rTMS in resistant mixed states: an exploratory study.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has shown efficacy in resistant unipolar depression, but its efficacy in bipolar disorders has not yet been extensively investigated. Mixed episodes are reported in up to 40% of acute bipolar admissions and are associated with severe psychopathology, comorbidity, high risk of suicide and poor treatment response. Right low-frequency rTMS (LF-rTMS) as an augmentation treatment might be effective for mixed states. METHODS: Forty patients were treated during a 4-week period with a mood stabilizer and subsequent rTMS (low frequency stimulation - 1Hz - applied to the right Dorso-Lateral Prefrontal Cortex (DLPFC)) as add-on treatment for 3 weeks. Response to LF-rTMS was assessed by the Hamilton Depression Rating Scale (HAM-D), the Young Mania Rating Scale (YMRS) and the Clinical Global Impressions-Bipolar Version (CGIBP) subscales. ANOVA with repeated measures performed on HAM-D, YMRS and CGI-BP subscales "change from the preceding phase" and "severity of illness" showed a statistically significant time effect from the baseline to the endpoint. RESULTS: For the HAM-D there was a 46.6% responder rate, of which 28.6% was remitted, while for the YMRS there was a 15% responder rate, all of which was remitted. LIMITATIONS: The open label-design of our study and the lack of a sham-controlled group represent a methodological limitation. CONCLUSIONS: The results suggest that LF-rTMS on the right DLFC might be a potential augmentation strategy in the treatment of both depressive and manic symptoms in mixed states.

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.

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.

rTMS age-dependent response in treatment-resistant depressed subjects: a mini-review.

BACKGROUND: In old age, depressive syndromes often affect people with chronic medical illnesses, cognitive impairment, and disability, which can worsen the outcomes of other medical disorders and promote disability. Repetitive magnetic transcranial stimulation (rTMS) is a simple and effective treatment in patients with treatment-resistant depression. Therefore the use of rTMS could be of particular potential benefit in treatment-resistant elderly patients, who often cannot tolerate the higher doses of drugs needed or show phenomena of intolerance and interaction. However, several studies assessing the efficacy of rTMS found smaller response rates in elderly patients when compared to younger samples. Nevertheless, the correlation between age and response is still a controversial issue, and there is no strong evidence to date. The aim of our study was to retest the effectiveness and safety of low-frequency rTMS in a 3 weeks active treatment in a group of resistant-depressed patients, and to investigate the role of age in the response to stimulation treatment. METHODS: Enrolled in this study were 102 treatment-resistant depressed patients. The patients were treated with low-frequency rTMS over the right dorso-lateral prefrontal cortex (DLPFC) for 3 weeks with a simple protocol (420 pulses per session for 15 sessions). At baseline, at the end of the second week, and at the end of the third week of treatment, the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A) were administered. RESULTS: Low-frequency rTMS on the prefrontal dorsolateral right area resulted in a statistically significant reduction of mean HAM-D scores in the entire group of patients at the end of treatment. The responder's rate in the whole group at the end of the third week was 56.86%. A significant inverse relationship between HAM-D reduction and age was found in the "older" (>60 years old) group, not in the "younger" (<60 years old) group. CONCLUSION: Results from this study show that low-frequency rTMS over the right DLPFC, with a relatively low number of pulses (420 pulses per session) and a relatively short period of treatment, is effective in the treatment of resistant patients (in a sample also including elderly patients) in a 3-weeks treatment protocol with a low reduction with the progress of age. Furthermore, we found a greater response in younger patients and an inverse correlation between age and treatment response. Adaptations of the protocol according to age are reviewed.

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

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-HT(3) receptors are indirect inhibitors of cortico-mesolimbic dopamine release, augmentation with the 5-HT(3) receptor antagonist ondansetron in combination with SSRIs and antipsychotics has potential efficacy in treatment-resistant OCD patients. To assess the efficacy and tolerability of ondansetron in combination with SSRIs and antipsychotics in patients with treatment-resistant OCD. 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. Of the 14 patients, nine (64.3%) experienced a treatment response (> or =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. 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.