Are 5-HT3 antagonists effective in obsessive-compulsive disorder? A systematic review of literature.

OBJECTIVE: The purpose of this literature database search-based review was to critically consider and evaluate the findings of literature focusing on efficacy and safety of 5-HT3 antagonists in the treatment of obsessive-compulsive disorder (OCD), so as to test whether preclinical data match clinical therapeutic trials. DESIGN: The PubMed database has been searched for papers on 5-HT3 antagonists and OCD in humans and for animal models of OCD and 5-HT3 receptors. RESULTS: Of the clinically tested 5-HT3 receptor antagonists, ondansetron has been used to treat OCD in five therapeutic studies, whereas granisetron only in one recent trial. Both showed some efficacy in open studies and superiority to placebo in double-blind studies, along with fair safety. No animal OCD model directly implicated 5-HT3 receptors. CONCLUSIONS: Overall, results indicate some utility, but the available literature is too scanty to allow for valid conclusions to be drawn. The mismatch between animal models of obsessive-compulsive disorder and clinical data with 5-HT3 antagonists needs more clinical data to ensure that it is not an artefact.

Gender Differences and Psychopathological Features Associated With Addictive Behaviors in Adolescents.

BACKGROUND: The aims of the study were to assess prevalence and gender differences of addictive behaviors (substance- and non-substance-related) in an adolescent population, and their association with psychopathological features and academic performance. MATERIAL AND METHODS: A sample of high school Italian students (n = 996; M = 240, F = 756) was examined using a self-report survey concerning sociodemographic characteristics, cigarette smoking, alcohol and substance use, perceived academic performance, activities, and behaviors (Internet use, gambling, and physical exercising). The Internet Addiction Test, the South Oaks Gambling Screen-revised Adolescent, and the Exercise Addiction Inventory-Short Form were administered to identify problematic behaviors. The Barratt Impulsiveness Scale for Adolescent, the Snaith-Hamilton Pleasure Scale, the Dissociative Experience Scale for Adolescent, and the Toronto Alexithymia Scale were used to investigate psychopathological dimensions. RESULTS: Frequent alcohol intake and lifetime substances consumption were more common among males. The occurrence of other addictive behaviors was 22.1% for problematic Internet use (M = F), 9.7% for at-risk/problematic gambling (M > F), and 6.2% for maladaptive physical exercise (M = F). We also found an association between substance-/non-substance-related addictive behaviors and psychopathological dimensions. Addictive behaviors were more frequent among students reporting poor school performance. CONCLUSION: Our study showed a relevant prevalence of addictive behaviors in a sample of Italian high school students, with specific gender differences. We underlined the cooccurrence of substance and non-substance-related addictive behaviors, and their association with worse school performance. Dissociative proneness, anhedonia, alexithymia, and impulsivity were associated with addictive behaviors in adolescents and might represent vulnerability factors for the development of psychiatric disorders in adulthood. A better understanding of psychopathological features associated with addictive behaviors might be useful for the prevention/early intervention.

Add-on deep Transcranial Magnetic Stimulation (dTMS) for the treatment of chronic migraine: A preliminary study.

INTRODUCTION: Deep Transcranial Magnetic Stimulation (dTMS) can be an alternative treatment to relieve pain in chronic migraine (CM). The aim of this study was to evaluate the effect of high-frequency dTMS in add-on to standard treatment for CM in patients not responding to effective abortive or preventive drug treatment. METHODS: We randomized 14 patients with International Classification of Headache Disorders, 3rd Edition (ICHD-3) treatment-resistant CM to add-on dTMS (n=7) or standard abortive or preventive antimigraine treatment (n=7). Three sessions of alternate day 10Hz dTMS consisting of 600 pulses in 10 trains were delivered to the dorsolateral prefrontal cortex (DLPFC), bilaterally, but with left hemisphere prevalence, for 12 sessions spread over one month. RESULTS: The add-on dTMS treatment was well tolerated. Patients treated with dTMS showed significant reduction of pain intensity, frequency of attacks, analgesic overuse, and depressive symptoms during treatment and one month later, compared to the month preceding treatment and at the same time-points compared to the control group. CONCLUSIONS: As compared to standard pharmacological treatment alone, add-on high-frequency dTMS of the bilateral DLPFC reduced the frequency and intensity of migraine attack, drug overuse, and depressive symptoms. This study supports the add-on dTMS treatment in treatment-resistant CM.

Add-on high frequency deep transcranial magnetic stimulation (dTMS) to bilateral prefrontal cortex reduces cocaine craving in patients with cocaine use disorder.

