Anastasios Konstantinidis

A polymorphism (5-HTTLPR) in the serotonin transporter promoter gene is associated with DSM-IV depression subtypes in seasonal affective disorder

Serotonergic mechanisms are thought to play an important role in the pathogenesis of seasonal affective disorder (SAD). The expression of the serotonin transporter (5-HTT) is regulated in part by an insertion/deletion polymorphism in the serotonin transporter gene promoter region (5-HTTLPR). The 5-HTTLPR short allele (s) has been associated with anxiety-related personality traits and depression, and one study observed an association between the 5-HTTLPR s-allele and SAD and the trait of seasonality. We genotyped 138 SAD patients and 146 healthy volunteers with low seasonality for 5-HTTLPR. No difference between patients and controls was found for genotype distribution and s-allele frequency. However, genotype distribution and allele frequencies were strongly associated with DSM-IV depression subtypes. Melancholic depression was associated with the 5-HTTLPR long (l) allele and atypical depression with the 5-HTTLPR s-allele (two-sided Fishers exact test: genotype distribution: P=0.0038; allele frequencies: P=0.007). Our data are compatible with the hypothesis of a disease process that is not causally related to 5-HTTLPR, but involves 5-HT neurotransmission and 5-HTTLPR somewhere on its way to phenotypic disease expression.

Actigraphy in Patients with Seasonal Affective Disorder and Healthy Control Subjects Treated with Light Therapy

BACKGROUND Abnormalities of the circadian rest-activity cycle are hypothesized to accompany the clinical picture of seasonal affective disorder (SAD). The purpose of this study was to investigate if bright light therapy (BLT) is able to reverse these disturbances. METHODS Seventeen SAD outpatients and 17 sex- and age-matched healthy control subjects were treated with BLT administered in the morning for 4 weeks. Activity levels were measured with wrist actigraphy. RESULTS SAD patients had 33% lower total (p = .031) and 43% lower daylight activity (p = .006) in week 1 compared with control subjects. The relative amplitude of the sleep-wake cycle was attenuated by 6% in patients (p = .025); they were phase delayed by 55 minutes (p = .023) and had significantly lower sleep efficiency (p = .030). Total (p = .002) and daylight activity (p = .001) increased after 4 weeks of treatment in SAD patients. Moreover, BLT led to increase of relative amplitude (p = .005), advance of delayed rhythms (p = .036), and improved sleep efficiency (p = .011) in patients. Intradaily stability, measuring the strength of coupling of the rhythm to external zeitgebers, increased by 9% both in patients and healthy control subjects (p = .032). CONCLUSIONS Treatment with BLT normalizes disturbed activity patterns and restores circadian rhythms in SAD patients. BLT might also stabilize the circadian rhythm in nondepressed individuals during the fall-winter season.

Switching antidepressant class does not improve response or remission in treatment-resistant depression.

Objective: The management of treatment-resistant depression is a much debated issue. In particular, the evidence supporting the commonly suggested sequential use of antidepressants from 2 different pharmacological classes is weak. This retrospective study was undertaken to investigate whether there is a better response in nonresponders switched to a different class of antidepressants (across-class) compared with nonresponders switched to an antidepressant from the same class (within-class). Methods: Three hundred forty patients with primary major depressive disorder were recruited in the context of a European multicenter project. Subjects whose current depressive episode had failed to respond to a first antidepressant trial of adequate dose and duration were included. Results: There was no significant difference in response or remission rates between the across-class and within-class groups after controlling for possible confounders. Conclusions: In depressed nonresponders to a previous antidepressant treatment, switching to a different class of antidepressants was not associated with a better response or remission rate.

