsets of a sample of 22 depressed patients with SAD on and off light therapy and in subsets of a sample of 24 normal controls. Cortisol levels did not differ between patients and controls, and levels in patients were not affected by light therapy. Prolactin levels were lower in patients than in controls throughout the day (p < 0.03) but were unaffected by light therapy. Independent of patient vs. control status, prolactin levels were higher in women than in men throughout the day (p < 0.003). Thyrotropin levels were no different in patients and controls, but levels in patients were lower following light therapy (p < 0.05).     

A multicenter study of the light visor for seasonal affective disorder: no difference in efficacy found between two different intensities

Fifty-five patients with winter seasonal affective disorder (SAD) were treated with a light visor, a newly developed portable light-delivery system, in a controlled parallel design. A dim (400 lux) visor was compared with a bright (6000 lux) visor for either 30 or 60 minutes in the morning for 1 week. Response rates for these two treatments were 36% and 56%, respectively; the duration of treatment sessions did not affect outcome. There was no evidence that the brighter visor was superior in efficacy to the dimmer one. Significantly greater relapse occurred following withdrawal of the dimmer visor. Alternative explanations for these findings are that the light visor is acting as a placebo or that it is equally effective over a wide range of intensities.     

Prediction of acute and late responses to light therapy from vocal (pitch) and self-rated activation in seasonal affective disorder

It was hypothesized that pre-treatment activation plays a role in the response to light therapy in Seasonal Affective Disorder (SAD). In 55 SAD patients (DSMIII-R) energetic and tense activation was assessed before light therapy via self-rating (AD-ACL) and voice sound characteristics (mean pitch and variation in pitch). These variables were studied in relation to the "acute" response to 4 days of light therapy (30 min, 10000 lux) and to a "late" response (11 (10) days after light therapy had stopped). Acute response was defined as the percent change in 3 times daily self-rated depressed mood (AMS) with respect to the average of 4 baseline days. "Late" response was defined as the percent change in HRSD or AMS scores between baseline and 11 (10) days after light therapy. It was found that patients having high pitched voices with small variation in this pitch benefitted more from light therapy than the patients with low pitch and large variation in pitch levels. This effect was only significant after the first day of light exposure. No other significant relations were found between baseline activation and acute or late responses to light therapy. Hence, light therapy seems to give extra comfort in "tense" patients, who become rapid responders to light therapy.     

Which environmental variables are related to the onset of seasonal affective disorder?

The regular fall-winter onset of seasonal affective disorder is believed to be related to seasonal changes in the environment. However, the high correlation among various environmental variables has made it difficult to distinguish which ones may play a causal role. Photoperiod should explain variations in onset risk across both latitude and day of the year because it varies as a function of only these 2 factors. In Study 1, the authors found this to be the case using data from 5 locations. Environmental factors that vary from year to year should explain variations in onset risk across both time of year and actual year. In Study 2, the authors examined data from 7 years at 1 location and failed to find evidence of this effect for daily hours of sunshine, mean daily temperature, and total daily radiation. Findings support photoperiod as being related to the onset of seasonal affective disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of meta-chlorophenylpiperazine infusions in patients with seasonal affective disorder and healthy control subjects. Diurnal responses and nocturnal regulatory mechanisms

BACKGROUND: Multiple lines of evidence suggest that brain serotonergic systems may be disturbed in seasonal affective disorder (SAD). Previously, we found that the serotonergic agent meta-chlorophenylpiperazine (m-CPP) produced increases in activation and euphoria in depressed patients with SAD, but not in patients with SAD following light treatment or in the summer, nor in healthy control subjects in any condition. In the present study, we attempted to replicate and extend this finding using better methods. METHODS: Seventeen outpatients with SAD and 15 control subjects underwent successive 3-week periods of bright light treatment and light avoidance in a randomized order. During the third week of each condition, on 2 different occasions, subjects were admitted to the hospital for a night of sleep (core temperatures were recorded), followed by infusions of m-CPP (0.08 mg/kg) or placebo the next morning. Dependent measures included the 24-item National Institute of Mental Health Self-Rating Scale, plasma corticotropin, cortisol, prolactin, growth hormone, and norepinephrine concentrations, and core temperatures. RESULTS: Meta-chlorophenylpiperazine produced (1) significant increases in "activation-euphoria" ratings only in depressed patients with SAD in the untreated condition and (2) blunted corticotropin and norepinephrine responses in patients with SAD compared with controls across both light treatment conditions. In both groups, light treatment was associated with significant reductions in nocturnal core temperatures, which were correlated with similarly significant reductions in mean diurnal growth hormone concentrations. In patients with SAD, (1) the reductions in nocturnal core temperatures also were correlated with the reductions in baseline depression ratings and (2) the reductions in mean growth hormone concentrations were significantly smaller compared with controls. CONCLUSIONS: The abnormal m-CPP-induced activation-euphoria responses represent a replicated state marker of winter depression in patients with SAD. The blunted m-CPP-induced responsiveness of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system may represent traitlike abnormalities. The improvements in mood following light treatment in patients with SAD seem to be associated with the lowering of nocturnal core temperatures. The findings, although not easily explained based on a uniform abnormality of serotonin receptors, are nonetheless compatible with the notion that selected regions of the central nervous system are deficient in serotonin transmission during winter depression.     

