Mauro García-Toro

Modest adjunctive benefit with transcranial magnetic stimulation in medication-resistant depression

BACKGROUND Controverted results have been obtained using high frequency transcranial magnetic stimulation (HF-rTMS) as an antidepressant treatment. METHODS Forty patients suffering from drug-resistant major depression received ten sessions of HF-rTMS at 90% of the motor threshold on the left prefrontal cortex or sham stimulation, added to their pharmacological treatment, in a randomized double-blind design. In a second open phase, patients still fulfilling criteria of inclusion received ten additional sessions of HF-rTMS at 90 or 110%. RESULTS Real, but not sham HF-rTMS, was associated with a significant decrease in the Hamilton Depression Rating Scale, but only twelve patients decreased more than 50%. CONCLUSIONS Left prefrontal HF-rTMS was effectively associated with antidepressant treatment, although the size effect was small. LIMITATIONS Shortage of the sample and control difficulties of the placebo effect. CLINICAL RELEVANCE Questionable in more than half of the patients studied.

High (20-Hz) and low (1-Hz) frequency transcranial magnetic stimulation as adjuvant treatment in medication-resistant depression

Studies of repetitive transcranial magnetic stimulation (rTMS) in depression have found antidepressant effects when high frequency stimulation (HF-rTMS; >1 Hz) is applied over the left prefrontal cortex (LPF). A few studies have also reported success with low frequency stimulation (LF-rTMS) to the right prefrontal cortex (RPF). Both HF-rTMS and LF-rTMS have been reported to work better in areas with cerebral hypometabolism or hypermetabolism, respectively. Thirty medication-resistant patients with major depression were randomized into three groups. The first group received sham rTMS and the second group received active rTMS (20-Hz rTMS to the LPF and 1-Hz rTMS to the RPF). The third group, however, received active rTMS that was focused on different regions of the brain after examination with single photon emission computed tomography (20-Hz rTMS to an area of relatively low activity and 1-Hz rTMS to an area showing relatively high activation). Patients and raters were blind to the treatment condition. Comparison of the sham rTMS group with the overall group that received active rTMS revealed statistically significant changes on the Hamilton Rating Scale for Depression after 10 sessions. This study demonstrated that combined 20+1-Hz rTMS was effective, but no additional advantages were obtained by focusing rTMS on areas identified by single photon emission tomography as showing high versus low levels of functional activity.

Low-frequency transcranial magnetic stimulation in patients with fibromyalgia and major depression.

OBJECTIVE To study the efficacy of low-frequency transcranial magnetic stimulation in patients with fibromyalgia and major depression. DESIGN Twenty-eight patients were randomly assigned to receive 20 sessions of real or sham transcranial magnetic stimulation of the right dorsolateral prefrontal cortex. The main stimulation parameters were 15 trains at 110% of the motor threshold for 60 seconds at a frequency of 1 Hz. Blinded external evaluators administered the fibromyalgia scales (FibroFatigue, Likert pain) and the depression scales (Hamilton Depression Rating Scale, Clinical Global Impression) during the study. RESULTS Both treatment groups (real and sham) improved their scores in some of the scales (FibroFatigue and Clinical Global Impression), although there were no differences between them. No improvements were observed in the Likert Pain Scale in either of the groups. CONCLUSION With the methodology used in this study, patients with fibromyalgia and major depression who received real magnetic stimulation did not present significant differences in symptoms with respect to those who received sham magnetic stimulation.

Functional cerebral asymmetry in affective disorders: new facts contributed by transcranial magnetic stimulation

A growing body of experimental data usually finds a slightly lower activation in the left hemisphere than in the right in depressive syndromes, whereas the opposite occurs in mania. Transcranial magnetic stimulation (TMS) seems to have a distinctive lateralized effect with manic or depressed patients. These clinical findings provide new elements for discussion of the significance of unbalanced hemispherical activation as a biological substrate in affective disorders. Based on these data and on the theories of chaos and complexity, a hypothesis for the physiopathology of affective disorders and the functional mechanism of TMS is proposed. This hypothesis is in agreement with valence theory.

Four hygienic-dietary recommendations as add-on treatment in depression: a randomized-controlled trial.

BACKGROUND Modifying diet, exercise, sunlight exposure and sleep patterns may be useful in the treatment of depression. METHOD Eighty nonseasonal depressive outpatients on anti-depressant treatment were randomly assigned either to the active or control group. Four hygienic-dietary recommendations were prescribed together. Outcome measures were blinded assessed before and after the six month intervention period. RESULTS A better evolution of depressive symptoms, a higher rate of responder and remitters and a lesser psychopharmacological prescription was found in the active group. LIMITATIONS Small sample size. Lacked homogeneity concerning affective disorders (major depression, dysthimia, bipolar depression). CONCLUSIONS This study suggests lifestyle recommendations can be used as an effective antidepressant complementary strategy in daily practice.

