Repetitive Transcranial Magnetic Stimulation to Supplementary Motor Area in Refractory Obsessive-Compulsive Disorder Treatment: a Sham-Controlled Trial.

BACKGROUND: Repetitive transcranial magnetic stimulation has been explored in patients with obsessive-compulsive disorder, but with negative or conflicting results. This randomized double-blind study was designed to assess the efficacy of 1-Hz repetitive transcranial magnetic stimulation over the presupplementary area. METHODS: Forty medication-resistant patients were assigned to 4 weeks of either active or sham repetitive transcranial magnetic stimulation targeting the presupplementary area with the help of a neuronavigation system. RESULTS: According to the Yale-Brown obsessive-compulsive scale, the baseline-week 4 evolution showed no significant differences between groups. Responder rates at week 4 were not different between groups (repetitive transcranial magnetic stimulation 10.5% vs sham 20%; P=.63). CONCLUSION: Low-frequency repetitive transcranial magnetic stimulation applied to the presupplementary area seems ineffective for the treatment of obsessive-compulsive disorder patients, at least in severe and drug-refractory cases such as those included in this study. Further research is required to determine profiles of responder patients and appropriate repetitive transcranial magnetic stimulation parameters for obsessive-compulsive disorder.

Transcranial cortical stimulation in the treatment of obsessive-compulsive disorders: efficacy studies.

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive brain stimulation methods that became widely used as therapeutic tools during the past two decades especially in cases of depression and schizophrenia. Low frequency rTMS and cathodal effect of tDCS inhibits cortical functioning while high frequency and anodal effect of tDCS have the opposite effect. Prolonged and repetitive application of either methods leads to changes in excitability of the human cortex that outlast the period of stimulation. Both rTMS and tDCS induce functional changes in the brain-modulating neural activity at cortical level. This paper reviews rTMS and tDCS effects in clinical trials for obsessive-compulsive disorder (OCD). Low frequency rTMS, particularly targeting the supplementary motor area and the orbital frontal cortex, seems to be the most promising in terms of therapeutic efficacy while older studies targeting the prefrontal dorsal cortex were not as successful. tDCS clearly needs to be investigated in large scale and sufficiently powered randomized control studies. From a general point of view, these non-invasive techniques hold promise as novel therapeutic tools for OCD patients.

Prevalence of psychotic disorders in an urban area of France.

BACKGROUND: Most data on the prevalence of psychotic disorders is limited to global estimates or restricted to schizophrenia. Consequently, there is limited information available about the prevalence of psychotic disorders more widely and outwith age and sex - specific prevalence values. The objective of this study is to provide period prevalence estimates, detailed by gender and age groups, for treated psychotic disorders in an adult population (aged 18 years and over) from an urban area in France. METHODS: Prospective reporting of cases treated over an 8-week period complemented by several methods estimating the number of potentially missed cases, including a leakage study. The study took place in an urban, well defined catchment area, with a population of 67 430 at risk subjects living in the east of a Paris suburb. RESULTS: The observed prevalence was of 3.72 per 1000 subjects at risk; after adjustment for potentially lost cases the estimate was of 4.60 per 1000 subjects at risk. Observed prevalence was higher in men (4.71 per 1000, Relative Risk = 1.68) and in the 35-45 age-band (6.05 per 1000, Relative Risk = 1.93). CONCLUSION: Global prevalence estimates of psychotic disorders in this study are in line with expected values based on studies conducted in other countries. Careful consideration of the causes of missed cases and gathering of complementary data are essential and could result in significant changes in prevalence estimates. Detailed estimates (by age) suggest that treated psychosis might not be a lifelong condition.

Prospective survey of psychiatric patients during the first confinement of the COVID 2019 pandemic.

In the early steps of an emerging infectious disease epidemic such as Covid-19, uncertainties about the nature of the disease, its spread and impact can lead to emotional distress. In addition, the studies on confinement during an epidemic have shown a psychological impact of this measure on the feelings of anxiety and depression in the general population. METHOD: We assessed the psychological health of 550 patients followed up in outpatient psychiatry, via a pandemic-related teleconsultation during the first confinement period between March and June 2020. Patients were assessed at the beginning and at the end of the confinement on their personal situation, social relationships, professional activity, anxiety and mood. We also evaluated patients' symptomatology and their quality of life. RESULTS: Patients were well informed about Covid-19 via the media and complied with the confinement and barrier procedures. They appreciated the phone-calls and the teleconsultation follow-up. A small proportion of patients were completely socially isolated mainly at the beginning of the confinement (10%). There was no difference between the beginning and the end of the confinement in terms of depressive and anxiety symptoms or quality of life. The women were more anxious and depressed than men. Only smoking was significantly increased during this period. CONCLUSION: The expected and feared health catastrophe in psychiatry during this first phase of the pandemic in 2020 did not occur. Will the psychiatric wave appear in the "post- pandemic", the future will tell.

Relationship between incidence and prevalence in psychotic disorders: An incidence-prevalence-mortality model.

