Poster

Reversal Learning as a Neuropsychological Indicator for the Neuropathology of Obsessive Compulsive Disorder? A Behavioral Study

[Author Affiliation]Ipek Percinel. 1 Department of Child and Adolescent Psychiatry, Osmaniye State Hospital, Osmaniye, Turkey.Kemal Utku Yazici. 2 Department of Child and Adolescent Psychiatry, Firat University Faculty of Medicine, Elazig, Turkey.Address correspondence to: Kemal Utku Yazici, MD, Firat University Faculty of Medicine, Department of Child and Adolescent Psychiatry, Elazig, Turkey, E-mail: dr.kemal.utku@outlook.comTo The Editor:The overall objective of psychopharmacological treatment in patients diagnosed with autism spectrum disorders (ASD) is to target irritability (aggression, tantrums, self-destructive behavior), hyperactivity, impulsivity, and stereotypical behavior (Posey et al. 2008). Although α-2 agonists, mood stabilizers, anticonvulsants, selective serotonin reuptake inhibitors, stimulants, and the typical antipsychotics can be used, atypical antipsychotics are the most common and are the first-line drugs used for treatment (Stigler and McDougle 2008). Studies using randomized, placebo-controlled trials (RCT) have shown that risperidone and aripiprazole were effective in the treatment of irritability, hyperactivity, impulsivity, and stereotypical behavior in patients with ASD (Young and Findling 2015). The number of studies that have investigated the effectiveness of psychopharmacological treatment in patients of a very young age diagnosed with ASD is very limited. Here, we present a treatment and follow-up process of a 23-month-old male patient diagnosed with ASD and treated with aripiprazole for irritability and hyperactivity.Case ReportA 20-month-old male patient was diagnosed with ASD at another center and was included in the rehabilitation program. At the age 23 months, the patient's existing irritability and hyperactivity symptoms worsened; therefore, he was admitted to our clinic. After a risk and benefits ratio evaluation, it was decided to start pharmacological treatment. The body weight of the patient was 13.2 kg. Therefore, a starting risperidone dose (0.25 mg/day [0.019 mg/kg]) was initiated and controlled, while a dose increase was planned. On the 3rd day of treatment, a spasm in the jaws, neck, and back was observed, and we requested a pediatric neurology consultation. The cause was determined to be extrapyramidal side effects. It was thought to be associated with risperidone and therefore, risperidone was discontinued. Immediately, aripiprazole was started (1 mg/day [0.08 mg/kg]). The dose of aripiprazole was increased every two weeks until it reached 3 mg/day (0.22 mg/kg). During the follow-up, the patient was clinically evaluated by using the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC)-Irritability and Hyperactivity subscales, Clinical Global Impressions-Severity (CGI-S) Scale, and Clinical Global Impressions-Improvement (CGI-I) Scale in 2 week intervals. The CGI evaluation was based on behavioral symptoms such as irritability and hyperactivity. At the time of admission, the patient's scale scores were as follows: CARS = 39, ABC-irritability = 30, ABC-hyperactivity = 39, and CGI-S = 5 (markedly ill). By the end of the 16-week-long treatment, the patient showed significant improvements in irritability and hyperactivity symptoms. In addition, a decrease in the CARS score was also observed. The patient tolerated the 3 mg/day aripiprazole treatment well. No side effects were observed, except for moderate levels of sedation. At the end of the 16-week- long treatment, the patient's scale scores were determined as follows: CARS = 31, ABC-irritability = 9, ABC-hyperactivity = 17, CGI-S = 3 (mildly ill), and CGI-I = 2 (much improved).DiscussionIn this article, we presented a 16 week follow-up of aripiprazole treatment in a 23- month-old boy diagnosed with ASD and having symptoms such as intense irritability and hyperactivity. These behavioral issues can result in functional impairment; therefore, behavioral interventions are typically prescribed. …

