Sarah Antonini

Unilateral low frequency versus sequential bilateral repetitive transcranial magnetic stimulation: is simpler better for treatment of resistant depression?

Repetitive transcranial magnetic stimulation (rTMS) efficacy in the treatment of major depression has been shown in both low frequency right-sided and high frequency left-sided stimulation over the dorsolateral prefrontal cortex (DLPFC). The aim of the present investigation was to evaluate the hypothesis of an additive effect of bilateral stimulation compare to sequential to unilateral stimulation. Sixty patients with treatment-resistant depression were assigned to receive either low-frequency rTMS over the right DLPFC (140 s x 1 Hz) followed by controlateral sham (unilateral group, n=20), low frequency right DLPFC rTMS followed by left DLPFC high frequency rTMS (5 s x 10 Hz) (bilateral group, n=20), or bilateral sham (sham group, n=20) in a 3 weeks double-blind, randomized trial. The primary outcome variable was the score on Hamilton Depression Scale (HAM-D). Low frequency right-sided and sequential bilateral stimulation showed different antidepressant efficacy at 3 weeks and across the full duration of the study, only the unilateral method appearing significantly more effective than sham at the end of the trial, and correlated to the higher percent of remitters (30% of the group vs. 10% -bilateral- and 5% -sham). Unilateral stimulation, but not bilateral, showed higher antidepressant efficacy compared to sham stimulation. The data suggest that right-sided low frequency stimulation may be a first line treatment alternative in resistant depression. To confirm and extend these findings further studies require a longer follow-up period, supported by biological observation and replication.

Ondansetron augmentation in treatment-resistant obsessive-compulsive disorder: A preliminary, single-blind, prospective study

AbstractBackground: Serotonin and dopamine neuronal systems have been implicated in the modulation of obsessive-compulsive disorder (OCD) symptoms. About 40% of OCD patients do not respond to first-line selective serotonin reuptake inhibitor (SSRI) treatment; among those, dopamine blocker augmentation has been reported to improve the rate of response by an additional one-third. Given that serotonin 5-HT3 receptors are indirect inhibitors of corticomesolimbic dopamine release, augmentation with the 5-HT3 receptor antagonist ondansetron in combination with SSRIs and antipsychotics has potential efficacy in treatment-resistant OCD patients. Objective: To assess the efficacy and tolerability of ondansetron in combination with SSRIs and antipsychotics in patients with treatment-resistant OCD. Method: In total, 14 patients with a DSM-IV diagnosis of OCD, who were treatment resistant and receiving stable treatment with SSRIs and antipsychotic augmentation, entered a 12-week, single-blind trial of ondansetron. The drug was initiated at a dosage of 0.25 mg twice daily for 6 weeks and was then titrated to 0.5 mg twice daily for 6 weeks. Results: Of the 14 patients, nine (64.3%) experienced a treatment response (≥25% reduction in the Yale-Brown Obsessive Compulsive Scale [YBOCS] score and a Clinical Global Impressions-Improvement [CGI-I] score of 1 or 2) at 12 weeks. The average reduction in YBOCS-rated symptoms for the whole group was 23.2%. None of the treated patients experienced symptom exacerbation or significant adverse effects. Conclusion: These results suggest that low-dose ondansetron may have promise as an augmentation strategy for some patients with OCD resistant to SSRIs and antipsychotic augmentation, but further controlled trials are required. Trial registration number (ClinicalTrials.gov): NCT00796497

Ondansetron augmentation in patients with obsessive-compulsive disorder who are inadequate responders to serotonin reuptake inhibitors: Improvement with treatment and worsening following discontinuation

OBJECT The aim of this study was to evaluate low-dose ondansetron as an augmentation strategy in patients with obsessive-compulsive disorder (OCD) who do not adequately respond to serotonin reuptake inhibits (SRIs). METHODS Twenty-one OCD patients who had not responded adequately to an SRI received 12 weeks of single-blind ondansetron augmentation initiated at 0.25mg BID for 2 weeks, and titrated to 0.5mg BID for an additional 10 weeks. Patients were rated every two weeks using the Yale-Brown Obsessive Compulsive Scale (YBOCS) and Clinical Global Impressions Scale (CGI). Treatment response was defined as an additional 25% reduction in YBOCS score from the score at the initiation of ondansetron augmentation, an end of treatment YBOCS score of ≤ 24 and a CGI-Improvement (CGI-I) score of ≤ 2. Upon completion of treatment course patients were followed for 4 weeks. RESULTS At week 12, twelve of the 21 (57%) patients were responders. The average reduction in the YBOCS score for the overall group was 27.2%. Responders had an average 44% YBOCS score reduction and 76.9% CGI-I reduction. After discontinuation of ondansetron the YBOCS worsened an average of 15.5% in the entire sample and 38.3% in the responder subsample. No clinically meaningful side effects were reported. CONCLUSION OCD patients who do not adequately respond to an SRI may benefit from augmentation with a low-dose of ondansetron. This may provide an alternative approach to augmentation with atypical antipsychotic agents, with a more favorable safety profile.

