A Case of Resistant Schizophrenia Successfully Treated With Clozapine/Long-acting Injectable Aripiprazole Combination.

BACKGROUND: Treatment-resistant schizophrenia (TRS) is a condition characterized by intense symptom severity and poor response to different antipsychotic agents. The first therapeutic option in TRS is clozapine, but often high/medium doses are not tolerated. Adding an oral antipsychotic to low doses of clozapine is a promising strategy in the management of TRS. On the contrary, there are few data on combined clozapine/long-acting injectable (LAI) medications, and none on clozapine/LAI-aripiprazole. CASE: A 21-year-old male schizophrenic patient, resistant to several oral and LAI medications, partially improved after clozapine 300 mg/d treatment. Unfortunately, he also reported excessive sedation and an episode of myoclonus, so clozapine was reduced to 150 mg/d, but no additional benefits were observed. Subsequently, LAI-aripiprazole (first 200 mg/mo, then 400 mg/mo) was added, and the patient's conditions dramatically improved over time. After 1 year of observation, symptoms reduction was 50% or greater, without significant adverse events. CONCLUSIONS: Clozapine use in TRS is often reduced or delayed due to the fear of serious adverse effects. Adding LAI-aripiprazole to low doses of clozapine may be a useful therapeutic option to obtain a good efficacy/tolerability balance.

Premenstrual Dysphoric Disorder Without Comorbid Psychiatric Conditions: A Systematic Review of Therapeutic Options.

OBJECTIVES: Premenstrual dysphoric disorder (PMDD) is a disabling condition affecting approximately 2% to 8% of women during reproductive age. It has been recently included in the mood disorder section of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, but its treatment as a primary psychiatric illness is still debated, because of the high prevalence of other mental disturbances in PMDD patients. On the other hand, clear clinical guidelines for PMDD patients not suffering from comorbid mental conditions are not yet available. The aim of the present study was therefore to systematically review the original articles pertaining to the treatment of PMDD in adult women free of any current or previous psychiatric comorbidity. METHODS: We searched PubMed to identify published studies on PMDD, including randomized controlled trials, open-label trials, and case series or case reports involving adult women with no history of comorbid mental conditions. The search was conducted in April 2015. RESULTS: We found 55 studies fulfilling our inclusion criteria, 49 of them focused on pharmacological/chemical agents and the remaining 6 on nonpharmacological interventions. CONCLUSIONS: Based on the results of our qualitative synthesis, the best therapeutic option in the treatment of adult PMDD patients free of other mental disorders are selective serotonin reuptake inhibitor antidepressants (especially paroxetine and fluoxetine) and low doses of oral estroprogestins. Other interventions, such as light therapy, cognitive behavioral therapy, food supplements, and herbal medicines, showed promising effects, but other investigations are needed to confirm their efficacy.

Functional magnetic resonance imaging of internet addiction in young adults.

AIM: To report the results of functional magnetic resonance imaging (fMRI) studies pertaining internet addiction disorder (IAD) in young adults. METHODS: We conducted a systematic review on PubMed, focusing our attention on fMRI studies involving adult IAD patients, free from any comorbid psychiatric condition. The following search words were used, both alone and in combination: fMRI, internet addiction, internet dependence, functional neuroimaging. The search was conducted on April 20(th), 2015 and yielded 58 records. Inclusion criteria were the following: Articles written in English, patients' age ≥ 18 years, patients affected by IAD, studies providing fMRI results during resting state or cognitive/emotional paradigms. Structural MRI studies, functional imaging techniques other than fMRI, studies involving adolescents, patients with comorbid psychiatric, neurological or medical conditions were excluded. By reading titles and abstracts, we excluded 30 records. By reading the full texts of the 28 remaining articles, we identified 18 papers meeting our inclusion criteria and therefore included in the qualitative synthesis. RESULTS: We found 18 studies fulfilling our inclusion criteria, 17 of them conducted in Asia, and including a total number of 666 tested subjects. The included studies reported data acquired during resting state or different paradigms, such as cue-reactivity, guessing or cognitive control tasks. The enrolled patients were usually males (95.4%) and very young (21-25 years). The most represented IAD subtype, reported in more than 85% of patients, was the internet gaming disorder, or videogame addiction. In the resting state studies, the more relevant abnormalities were localized in the superior temporal gyrus, limbic, medial frontal and parietal regions. When analyzing the task related fmri studies, we found that less than half of the papers reported behavioral differences between patients and normal controls, but all of them found significant differences in cortical and subcortical brain regions involved in cognitive control and reward processing: Orbitofrontal cortex, insula, anterior and posterior cingulate cortex, temporal and parietal regions, brain stem and caudate nucleus. CONCLUSION: IAD may seriously affect young adults' brain functions. It needs to be studied more in depth to provide a clear diagnosis and an adequate treatment.

