Abstract
Background: Recent studies suggest that atypical antipsychotics may be effective augmentation strategies for the treatment of posttraumatic stress disorder (PTSD). Limited data were available on the newest agent, aripiprazole, so we aimed to evaluate its efficacy and tolerability in the treatment of PTSD.

Methods: A 12-week, prospective, open-label, flexible-dose, adjunctive trial of aripiprazole was conducted in military veterans meeting DSM-IV criteria for PTSD. Concomitant psychiatric medications continued unchanged, except for other neuroleptics which were not allowed. The primary outcome variable was change from baseline in the Clinician Administered PTSD scale (CAPS).

Results: All 17 subjects were male, with an average age of 57 years. Total CAPS scores decreased from 78.2 (SD=17.8) at baseline to 60.0 (23.5) at study end (p=0.002). Re-experiencing (CAPS-B) and avoidance/numbing symptoms (CAPS-C) were significantly improved, and trend level reductions were observed in hyperarousal symptoms (CAPS-D). Fifty-three percent (9/17) were considered responders, as defined by a decrease in total CAPS scores of at least 20%. Reductions in the Positive and Negative Symptom Scale (PANSS) total score and positive and general psychopathology subscale scores were statistically significant. The final average dose of aripiprazole was 13.06 (SD=6.45) mg daily. Nine patients discontinued because of side effects. The most common adverse events consisted of gastro-intestinal disturbances, sedation, and psychomotor activation. Tolerability was improved with lower starting doses (e.g. 5 mg daily) and slow titration.

Conclusions: Addition of aripiprazole to ongoing treatment further reduced PTSD symptoms in military veterans with severe PTSD. These preliminary findings await confirmation in randomized, controlled trials.

Bipolar-I Patient Characteristics Associated with Differences in Antimanic Medication Prescribing
By Alisa B. Busch, MD, Richard G. Frank, PhD, Gary Sachs, MD, Sharon-Lise T. Normand, PhD

Abstract
Objective: Second-generation antipsychotics offer more choice in antimanic pharmacologic treatment. Unclear though is whether they are expanding antimanic treatment, replacing mood stabilizers, or if/which patient characteristics influence prescribing choices. We studied the association between patient characteristics and patient-reported antimanic medication use upon entry in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

Experimental Design: Observational study using STEP-BD baseline data from bipolar-I patients (N=1,943) during years 2000-2004. Two logistic regression models (binomial and multinomial) were estimated to examine associations between patient characteristics and patient-reported drug use: 1) any antimanic medication (antipsychotic or mood stabilizer), and 2) mood stabilizer, antipsychotic monotherapy, or neither.

Principal Observations: At study entry over 80% of participants reported receiving at least one antimanic medication; 73% a mood stabilizer specifically. In general, there was no association between study year and the odds of entering on antimanic medication. Measures of psychiatric severity or complexity were more likely to be associated with differences in the drugs used; co-occurring medical conditions were not. Depressed states were associated with similar odds of antipsychotic monotherapy as elevated or mixed states. Compared to whites, blacks had greater odds of entering on antipsychotic monotherapy relative to a mood stabilizer.

Conclusions: Despite increasing pharmacotherapy options, we found no evidence that over time more patients received antimanic medication. Not all prescribing differences were consistent with the medical literature. Also, blacks were more likely to receive antipsychotic monotherapy, even after adjusting for clinical characteristics. Future research examining provider characteristics that influence prescribing is needed.

Neuropsychological Functioning in Patients with Posttraumatic Stress Disorder Following Short-Term Paroxetine Treatment
By Negar Fani, MS, Noriyuki Kitayama, MD, Ali Ashraf, MD, Lai Reed, MBA, Nadeem Afzal, MD, Farhan Jawed, MD, J. Douglas Bremner, MD

ABSTRACT
A previous study found improvements in verbal declarative memory in patients with Posttraumatic Stress Disorder (PTSD) following one year of open-label paroxetine treatment. The purpose of the present study was to replicate prior findings and to extend the previous study by comparing the effects of paroxetine versus placebo on cognition in patients with PTSD.