Gender differences in the psychopathology of depressed inpatients

Abstract.In the last few years there has been increased scientific effort to describe the gender–specific psychopathological features of depression. Until now these studies have not been entirely conclusive, which could be the result of methodological difficulties. This report investigates sex differences in the symptom presentation in an inpatient population: 104 female and 113 male patients suffering from a depressive episode according to ICD–10 were admitted to the inpatient treatment at the Department of General Psychiatry in Vienna. A psychopathological rating according to the standardized documentation system of the AMDP (Association for Methodology and Documentation in Psychiatry) was performed at admission and discharge. At admission into the hospital women tended to show more affective lability (p = 0.025), whereas men had higher scores in affective rigidity (p = 0.032), blunted affect (p = 0.002), decreased libido (p = 0.028), hypochondriasis (p = 0.016) and hypochondriac delusions (p = 0.039). At discharge from the hospital women had significantly higher scores in dysphoria (p = 0.010), while men were more prone to have compulsive impulses (p = 0.030). Although our results were obtained in a selected sample of inpatients at a university hospital, they are indicative of psychopathological differences between men and women in the core symptoms of depression. These differences may influence diagnostic practice and gender specific treatment of depression.

Monoaminergic function in the pathogenesis of seasonal affective disorder.

Seasonal affective disorder/winter type (SAD) is characterized by recurrent depressive episodes during autumn and winter alternating with non-depressive episodes during spring and summer. Light therapy with full-spectrum, bright white light has been shown to be effective for this condition. Several hypotheses have been discussed in the literature about the pathogenesis of SAD. The most prominent includes disturbances in central monoaminergic transmission. Evidence can be inferred from studies showing a seasonal rhythm of central and peripheral serotonergic functioning which may be a predisposing factor for SAD. Some of the symptoms of SAD are believed to represent an attempt to overcome a putative deficit in brain serotonergic transmission. Moreover, 5-HT receptor challenge studies suggest altered activity at or downstream to central 5-HT receptors. Monoamine depletion studies support hypotheses about serotonergic and catecholaminergic dysfunctions in SAD and suggest that light therapy may well compensate for this underlying deficit. Further, albeit indirect, support for the importance of monoaminergic mechanisms in SAD and its involvement in the mechanism of the action of light therapy comes from studies showing antidepressant efficacy of serotonergic and noradrenergic antidepressants in the treatment of SAD. Altogether, disturbances in brain monoaminergic transmission seem to play a key role in the pathogenesis of SAD; monoaminergic systems may also play an important role in the mechanisms of the action of light therapy.

No association of clock gene T3111C polymorphism and affective disorders

CLOCK was hypothesised to be related to susceptibility of affective disorders. To test subsamples of affectively disordered patients, we examined age of onset (AoO), numbers of episodes and melancholic type of clinical manifestation. Using PCR and RFLP, we investigated in patients with unipolar depression and bipolar disorder (BP) whether the CLOCK T3111C SNP is associated with affective disorders (n=102) compared to healthy controls (n=103). No differences were found either in genotype or allele frequency distributions of T3111C polymorphism between patients compared to healthy controls (p>0.2). No deviations from Hardy-Weinberg Equilibrium (HWE) were detected either in patients, or healthy controls. Results suggest that there is no association between the T3111C SNP and affective disorders in general. Data of our sample replicate prior findings of Desan et al. [Am. J. Med. Genet. 12 (2000) 418]. Subsamples of patients with high numbers of affective episodes did show some deviations in genotypes (p=0.0585).

Hyponatraemia during psychopharmacological treatment: results of a drug surveillance programme

Hyponatraemia (HN) can be a life-threatening medical condition which may lead to severe neurological and psychiatric symptoms. The AMSP (Arzneimittelsicherheit in der Psychiatrie) is a multicentre drug surveillance programme that assesses severe or new adverse drug reactions during psychopharmacological treatment in psychiatric inpatients. We report on a total of 263 864 psychiatric inpatients monitored from 1993 to 2007 in 80 psychiatric hospitals in Germany, Switzerland and Austria. During this period plasma sodium levels below 130 mmol/l (severe HN according to AMSP) were reported in 93 patients (relative frequency 0.04%). On average, the plasma sodium levels of all cases were 119.7 mmol/l (±5.8 s.d.); median 121 mmol/l (range 104-129 mmol/l). Patients who showed no clinical signs (n=65, 70%) had a mean sodium level of 121.3 mmol/l (±5.0 s.d.); median 122 mmol/l (range 114-129 mmol/l). By contrast, patients with clinical symptoms (n=28, 30%) had a mean sodium level of 116.0 mmol/l (±6.0 s.d.); median 117 mmol/l (range 104-125 mmol/l). HN was mainly observed during treatment with selective serotonin reuptake inhibitors (SSRIs) (0.06%), Serotonin noradrenaline reuptake inhibitors (SNRIs) (0.08%), carbamazepine (0.10%) and oxcarbazepine (1.29%); the highest rate was found for oxcarbazepine. Antipsychotics, mirtazapine and tricyclic antidepressants were only rarely involved in HN (0.003-0.005%). Combinations of several drugs known to induce HN significantly increased the risk of HN, e.g. more than 10-fold for SSRI+diuretics+ACE inhibitors (0.37%) vs. SSRI given alone (0.02%). This is clinically relevant because such combinations, e.g. SSRI+diuretics may occur especially in elderly patients, who are in general at higher risk of developing HN.

