SUMMARY. Aims. Literature data show that one third of patients discontinue antidepressant therapy within the first month of treatment. The aim of this study was to evaluate whether paroxetine liquid solution 10 mg/ml may influence adherence in patients receiving long-term treatment. Methods. 71 subjects affected by mood disorders or panic disorder were monitored for six months. The study sample was divided into two groups: controls (n=33) maintained their own therapy with paroxetine tablets; 38 patients maintained the same dosage of paroxetine, but shifted to liquid formulation 10 mg/ml. Compliance and general wellness were evaluated with the Medication Adherence Rating Scale (MARS) and the World Health Organization Quality of Life questionnaire (WhoQol). Data were analyzed using analysis of variance (ANOVA) and multivariate analysis of covariance (MANCOVA). Results. Significant differences were found in MARS scores: patients on oral solution 10 mg/ml showed an improvement of compliance month by month. In addition, age, formulation and quality of life had a significant im pact on patient compliance. Significant correlations were found between MARS and quality of life. A specific paroxetine for mulation could be a variable able to influence adherence to psychopharmacological treatment. The same consideration can be made for quality of life, sex and age that showed a trend towards improved adherence when compared with controls. In particular, the WhoQol subscale analysis of delta scores showed a significant difference in self-perception of quality of life in patients treated with paroxetine either in tablet or drop formulation. Discussion. Formulation in drops 10 mg/ml is equally effective to tablets, but it may allow patients having a higher cognition and control on drug assumption.

Introduction Major depression affects 1.5%-19% general population. High use of healthcare services and increase in morbidity and mortality are common consequences. Despite of appropriate pharmacological treatment, 30-40% of patients don't achieve significant improvement. TRD refers to no remission after two adequate trials of antidepressants: these patients qualify for ECT. Objectives Our Mood Disorder Unit treats about 600 patients/year, 4% undergo ECT for TRD. Aim Ongoing, retrospective, observational study on 73 TRD patients treated with ECT 2/week, considering acute and late responsiveness 1 and 12 months later. Methods Sample of 52 (71.22%) patients with Recurrent Major Depression and 21 (28.78%) with Bipolar Disorder, collecting epidemiological and clinical data. Clinical course assessment through weekly Hamilton Rating Scale for Depression (HRSD); follow-up evaluation after 12 months, with telephone interviews. Results 73 inpatients, 26(35.62%) males, 47(64.38%) females with 4.31±3.43 previous episodes; mean age 59.42±11.60 years. Average duration of reference episode 52.71±39.42 weeks with HRSD initial score 30.16±4.76. Each patient was treated with 6.92±2.90 ECT applications. 64(87.67%) patients responded to treatment (50% reduction of HRSD initial score), 33(45.21%) achieved remission (HRSD≤8); 18(24.66%) patients maintained 12-months remission. Conclusion Our experience strengthens pivotal role of ECT in TRD. Each patient had long-lasting, severe episode under 1 year-long unsuccessful pharmacological therapy. ECT managed to quickly ameliorate their clinical course. We didn't record any adverse event. ECT showed similar relapse rates compared to conventional pharmacological treatment. This procedure requires further studies about long-term outcome.

AIMSLiterature data show that one third of patients discontinue antidepressant therapy within the first month of treatment. The aim of this study was to evaluate whether paroxetine liquid solution 10 mg/ml may influence adherence inpatients receiving long-term treatment.METHODS71 subjects affected by mood disorders or panic disorder were monitored for six months. The study sample was divided into two groups: controls (n=33) maintained their own therapy with paroxetine tablets; 38 patients maintained the same dosage of paroxetine, but shifted to liquid formulation 10 mg/ml. Compliance and general wellness were evaluated with the Medication Adherence Rating Scale (MARS) and the World Health Organization Quality of Life questionnaire (WhoQol). Data were analyzed using analysis of variance (ANOVA) and multivariate analysis of covariance (MANCOVA).RESULTSSignificant differences were found in MARS scores: patients on oral solution 10 mg/ml showed an improvement of compliance month by month. In addition, age, formulation and quality of life had a significant impacton patient compliance. Significant correlations were found between MARS and quality of life. A specific paroxetine formulation could be a variable able to influence adherence to psychopharmacological treatment. The same consideration can be made for quality of life, sex and age that showed a trend towards improved adherence when compared with controls. Inparticular, the WhoQol subscale analysis of delta scores showed a significant difference in self-perception of quality of life inpatients treated with paroxetine either in tablet or drop formulation.DISCUSSIONFormulation in drops 10 mg/ml is equally effective to tablets, but it may allow patients having a higher cognition and control on drug assumption.

