Disrupted relationship between blood glucose and brain dopamine D2/3 receptor binding in patients with first-episode schizophrenia.

An elemental function of brain dopamine is to coordinate cognitive and motor resources for successful exploitation of environmental energy sources. Dopamine transmission, goal-directed behavior, and glucose homeostasis are altered in schizophrenia patients prior to and after initiation of pharmacological treatment. Thus, we investigated the relationship between blood glucose levels and brain dopamine signaling in drug-naïve patients with first-episode psychosis. We quantified blood glucose levels and binding of the dopamine D2/3 receptor agonist radioligand (+)-[11C]-PHNO in 15 medication-naïve patients and 27 healthy volunteers employing positron emission tomography. Whole-brain voxel-wise linear model analysis identified two clusters of significant interaction between blood glucose levels and diagnosis on (+)-[11C]-PHNO binding-potential values. We observed positive relationships between blood glucose levels and binding-potential values in healthy volunteers but negative ones in patients with first episode psychosis in a cluster surviving rigorous multiple testing correction located in the in the right ventral tegmental area. Another cluster of homologous behavior, however at a lower level of statistical significance, comprised the ventral striatum and pallidum. Extracellular dopamine levels are a major determinant of (+)-[11C]-PHNO binding in the brain. In line with the concept that increased dopamine signaling occurs when goal-directed behavior is needed for restoring energy supply, our data indicate that in healthy volunteers, extracellular dopamine levels are high when blood glucose levels are low and vice-versa. This relationship is reversed in patients with first-episode psychosis, possibly reflecting an underlying pathogenic alteration that links two seemingly unrelated aspects of the illness: altered dopamine signaling and dysfunctional glucose homeostasis.

Mid-Pleistocene transition in glacial cycles explained by declining CO2 and regolith removal.

Variations in Earth's orbit pace the glacial-interglacial cycles of the Quaternary, but the mechanisms that transform regional and seasonal variations in solar insolation into glacial-interglacial cycles are still elusive. Here, we present transient simulations of coevolution of climate, ice sheets, and carbon cycle over the past 3 million years. We show that a gradual lowering of atmospheric CO2 and regolith removal are essential to reproduce the evolution of climate variability over the Quaternary. The long-term CO2 decrease leads to the initiation of Northern Hemisphere glaciation and an increase in the amplitude of glacial-interglacial variations, while the combined effect of CO2 decline and regolith removal controls the timing of the transition from a 41,000- to 100,000-year world. Our results suggest that the current CO2 concentration is unprecedented over the past 3 million years and that global temperature never exceeded the preindustrial value by more than 2°C during the Quaternary.

Seasonal variation of availability of serotonin transporter binding sites in healthy female subjects as measured by [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and single photon emission computed tomography.

BACKGROUND: Previous studies have indicated annual variations in central and peripheral serotonergic activity. In the present study we studied five women in summer and six women in winter and evaluated possible differences in availability of brain serotonin transporters between summer and winter. METHODS: We employed the single photon emission computed tomography ligand [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane ([123I] beta-CIT) to visualize binding to the serotonin transporter site in the human thalamus/hypothalamus midbrain area in vivo. Brain imaging studies were performed in one group between May and August and in the other between November and December. RESULTS: We found significant differences in displaceable [123I] beta-CIT binding in the region corresponding to thalamus/hypothalamus between the summer group and the winter group (1.9 +/- 0.3 vs. 1.4 +/- 0.2, respectively; p < .01). CONCLUSIONS: The results of the present study suggest reduced brain serotonin transporter availability in winter. This finding further substantiates evidence of seasonal variations in brain serotonergic function.

The effects of light therapy on mini-mental state examination scores in demented patients.