Neural correlates of negative emotion processing in bipolar disorder.

INTRODUCTION: Bipolar disorder type I (BD-I) is characterized by a severe impairment in emotional processing during both acute and euthymic phases of the illness. The aim of the present study was to investigate negative emotion processing in both euthymic patients and non-affected first-degree relatives, looking for state and trait markers of BD-I. METHODS: 22 healthy relatives of BD-I patients (mean age 31.5±7.3 years; 15 females), 23 euthymic BD-I patients (mean age 35.2±7.9 years; 14 females), and 24 matched controls (mean age 32.5±6.2 years; 16 females) performed an IAPS-based emotional task during 1.5T fMRI. They were required to identify vegetable items (targets) inside neutral or negative pictures. RESULTS: Euthymic BD-I patients showed a significant reduced accuracy in target detection during both neutral and negative images presentation, whereas first-degree relatives performed similarly to normal comparisons. We found a reduced activation of Left precuneus during negative images condition in the patients only. By contrast, both patients and relatives hyperactivated the Left insula and hypoactivated the Right supramarginal gyrus with respect to controls. Moreover, relatives showed an increased activation of Right lingual gyrus and lower activation of pre-supplementary motor area and Right superior frontal gyrus. CONCLUSIONS: During a negative emotion task, euthymic BD-I patients and non-affected first-degree relatives shared an abnormal activation of a limbic area (Left insula) coupled with a reduced activation of a parietal region (Right supramarginal gyrus), thus suggesting a trait-like anomalous processing of affective contents. On the other hand, functional abnormalities found only in unaffected relatives and not in patients and controls may correspond to resilience factors.

Sustained attention in psychosis: Neuroimaging findings.

To provide a systematic review of scientific literature on functional magnetic resonance imaging (fMRI) studies on sustained attention in psychosis. We searched PubMed to identify fMRI studies pertaining sustained attention in both affective and non-affective psychosis. Only studies conducted on adult patients using a sustained attention task during fMRI scanning were included in the final review. The search was conducted on September 10(th), 2013. 15 fMRI studies met our inclusion criteria: 12 studies were focused on Schizophrenia and 3 on Bipolar Disorder Type I (BDI). Only half of the Schizophrenia studies and two of the BDI studies reported behavioral abnormalities, but all of them evidenced significant functional differences in brain regions related to the sustained attention system. Altered functioning of the insula was found in both Schizophrenia and BDI, and therefore proposed as a candidate trait marker for psychosis in general. On the other hand, other brain regions were differently impaired in affective and non-affective psychosis: alterations of cingulate cortex and thalamus seemed to be more common in Schizophrenia and amygdala dysfunctions in BDI. Neural correlates of sustained attention seem to be of great interest in the study of psychosis, highlighting differences and similarities between Schizophrenia and BDI.

Lamotrigine augmentation in premenstrual dysphoric disorder: a case report.

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome, characterized by depressive, anxious, and somatic symptoms, associated to a significant reduction in social functioning and quality of life. Although selective serotonin reuptake inhibitors (SSRIs) and oral contraceptives show a substantial effectiveness in PMDD, a wide percentage of women affected by PMDD do not respond to those first-line treatments. We present the case of a 42-year-old woman, affected by a disabling form of PMDD, who partially responded to an SSRI treatment and significantly improved after an add-on therapy with lamotrigine. We therefore suggest that lamotrigine may be an efficacious and safe augmentation strategy in severe PMDD cases showing unsatisfactory or partial response to SSRI treatments.

Impaired sustained attention in euthymic bipolar disorder patients and non-affected relatives: an fMRI study.

OBJECTIVE: Behavioral deficits in sustained attention have been reported during both acute and euthymic phases of type I bipolar disorder (BD-I) and also in non-affected relatives of bipolar disorder (BD) patients. In particular, selective failure in target recognition was proposed as a potential trait marker for BD, but there are few studies exploring the neural correlates. The aim of the present study was to analyze the behavioral and functional magnetic resonance imaging (fMRI) response of euthymic BD-I patients and non-affected relatives during a sustained attention task. METHODS: Twenty-four euthymic BD-I patients, 22 non-affected first-degree relatives of BD-I subjects, and 24 matched controls underwent a continuous performance test (CPT) with two levels of difficulty during event-related fMRI scanning. RESULTS: Both patients and relatives showed a lower accuracy in target detection when compared to controls. The fMRI data analysis revealed between-group differences in several brain regions involved in sustained attention. During error in target recognition, both patients and relatives showed a larger activation in the bilateral insula and the posterior part of the middle cingulate cortex. By contrast, during correct target response, only patients failed to activate the right insula, whereas relatives showed an increased activation of the left insula and bilateral inferior parietal lobule - limited to the higher attention load - and an augmented deactivation of the posterior cingulate/retrosplenial cortex. CONCLUSIONS: A selective impairment in target recognition during a CPT was behaviorally and functionally detectable in both euthymic BD-I patients and non-affected first-degree relatives, suggesting that specific sustained attention deficits may be a potential trait marker for BD-I.