Autobiographical memory style in seasonal affective disorder and its relationship to future symptom remission.

Autobiographical memory was examined in participants with seasonal affective disorder (SAD). In Experiment 1, participants with SAD performed an autobiographical memory task (AMT) in the winter when depressed. The AMT required participants to generate autobiographical memories to positive and negative cue words. Symptom levels were reassessed in the summer, when participants were remitted. The number of overly general memories to positive cues generated when the SAD participants were depressed predicted symptom levels when remitted, over and above initial symptom levels, with greater winter overgenerality being associated with high levels of summer symptoms. However, this was dependent on the exact measure of depressive symptoms used. The degree of overgenerality of memories in SAD participants was further investigated in Experiment 2. Results revealed that SAD participants did not show elevated recall of overgeneral memories relative to controls. The results as a whole indicate that, even when levels of general memories are no greater in a given target group than in controls, the absolute level of general memories to positive cues words is still independently related to symptom outcome. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The efficiency of alprazolam for seasonal affective disorder (SAD, autumn/winter type)]

Tricyclic antidepressants, or "tricyclics" as they are commonly called, are effective in reducing pain in chronic neurological and musculoskeletal disorders. Tricyclics appear to be effective in the control of chronic orofacial pain of non-inflammatory origin, and include amitriptyline, doxepin, nortriptyline and desipramine. Daily doses of the medications are smaller for the management of pain than doses typically used in the treatment of depression. Certain medical conditions may contraindicate tricyclic trials, while others may warrant starting at a lower dose with more conservative dose adjustments. Common side effects include dry mouth, sedation, constipation and orthostasis. Tricyclics are just one therapeutic modality which can be considered in the management and treatment of chronic refractory orofacial pain that is suspected to arise from neurogenic or myofascial etiologies.     

Melatonin in light treatment of patients with seasonal and nonseasonal depression

Melatonin as a marker of circadian rhythm and the effect of bright light on melatonin were studied in 63 depressed patients, 42 with a seasonal pattern and 21 with a nonseasonal pattern. The patients were matched for age, time of treatment and severity of depression. Before light treatment, blood was sampled for melatonin and depression was clinically rated with the Comprehensive Psychopathological Rating Scale and Hamilton Depression Rating Scale. Two hours of light treatment, 350 cd/m2, was given daily for 10 days 0600 to 0800 or 1800 to 2000. Of the 42 patients with seasonal depression, 26 were treated with morning light and, 16 with evening light. The melatonin amplitude was significantly decreased by light, and the melatonin phase position was advanced by morning light and delayed by evening light. All patients except for 3 in each group changed in the expected direction. Although the patients with seasonal pattern had a more favorable outcome than patients with nonseasonal pattern, there was no difference in therapeutic outcome related to the baseline melatonin phase position. The hypothesis that the short term clinical effects of light therapy either in the morning or evening are related to pretreatment melatonin levels or alteration of melatonin amplitude or phase position was not supported in the study. There was also no significant difference between the seasonal and nonseasonal patients related to the degree of light suppression of melatonin and the rebound effect of serum melatonin levels following bright level exposure between 2200 and 2300 before regular light treatment.     

Primary affective disorder: Thought disorder in depression.

To investigate the occurrence of 1 type of thought disorder in depression, here defined as impairment in abstractive performance, 65 hospitalized depressed patients and 49 normal controls were compared on the Category Test (CT). 36 patients had been diagnosed as bipolar and 29 as unipolar. Analysis of covariance indicated that the depressed groups had significantly more errors than the control group on the CT, suggesting that severely depressed patients show the type of thought disorder defined in this study. No significant differences were found, however, between the CT scores of the unipolar and bipolar groups. The possibility that some features of the depressed state can be described as cerebral dysfunction is discussed. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Misdiagnosis of bipolar affective disorder as personality disorder

Patients with longstanding recurrent behavioural disturbance, unstable interpersonal relationships and periodic affective symptoms are often diagnosed as having a cluster B personality disturbance using DSM-III-R criteria. Two women are described who were diagnosed as having a personality disorder on several admissions to hospital, but in whom closer inquiry revealed evidence of bipolar affective disorder. Since treatment with lithium and adjunctive mood-stabilizing drugs neither patient has required further admissions to hospital within the past five years.