BACKGROUND: Preliminary evidence suggests that demented patients may experience beneficial effects of light therapy. The authors tested whether bright light therapy (BLT) is capable of improving cognitive functions in patients with Alzheimer-type dementia (AD) or vascular dementia (VD). METHODS: Twenty-three patients with AD or VD were randomly assigned to either evening BLT or dim light therapy (DLT). Effects of light therapy on cognitive functions were assessed before and after light therapy using Mini-Mental State Examination (MMSE) scores. Body temperature rhythm (BTR) was additionally recorded pre- and posttreatment. RESULTS: Irrespective of their diagnosis, patients treated with BLT (p =.0012) but not with DLT (p =.73) showed a statistically significant increase in MMSE total scores after light therapy. Evening BLT simultaneously induced a significant phase delay of 56 min on BTR (p =.025). CONCLUSION: Our preliminary results suggest that short-term evening BLT may exert beneficial effects on cognitive functioning in patients with dementia.

[123I]-beta-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder.

BACKGROUND: Numerous findings indicate alterations in brain serotonin systems in seasonal affective disorder (SAD). [(123)I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([(123)I]-beta-CIT) labels serotonin transporters (5-HTTs) in the midbrain. We performed a [(123)I]-beta-CIT single photon emission computer tomography (SPECT) study under the hypothesis of lower [(123)I]-beta-CIT binding reflecting reduced central 5-HTT availability in depressed SAD patients. METHODS: Depressed SAD patients and healthy control subjects were investigated using [(123)I]-beta-CIT SPECT 4 hours and again 24 hours after tracer injection. Subjects had either never used psychotropic medication or had been drug-free for at least 6 months prior to the investigation. Specific-to-nondisplaceable partition coefficient (V(3)") was calculated for the thalamus-hypothalamus and the midbrain-pons; the cerebellum served as a reference region. RESULTS: Patients showed a reduction in V(3)" in thalamus-hypothalamus (2.41+/-0.3 vs. 2.84+/-0.4; p = .026) 24 hours post tracer injection (p.i.). No difference between patients and control subjects was found in midbrain-pons (1.31+/-0.2 vs. 1.42+/-0.2; p = .39). No differences were detected in the SPECT acquisitions 4 hours p.i. CONCLUSIONS: Depressed SAD patients showed lower specific-to-nondisplaceable [(123)I]-beta-CIT binding in the region of interest (ROI) thalamus-hypothalamus. The small size of the midbrain-pons ROI may have contributed to the failure to show a difference in this ROI as well. Similar to reduced midbrain 5-HTT availability in nonseasonal depression, depression in SAD seems to be associated with reduced 5-HTT availability to the thalamus-hypothalamus.

[123I] beta-CIT and single photon emission computed tomography reveal reduced brain serotonin transporter availability in bulimia nervosa.

BACKGROUND: Impaired serotonin transmission has been implicated in the pathophysiology of eating disorders. We investigated the in vivo availability of brain serotonin transporters and dopamine transporters in bulimia nervosa patients. METHODS: Approximately 24 hours after injection of [123I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([123I] beta-CIT), single photon emission computed tomography scans were performed in 10 medication-free, female bulimic patients and 10 age-matched, healthy females. For quantification of brain serotonin transporter and dopamine transporter availability, a ratio of specific to nonspecific [123I] beta-CIT brain binding was used (V(3)" = target region - cerebellum/cerebellum). RESULTS: Drug-free bulimia nervosa patients showed a 17% reduced brain serotonin transporter availability in the hypothalamus and thalamus, as compared with healthy control subjects (2.4 +/- 0.4 vs. 2.9 +/- 0.4, p =.026), and a similar reduction in striatal dopamine transporter availability. There was a negative correlation of illness duration and serotonin transporter availability (r = -.65; p =.042) and a strong positive correlation between hypothalamic/thalamic and striatal V(3)" (r =.80, p <.001). CONCLUSIONS: This first report of reduced [123I] beta-CIT binding in a relatively small group of patients with bulimia nervosa suggests a reduced hypothalamic and thalamic serotonin transporter availability in bulimia, which is more pronounced with longer duration of illness.

No evidence for in vivo regulation of midbrain serotonin transporter availability by serotonin transporter promoter gene polymorphism.

