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.

Effects of tryptophan depletion in drug-free depressed patients who responded to total sleep deprivation.

BACKGROUND: There is some evidence that sleep deprivation (SD) might exert its antidepressant properties by involving serotonergic mechanisms. We investigated the effects of short-term tryptophan depletion (TD) on depressed patients who responded to a single night of total SD. METHODS: Drug-free depressed inpatients (n = 30) were randomly assigned to either TD or sham depletion. Tryptophan depletion was induced by a 24-hour low-tryptophan diet (day 1) followed the next morning by ingestion of a tryptophan-free amino acid mixture (day 2). During sham depletion, the diet and the amino acid beverage were supplemented with tryptophan. Sleep deprivation was performed from day 1 until day 2. Only SD responders received the amino acid beverage the morning after SD. Behavioral ratings and total and free plasma tryptophan levels were obtained before and after the test sessions. RESULTS: Twenty-two of 30 patients showed a favorable outcome after SD. As predicted, TD significantly lowered total and free plasma tryptophan levels, whereas both levels increased during sham depletion. No acute effects on mood were observed during the day after SD in either treatment group. Unexpectedly, TD, but not control testing, prevented the depressive relapse after the recovery night in most of the patients. CONCLUSIONS: Tryptophan depletion did not reverse the antidepressant effects of SD, but it prevented the relapse beyond a night of recovery sleep. These findings suggest that SD does not act via a single monoamine-related mechanism, but they allow the assumption that TD may induce neurochemical alterations that transiently improve depression.

Effects of tryptophan depletion on drug-free patients with seasonal affective disorder during a stable response to bright light therapy.

BACKGROUND: A dysfunction of the serotonin system may play a major role in the pathogenesis of seasonal affective disorder. Bright light therapy has been shown to be effective in the treatment of winter depression in patients with seasonal affective disorder. Light therapy-induced remission from depression may be associated with changes in brain serotonin function. METHODS: After at least 2 weeks of clinical remission, 12 drug-free patients who had had depression with seasonal affective disorder underwent tryptophan depletion in a double-blind, placebo-controlled, balanced cross-over design study. RESULTS: Short-term tryptophan depletion induced a significant decrease in plasma free and total tryptophan levels (P < .001 for both, repeated measures analysis of variance), with peak effects occurring 5 hours after ingestion of a tryptophan-free amino acid drink. It emerged that tryptophan depletion leads to a transient depressive relapse, which was most pronounced on the day after the tryptophan-depletion testing. No clinically relevant mood changes were observed in the control testing. CONCLUSIONS: The maintenance of light therapy-induced remission from depression in patients with seasonal mood cycles seems to depend on the functional integrity of the brain serotonin system. Our results suggest that the serotonin system might be involved in the mechanism of action of light therapy.

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.

[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.

[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.

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.

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

OBJECTIVE: Brain serotonin systems might be involved in the pathophysiology of seasonal affective disorder. The authors tested whether tryptophan depletion alters the mood of depressed patients with seasonal affective disorder. METHOD: Eleven drug-free depressed patients with seasonal affective disorder underwent tryptophan depletion in a placebo-controlled, double-blind crossover study. Tryptophan depletion was induced by a 24-hour low-tryptophan diet and by ingestion of a tryptophan-free amino acid beverage. During control testing the diet and the beverage were supplemented with tryptophan. Behavioral ratings and plasma total and free tryptophan levels were obtained before the diet started and several times after administration of the beverages. RESULTS: The diet and the tryptophan-free amino acid drink reduced plasma total and free tryptophan levels by 79.0% and 87.5%, respectively. Both levels increased during control testing. No significant behavioral changes were induced by tryptophan depletion or control testing. CONCLUSIONS: The failure of tryptophan depletion to exacerbate the depressive syndrome suggests that dysfunctional serotonergic activity does not play a primary, direct role in the pathogenesis of winter depression.

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.

A risk-benefit assessment of mirtazapine in the treatment of depression.