Background: Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder that affects approximately 2-3% of the world population. The first-line treatments are selective serotonin reuptake inhibitors and cognitive behavioral therapy. Despite that, approximately 40- 60% of patients remain treatment refractive. Aim of work: Evaluating the efficacy of different frequencies of repetitive transcranial magnetic stimulation (rTMS) applied over the right dorsolateral prefrontal cortex (DLPFC) as an adjunctive treatment for resistant OCD. Patient and Methods: Thirty patients with treatment resistant OCD were randomly assigned to 2 weeks either active LF (1 Hz, n=10), HF (10 Hz, n=10) with parameters (25-minute trains, 1,500 pulses/day at 100% of the resting motor threshold RMT, 5 sessions/week) or sham (n=10) (same HF parameters with coil tilting). OCD, anxiety and depressive symptoms were assessed using: Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Anxiety Scale (HAM-A), Beck Depression Inventory (BDI) and Clinical Global Impression-Severity scale (CGI-S) before and immediately after sessions and 3 months later. Results: A repeated-measures analysis of variance (ANOVA) revealed a non-significant reduction in Y-BOCS scores in the active groups compared with the sham group after 2 weeks and 3 months later. Similarly, there was non-significant effect of time and time×group interaction on scores of (HAM-A) (CGI-S). While there was a significant effect of time and time×group interaction on scores of (BDI) after 2 weeks with active stimulation especially LF-rTMS not after 3 months. There were no reports of serious adverse effects following the active or sham rTMS treatments. Conclusion: Neither LF nor HF rTMS over the right DLPFC appeared to be superior to sham rTMS for relieving OCD and anxiety symptoms in patients with treatment-resistant OCD. However, rTMS has a role in improving depressive symptoms, especially with LF-rTMS. Further trials with larger sample sizes should be conducted to confirm the present findings.

Special Report: Women’s Reproductive Mental Health—A Clinical Framework

“Ms. A” was a 35-year-old married Caucasian health care professional with a history of recurrent major depressive disorder that responded well to treatment with a selective serotonin reuptake inhibitor (SSRI). She discontinued her antidepressant prior to conception for a planned pregnancy because she did not want to expose her baby to medication. She soon relapsed, and by the first trimester of her pregnancy, she was in a major depressive episode. Her symptoms included anhedonia, tearfulness, irritability, insomnia, and diminished appetite. She presented for participation in an open-label pilot trial of omega-3 fatty acids for antenatal major depressive disorder (1). At intake, after hearing the risks and benefits of available treatment options, Ms. A declined antidepressant medication and a referral for psychotherapy and consented to participate in the study of omega-3 fatty acids, which she started at 16 weeks’ gestation. She was assessed every 2 weeks throughout pregnancy. At 8 weeks she had not responded to omega-3 fatty acids and was again presented with other treatment options, including medication and psychotherapy. She again declined these treatments and continued to do so throughout the remainder of her pregnancy. She was concerned about the safety of medications in pregnancy and believed that taking medication would make her a bad mother. She also declined referral for psychotherapy, stating that she was “too busy.”

In Japan, brain docking has enhanced the detection of unruptured intracranial aneurysms in healthy adults. At our institution, surgical clipping is the first-line treatment for unruptured intracranial aneurysms (UIA). In this study, the differences in neurological and radiological outcomes, as well as cognitive and psychological results, between standard clipping and keyhole clipping for these aneurysms detected via brain docking were evaluated. The study included 131 aneurysms detected via "brain dock." Of these, 65 were treated with keyhole clipping surgery (keyhole clipping group), and 66 were treated with standard clipping surgery (standard clipping group). Evaluations at 3 months included the National Institutes of Health Stroke Scale, modified Rankin Scale, Mini-Mental State Examination, Hasegawa's Dementia Scale-revised, Beck Depression Inventory, Hamilton Rating Scale for Depression, and radiological abnormalities. The mean operative time and postoperative hospitalization period were significantly shorter in the keyhole clipping group than in the standard clipping group (p < 0.001). Between the groups, no significant differences in postoperative neurological complications or radiological abnormalities were found. The keyhole clipping group demonstrated slightly but significantly better Beck Depression Inventory and Hamilton Rating Scale for Depression scores than the standard clipping group (Beck Depression Inventory, p = 0.046; Hamilton Rating Scale for Depression, p < 0.01). Both the Beck Depression Inventory and Hamilton Rating Scale for Depression scores at 3 months were significantly enhanced (p < 0.001) in the keyhole clipping group. These findings propose that keyhole clipping could be considered a new therapeutic option for small UIA detected via brain docking.