Altered brain response without behavioral attention deficits in healthy siblings of schizophrenic patients: an event-related fMRI study.

Attention deficits are common in schizophrenics and sometimes reported in their healthy relatives. The aim of this study was to analyse the behavioural performance and the brain activation of healthy siblings of schizophrenic patients during a sustained-attention task. Eleven healthy siblings of schizophrenic patients and eleven matched controls performed a Continuous Performance Test (CPT), during 1.5 T fMRI. The stimuli were presented at three difficulty-levels, using different degrees of degradation (0, 25 and 40%). There were no significant differences in CPT performance (mean reaction time and percentage of errors) between the two groups. Performance worsened with increasing degradation in both groups. Differences were found when comparing the BOLD signal change in the medial frontal gyrus/dorsal anterior cingulate, right precentral gyrus, bilateral posterior cingulate and bilateral insula. The most evident between group differences were observed in the left insula/inferior frontal gyrus: siblings showed a larger activation during wrong responses and a reduced activation during correct responses in the degraded runs. In conclusion, healthy siblings of schizophrenic patients showed differences in brain function in several brain regions previously reported in schizophrenic subjects, in the absence of behavioral attention deficits. The differences were greater in the two more difficult levels of attention demand and might be expressions of altered and/or compensatory mechanisms in subjects at increased risk for schizophrenia.

Alexithymia and its relationships with dissociative experiences and Internet addiction in a nonclinical sample.

The aim of the present study was to evaluate alexithymia, dissociative experiences, and Internet addiction (IA) in a nonclinical sample of 312 undergraduate students, identifying predictive factors associated with the possible risk of developing IA. We found that alexithymics had more consistent dissociative experiences, lower self-esteem, and higher obsessive-compulsive symptoms than nonalexithymics. In addition, alexithymics reported a higher potential risk for IA when compared to nonalexithymics. Difficulty in identifying feelings, higher dissociative experiences, lower self-esteem, and higher impulse dysregulation were associated with higher IA. Thus, a combination of alexithymia, dissociative experiences, low self-esteem, and impulse dysregulation may be a risk factor for IA, at least in a nonclinical sample.

Alexithymia and its relationships with C-reactive protein and serum lipid levels among drug naïve adult outpatients with major depression.

Several studies have investigated the relationship between C-reactive protein (CRP) and serum lipid levels in Major Depression (MD), but no study has, to date, evaluated the impact of alexithymia on these parameters. Therefore, the aim of the present cross-sectional study was to evaluate the relationship between alexithymia, suicide risk, C-reactive protein (CRP) and serum lipid levels in adult outpatients suffering from moderate to severe MD. CRP and serum lipid levels data were analyzed in 145 drug-naïve adult outpatients (69 men, 76 women) with a DSM-IV diagnosis of MD. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20), depression severity was evaluated with the 17-item Hamilton Depression Rating Scale (HAM-D) and suicide risk was determined using the Scale of Suicide Ideation (SSI). Alexithymics showed altered serum lipid levels and higher CRP than non-alexithymics. In the linear regression models, lower total cholesterol levels and "Difficulty in Identifying Feelings" dimension of TAS-20 were significantly associated with depression severity, whereas lower high-density lipoprotein levels and "Difficulty in Identifying and Describing Feelings" dimensions of TAS-20 were associated with higher suicide risk. Authors discuss study limitations and future research needs.

Insight and perceived expressed emotion among adult outpatients with obsessive-compulsive disorder.

OBJECTIVE: To elucidate the relationships between insight and perceived expressed emotion (EE) in a sample of adult outpatients with obsessive-compulsive disorder (OCD). METHODS: The study involved 75 subjects with OCD. Subjects were assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), with the score on item 11 used as a measure of insight level. Perceived EE was evaluated using the Family Emotional Involvement and Criticism Scale (FEICS). The Montgomery Asberg Depression Rating Scale (MADRS) was used to evaluate depressive symptoms. RESULTS: Poor or absent insight was found to be associated with higher perceived EE and significantly higher OCD severity, as well higher familial perceived criticism and more compulsions and depressive symptoms.