Methods: Eighteen participants with PTSD underwent assessment of neuropsychological function, following which they were randomized to receive controlled-release (CR) paroxetine or placebo, given in a variable dose in a double-blind manner for three months. Neuropsychological testing was then repeated. Subjects who had received placebo were then treated with open-label paroxetine CR and re-assessed.

Results: Paroxetine CR treatment resulted in a significant increase in verbal declarative memory function in the group as a whole, as measured by the Wechsler Memory Scale-Revised, the Selective Reminding Test, and novel paragraph recall, and explicit recall of neutral words. Although we found patterns of improved test performance with paroxetine versus placebo treatment, these differences were not statistically significant.

Conclusion: These findings replicate an earlier finding that open label treatment with paroxetine CR is associated with improvements in verbal declarative memory function. The current study did not show a statistically significant difference between the effects of paroxetine and placebo on memory function, which may in part be related to our small sample size.

Differential efficacy of memantine for obsessive-compulsive disorder vs. generalized anxiety disorder: an open-label trial
By Jamie D. Feusner, MD; Lauren Kerwin, BA; Sanjaya Saxena, MD;
Alexander Bystritsky, MD, PhD

Abstract
Objective: A substantial proportion of patients with obsessive-compulsive disorder (OCD) and generalized anxiety disorder (GAD) do not respond to, or are intolerant of, standard treatments. Additional treatment strategies are therefore necessary. Excessive action of the excitatory neurotransmitter glutamate may play a role in the pathophysiology of OCD and possibly GAD. Memantine blocks the excitatory action of glutamate at the N-methyl-D-aspartate (NMDA) receptor under pathological conditions. The objective of this study was to compare the efficacy and safety of memantine in OCD and GAD, and to probe relative effects on OCD and anxiety symptoms.
Method: Ten OCD and 7 GAD subjects received 12 weeks of open-label memantine 10 mg twice daily, as either monotherapy or augmentation of their existing medication. Primary outcome measures were the Yale-Brown Obsessive Compulsive Scale (YBOCS) for the OCD group, the Hamilton Anxiety Rating Scale (HARS) for the GAD group, and the Clinical Global Impression-Improvement Scale (CGI-I) for both groups.
Results: The OCD group experienced a significant mean 40.6% reduction in YBOCS scores at endpoint (t=4.75, p<0.001). Three of 10 of OCD subjects were classified as responders, although 7 of 10 experienced a ≥45% reduction in YBOCS scores. The GAD group experienced a mean 22.4% reduction in HARS scores (t=3.56, p=0.012). None of the GAD subjects were responders, and none experienced a ≥50% reduction in HARS scores. Memantine was well tolerated, and there were no serious adverse effects.
Conclusions: These results suggest that memantine may have preferential efficacy in the treatment of OCD versus GAD. These preliminary findings warrant larger, placebo-controlled studies in OCD.

Atypical Antipsychotic Drugs and Diabetes Mellitus in the US Food and Drug Administration Adverse Event Database: A Systematic Bayesian Signal Detection Analysis
By Ross A. Baker PhD MBA, Andrei Pikalov MD PhD, Quynh-Van Tran PharmD,
Tatyana Kremenets PhD, Ramin B. Arani PhD, P. Murali Doraiswamy MD

Abstract
Background: Prior literature suggests that the risk of diabetes-related adverse events (DRAEs) differs between atypical antipsychotics. The present study evaluated the potential association between atypical antipsychotics or haloperidol and diabetes using data from the FDA AERS database.
Methods: Analysis of AERS data was conducted for clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole or haloperidol with 24 DRAEs from the Medical Dictionary for Regulatory Activities using a Multi-item Gamma Poisson Shrinker (MGPS) data-mining algorithm. Using MGPS, adjusted reporting ratios (Empiric Bayes Geometric Mean or EBGM) and 90% confidence intervals (CIs; EB05–EB95) were calculated to estimate the degree of drug–event association relative to all drugs and events. Logistic regression odds ratios and 90% CIs (LR05–LR95) were calculated for diabetes mellitus events.
Results: All six atypicals had an EB05 ≥2 for at least one DRAE. The most common event was diabetes mellitus (2,784 cases). Adjusted reporting ratios (CIs) for diabetes mellitus were: olanzapine 9.6 (9.2–10.0; 1306 cases); risperidone 3.8 (3.5–4.1; 447 cases); quetiapine 3.5 (3.2–3.9; 283 cases); clozapine 3.1 (2.9–3.3; 464 cases); ziprasidone 2.4 (2.0–2.9; 74 cases); aripiprazole 2.4 (1.9–2.9; 71 cases); haloperidol 2.0 (1.7–2.3; 139 cases). Logistic regression odds ratios agreed with adjusted reporting ratios.
Conclusions: In the AERS database, lower associations with DRAEs were seen for haloperidol, aripiprazole and ziprasidone, and higher associations were seen for olanzapine, risperidone, clozapine and quetiapine. Our findings support differential risk of diabetes across atypical antipsychotics, reinforcing the need for metabolic monitoring of patients taking antipsychotics.