Several factors have led to suggestions that anxiety and depression are actually the same disease: very frequently, they co-exist; there is an overlap of symptoms between the two conditions; a number of similar agents can be used to treat both mental states; the same neurotransmitters are involved in both anxiety and depressive disorders; and stress can predispose both. Selective serotonin reuptake inhibitors (SSRIs) have shown efficacy in a number of neuroses: depression; obsessive–compulsive disorder (OCD) and anxiety disorders (panic disorder [PD], social anxiety disorder [SAD], generalised anxiety disorder and post-traumatic stress disorder). Furthermore, other drugs, for example, tricyclic antidepressants and monoamine oxidase inhibitors, are effective in treating both depression and some anxiety disorders. Yet some drugs are only effective in anxiety, for example, benzodiazepines, and this suggests that the two states are actually different. Despite the broad range of conditions that are treated by SSRIs, a number of differences are clear when SSRIs are used in depressive and anxious states. When used in PD and OCD, the effective dose of the SSRI is often higher than when used to treat depression. Furthermore, SSRIs often work more slowly in patients with anxiety compared with those with depression. In order to assess which serotonergic pathways and mechanisms are involved in these conditions, tryptophan depletion tests can be performed. Tryptophan is the precursor to serotonin (5-HT), so if the SSRI treatment effects are dependent on an increase in synaptic 5-HT levels, depletion will result in a relapse in symptoms. However, if the SSRI treatment works through post-receptor events, then tryptophan depletion will have little effect on the individual's symptoms. In depression, tryptophan depletion induced relapse in patients treated and controlled on SSRIs, but not in those recovered on noradrenergic agents such as desipramine. In some anxious states (PD and SAD), our work has shown that relapse was also experienced following tryptophan depletion, indicating that the SSRIs are acting via increasing 5-HT levels at the synapse in these conditions. However, other studies have found no effect of the tryptophan depletion test. This suggests that in OCD, SSRIs act post-synaptically and therefore have a different mechanism of action in OCD patients compared with depressed patients. In summary, although most SSRIs are effective in the treatment of both depression and anxiety, differences in dose, time to onset of action and, in some cases, mechanism of action are evident when treating the two conditions.

Impulsivité et problèmes d’internalisation et d’externalisation chez l’adolescent

FC10-04 - Efficacy of auditory stimulation programs for the treatment of depression, dysthymia and symptoms of burnout - RCT results

Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activity. In 6- to 24-week well designed trials, oral paroxetine 10 to 50 mg/day was significantly more effective than placebo, at least as effective as tricyclic antidepressants (TCAs) and as effective as other SSRIs and other antidepressants in the treatment of major depressive disorder. Relapse or recurrence over 1 year after the initial response was significantly lower with paroxetine 10 to 50 mg/day than with placebo and similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine 10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in 6- to 12-week trials in patients aged > or = 60 years with major depression. Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar to that of TCAs in patients with comorbid illness, and was more effective than placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to 60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder (social phobia), generalised anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Improvement was maintained or relapse was prevented for 24 weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients with OCD and panic disorder and similar to that of imipramine but greater than that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally well tolerated in adults, elderly individuals and patients with comorbid illness, with a tolerability profile similar to that of other SSRIs. The most common adverse events with paroxetine were nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor and decreased appetite. In conclusion, paroxetine, in common with other SSRIs, is generally better tolerated than TCAs and is a first-line treatment option for major depressive disorder, dysthymia or minor depression. Like other SSRIs, paroxetine is also an appropriate first-line therapy for OCD, panic disorder, social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI currently approved for the treatment of social anxiety disorder and GAD, which makes it the only drug of its class indicated for all five anxiety disorders in addition to major depressive disorder. Thus, given the high degree of psychiatric comorbidity of depression and anxiety, paroxetine is an important first-line option for the treatment of major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD.

Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activity. In 6- to 24-week well designed trials, oral paroxetine 10 to 50 mg/day was significantly more effective than placebo, at least as effective as tricyclic antidepressants (TCAs) and as effective as other SSRIs and other antidepressants in the treatment of major depressive disorder. Relapse or recurrence over 1 year after the initial response was significantly lower with paroxetine 10 to 50 mg/day than with placebo and similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine 10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in 6- to 12-week trials in patients aged > or =60 years with major depression. Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar to that of TCAs in patients with comorbid illness, and was more effective than placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to 60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder (social phobia), generalised anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Improvement was maintained or relapse was prevented for 24 weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients with OCD and panic disorder and similar to that of imipramine but greater than that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally well tolerated in adults, elderly individuals and patients with comorbid illness, with a tolerability profile similar to that of other SSRIs. The most common adverse events with paroxetine were nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor and decreased appetite. In conclusion, paroxetine, in common with other SSRIs, is generally better tolerated than TCAs and is a first-line treatment option for major depressive disorder, dysthymia or minor depression. Like other SSRIs, paroxetine is also an appropriate first-line therapy for OCD, panic disorder, social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI currently approved for the treatment of social anxiety disorder and GAD, which makes it the only drug of its class indicated for all five anxiety disorders in addition to major depressive disorder. Thus, given the high degree of psychiatric comorbidity of depression and anxiety, paroxetine is an important first-line option for the treatment of major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD.

When fluvoxamine treats only depression and clomipramine treats only obsessive-compulsive disorder--combine them?

[Author Affiliation]Murat Kardas. 1 Department of Pediatrics; Department of Pediatric Gastroenterology, Hepatology and Nutrition; and Department of Child and Adolescent Psychiatry, Bezmialem Vakif University, Istanbul, Turkey.Banu Bal Cermik. 1 Department of Pediatrics; Department of Pediatric Gastroenterology, Hepatology and Nutrition; and Department of Child and Adolescent Psychiatry, Bezmialem Vakif University, Istanbul, Turkey.Sema Ekmekci. 1 Department of Pediatrics; Department of Pediatric Gastroenterology, Hepatology and Nutrition; and Department of Child and Adolescent Psychiatry, Bezmialem Vakif University, Istanbul, Turkey.Selcuk Uzuner. 1 Department of Pediatrics; Department of Pediatric Gastroenterology, Hepatology and Nutrition; and Department of Child and Adolescent Psychiatry, Bezmialem Vakif University, Istanbul, Turkey.Selim Gokce. 1 Department of Pediatrics; Department of Pediatric Gastroenterology, Hepatology and Nutrition; and Department of Child and Adolescent Psychiatry, Bezmialem Vakif University, Istanbul, Turkey.Address correspondence to: Selim Gokce, MD, Department of Pediatric Gastroenterology Hepatology and Nutrition, Bezmialem Vakif University, Adnan Menderes Bulvari, Fatih, 34093, Istanbul, Turkey, E-mail: drgokce0007@yahoo.comTo the Editor:Posttraumatic feeding disorder (PTFD) is characterized by acute onset of severe and consistent food refusal following a traumatic event or repetetive traumatic insults to the oropharynx (Chatoor 2009). The children refuse to either drink liquids or eat any solid food, and, in severe cases, refuse all oral feeding. If untreated, food refusal potentially threatens the child's nutritional status, health, growth, and age-appropriate feeding development. Unfortunately, a standard treatment for this condition is not described.Herein, we present a 12-year-old male patient who developed severe food refusal after a choking experience. He was resistant to behavioral therapy. Lorazepam, a benzodiazepine with acute anxiolytic effect, resulted in dramatic improvement.Case ReportA 12-year-old male patient was admitted to hospital for severe refusal to drink or to eat any food, after a choking episode while eating nuts that had occurred 5 days before. He described something stuck in his oropharynx, and was continiously displaying a stereotypic swallowing movement. Past history was unremarkable. Family history revealed a conflicting relationship between the parents, but they were reluctant to give detailed information. Physical examination together with fiberendoscopic evaluation of the throat was unremarkable. Broncoscopic and upper gastrointestinal endoscopic examinations were all normal as well. Psychiatric assesment revealed that the patient was afraid of choking and dying when feeding, and that he diplayed severe anxiety when food presented to his mouth. Behavioral therapy (gradual desensitization method) was started. The patient did not respond to this approach and at the end of first week lorazepam (Ativan p.o.) was added to the treatment regimen. Clinical response was dramatic, and resulted in full restoration of oral feeding within 48 hours. Lorazepam was withdrawn during the clinical course, and the patient was discharged. Clinical symptoms and signs did not relapse.DiscussionPTFD is first described by Chatoor et al. (1988) in latency-age children refusing to eat any solids after they had experienced a choking episode and severe gagging. PTFD was later described in infants and toddlers as well (Chatoor 1991). The children are generally preoccupied with the fear of choking and dying. They display intense anxiety, and sometimes panic when food is introduced into the mouth. It can occur at any age, from infancy to adulthood. A standard treatment for this condition has not been described. Therefore, each child with a PTFD needs to be assessed individually to determine which treatment is most appropriate for the child and the family. …