The role of duloxetine in the treatment of anxiety disorders.

Anxiety disorders (ADs) are the most common type of psychiatric disorders, with a mean incidence of 18.1% and a lifetime prevalence of 28.8%. Pharmacologic options studied for treating ADs may include benzodiazepines, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRIs), noradrenergic and specific serotonergic drug (NaSSA) and dual-reuptake inhibitors of serotonin and norepinephrine (SNRIs). In this context, the development of SNRIs (venlafaxine and duloxetine) has been particularly useful. As a dual-acting intervention that targets two neurotransmitter systems, these medications would appePar promising for the treatment of ADs. The purpose of this review was to elucidate current facts and views about the role of duloxetine in the treatment of ADs. In February 2007, duloxetine was approved by FDA for the treatment of generalized anxiety disorder (GAD). The results of trials evaluating the use duloxetine in the treatment of GAD are supportive on its efficacy even if further studies on long-term use are needed. Apart from some interesting case reports, no large studies are, to date, present in literature about duloxetine and other ADs such as panic disorder, social anxiety disorder, obsessive-compulsive disorder and post-traumatic stress disorder. Therefore, the clinical efficacy and the relative good tolerability of duloxetine may be further investigated to widen the therapeutic spectrum of ADs.

Alexithymia and its relationships with body checking and body image in a non-clinical female sample.

The aim of the present study was to evaluate in a non-clinical sample of undergraduate women, the relationships between alexithymia, body checking and body image, identifying predictive factors associated with the possible risk of developing an Eating Disorder (ED). The Toronto Alexithymia Scale (TAS-20), Body Checking Questionnaire (BCQ), Eating Attitudes Test (EAT-26), Body Shape Questionnaire (BSQ), Interaction Anxiousness Scale (IAS), Rosenberg Self-Esteem Scale (RSES) and the Beck Depression Inventory (BDI) were completed by 254 undergraduate females. We found that alexithymics had more consistent body checking behaviors and higher body dissatisfaction than nonalexithymics. In addition, alexithymics also reported a higher potential risk for ED (higher scores on EAT-26) when compared to nonalexithymics. Difficulty in identifying and describing feelings subscales of TAS-20, Overall appearance and Specific Body Parts subscales of BCQ as well as lower self-esteem was associated with higher ED risk in a linear regression analysis. Thus, a combination of alexithymia, low self-esteem, body checking behaviors and body dissatisfaction may be a risk factor for symptoms of ED at least in a non-clinical sample of university women.

Alexithymia, fear of bodily sensations, and somatosensory amplification in young outpatients with panic disorder.

To elucidate the relationships between alexithymia, fear of bodily sensations, and somatosensory amplification in young patients with panic disorder (PD), authors evaluated 84 patients. Measures were the Panic Attack and Anticipatory Anxiety Scale, the Toronto Alexithymia Scale (TAS-20), the Body Sensations Questionnaire (BSQ), the Somatosensory Amplification Scale, the Agoraphobic Cognitions Questionnaire (ACQ), and the Hamilton Rating Scale for Depression. Alexithymic patients showed higher scores on all rating scales. Higher BSQ and ACQ scores, together with the Difficulty in Identifying Feelings and Difficulty in Describing Feelings subscales of the TAS-20 were predictors of severity of PD. Results of the present study do not support a direct role of somatosensory amplification in PD. Authors discuss study limitations and future research needs.

Treatment of premenstrual dysphoric disorder (PMDD) with a novel formulation of drospirenone and ethinyl estradiol.

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS). Pharmacologic options studied for treating severe PMS and PMDD may include selective serotonin reuptake inhibitors, anxiolytic agents, gonadotropin-releasing hormone agonists and the diuretic spironolactone. However, the use of combined oral contraceptives (COC) may be a therapeutic option in treating PMS and PMDD. The combination of drospirenone with ethinylestradiol (EE/drospirenone) was approved for marketing as an oral contraceptive in Europe and the United States. The preparation is characterized by a high contraceptive efficacy in combination with excellent cycle control, good tolerability, and a favourable impact on lipid and glucose metabolism. Recently, some placebo-controlled, randomized studies have tested clinical efficacy and tolerability of this COC in the treatment of PMDD. The aim of the present review was to elucidate the possible benefits or disadvantages of PMDD treatment with this novel formulation of EE/drospirenone. The results of trials evaluating the use of EE/drospirenone combination in the treatment of PMDD are encouraging but further studies are needed. However, the reported clinical efficacy and the relative good tolerability of EE/drospirenone may contribute to widen the therapeutic spectrum of PMDD.