Background: Transcranial Magnetic Stimulation (TMS) is an effective technique in the treatment of depression, specifically in drug‐resistant patients. However, there is little data available on the influence of genetic variables on TMS response. Methods: We analyzed the role of three genetic polymorphisms that affected the antidepressant response: serotonin transporter promoter region (SERTPR) polymorphism, 5‐HT1A serotonergic receptor promoter region polymorphism (rs6295), and the coding region of COMT gene polymorphism (rs4680). Ninety patients with a major depressive drug‐resistant episode due to a Major Depressive Disorder or to a Bipolar Disorder were included in our study. Patients underwent high frequency TMS, focused on the left prefrontal cortex, for 2 weeks. At study completion, the response rate was 45.5%. Effects of gene polymorphisms on clinical improvement were analyzed with an analysis of variance with each gene (SERTPR, 5‐HT1A, and COMT) as factors and the Hamilton Rating Scale for Depression variation from baseline to the end of the treatment as a dependent variable. Results: We found a significant model in which three factors were not significant (diagnosis, COMT, and SERTPR), whereas factor 5‐HT1A showed a significant influence on the outcome, with patients with C/C genotype showing a greater improvement than G/G and C/G and no difference between G/G and C/G. Conclusion: According to our data, 5‐HT1A polymorphism may play a role in influencing TMS response. The effect of COMT and SERTPR did not reach statistical significance. The analysis of these and other candidate genes in larger samples could help explain genetic influence on TMS response. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.

Background: We have investigated the efficacy of high-frequency left (HFL) versus low-frequency right (LFR) repetitive transcranial magnetic stimulation (rTMS) in depression, focusing on specific symptoms as possible predictors of outcome for these two different types of stimulation. Method: Seventy-four outpatients with a major depressive episode treated with an adequate antidepressant dosage for at least 4 weeks were included in our study and randomly assigned to two different groups: HFL or LFR rTMS. The Hamilton Rating Scale for Depression (HAM-D) items were pooled into 6 factors to evaluate specific symptoms as possible predictors of response. Results: Twenty-one out of 32 patients (65.6%) and 24 out of 42 patients (57.1%) were responders in the HFL and LFR groups, respectively. No significant difference in response rate was observed. Considering the whole sample, we found an inverse correlation between activity and HAM-D score reduction and a significant positive relation between somatic anxiety and outcome. An inverse correlation between psychic anxiety and HAM-D score reduction emerged considering the HFL group. In the LFR group, there was a significant negative relationship between baseline activity and the outcome. Conclusion: These findings support the hypothesis that LFR rTMS could be as effective as HFL rTMS and more suitable for patients with a higher anxiety degree, particularly in bipolar patients.

Lucca, Adelio MD; Rossini, David MD; Malaguti, Alessia MD; Zanardi, Raffaella MD; Magri, Lorenzo PsyD; Smeraldi, Enrico MD Author Information

Bi-directional enduring changes of cortical plasticity 69 induced by a novel paired stimulation protocol Workshop-New prospects of transcranial electrical stimulation (tES) Future prospects of transcranial electrical stimulation (tES) 84 Marco Cambiaghi-Letizia Leocani Electrophysiological effects of transcranial direct current 87 stimulation (tDCS) in the visual system: evidence from a mice study Elena Olgiati-Nadia Bolognini-Angela Rossetti-Angelo Maravita Modulating crossmodal spatial orienting by non-invasive 91 brain stimulation Michela Balconi-Davide Crivelli-Adriana Bortolotti Detection of facial expression of emotion and self-report measures 95 in empathic situations are influenced by ACC inhibition: rTMS evidences Michela Balconi-Chiara Ferrari-Simona Amenta Dorsolateral prefrontal cortex involvement 100 in recognition memory. A rTMS study on stress-related words Marco Sandrini-Anna Fertonani-Carlo Miniussi A transcranical direct current stimulation study on working memory 104 Lara Bardi-Ryota Kanai-Vincent Walsh Parietal asymmetry in local/global and salience-based selection: 107 a tDCS study Workshop-New prospects of transcranial electrical stimulation (tES)