The highly specific mechanism of action of the selective serotonin re-uptake inhibitors (SSRIs) confers advantages on this group, relative to other classes of antidepressant, and thus represents a significant advance in the pharmacotherapy of depression. Whilst their clinical efficacy is equivalent to that of the tricyclic antidepressants (TCAs), the SSRIs have a greatly reduced risk of toxicity in overdose and have been shown to be significantly better tolerated. Specifically, the SSRIs have a low incidence of anticholinergic effects and are essentially devoid of cardiotoxicity. This tolerability advantage may be of significance in improving compliance and hence cost-effectiveness of treatment, particularly in the long term. Despite a lack of sedative effect, there is evidence that SSRIs are more effective than TCAs in the treatment of depression with anxiety. In addition, the SSRIs have been shown to be effective in obsessive-compulsive disorder, panic disorder and social phobia. Although superior efficacy has not been demonstrated for any one of the SSRIs, the structural diversity of this group is reflected in emerging qualitative and quantitative differences in side effects and drug interaction potential. Many of these differential features reflect important variations in pharmacological and pharmacokinetic profiles, including dosage flexibility, washout times, dose-plasma level proportionality and age-related changes in plasma levels. Fluoxetine, for example, has a considerably longer half-life than other SSRIs and side effects and drug interactions may thus occur for an extended period following discontinuation of treatment. Significant differences in the potential for drug interactions in this group are related to their relative potency for inhibition of important liver drug-metabolising enzymes including CYPIID6, CYPIA2 and CYPIIIA4. Large comparative clinical trials of the different SSRIs have yet to be undertaken; however, the differences that have already become apparent provide important information enabling the physician to choose an SSRI appropriate to the individual patient.

To describe the cognitive and functional impairment in individuals with the first episode of major depressive disorder (MDD) as compared to controls and individuals with recurrent MDD. Also to describe the functional and cognitive trajectory after the first episode of MDD. A total of 52studies were included in our systematic review. 32studies compared the cognitive performance between first episode of depression (FED) and controls, 11studies compared the cognitive performance between recurrent depression (RD) and FED, 10 compared global functioning between RD and FED, fourstudies assessed cognition in FED over time, and twostudies assessed global functioning in FED over time. The majority of studies (n=22/32, 68.8%) found that FED subjects performed significantly worse than controls on cognitive tests, with processing speed (n=12) and executive/working memory (n=11) being the most commonly impaired domains. Seven out of 11studies (63.6%) found that RD performed significantly worse than FED, with verbal learning and memory being the most commonly impaired domain (n=4). Most studies (n=7/10, 70%) did not find a significant difference in global functioning between RD and FED. In three of fourlongitudinal studies assessing cognition, subgroup analyses were used instead of directly assessing cognition in FED over time while the remaining study found significant cognitive declines over time in FED when compared to controls. The two longitudinal studies assessing functional trajectory found that functioning significantly improved over time, possibly due to the improvement of depressive symptoms. There is strong evidence that cognitive impairment is present during the first episode of depression, and individuals with multiple episodes display greater cognitive impairment than individuals with a single episode. Future studies aimed at identifying predictors of cognitive and functional impairment after the first episode of depression are needed to describe the functional and cognitive trajectory of individuals with the first episode of MDD over time.