Persistence of chronic major depression: A national prospective study

BACKGROUND Chronic major depressive disorder (CMDD) is highly prevalent and associated with high personal and societal cost. Identifying risk factors for persistence and remission of CMDD may help in developing more effective treatment and prevention interventions. METHODS Prospective cohort study of individuals participating in the National Epidemiologic Survey on Alcohol and Related Conditions (Wave 1; n=43,093) and its 3-year follow-up (Wave 2; n=34,653) who met a diagnosis of CMDD at the Wave 1 assessment. RESULTS Among the 504 respondents who met criteria for present CMDD at Wave 1, only 63 (11.52%) of them continued to meet criteria of CMDD. A history of childhood sexual abuse, earlier onset of MDD, presence of comorbidity and a history of treatment-seeking for depression predicted persistence of CMDD three years after the baseline evaluation. LIMITATIONS Our sample is limited to adults, our follow-up period was only three-years and the diagnosis of CMDD at baseline was retrospective. CONCLUSIONS CMDD shows high rates of remission within three years of baseline assessment, although some specific risk factors predict a persistent course. Given the high personal and societal cost associated with CMDD, there is a need to develop and disseminate effective interventions for CMDD.

Age predicts low-frequency transcranial magnetic stimulation efficacy in major depression

BACKGROUND Transcranial magnetic stimulation (TMS) effectiveness in major depression has so far been studied mainly with high-frequency (>1 Hz) administration (HF-TMS). However, some available studies with low-frequency TMS (LF-TMS) have provided similar response rates to HF-TMS with better tolerance, but the evidence is mixed and controversial. METHODS Randomized, controlled, two arm, clinical trial. 34 Major Depression patients were randomly assigned to receive 20 sessions of real or sham TMS of the right dorsolateral prefrontal cortex as adjuvant treatment to pharmacotherapy. The main stimulation parameters were 20 trains at 110% of the motor threshold for 60 s at a frequency of 1 Hz. Blinded external evaluators administered the Hamilton Depression Rating Scale. RESULTS Both treatment groups significantly improved, although there were no statistical differences between them. In the real TMS group patients age inversely correlated with improvement of depressive symptoms at the end of the study (r=-0683 p=0.002). The percentage of decrease in scores on the Hamilton Scale was greater in subjects younger than 45 years old vs. others (41.3 +/- 22.6 vs. 15.1 +/- 15.8; t=2.8 df=16, p=0.011). These real TMS subgroups did not differ significantly in their history of previous depressive disorders, or in the refractoriness indicators of the current episode. LIMITATIONS Small size and highly refractory sample. CONCLUSION Only younger patients benefited from LF-rTMS as adjuvant treatment to antidepressants in this study.

Treatment patterns in major depressive disorder after an inadequate response to first-line antidepressant treatment

BackgroundThe aim of the study was to determine the most common pharmacological strategies used in the management of major depressive disorder (MDD) after an inadequate response to first-line antidepressant treatment in clinical practice.MethodsMulticenter, non-interventional study in adult outpatients with a DSM-IV-TR diagnosis of MDD and inadequate response to first-line antidepressant medication. Multiple logistic regression analyses were performed to identify independent factors associated with the adoption of a specific second-line strategy.ResultsA total of 273 patients were analyzed (mean age: 46.8 years, 67.8% female). Baseline mean Montgomery-Asberg Depression Rating Scale total score was 32.1 (95%CI 31.2-32.9). The most common strategies were: switching antidepressant medication (39.6%), augmentation (18.8%), and combination therapy (17.9%). Atypical antipsychotic drugs were the most commonly used agent for augmenting antidepressant effect. The presence of psychotic symptoms and the number of previous major depressive episodes were associated with the adoption of augmenting strategy (OR = 3.2 and 1.2, respectively).ConclusionThe switch to another antidepressant agent was the most common second-line therapeutic approach. Psychiatrists chose augmentation based on a worse patients’ clinical profile (number of previous episodes and presence of psychotic symptoms).

Hygienic-dietary recommendations for major depression treatment: Study protocol of a randomized controlled trial

BackgroundDepression is a highly prevalent and disabling mental disorder with an incidence rate which appears to be increasing in the developed world. This fact seems to be at least partially related to lifestyle factors. Some hygienic-dietary measures have shown their efficacy as a coadjuvant of standard treatment. However, their effectiveness has not yet been proved enough in usual clinical practice.MethodsMulticenter, randomized, controlled, two arm-parallel, clinical trial involving 300 patients over 18 years old with a diagnosis of Major Depression. Major depression will be diagnosed by means of the Mini-International Neuropsychiatric Interview. The Beck Depression Inventory total score at the end of the study will constitute the main efficacy outcome. Quality of Life and Social and Health Care Services Consumption Scales will be also administered. Patients will be assessed at three different occasions: baseline, 6-month follow-up and 12-month follow-up.DiscussionWe expect the patients in the active lifestyle recommendations group to experience a greater improvement in their depressive symptoms and quality of life with lower socio-sanitary costs.Trial registrationISRCTN73931675

Effectiveness of hygienic-dietary recommendations as enhancers of antidepressant treatment in patients with Depression: Study protocol of a randomized controlled trial

BackgroundIn recent years some studies have been published supporting the efficacy of light exposure, physical activity, sleep control and a Mediterranean diet pattern on the improvement or prevention of Depression. However, to our knowledge, there have been no studies using all these measures together as an adjuvant antidepressant strategy.MethodsMulticenter, randomized, controlled, two arm-parallel, clinical trial. Eighty depressed patients undergoing standard antidepressant treatment will be advised to follow four additional hygienic-dietary recommendations about exercise, diet, sunlight exposure and sleep. Outcome measures will be assessed before and after the 6 month intervention period.DiscussionWe expect the patients in the active recommendations group to experience a greater improvement in their depressive symptoms. If so, this would be a great support for doctors who might systematically recommend these simple and costless measures, especially in primary care.Trial RegistrationISRCTN59506583