INTRODUCTION: Cocaine dependence is a substantial public health problem. The aim of this study is to evaluate the effect of high frequency deep transcranial magnetic stimulation (dTMS) on craving in patients with cocaine use disorder (CUD). METHODS: Seven men (mean age, 48.71 years; standard deviation [SD], 9.45; range 32-60 years) with CUD and no concurrent axis 1 or 2 disorder save nicotine abuse, underwent three sessions of alternate day 20Hz dTMS in 20 trains delivered to the dorsolateral prefrontal cortex (DLPFC) preferentially to the left hemisphere, for 12 sessions spread over one month, added to unchanged prior drug treatment. We used a visual analogue scale (VAS) to measure cocaine craving the week before, each week during, and one month after dTMS treatment. RESULTS: DLPFC stimulation significantly reduced craving over time: within-subjects main effect of time of treatment (ANOVA, F[3,18]=46.154; p<0.001; η(2)=0.88). The reduction of craving from baseline was significant at two weeks (p<0.001), and four weeks (p<0.001) of treatment, and at the week eight, four weeks after treatment interruption (p=0.003), although the increase of craving was significant from week four and eight (p=0.014). CONCLUSION: dTMS over left DLPFC reduced craving in CUD patients in a small sample that is to be considered preliminary. However, maintenance sessions would be needed to maintain the achieved results. Our findings highlight the potential of noninvasive neuromodulation as a therapeutic tool for cocaine addiction.

Executive functions in obsessive-compulsive disorder: An activation likelihood estimate meta-analysis of fMRI studies.

OBJECTIVES: To identify activation changes assessed in functional magnetic resonance imaging (fMRI) studies of obsessive-compulsive disorder (OCD) through Activation Likelihood Estimate meta-analysis. METHODS: We included 28 peer-reviewed standard stereotactic space studies assessing adult OCD patients (OCDpts) vs. healthy controls (HCs) with fMRI during executive task performance. RESULTS: In within-group analyses, HCs showed task-related activations in bilateral inferior frontal gyri, right middle frontal gyrus, right inferior parietal lobule, right claustrum, bilateral cingulate gyri, and left caudate body. OCDpts showed task-related left-sided activations in the superior, medial, and inferior frontal gyri, and thalamus, and bilateral activations in the middle frontal gyri, inferior parietal lobule, and insular cortices. Subtraction analysis showed increased left middle frontal gyrus activation in OCDpts. In between-groups analyses, OCDpts hypoactivated the right caudate body, left putamen, left ACC, and right medial and middle frontal gyri. Right caudate hypoactivation persisted also after applying Family-wise error algorithms. CONCLUSIONS: This meta-analysis confirms that during executive functioning OCDpts show a functional deficit of the right caudate body, which could represent a major neural functional correlate of their illness.

Effectiveness of long-acting risperidone in a patient with comorbid intellectual disability, catatonic schizophrenia, and oneiroid syndrome.

A patient with comorbid intellectual disability, catatonic schizophrenia, and recurrent oneiroid state of consciousness improved on long-acting risperidone and remains well at the three-year follow-up. We report a case treated with 50 mg long-acting risperidone administered every 14 days, who has been followed-up for three years. We studied his regional cerebral blood flow through technetium-99 m hexamethylpropyleneamine oxime single-photon emission computed tomography after two years of treatment. Symptoms of catatonic schizophrenia improved after two months of treatment, followed suit by oneiroid syndrome remission. Two years later, his brain perfusion was normal. No side effect has occurred since the patient was started on long-acting risperidone. Long-acting risperidone proved to be safe and effective in treating symptoms of catatonia and oneiroid syndrome.

Treatment-resistant, five-year long, postpartum-onset Capgras episode resolving after electroconvulsive therapy.

Postpartum psychosis, which rarely presents with Capgras syndrome (delusional misidentification), requires rapid symptom resolution. First-line drugs have important drawbacks, such as delayed onset of clinical response and secretion in breast milk. In this report, we report successful treatment of a treatment-resistant woman presenting with treatment-resistant Capgras syndrome, with onset during postpartum. A 36-year-old woman had presented with Capgras syndrome during postpartum. For more than five years, she believed her son and other family members were substituted by impostors. All adequately administrated treatments were unsuccessful. We suggested electroconvulsive therapy to overcome treatment resistance. After six electroconvulsive therapy sessions, delusions of doubles subsided and other symptoms improved. She was discharged two weeks later with a mood stabilizer and low-dose atypical antipychotic combination and is well at the one-and-a-half-year follow-up. Electroconvulsive therapy followed by a mood stabilizer-antipsychotic drug combination showed rapid, permanent, and effective control of long-standing Capgras syndrome in a young woman.