BACKGROUND: A polymorphism in the serotonin transporter promoter gene region (5-HTTLPR) has been shown to influence the quantity of serotonin transporter expressed in human cell lines: the 5-HTTLPR short allele (s) has been associated with reduced 5-HTT expression when compared to cells carrying the 5-HTTLPR long allele (l). We performed a single photon emission computed tomography (SPECT) study using the ligand [(123)I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT) to measure 5-HTT availability in 16 healthy subjects genotyped for 5-HTTLPR. METHODS: SPECT scans were performed 24 hours after tracer injection, regions of interest anatomically corresponding to the thalamus-hypothalamus and mesencephalon-pons areas were compared to the binding in the cerebellum, representing the nondisplaceable [(123)I]-beta-CIT-binding (results expressed as target activity minus cerebellum activity/cerebellum activity). DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods. RESULTS: Specific binding ratios in the thalamus-hypothalamus were 2.65 +/- 0.4 in subjects with the l/l genotype (n = 3), 2.76 +/- 0.5 in subjects with the l/s genotype (n = 9), and 2.77 +/- 0.4 in subjects with the s/s genotype (n = 4). Binding ratios in the mesencephalon-pons were 1.43 +/- 0.3 (l/l; n = 3), 1.37 +/- 0.3 (l/s; n = 9), and 1.28 +/- 0.3 (s/s; n = 4). None of these differences was statistically significant. CONCLUSIONS: Our data provide no evidence for in vivo functional regulation of 5-HTT availability by 5-HTTLPR in the thalamus-hypothalamus and mesencephalon-pons of healthy subjects.

Imaging serotonin and dopamine transporters with 123I-beta-CIT SPECT: binding kinetics and effects of normal aging.

UNLABELLED: [123I]beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane (CIT) is a useful ligand for dopamine transporters (DATs) and serotonin transporters (5-HTTs). Previous SPECT studies have shown a state of sustained equilibrium in the striatum on day 2 after injection that allows quantification of striatal DATs using a simple ratio of specific-to-nondisplaceable binding. The aim of this study was to investigate the kinetics of [123I]beta-CIT uptake in the thalamus, hypothalamus, and midbrain, areas known to contain 5-HTTs in high densities. METHODS: SPECT with a triple-head camera was performed on 16 healthy volunteers (13 women, 3 men; mean age [+/-SD], 32 +/- 11 y) after intravenous bolus injection of 130 +/- 20 MBq (3.5 +/- 0.5 mCi) [123I]beta-CIT. Two individuals were scanned 1, 2, 4, 7, 10, 13, 16, and 24 h after injection, and the remaining 14 were scanned 4, 7, 10, 20, and 24 h after injection. Values from 19 previously examined healthy volunteers (8 women, 11 men; mean age, 52 +/- 20 y) were included in the analysis to study the age dependency of beta-CIT binding in striatal and 5-HTT-rich brain areas in a larger control sample. RESULTS: Peak uptake 4 h after injection, followed by stable uptake until 10 h and a slow decrease until 24 h, was observed in the thalamus-hypothalamus region. Activity in the midbrain-pons region peaked 2 h after injection. Because of a concomitant slow but steady decline of uptake in reference regions starting 4 h after injection, a higher stability of binding ratios for 5-HTT-rich brain areas was observed on day 2, suggesting that a state of transient equilibrium is reached between 20 and 24 h but that conditions are only close to transient equilibrium between 4 and 10 h after injection for 5-HTT-rich brain areas. In addition to an age-related decline of striatal [123I]beta-CIT binding of 6.6% per decade, a significant age-associated decrease of beta-CIT binding of 3-4% per decade was found in 5-HTT-rich brain areas. The decline of beta-CIT binding in these regions may be explained, at least in part, by a loss of monoamine transporters with age but may also be related to age-associated morphologic changes. CONCLUSION: [123I]beta-CIT appears to be a suitable ligand for imaging serotonin transporters with SPECT. However, careful age matching is warranted for [123I]beta-CIT SPECT studies of 5-HTT changes in patients with neuropsychiatric disorders.

Suicidal tendencies as a complication of light therapy for seasonal affective disorder: a report of three cases.