OBJECTIVES: Incidence-prevalence-mortality (IPM) models have been developped to estimate incidence or prevalence when one of these two measures is unavailable. We aimed to test the consistency of an IPM model of psychotic disorders on a recent incidence-prevalence couple dataset and to identify potential causes of inconsistency by applying the model to (a) the whole population, (b) female and male subgroups, (c) migrant subgroups, and (d) psychotic disorders with age at onset (AAO) between 18 and 24 (18-24 AAO). METHODS: We modelled prevalence (MP) using incidence data and the expected mortality and remission values. We then compared the MP to the observed prevalence (OP). RESULTS: In the whole population, the model significantly underestimated the prevalence (MP = 3.30, 95% CI [2.97, 3.66]; OP = 4.98, 95% CI [4.58, 5.41]). The results were similar for the two genders. In the migrants group, results were in the opposite direction, the model significantly overestimating the prevalence. Finally, in the 18-24 AAO subgroup, the model performed well, with OP and MP not significantly different. CONCLUSION: These results suggest that standard IPM models do not perform well for psychotic disorders and more complex models taking into account the heterogeneity of the sample (in terms of remission, mortality, population movements, etc.) need to be developed.

High-Frequency Neuronavigated rTMS in Auditory Verbal Hallucinations: A Pilot Double-Blind Controlled Study in Patients With Schizophrenia.

INTRODUCTION: Despite extensive testing, the efficacy of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of temporo-parietal targets for the treatment of auditory verbal hallucinations (AVH) in patients with schizophrenia is still controversial, but promising results have been reported with both high-frequency and neuronavigated rTMS. Here, we report a double-blind sham-controlled study to assess the efficacy of high-frequency (20 Hz) rTMS applied over a precise anatomical site in the left temporal region using neuronavigation. METHODS: Fifty-nine of 74 randomized patients with schizophrenia or schizoaffective disorders (DSM-IV R) were treated with rTMS or sham treatment and fully evaluated over 4 weeks. The rTMS target was determined by morphological MRI at the crossing between the projection of the ascending branch of the left lateral sulcus and the superior temporal sulcus (STS). RESULTS: The primary outcome was response to treatment, defined as a 30% decrease of the Auditory Hallucinations Rating Scale (AHRS) frequency item, observed at 2 successive evaluations. While there was no difference in primary outcome between the treatment groups, the percentages of patients showing a decrease of more than 30% of AHRS score (secondary outcome) did differ between the active (34.6%) and sham groups (9.1%) (P = .016) at day 14. DISCUSSION: This controlled study reports negative results on the primary outcome but demonstrates a transient effect of 20 Hz rTMS guided by neuronavigation and targeted on an accurate anatomical site for the treatment of AVHs in schizophrenia patients.

A double-blind sham controlled study of right prefrontal repetitive transcranial magnetic stimulation (rTMS): therapeutic and cognitive effect in medication free unipolar depression during 4 weeks.

BACKGROUND: Transcranial magnetic stimulation (TMS) has become a therapeutic tool in psychiatric diseases. METHODOLOGY: The objective was to evaluate the efficacy of TMS in unipolar depression: the percentage of responders (>50% HDRS reduction) and remission (HDRS score < or =8, after four weeks of active TMS treatment in depressed patients free of any antidepressive agent versus placebo-TMS. RESULTS: 27 patients were randomized in two groups: rTMS (N=11) versus sham TMS (N=16). Statistical differences were detected between sham and TMS treated groups on remission (0/16 versus 4/11 p=0.032, 1/16 versus 6/11 0.028 and 1/16 versus 7/11 p=0.011 at day 14, day 21 and day 28, respectively) and on response (2/16 versus 5/11 at day 14 (NS), 2/16 versus 7/11 p=0.0115 at day 21 and 1/16 versus 7/11 (p=0.025) day 28, respectively, using the exact Fisher test). Significant differences were observed between day 1 versus day 8 (p<0.01), day 15, day 21 and day 28 (p<0.001) in TMS group and only versus day 21 (p<0.01) and day 28 (p<0.05) for the sham group. ANOVA comparison between TMS and sham groups was significant at day 14 and day 28 (p<0.05). LIMITATIONS: The few number of patients. CONCLUSION: Our study has shown an efficacy of right rTMS in free medication unipolar depression over a month. Nevertheless, number of patients included is limited and multicentric studies will be necessary to specify the antidepressive action of TMS.

Spatial distribution of psychotic disorders in an urban area of France: an ecological study.

Previous analyses of neighbourhood variations of non-affective psychotic disorders (NAPD) have focused mainly on incidence. However, prevalence studies provide important insights on factors associated with disease evolution as well as for healthcare resource allocation. This study aimed to investigate the distribution of prevalent NAPD cases in an urban area in France. The number of cases in each neighbourhood was modelled as a function of potential confounders and ecological variables, namely: migrant density, economic deprivation and social fragmentation. This was modelled using statistical models of increasing complexity: frequentist models (using Poisson and negative binomial regressions), and several Bayesian models. For each model, assumptions validity were checked and compared as to how this fitted to the data, in order to test for possible spatial variation in prevalence. Data showed significant overdispersion (invalidating the Poisson regression model) and residual autocorrelation (suggesting the need to use Bayesian models). The best Bayesian model was Leroux's model (i.e. a model with both strong correlation between neighbouring areas and weaker correlation between areas further apart), with economic deprivation as an explanatory variable (OR = 1.13, 95% CI [1.02-1.25]). In comparison with frequentist methods, the Bayesian model showed a better fit. The number of cases showed non-random spatial distribution and was linked to economic deprivation.