Antidepressant effectiveness of deep Transcranial Magnetic Stimulation (dTMS) in patients with Major Depressive Disorder (MDD) with or without Alcohol Use Disorders (AUDs): a 6-month, open label, follow-up study.

INTRODUCTION: Co-occurrence of Major Depressive (MDD) and Alcohol Use Disorders (AUDs) is frequent, causing more burden than each disorder separately. Since the dorsolateral prefrontal cortex (DLPFC) is critically involved in both mood and reward and dysfunctional in both conditions, we aimed to evaluate the effects of dTMS stimulation of bilateral DLPFC with left prevalence in patients with MDD with or without concomitant AUD. METHODS: Twelve MDD patients and 11 with concomitant MDD and AUD (MDD+AUD) received 20 dTMS sessions. Clinical status was assessed through the Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impressions severity scale (CGIs), craving through the Obsessive Compulsive Drinking Scale (OCDS) in MDD+AUD, and functioning with the Global Assessment of Functioning (GAF). RESULTS: There were no significant differences between the two groups in sociodemographic (age, sex, years of education and duration of illness) and baseline clinical characteristics, including scores on assessment scales. Per cent drops on HDRS and CGIs scores at the end of the sessions were respectively 62.6% and 78.2% for MDD+AUD, and 55.2% and 67.1% for MDD (p<0.001). HDRS, CGIs and GAF scores remained significantly improved after the 6-month follow-up. HDRS scores dropped significantly earlier in MDD+AUD than in MDD LIMITATIONS: The small sample size and factors inherent to site and background treatment may have affected results. CONCLUSIONS: High frequency bilateral DLPFC dTMS with left preference was well tolerated and effective in patients with MDD, with or without AUD. The antidepressant effect of dTMS is not affected by alcohol abuse in patients with depressive episodes. The potential use of dTMS for mood modulation as an adjunct to treatment in patients with a depressive episode, with or without alcohol abuse, deserves further investigation.

Add-on deep transcranial magnetic stimulation (dTMS) in patients with dysthymic disorder comorbid with alcohol use disorder: a comparison with standard treatment.

OBJECTIVES: Dorsolateral prefrontal cortex (DLPFC) is dysfunctional in mood and substance use disorders. We predicted higher efficacy for add-on bilateral prefrontal high-frequency deep transcranial magnetic stimulation (dTMS), compared with standard drug treatment (SDT) in patients with dysthymic disorder (DD)/alcohol use disorder (AUD) comorbidity. METHODS: We carried-out a 6-month open-label study involving 20 abstinent patients with DSM-IV-TR AUD comorbid with previously developed DD. Ten patients received SDT for AUD with add-on bilateral dTMS (dTMS-AO) over the DLPFC, while another 10 received SDT alone. We rated alcohol craving with the Obsessive Compulsive Drinking Scale (OCDS), depression with the Hamilton Depression Rating Scale (HDRS), clinical status with the Clinical Global Impressions scale (CGI), and global functioning with the Global Assessment of Functioning (GAF). RESULTS: At the end of the 20-session dTMS period (or an equivalent period in the SDT group), craving scores and depressive symptoms in the dTMS-AO group dropped significantly more than in the SDT group (P < 0.001 and P < 0.02, respectively). CONCLUSIONS: High frequency bilateral DLPFC dTMS with left preference was well tolerated and found to be effective as add-on in AUD. The potential of dTMS for reducing craving in substance use disorder patients deserves to be further investigated.

Mitochondrial myopathy and comorbid major depressive disorder: effectiveness of dTMS on gait and mood symptoms.

BACKGROUND: Mitochondrial myopathies (MMs) often present with leukoencephalopathy and psychiatric symptoms, which do not respond to or worsen with psychiatric drugs. CASE REPORT: A 67-year-old woman with a 10-year history of probable chronic progressive external ophthalmoplegia, an MM, had drug-resistant, anxious-depressive symptoms. Since she had never had seizures, we proposed 20 sessions of deep transcranial magnetic stimulation (dTMS) for her depression. Surprisingly, besides the expected improvement of depression, we observed marked improvement of movement disorder that lasted as long as the patient was undergoing dTMS. She also improved her performance on neuropsychological tests of executive function and cognitive speed. Depressive symptom improvement was persistent, while anxiety symptoms recurred after the end of the sessions. CONCLUSIONS: dTMS may be an alternative antidepressant strategy in patients with MMs, provided that they are free from seizures. The mechanism of improvement of motor disturbance may relate to dorsolateral prefrontal cortex stimulation and improved executive function and needs further investigation.