BACKGROUND: Suicidality in seasonal affective disorder (SAD) subjects treated with bright light therapy seems to be a rare phenomenon. We report on three SAD patients with predominant atypical symptoms who presented for treatment in our clinic for SAD. Two suffered from bipolar disorder, one from recurrent major depressive disorder. METHOD: All subjects were drug-free and treated with bright light therapy as a monotherapy for the first time. Treatment response was assessed weekly by standardized rating instruments, using the Hamilton Rating Scale for Depression (HAM-D) and the HAM-D-SAD addendum for assessment of atypical symptoms. RESULTS: Within the first week after beginning bright light therapy, two subjects attempted suicide. The third patient developed suicidal thoughts that were so acute and overwhelming that we had to discontinue bright light therapy and start with psychopharmacologic treatment in an inpatient setting. CONCLUSION: It is suggested that bright light-induced amelioration of drive and mood can be dissociated as can be the case in the "critical time" of antidepressant therapy. The authors believe the collection of prevalence data on suicide and SAD would be worthwhile.

In vivo (123)I IBZM SPECT imaging of striatal dopamine 2 receptor occupancy in schizophrenic patients.

RATIONALE: Single photon emission computed tomography (SPECT) using (123)I iodobenzamide (IBZM) as tracer substance has been shown to be a useful tool to visualize dopamine 2 (D2) receptor occupancy. OBJECTIVES: We investigated the striatal D2 receptor occupancy of zotepine which is referred to the class of atypical antipsychotic drugs. METHODS: (123)I IBZM and SPECT were used to visualize striatal dopamine 2 (D2) receptor occupancy in zotepine-treated schizophrenic patients. Two groups of schizophrenic patients receiving either 150 mg/day zotepine (n=6) or 300 mg/day (n=6) underwent examination. For the quantification of striatal D2 receptor occupancy, striatal IBZM binding in patients treated with antipsychotics was compared to untreated healthy controls (n=8) reported earlier. RESULTS: Zotepine led to a mean overall striatal D2 receptor occupancy of 73%. Patients with 150 mg daily showed a significantly lower occupancy (65.8%, SD=6.2) than patients with 300 mg/day (77.8%, SD=10.7; P<0.05). No clinically relevant extrapyramidal side effects occurred during treatment with zotepine. CONCLUSIONS: There was no correlation between the degree of striatal D2 receptor occupancy and clinical improvement.

Reboxetine in seasonal affective disorder: an open trial.

Seasonal affective disorder (SAD), winter type, is a condition characterized by the annual recurrence of depressive episodes during fall/winter, alternating with spring/summer euthymia or hypomania. Various neurotransmitters have been implicated in the etiology of SAD, the strongest evidence involving serotonin. Recently, increasing attention has been paid to the potential role of catecholaminergic pathways in the pathophysiology of SAD. We investigated the efficacy and tolerability of reboxetine, a selective noradrenaline inhibitor, in patients with SAD. Eleven out of sixteen patients who were included in a 6-week drug surveillance during winter season experienced full remission of depressive symptoms. Nine patients reported a rapid relief of preexistent severe atypical depressive symptoms within the first treatment week. Reboxetine might therefore be an effective and well-tolerated treatment option for SAD patients. In conclusion, our preliminary results are in line with evidence from recent studies suggesting that catecholaminergic systems might also be involved in the pathophysiology of SAD.

No change in striatal dopamine re-uptake site density in psychotropic drug naive and in currently treated Tourette's disorder patients: a [(123)I]-beta-CIT SPECt-study.

