Lorenzo Magri

Transcranial magnetic stimulation in treatment-resistant depressed patients: A double-blind, placebo-controlled trial

This 5-week, randomized, double-blind, placebo-controlled trial investigated the efficacy and tolerability of high frequency repetitive transcranial magnetic stimulation (rTMS) directed to the left prefrontal cortex in drug-resistant depressed patients. Fifty-four patients were randomly assigned to receive 10 daily applications of either real or sham rTMS. Subjects assigned to receive active stimulation were divided into two further subgroups according to the intensity of stimulation: 80% vs. 100% of motor threshold (MT). At study completion, the response rates were 61.1% (n=11), 27.8% (n=5) and 6.2% (n=1) for the 100% MT group, 80% MT group and sham group, respectively. A significant difference (Pearson chi(2) test) was found between the 100% MT and sham groups, while the 80% MT group did not differ significantly from the sham group. Between the two active groups, a marginally significant difference was observed. Analysis of variance with repeated measures on Hamilton Depression Rating Scale scores revealed a significantly different decrease over time of depressive symptomatology among the three treatment groups. Treatment response appeared to be unrelated to the demographic and clinical characteristics recorded, and on the whole the technique was well tolerated. The results of this double-blind trial showed that rTMS may be a useful and safe adjunctive treatment for drug-resistant depressed patients.

Response to SSRIs and role of the hormonal therapy in post-menopausal depression.

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.

A Symptom-Specific Analysis of the Effect of High-Frequency Left or Low-Frequency Right Transcranial Magnetic Stimulation over the Dorsolateral Prefrontal Cortex in Major Depression

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.

Role of serotonergic gene polymorphisms on response to transcranial magnetic stimulation in depression

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-HT(1A) 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-HT(1A) 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.

Role of COMT, 5-HT(1A) , and SERT genetic polymorphisms on antidepressant response to Transcranial Magnetic Stimulation.

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.

New perspectives on techniques for the clinical psychiatrist: Brain stimulation, chronobiology and psychiatric brain imaging

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.