The 5-HT2A receptor is a key modulator of the serotonin pathway. We previously observed a marginal association between 5-HT2A gene variants and antidepressant efficacy in Japanese and Italian population but in the opposite direction. In the present report, we hypothesize that discrepant findings on 5-HT2A gene variants could be due to both the effect of ethnicity and a possible specific effect on some symptom improvement. The sample comprised 203 patients affected by mood disorders and treated for major depression with paroxetine or fluvoxamine. The total depressive scores for all patients were analyzed in previous reports, but symptomatologic clusters were not examined previously. The 21-item Hamilton Rating Scale for Depression (HAM-D) was administered to evaluate depressive symptoms at baseline and bi-weekly over 6 weeks of treatment. All patients were genotyped for the 5-HT2A T102C polymorphism. Compared with patients with the 5-HT2A T and C variants, in the Japanese sample T allele carriers showed selective and slower score reductions than C allele carriers in delusion and activity symptoms; on the other hand, in the Italian sample, C allele carriers showed a slower and selective score reduction compared with T allele carriers in Somatic anxiety, while they did not differ from other patients on the other scores. Despite the limitations of the small sample size and modest significance levels, these findings suggest that response to SSRIs is not a unitary phenomenon and discrepant findings across ethnic groups may be due to differential effects of gene variants.

This review summarizes a scientific dialogue between representatives in non-pharmacological treatment options of affective disorders. Among the recently introduced somatic treatments for depression those with most evidenced efficacy will be discussed. The first part of this article presents current opinions about the clinical applications of transcranial magnetic stimulation in the treatment of depression. The second part explains the most relevant uses of chronobiology in mood disorders, while the last part deals with the main perspectives on brain imaging techniques in psychiatry. The aim was to bridge gaps between the research evidence and clinical decisions, and reach an agreement on several key points of chronobiological and brain stimulation techniques, as well as on relevant objectives for future research.

transcranial direct current stimulation (tDCS) is recently receiving a renewed interest as a tool for the treatment of major depressive episodes. The aim of this study is to test the potential of tDCS as add-on therapy in drug-resistant depressed patients.

Object: Antidepressant efficacy is different in controlled trials (RCTs) and naturalistic studies. This paper reviewed exclusion criteria that are usually applied to RCTs focusing on their limitations in extrapolating data to implement guidelines for the routine treatment of depression. In addition it ascertained the representativeness of a "naturalistic" sample of inpatients treated at our mood disorder center comparing their sociodemographic and clinical characteristics to the features of mood disorder individuals reported by epidemiological studies.Method: 508 patients who met DSM IV criteria for major depressive episode and either bipolar or major depressive disorder were compared to 316 nonpsvchiatric controls on their social profiles. Structured interviews and rating scales were used for the clinical evaluation of the patient sample.Results: Common exclusion criteria of RCTs are: 1) unavailable informed consent 2) age over 65 years 3) diagnosis of bipolar disorder 4) presence of psychotic symptoms 5) mild depression (RDRS<20) 6) comorbid psychiatric disorders (axis I) 7) concurrent medical conditions (axis III). Details of our research sample: 52% of patients had bipolar depression, 49% psychotic features, 86% positive family history of mood disorders, 48% comorbid personality disorders and 66% were classified as severe mood disorders by all these featttres and high recurrence of affective episodes. Depressed patients were not markedly different from controls in their social profiles. General population: about 30% of mood disorder cases in the general population are bipolar and 20%-25% have psychotic depression. Epidemiological studies show that mood disorder patients are more frequently single and unemployed and have lower education level than the normal population.Conclusions: Our naturalistic sample, recruited in a specialized research center, included many patients who are not usually enrolled in RCTs but were still somewhat different from the general population of mood disorder individuals as for sociodemographic and clinical features. Thus, if selection criteria limit the representativeness of RCTs, research setting is the main bias in naturalistic studies.