[Other therapeutic strategies]. / Dépression résistante : les autres stratégies thérapeutiques.

Non-selective and irreversible MAOI have become as third or fourth-line strategy for the management of treatment-resistant depression. Non-selective and irreversible MAOI requires careful monitoring of drug interactions and dietary restrictions. Nutritional supplements such as omega-3 have been found to produce beneficial effects in the management of treatment-resistant depression when administered in combination with the ongoing antidepressant treatment. The glutamate antagonist ketamine has been found to produce beneficial effects in the management of treatment-resistant depression while administered alone. Dopamine and/or norepinephrine agonists, such as methylphenidate, modafinil or pramipexole, have been found to produce beneficial effects in the management of treatment-resistant depression when administered in combination with the ongoing antidepressant treatment.

[Switching and combining strategies of antidepressant medications]. / Dépression résistante : les stratégies de changement et d'association de médicaments antidépresseurs.

Switching antidepressant medication may be helpful in depressed patients having no benefit from the initial antidepressant treatment. Before considering switching strategy, the initial antidepressant treatment should produce no therapeutic effect after at least 4 weeks of administration at adequate dosage. Choosing an antidepressant of pharmacologically distinct profile fails to consistently demonstrate a significant superiority in terms of effectiveness over the switching to another antidepressant within the same pharmacological class. Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most recommended strategy of antidepressant combinations. Augmenting SSRI with tricyclic drugs is now a less recommended strategy of antidepressant combinations given the increased risk for the occurrence of pharmacokinetic drug-drug interactions and adverse effects.

[Potentiation strategies]. / Dépression résistante : les stratégies de potentialisation.

Lithium is among the most classically recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with lithium requires achieving plasma levels above 0.5 mEq/L. Mood-stabilizing antiepileptic drugs such as carbamazepine, valproate derivatives or lamotrigine have not demonstrated conclusive therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Thyroid hormones are considered among the currently recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with thyroid hormones requires achieving plasma concentration of TSH close to the lower limits at the normal range (0.4 µUI/L) or even below it. Second-generation antipsychotics such as aripiprazole or quetiapine have consistently demonstrated significant therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Second-generation antipsychotics however require the careful monitoring of both cardiovascular and metabolic adverse effects.

[How to define treatment-resistant depression?]. / Quelle définition pour la dépression résistante ?

The most largely used definition of the treatment-resistant depression relies on the failure of two successive trials of antidepressant treatment at an adequate dose and duration. The absence of response to previous antidepressant treatments should be assessed using specific and appropriate clinical instruments enabling a correct staging of the therapeutic resistance. A wide range of socio-demographic and clinical factors (i.e. psychiatric/somatic comorbidities) are classically associated with the therapeutic resistance. The aim of the treatment of major depression is to achieve a complete clinical remission. The presence of residual symptoms increases the risk for the subsequent occurrence of relapses and recurrences, hence facilitating the development of therapeutic resistance. The treatment-resistant depression has a deleterious impact on the social, familial or professional functioning, thereby leading to an impaired quality of life with serious socioeconomic consequences and costs.

Repetitive transcranial magnetic stimulation as an add-on therapy in the treatment of mania: a case series of eight patients.

The aim of this study is to assess the efficacy of repetitive transcranial magnetic stimulation (rTMS) as an add-on therapy in the treatment of manic bipolar patients. Eight patients were enrolled in an open trial. They received fast rTMS (five trains of 15 s, 80% of the motor threshold, 10 Hz) over the right dorsolateral prefrontal cortex (DLPFC). They were evaluated using the Mania Assessment Scale (MAS) and the Clinical Global Impression (CGI) at baseline and at day 14. All patients were taking medication during the treatment trial. There was a significant improvement of manic symptoms at the end of the trial. No side effects were reported. The results show a significant improvement of mania when patients are treated with fast rTMS over the right DLPFC. However, these results have to be interpreted with caution since they derive from an open case series and all the subjects were taking psychotropic medication during rTMS treatment. Double-blind controlled studies with a sham comparison condition should be conducted to investigate the efficiency of this treatment in manic bipolar disorders.

Patients' health literacy in psychotic disorders.

Compliance and relapse are major issues in the treatment of psychotic disorders. About 50% of subjects with schizophrenia do not comply with treatment and relapse rates of 65% are reported after one year and 80% after two years. Drug treatments are effective against psychotic symptoms, but cannot promote functional recovery or prevent relapses when prescribed alone. The factors influencing compliance include side effects and the patients' awareness of their illness. Psychosocial interventions, cognitive remediation and psychotherapy have been proposed as adjuvant treatments to increase compliance and to decrease the rate of relapse. Most of these interventions have been shown to increase compliance and to decrease the rate of relapse, but the most robust results have been achieved with cognitive behavioral therapy.