Citalopram versus desipramine in treatment resistant depression: Effect of continuation or switching strategies. A randomized open study

Abstract Objectives. Evidence in favour of switching between selective serotonin reuptake inhibitor (SSRI) and tricyclic (TCA) antidepressants in treatment resistant depression has been tested in a few studies only, consequently a prospective study was undertaken to evaluate the impact of switching strategies. Methods. One hundred eighty-nine patients who failed to respond to a previous antidepressant were randomised to four arms: firstly they received citalopram or desipramine for a 4-week period; secondly, those who failed to respond were treated for a further 4-week period with the same antidepressant (citalopram-citalopram and desipramine-desipramine arms) or switched to the alternate one (citalopram-desipramine and desipramine-citalopram arms). Results. There was no difference in the first 4-week phase between patients receiving citalopram versus desipramine in Hamilton Rating Scale for Depression (HRSD), Montgomery–Asberg Depression Rating Scale (MADRS), and Clinical Global Impression (CGI) scores. In the second 4-week phase remitter rates were higher among non-switched patients (P = 0.04). Moreover, considering HRSD and MADRS, switched patients reported significantly higher scores (P ≤ 0.02 for both scales at each time-point). Conclusions. This study supports the thesis that switching from an SSRI to a TCA (and vice versa) in non-responders to a 4-week trial of an SSRI/TCA is not associated with improved response. The result goes in the opposite direction to that predicted by current guidelines.

Bright light therapy in seasonal affective disorder - does it suffice?

Bright light therapy (BLT) has been proposed as treatment of choice for seasonal affective disorder (SAD). However, conventional antidepressants have also been found to be effective in this condition. We examined the psychopharmacologic medication in a clinical sample of 553 SAD patients, who had been treated with BLT, to assess the importance of drug treatment and to critically question the effectiveness of BLT. Forty-nine percent of our patients received psychopharmacologic treatment and about one third (35.4%) was treated with antidepressants, suggesting that BLT does not suffice as only antidepressant regimen for all SAD patients. Furthermore, our results show that only few patients with bipolar affective disorder were willing to accept long-term medication. Opposed to treatment guidelines, patients with several depressive episodes did not receive antidepressant maintenance medication or mood stabilizers more often than patients with only a few episodes.

Clonazepam in the long-term treatment of patients with unipolar depression, bipolar and schizoaffective disorder

Abstract The value of a long-term treatment with clonazepam in the prophylaxis of affective disorder is discussed controversially in the scientific literature. Altogether there are only a few reports on the use of this compound as a mood stabilizer, most of them describing patients suffering from bipolar affective disorder. The aim of this investigation was to evaluate clonazepam as a phase prophylactic medication in affective disorder. We conducted a retrospective chart review in 34 out-patients of our lithium clinic (15 suffering from unipolar depression, 15 from bipolar disorder, four from schizoaffective disorder), who had been treated with clonazepam as a long-term medication. Clonazepam was either given as monotherapy, or as in the case of lithium non-responders, as adjunctive therapy. Patients with unipolar depression had significantly (P=0.026) less depressive episodes after initiation of treatment with clonazepam. Patients with bipolar disorder did not benefit from this therapy. Neither manic/hypomanic phases nor depressive episodes were reduced in this group of patients. Interestingly, clonazepam also reduced affective phases in our four schizoaffective patients on a trend level. Our results indicate that patients with unipolar depression may benefit from a maintenance treatment with clonazepam. Due to methodological limitations our results need to be replicated in controlled double-blind randomized clinical trials.