Mirtazapine is the first of a new class of antidepressants, the noradrenergic and specific serotonergic antidepressants (NaSSA). Its antidepressant effect appears to be related to its dual enhancement of central noradrenergic and serotonin 5-HT1 receptor-mediated serotonergic neurotransmission. Mirtazapine possesses a number of useful pharmacokinetic characteristics such as good absorption, linear pharmacokinetics over the recommended dosage range (15 to 80 mg/day), and an elimination half-life of 20 to 40 hours, thereby allowing once-daily administration. However, since the drug is extensively metabolised by the hepatic cytochrome P450 (CYP) system and is excreted mainly in the urine, its clearance may be reduced by hepatic or renal impairment. In vitro data suggest that from a clinical point of view it is unlikely that mirtazapine would inhibit the metabolism of coadministered drugs metabolised by CYP1A2, CYP2D6 or CYP3A4. In vivo data from a study in extensive and poor metabolisers of debrisoquine indicate that strong inhibitors of CYP2D6 would have no effect on the concentration of racemic mirtazapine. In some placebo-controlled studies mirtazapine showed an early onset of antidepressant action, with significant reductions in total Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale scores (relative to placebo) noted as early as 1 week after starting treatment. This therapeutic advantage was subsequently maintained during treatment, with mirtazapine proving significantly superior to placebo at treatment end-point in the majority of studies. In comparative trials, the antidepressant efficacy of mirtazapine was comparable with that of tricyclic antidepressants such as amitriptyline, clomipramine and doxepin, and in 2 studies superior to that of trazodone and fluoxetine. Mirtazapine appears to have a broad spectrum of activity, reflected in its efficacy in a variety of clinical settings. Its additional beneficial effects on the symptoms of anxiety and sleep disturbance associated with depression may reduce the need for concomitant anxiolytic and hypnotic medication seen with some antidepressants. Mirtazapine has demonstrated superior tolerability to the tricyclic antidepressants and trazodone, primarily on account of its relative absence of anticholinergic, adrenergic and serotonin-related adverse effects, in particular gastrointestinal adverse effects and sexual dysfunction. It appears that increased sedation associated with the drug is related to subtherapeutic dosages, and that it is reported in substantially fewer patients when the drug is used in appropriate dosages (> or = 15 mg as a single evening dose) from the beginning of treatment. Although 2 cases of reversible severe symptomatic neutropenia have been reported in clinical trials, there have been no additional reports of symptomatic neutropenia since the introduction of this drug to various countries in September 1994. Currently available data and initial clinical experience suggest that with its combination of dual action, simple pharmacokinetics, and clinical efficacy and tolerability, mirtazapine appears to be an important advance in the pharmacotherapy of depression.

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.

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.

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.

[Mirtazapine in inpatient treatment of depressed patients]. / Mirtazapin bei stationär behandelten depressiven Patienten.

Mirtazapine is a new antidepressant with a specific pharmacological profile which is different from all other currently available antidepressants. It is a so-called noradrenergic and specific serotonergic antidepressant (NaSSA). 46 in-patients were treated with mirtazapine. The mean dose was 56 mg mirtazapine per day (SD: 23; range: 15 to 90). The duration of treatment was 3.6 weeks (SD +/- 3.4). Patients presented with following diagnosis: 29 (= 63%) were diagnosed as having a unipolar depression, 26% (n = 12) suffered from a depression in the course of a bipolar disorder. 37% (n = 17) were moderately depressed, 52% (n = 24) were severely depressed. 2 patients (= 4%) met ICD-10 (international Classification of Diseases) criteria for a schizoaffective disorder, 2 patients (= 4%) suffered from dysthymia. 1 patient suffered from an organic depressive disorder. The efficacy of the treatment was evaluated with CGI (Clinical Global Impression), when patients were discharged from hospital. 68% of the patients were in partial or full remission (CGI 2, 3 and 4), 17% were unimproved (CGI 5 and 6), in 15% of the patients the treatment was stopped before. Our observations are indicative that mirtazapine is effective in the treatment of moderately and severely depressed patients and therefore confirm the data obtained in phase III-trials. Furthermore we found mirtazapine in either mono- or combination-therapy with various other antidepressants to be tolerated well. Side effects did not cause in a single patient a discontinuation in treatment.

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.