BACKGROUND: There is evidence that Tourette's disorder (TD) is associated with abnormalities in the dopaminergic system involving the dopamine transporter (DAT). Data from [(123)I]-beta-CIT single photon emission computed tomography (SPECT) studies and postmortem findings concerning DAT densities in TD patients are not conclusive. The objective of our study was to measure DAT densities with [(123)I]-beta-CIT binding in TD patients who were either psychotropic drug naive or currently treated with antipsychotics (AP) and healthy controls. METHOD: Altogether 20 TD patients were investigated. A total of 15 patients were psychotropic drug naive and five were currently treated with AP. Ten psychotropic drug naive patients were compared with ten age and sex matched healthy subjects. Five currently treated patients were compared with five age and sex matched psychotropic drug naive TD patients. The investigation was carried out using [(123)I]-beta-CIT (2-beta-carbomethoxy-3-beta(4-iodophenyl)-tropane and SPECT. Regions of interest (ROI) were drawn over the striatum and the cerebellum. RESULTS: The DAT densities measured by the striatal/cerebellar (S/C) binding ratio did not differ between drug naive TD patients and the controls. The difference between currently AP treated and psychotropic drug naive TD patients did not reach the level of significance. There was no correlation between the ratio and severity of tics and illness. CONCLUSION: Our study with psychotropic drug naive TD patients contributed to clarify the inconsistent results concerning the DAT.

Prevalence of premenstrual dysphoric disorder in female patients with seasonal affective disorder.

BACKGROUND: Both seasonal affective disorder/winter type (SAD) and premenstrual dysphoric disorder (PMDD) are cyclical disorders characterized by so-called atypical depressive symptoms. In the present study we compared the point prevalence rates of PMDD between a sample of premenopausal female patients suffering from SAD and healthy female controls. METHODS: Forty-six female patients with SAD and 46 healthy controls were included in our study. All subjects underwent a semistructured clinical interview according to DSM IV criteria and completed the Seasonal Pattern Assessment Questionnaire. PMDD was diagnosed in a self-rating interview for PMDD according to DSM IV criteria. To verify the diagnosis of PMDD, all patients were followed up in stable summer remission using daily self-rating scales for two full menstrual cycles. RESULTS: Patients with SAD fulfilled significantly more often the diagnostic criteria for PMDD than female healthy controls (46% vs. 2%, respectively; chi-square: P<0.001). CONCLUSIONS: These results provide preliminary evidence for a high point prevalence rate of PMDD in premenopausal females with SAD. CLINICAL IMPLICATIONS: It would be worthwhile to investigate whether an additional diagnosis of PMDD has an impact on the clinical outcome and the response to bright light therapy in female patients with SAD.

Tryptophan depletion: a predictor of future depressive episodes in seasonal affective disorder?

Patients with seasonal affective disorder (SAD) do not necessarily experience depressive episodes every winter. We assessed whether the behavioural response to tryptophan depletion in summer when patients are fully remitted and off therapy is capable of predicting a future depressive episode of SAD. In a prospective study design, we followed up 11 consenting SAD patients who had undergone tryptophan depletion during summer. We evaluated how many of these patients would develop a depressive episode in the subsequent fall/winter. Seven out of eight patients who relapsed during tryptophan depletion in summer developed a depressive episode in the subsequent winter. Two out of the three patients who did not relapse during tryptophan depletion remained well during the follow-up period. Our preliminary findings suggest that those SAD patients who develop depressive symptoms during tryptophan depletion when they are fully remitted and off therapy remain at high risk to experience a depressive episode of SAD also in the subsequent winter.

Zotepine in the treatment of acute hospitalized schizophrenic episodes.

The atypical antipsychotic zotepine was studied in an open, multicentre uncontrolled, post-marketing surveillance study in 108 schizophrenic patients hospitalized in 12 trial centres in Austria. Within the dosage range of 50-450 mg (mean at the end of the study, 207 +/- 125 mg/day), a significant reduction of positive as well as negative symptoms was noted. There was no increase in extrapyramidal side-effects during the study and a significant decrease in akathisia scores. The medication was well tolerated during the 42-day observation period. Zotepine improved both positive and negative symptoms and was not accompanied by extrapyramidal side-effects, justifying its classification as an atypical antipsychotic.

Behavioral effects of tryptophan depletion in seasonal affective disorder associated with the serotonin transporter gene?