Low-Frequency rTMS over Right Dorsolateral Prefrontal Cortex in the Treatment of Resistant Depression: Cognitive Improvement Is Independent from Clinical Response, Resting Motor Threshold Is Related to Clinical Response

Background: Clinical studies have shown that repetitive transcranial magnetic stimulation (rTMS) is effective in a certain percentage of treatment-resistant depression (TRD). The left dorsolateral prefrontal cortex (DLPFC) 10 Hz rTMS stimulation received FDA approval in 2008, although different rTMS protocols have also shown their effectiveness in reducing depressive symptoms. We investigated the clinical, cognitive and neurophysiologic effects of a 3 weeks’ protocol of low-frequency rTMS applied over the right DLPFC in resistant depression. Methods: Twenty-eight patients with TRD (age range 28–55) received low-frequency rTMS (1 Hz) over the right DLPFC in a 3-week open trial. Hamilton scales for depression and anxiety, Corsi block-tapping test, phonemic verbal fluency, right and left resting motor thresholds were evaluated in each subject over the trial period. Results: At the end of the trial 42.9% of the subjects were considered as responders. A significant reduction of both HAMD (p < 0.001) and HAMA (p < 0.01) total scores was observed. At the 3rd week, the performances in Corsi test (p < 0.02) and phonemic verbal fluency (p = 0.065) were improved independently from depressive symptoms variation. At the end of the rTMS protocol, a significantly decreased left hemisphere resting motor threshold was registered (p < 0.01), while right hemisphere resting motor threshold did not show significant variation. Conclusion: Low-frequency rTMS over the right DLPFC appeared effective in 42.9% of depressive resistant subjects in this sample. A significant decrease in left hemisphere resting motor threshold was observed only in responders, while a trend for improvement in cognitive function has been found and appeared independent from clinical response.

Major depression and bipolar disorders in CADASIL: a study using the DSM-IV semi-structured interview.

Valenti R, Pescini F, Antonini S, Castellini G, Poggesi A, Bianchi S, Inzitari D, Pallanti S, Pantoni L. Major depression and bipolar disorders in CADASIL: a study using the DSM‐IV semi‐structured interview.
Acta Neurol Scand: 2011: 124: 390–395.
© 2011 John Wiley & Sons A/S.

Facial Affect Recognition in CADASIL Patients

We explored the capacity of Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) patients to recognize facial expressions. Twenty-three consecutive CADASIL patients and 23 age-matched, gender-matched, and education-matched controls were assessed with a semi-structured psychiatric interview, cognitive tests, and the Ekman and Friesen test. Cases and controls (5 males, 18 females) had a mean age (+SD) of 52.4 + 15.7 and 54.0 + 15.3 years, respectively, and a Mini-Mental State Examination (MMSE) mean score of 27.8 + 2.2 and 28.9 + 1.3 (p < .05). Eighteen out of the 23 (78.3%) CADASIL patients and 10 (43.5%) controls were diagnosed as affected by major depression according to DSM-IV criteria (p < .05). The CADASIL patients had an impaired ability of emotion recognition in comparison with controls, particularly for fear expression. This effect was not mediated by depression, cognitive impairment, and MMSE score. Facial affect recognition is reduced in the CADASIL patients and this impairment might represent an early manifestation of the disease.

Contents Vol. 65, 2012

A. Drago, Naples G. Erdmann, Berlin A. Fischer, Göttingen J.M. Ford, San Francisco, Calif. S. Galderisi, Naples M. Hatzinger, Solothurn U. Hegerl, Leipzig K. Hirata, Mibu M. Kato, Osaka J. Kornhuber, Erlangen D. Lehmann, Zürich P. Monteleone, Naples G. Okugawa, Osaka G.N. Papadimitriou, Athens M. Popoli, Milano M. Reuter, Bonn F. Rösler, Marburg G. Ruigt, Oss J.K. Rybakowski, Poznan F. Schneider, Aachen R. Schwarting, Marburg M. Shigeta, Tokyo D. Souery, Brussels A. Steiger, Munich P. Willner, Swansea Associate Editors

Repetitive transcranial magnetic stimulation (RTMS) as augmentation treatment in bipolar mixed state

Objective: Manic and depressive symptoms often co-occur in bipolar I or II disorder, characterizing a common, severe and complex clinical state. Mixed states (MS) are difficult to treat and are overrepresented in treatmentresistant subgroups. Antidepressants, even though they are associated with mood stabilizers, often increase manic dimension severity compared to mood stabilizers alone. Repetitive Transcranial Magnetic Stimulation (rTMS) has been poorly investigated in bipolar disorder, particularly in MS, whereas it represents an effective, welltolerated treatment for depression. Taking into account the documented low risk of rTMS treatment to induce mania in bipolar depression, we tested rTMS as an augmentative strategy for acute treatment of MS.