While the efficacy of repetitive transcranial magnetic stimulation (rTMS) in Major Depressive Disorder (MDD) is well established, the debate is still open in relation to bipolar depression and to a possible different effectiveness of high vs. low stimulation. The present study was aimed to assess and compare the efficacy and tolerability of different protocols of augmentative rTMS in a sample of patients with current Major Depressive Episode (MDE), poor drug response/treatment resistance and a diagnosis of MDD or bipolar disorder.

Thirty-three patients were recruited in a 4-week, blind-rater, rTMS trial and randomised to the following three groups of stimulation: (1) (n = 10) right dorsolateral prefrontal cortex (DLPFC) 1 HZ, 110% of the motor threshold (MT), 420 stimuli/day; (2) (n = 10) right DLPFC, 1 Hz, 110% MT, 900 stimuli/day; (3) (n = 13) left DLPFC, 10 Hz, 80% MT, 750 stimuli/day.

Twenty-nine patients completed the treatment, showing a significant reduction of primary outcome measures (HAM-D, MADRS and CGI-S total scores: t = 8.1, P < 0.001; t = 8.6, P < 0.001; t = 4.6, P < 0.001 respectively). No significant differences in terms of efficacy and tolerability were found between high vs. low frequency and between unipolar and bipolar patients. Side effects were reported by 21% of the sample. One of the 4 dropouts was caused by a hypomanic switch.

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.

rTMS is a non invasive technique, used for the stimulation of the Dorsolateral Prefrontal Cortex (DLPFC) by means of coil-generated magnetic fields [1,2]. The present study was aimed to assess efficacy and tolerability of augmentative low and high frequency rTMS in TRD patients, with current moderate-severe major depressive episode.

24 patients with a diagnosis of drug-resistant Major Depressive Episode (Unipolar or Bipolar Depression) were treated with 4 weeks of rTMS. Subjects were randomly assigned to one of the following treatments: right DLPFC, 1 Hz, 110% of motor threshold (MT), 420 stimuli/day; right DLPFC, 1 Hz, 110% MT, 900 stimuli/day; left DLPFC, 10 Hz, 80% MT, 750 stimuli/day, according to safety guidelines [3]. Analyses were performed using t-test and ANOVA.

3 subjects dropped out at the 1st or 2nd weeks of stimualtion. 21 patients completed the treatment, showing a statistically significant score reduction at HAM-D, MADRS, HAM-A e CGI-s (tr = 9.05, p < 0.005; tr = 7.93, p < 0.005; tr = 6.81, p < 0.005; tr = 4.37, p < 0.005). Response (reduction of HAM-D score of 50%) was achieved by 2 patients, one of whom considered remitter (HAM-D≤8). Partial response (reduction of HAM-D score between 25-50%) was obtained by 12 patients. No significant difference was observed in terms of efficacy between high vs low frequency. With respect to tolerability, only mild and transient side-effects were reported (discomfort, headache, insomnia). One patient withdrew because of hypomanic switch.

Both augmentative low and high-frequency rTMS appeared to be equally effective and well tolerated in the treatment of TRD.

Few questionnaires on the psychopathological onset and latency to treatment in psychiatric patients are currently available.

In this perspective we developed a brief questionnaire: the Psychopathological Onset Latency and Treatment Questionnaire (POLQ).

The questionnaire was administered to 265 patients with any psychiatric diagnosis. Statistical analyses were performed using SPSS.

The sample showed the following demographic variables in terms of age (48 ± 15 years), occupation (17% unemployed) and familiarity (54%). Clinical variables included: age at onset (30.66 ± 15 years), age at first diagnosis (36 ± 19 years) and age at first drug treatment (35 ± 14 years). the most common symptoms at onset were related to the anxiety spectrum (41.2%), mood spectrum (24.5%) or both (25.3%). Stressful life-events in relation to onset occurred in 63% of patients (12.1% familiar issues, 11.3% work problems, bereavement or end of a relationship in 16.6%). Most frequent first diagnoses were major depressive episode (26.8%), manic/hypomanic/mixed episode (13.6%) and anxiety disorders (11.7%). Average latency to the first visit was 34 months. in the 76.2% of the sample, the first contact was with a psychiatrist, a psychologist in 15.8%; 78.1% were treated with drugs as a first treatment, 11.7% with psychotherapy, 7.2% with both. the average duration of first treatment was 23 months (4 weeks - 360 months) and reasons for discontinuation were: lack of efficacy (23.8%) or complete remission (21.9%).

POLQ resulted to be a useful and reliable instrument in the collection of information on the psychopatological onset and latency to treatment.

Major depressive disorder (MDD) is a prevalent burdensome disease, which frequently remains untreated. The duration of untreated illness (DUI) is modifiable parameter and a valid predictor of outcome. Previous investigation in patients with MDD revealed a DUI of different years, while recent reports have documented a reduction of DUI across time, in patients with different psychiatric disorders.

The present study was aimed to investigate potential differences in terms of DUI and related variables in patients with MDD across time.

An overall sample of 188 patients with MDD was divided in two subgroups on the basis of their epoch of onset (onset before and after year 2000). DUI and other onset-related variables were assessed through a specific questionnaire and compared between the two subgroups.

The whole sample showed a mean DUI of approximately 4.5 years, with a lower value in patients with more recent onset compared to the other subgroup (27.1 ± 42.6 vs. 75.8 ± 105.2 months, P < .05). Moreover, patients with onset after 2000 reported higher rates of onset-related stressful events and lower ones for benzodiazepines prescription (65% vs. 81%; P = 0.02; 47% vs. 30%; P = 0.02).

The comparison of groups with different epochs of onset showed a significant reduction in terms of DUI and benzodiazepines prescription, and a higher rate of onset-related stressful events in patients with a more recent onset. Reported findings are of epidemiologic and clinical relevance in order to evaluate progress and developments in the diagnostic and therapeutic pathways of MDD in Italian and other countries.

The authors have not supplied their declaration of competing interest.

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).

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.

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, parahippocampus and posterior cingulate 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.

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 substance-induced psychosis.