There is some evidence that the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) may be involved in the pathogenesis of seasonal affective disorder (SAD). Short-term tryptophan (TRP) depletion was carried out in 18 drug-free remitted patients who met DSM-IV criteria for SAD. Behavioral effects were measured with the Hamilton Depression Rating Scale (HDRS) both 24 h before and 24 h after TRP depletion. Some of the patients showed behavioral responses such as lowered mood, feelings of guilt, loss of interest, agitation, loss of energy, fatigue, social withdrawal, increased appetite, and carbohydrate craving. It was the aim of our study to investigate whether the genotypes of the serotonin transporter gene were associated with symptoms of transient depressive relapse after TRP depletion. In addition, we matched the SAD patients with healthy control subjects to see if alleles and genotypes of the serotonin transporter gene were associated with SAD. High molecular weight DNA was isolated from peripheral blood leukocytes using standard methods. For the 5-HTT receptor gene, a 17-bp repetitive element of intron 2 was genotyped (variable number tandem repeat, VNTR). Alterations in HDRS scores after TRP depletion showed no significant association with alleles or genotypes of the 5-HTT gene, although heterozygotes showed a trend toward increased HDRS scores. The serotonin transporter is known to play a critical role in the termination of serotonergic neurotransmission by sodium-dependent uptake of 5-HT into the presynaptic neuron. The present study in a small group of SAD patients was unable to demonstrate that the 5-HTT gene plays a role in the pathogenesis of SAD or in short-term depressive relapse after TRP depletion.

Monoamine depletion in non-pharmacological treatments for depression.

Non-pharmacological treatments such as light therapy for seasonal affective disorder or sleep deprivation for non-seasonal depression have been shown to treat depression effectively. With the use of the tryptophan depletion paradigm and the catecholamine depletion paradigm we assessed the role of brain serotonergic and catecholaminergic systems respectively. We found that disturbances in brain serotonin systems play a key role in the pathogenesis of seasonal affective disorder and that light therapy may compensate for the underlying deficit. Moreover there is evidence that catecholaminergic systems may be involved in the mechanism of action of light therapy. Tryptophan depletion studies suggest that sleep deprivation does not exert its antidepressant effects by involving brain serotonin systems alone. Interestingly, tryptophan depletion prevented the relapse after the recovery night, possibly by enhancing brain serotonin transmission after the depletion procedure.

Inpatient treatment of major depression in Austria between 1989 and 2009: impact of downsizing of psychiatric hospitals on admissions, suicide rates and outpatient psychiatric services.

BACKGROUND: During the last 20 years Austrian psychiatric services underwent fundamental changes, as a focus was set on downsizing psychiatric hospitals. Little is known about how restructuring of mental health services affected patients with major depression and suicide rates. METHODS: Monthly hospital discharges from all hospitals in Austria with the diagnosis of unipolar major depression as primary reason for inpatient treatment were obtained for the time period between 1989 and 2008. These data were correlated with relevant parameters from the general health system, such as number of hospital beds, suicide rate, density of psychotherapists and sales of antidepressants. RESULTS: While the number of psychiatric beds was reduced by almost 30%, the total annual numbers of inpatient treatment episodes for depression increased by 360%. This increase was stronger for men than for women. Further on this development was accompanied by a decrease in the suicide rate and an improvement in the availability of professional outpatient mental health service providers. LIMITATIONS: Only aggregated patient data and no single case histories were available for this study. The validity of the correct diagnosis of unipolar major depression must be doubted, as most likely not all patients were seen by a clinical expert. CONCLUSIONS: Our data show that although inpatient treatment for unipolar major depression dramatically increased, reduction of psychiatric beds did not lead to an increase of suicide rates.

Treatment of seasonal affective disorder with duloxetine: an open-label study.

OBJECTIVE: The aim of this observational study was to evaluate the effects of duloxetine in the treatment of seasonal affective disorder (SAD). PATIENTS AND METHODS: 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. RESULTS: 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%. CONCLUSIONS: Our preliminary results indicate that duloxetine might be effective and able to ameliorate the negative social consequences of SAD.

Escitalopram in seasonal affective disorder: results of an open trial.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: These results suggest that escitalopram is an efficacious and altogether safe treatment for seasonal depression.