Transcranial magnetic stimulation (TMS) has been extensively studied as a treatment for Major Depression. However, no data are available about the role of genetic variables on the response to this treatment. We analysed the role of two polymorphisms that influence the response to antidepressants: the polymorphisms of the serotonin transporter promoter region (SERTPR) and of the 5-HT1A serotonergic receptor promoter region (-1019C/G). Ninety-nine patients from two double-blind, randomised, sham-controlled TMS trials were enrolled. There was a significant influence (p=0.016) of the SERTPR polymorphism on treatment outcome, without differences between active and sham stimulation. Conversely, there was a significant (p=0.014) interaction between 5-HT1A genotype and type of stimulation: C/C patients showed a higher difference between active and sham stimulation, indicating that these patients benefited more by TMS than C/G and G/G subjects. Our sample has not the power to control for the possible influence of different medications on these results.

Rossini, David MD; Serretti, Alessandro MD; Franchini, Linda MD; Mandelli, Laura; Smeraldi, Enrico MD; Zanardi, Raffaella MD Author Information

It is often stated that depressive phenomenology and prognosis differ between elderly and younger depressed patients, in the direction of more severe symptoms and a poorer outcome in elderly individuals. However, studies addressing the topic remain largely inconclusive, and it has been suggested that potential biases connected with age may have confounded previous assessments. In this work we evaluated a sample of 93 elderly depressed individuals (>60 years) and 186 younger patients. All patients were assessed with the 21-item Hamilton Depression Rating Scale at intake and prospectively followed for 6 weeks during treatment with antidepressants. A number of clinical and demographic features were taken into account to investigate depressive phenomenology and outcome in late-life depression. We found that the high likelihood of medical disorders in elderly patients explained the more severe depressive symptomatology observed in this population. However, independently from physical problems, recovery was slightly slower in elderly compared with younger individuals. Finally, patients who developed their first lifetime episode late in life (>60 years) showed a form of symptomatology similar to that in elderly patients with an earlier onset, but they showed a more positive outcome. In conclusion, the present work suggests that depression in old age is similar to depression in other ages, except for a slightly slower response to pharmacotherapy. Minor health problems increase the severity of depression, but they do not interfere crucially with the efficacy of antidepressant treatment. Finally, late-onset depression is associated with a positive outcome.

Depressive symptoms have a large impact on cognitive test performance of mood disorder patients. After remission, some improvement of cognitive functioning has been observed, but also stable deficits have been reported both during depression and remission. In the present study, the authors aimed to investigate the cognitive functioning of mood disorder patients in relation to early symptomatic recovery, by comparing performances at the Wechsler Adult Intelligence Scale-Revised (WAIS-R) of responders and non-responders to the antidepressant treatment. The sample was composed of 51 hospitalized patients for a major depressive episode (major depressives/bipolars = 37/14). All patients were treated with fluvoxamine and evaluated at baseline and after 4 weeks using the 21-item Hamilton Rating Scale for Depression. All subjects were once assessed for their cognitive functioning with the WAIS-R, at the end of the fourth week of treatment. In the current sample, patients who showed a significant symptomatic remission after 4 weeks of treatment showed higher total WAIS-R scores and a lower incidence of cognitive impairment, compared to non-responders to treatment. No major differences could be observed on any particular subtest, but rather a global improving of scores in responders compared to non-responders to pharmacotherapy. Pre-treatment illness severity, that was significantly higher among non-responders, was significantly associated with patients' intelligence quotient scores. Despite a number of limitations, present data support a strong effect of depressive symptoms on patients WAIS-R performances and an early global improvement of cognitive functioning concurrent with symptomathology recovery during pharmacological treatment.

The aim of this study is to prospectively evaluate the antidepressant response to SSRIs in depressed post-menopausal women with or without hormonal therapy (HT), and to analyze the possible influence of basal serum levels of gonadotropins and sexual hormones on the antidepressant response. 170 post-menopausal women with a depressive episode (DSM-IV criteria)--47 on HT and 123 not on HT--started the treatment with an SSRI. Depressive symptoms were assessed at baseline and 7 weeks thereafter by raters blind to treatment regimen. Response rates were 63.2% in the group without HT and 83.7% in the HT group (p=0.013). An inverse correlation emerged between the basal levels of LH and the improvement in HRSD scores (p=0.001) in the group without HT. In conclusion, HT appeared to improve the antidepressant response to SSRIs. Furthermore, in post-menopausal women, LH basal levels may be taken into account as possible predictor of response.