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Present results indicate that patients with different anxiety disorders may wait for years (from 3 up to 8) before receiving a first adequate pharmacological treatment. Differences in terms of age at onset, age at the first pharmacological treatment and, ultimately, in DUI in specific anxiety disorders may depend on multiple clinical and environmental factors. Latency to non-pharmacological interventions (e.g. psychoeducation and different forms of psychotherapy) needs to be addressed and correlated with DUI in future studies.

Background:Major Depression (MD) and treatment-resistant depression (TRD) are worldwide leading causes of disability and therapeutic strategies for these impairing and prevalent conditions include pharmacological augmentation strategies and brain stimulation techniques. In this perspective, repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique with a favorable profile of tolerability which, despite being recently approved by the Food and Drug Administration (FDA) for the treatment of patients with medication-refractory unipolar depression, still raises some doubts about most effective parameters of stimulation.Methods:A literature search was performed using PubMed for the years 2001 through February 2011 in order to review meta-analytic studies assessing efficacy and safety issues for rTMS in depressive disorders. Fifteen meta-analyses were identified and critically discussed in order to provide an updated and comprehensive overview of the topic with specific emphasis on potentially optimal parameters of stimulation.Results:First meta-analyses on the efficacy of rTMS for the treatment of MD and TRD have shown mixed results. On the other hand, more recent meta-analytic studies seem to support the antidepressant efficacy of the technique to a greater extent, also in light of longer periods of stimulation (e.g. > 2 weeks).Conclusion:rTMS seems to be an effective and safe brain stimulation technique for the treatment of medication refractory depression. Nevertheless, further studies are needed to better define specific stimulation-related issues, such as duration of treatment as well as durability of effects and predictors of response.

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Keywords:Bipolar disorder Substance-induced psychosis Magnetic resonance imaging (MRI) Positron emission tomography (PET) Gray matter Cerebral metabolism A B S T R A C TBackground: Bipolar disorder (BD) may be characterized by the presence of psychotic symptoms and comorbid substance abuse. In this context, structural and metabolic dysfunctions have been reported in both BD with psychosis and addiction, separately. In this study, we aimed at identifying neural substrates differentiating psychotic BD, with or without substance abuse, versus substance-induced psychosis (SIP) by coupling, for the first time, magnetic resonance imaging (MRI) and positron emission tomography (PET). Methods: Twenty-seven BD type I psychotic patients with (n = 10) or without (n = 17) substance abuse, 16 SIP patients and 54 healthy controls were enrolled in this study. 3T MRI and 18-FDG-PET scanning were acquired. Results: Gray matter (GM) volume and cerebral metabolism reductions in temporal cortices were observed in all patients compared to healthy controls. Moreover, a distinct pattern of fronto-limbic alterations were found in patients with substance abuse. Specifically, BD patients with substance abuse showed volume reductions in ventrolateral prefrontal cortex, anterior cingulate, insula and thalamus, whereas SIP patients in dorsolateral prefrontal cortex and posterior cingulate. Common alterations in cerebellum and parahippocampus were found in both BD with substance abuse and SIP. Finally, a unique pattern of GM volumes reduction, with concomitant increased of striatal metabolism, were observed in SIP patients. Conclusions: These findings contribute to shed light on the identification of common and distinct neural markers associated with bipolar psychosis and substance abuse. Future longitudinal studies should explore the effect of single substances of abuse in patients at the first-episode of BD and substanceinduced psychosis.ß 2016 Elsevier Masson SAS. All rights reserved.

Augmentative rTMS appeared to be effective and well tolerated for the acute treatment of unipolar and bipolar depression with features of poor drug response/treatment resistance, showing a comparable effectiveness profile between protocols of high and low frequency stimulation.

Aims Psychiatric disorders represent highly impairing conditions, often underdiagnosed and undertreated, with a conspicuous duration of untreated illness (DUI). Given that social and cultural factors influence the DUI and assuming that progress in diagnosis and treatment determines a reduced latency to pharmacotherapy, we assessed and compared DUI and related variables in a large sample of psychiatric patients (n = 562) whose onset occurred within three different a priori‐defined epochs. Methods Two temporal cut‐offs were established – the year 1978, when Law 180 (redefining standards for mental care) was introduced in Italy, and the year 2000 – in order to divide patients into three subgroups: onset before 1978, onset 1978–2000 and onset after 2000. Results A significant difference in terms of age at onset, age at first diagnosis and age at first treatment was observed in patients with onset 1978–2000 and in those with onset after 2000. In addition, a significant reduction of the DUI was found across epochs (onset before 1978: 192.25 ± 184.52 months; onset 1978–2000: 77.00 ± 96.63 months; and onset after 2000: 19.00 ± 31.67 months; P < 0.001). Furthermore, the proportion of patients with onset‐related stressful events, use of benzodiazepines and neurological referral was found to be significantly different between the three epochs (χ2 = 23.4, P < 0.001; χ2 = 9.92, P = 0.007; χ2 = 16.50, P = 0.011). Conclusions Present data indicate a progressive, statistically significant reduction of latency to treatment and other related changes across subsequent epochs of onset in patients with different psychiatric disorders. Future studies will assess specific changes within homogeneous diagnostic subgroups.

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