Alexithymia and body image in adult outpatients with binge eating disorder.

OBJECTIVE: The current study elucidates the relations between alexithymia and body image in patients with binge eating disorder (BED). METHOD: One hundred one patients with BED were evaluated. Alexithymia was measured with the Toronto Alexithymia Scale (TAS-20). The severity of BED was measured with the Binge Eating Scale (BES). Body concerns were assessed with the Body Shape Questionnaire-Short Version (BSQ-S), the Body Uneasiness Test (BUT), and the Body Attitude Test (BAT). Additional measures were the Rosenberg Self-Esteem Scale (RSES) and the Beck Depression Inventory (BDI). RESULTS: The prevalence of alexithymia in our sample was 39.6% (n = 40) and individuals with alexithymia showed higher scores on all rating scales. Higher body dissatisfaction, lower self-esteem, depressive symptoms, and the Difficulty in Identifying Feelings/Difficulty in Describing Feelings subscales of the TAS-20 were predictors of the severity of BED in the linear regression analysis. CONCLUSION: Alexithymia was associated with more severe BED. Individuals with alexithymia and BED exhibited significantly poorer appearance evaluation and body satisfaction as well as higher depressive symptoms than individuals without alexithymia.

Olanzapine augmentation in treatment-resistant panic disorder: a 12-week, fixed-dose, open-label trial.

The purpose of our study was to evaluate the efficacy and tolerability of low-dose olanzapine augmentation in selective serotonin reuptake inhibitor (SSRI)-resistant panic disorder (PD) with or without agoraphobia. In this 12-week, open-label study, 31 adult outpatients with treatment-resistant PD who had previously failed to respond to SSRI treatment were treated with fixed dose of olanzapine (5 mg/d) in addition to SSRI. Efficacy was assessed using the Panic Attack and Anticipatory Anxiety Scale (PAAAS), the Agoraphobic Cognitions Questionnaire (ACQ), the Hamilton Rating Scale for Anxiety (HAM-A), the Hamilton Rating Scale for Depression (HAM-D), the Global Assessment of Functioning Scale (GAF), and the Clinical Global Impression of Improvement (CGI-I). Twenty-six patients completed the trial period with a dropout rate of 16.1%. At week 12, 21 patients were responders (81.8%), and an overall improvement on all rating scales was observed in all patients both with or without agoraphobia. Fifteen patients (57.7%) achieved remission. Olanzapine was well tolerated and the most frequent adverse effects were mild-to-moderate weight gain and drowsiness. No extrapyramidal symptoms were reported. Olanzapine appears to be effective as augmentation strategy in the treatment of SSRI-resistant PD, but study limitations must be considered and placebo-controlled studies are needed.

Mirtazapine treatment of generalized anxiety disorder: a fixed dose, open label study.

We investigated the efficacy of mirtazapine in the treatment of generalized anxiety disorder (GAD). Forty-four adult outpatients with GAD were treated openly with a fixed dose of mirtazapine (30 mg) for 12 weeks. The primary outcome measure was the change from baseline in total score on the Hamilton Rating Scale for Anxiety (HAM-A). The Clinical Global Impression of Improvement (CGI-I) was rated at the endpoint. Patients with a reduction of 50% or more on the HAM-A total score and a CGI-I score of 1 or 2 at endpoint were considered responders to treatment; remission was defined as a HAM-A score

Insight and alexithymia in adult outpatients with obsessive-compulsive disorder.

OBJECTIVE: To elucidate the relationships between insight and alexithymia in a sample of adult outpatients with obsessive-compulsive disorder (OCD). METHODS: 112 adult outpatients with OCD were tested. Severity of OCD was assessed with the first 10-items of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and score for item # 11 on the Y-BOCS was considered as a measure of insight. Alexithymia was measured with 20-item Toronto Alexithymia Scale (TAS-20). Additional measures were Maudsley Hospital Obsessive Compulsive Inventory (MOCI) and Montgomery Asberg Depression Rating Scale (MADRS). RESULTS: Of the patients, 29.5% showed poor or no insight. Patients with poor or no insight were more alexithymic than patients with excellent, good and moderate insight. TAS-20 total score and subfactors positively correlated with score for item # 11 on the Y-BOCS, severity of OCD and MADRS scores. In stepwise regression model, MADRS scores, factor 3 of TAS-20 (Externally Oriented Thinking), somatic and hoarding-saving obsessions were significantly associated with lower insight. CONCLUSIONS: Results show a relationship between poor or absent insight and high alexithymia levels in OCD patients.