Early Symptom Change Prediction of Remissionin Depression Treatment
By Martin M. Katz, PhD, Adam L. Meyers, MS, Apurva Prakash, BA,
Paula J. Gaynor, PhD, and John P. Houston, MD

ABSTRACT
Objectives: This study investigated hypothesized early symptom changes as differential predictors of long-term remission for duloxetine and escitalopram.
Experimental Design: This was a post-hoc analysis from a placebo-controlled, randomized, double-blind study of patients with major depressive disorder treated for 8 weeks with duloxetine 60 mg/day (N=273) or escitalopram 10 mg/day (N=274), and for another 6 months with duloxetine up to 120 mg/day or escitalopram up to 20 mg/day. Odds ratios (ORs) for successful treatment (sustained remission), defined as a 17-item Hamilton Depression Rating Scale (HAMD-17) score ≤7 over 8 months, were determined for improvement in HAMD-17 depressed mood, retardation, and anxiety symptom factor subscales (20% decrease), along with associated positive predictive values (PPVs) and negative predictive values (NPVs).
Principal Observations: For both drugs, 2-week HAMD-17 improvement on all symptom subscales (except sleep for duloxetine) significantly predicted remission with ORs >2.0. In a follow-up analysis, specific subscale items for psychological anxiety, motor retardation, and suicidality significantly predicted remission for duloxetine, and psychological and somatic anxiety for escitalopram. Notably, high NPVs on the Maier subscale indicated that a lack of 20% improvement on the “core” depression factor by Week 2 was highly predictive of unsuccessful treatment outcome over 8 months.
Conclusions: In accord with hypotheses, early symptom changes were specific to treatment, with early response in the core depression factor (Maier subscale), anxiety, and motor activity for duloxetine, and core factor and anxiety for escitalopram. Lack of early response in depression symptom subscales was highly predictive of lack of sustained remission.

Does risperidone improve hyperacusia in children with autism?
By Ahmad Ghanizadeh, MD

Introduction
Many of children with autism have hyperacusia, an increased perception to sound. It can lead to their avoidance from some sounds or they may cover their ears. There was not found any published report about possible effect of any medication for improving of hyperacusia in children with autism.

Case report
The patient is a 5 and half year old girl with autism and hyperacusia. According to her mother’s report, severity of hyperacusia was improved after taking risperidone.

Conclusion
Hyperacusia was improved after initiation of risperidone and disappeared after discontinuation of risperidone. It was re-happened in re-challenge test. This is in support of the role of risperidone. To the author’s knowledge, this is the first report of possibly risperidone effect on hyperacusia in literature.

A case of stuttering during treatment with levomepromazine
By Branimir Margetić, MD, Branka Aukst-Margetić, MD, M.Sc., Branko Krajinović MD

Stuttering is a disturbance in the normal fluency and time patterning of speech, characterized by sound and syllable repetitions, sound prolongations and broken words. Acquired stuttering that begins in adulthood is rather unusual. It might be associated with different neurological disorders, like traumatic brain injuries, strokes, or extrapyramidal diseases. Rarely, it has been also reported as a side effect of different psychopharmacologic drugs, including selective serotonin reuptake inhibitors, tricyclic antidepressants, phenothiazines, olanzapine, clozapine and risperidone.
To our best knowledge, there is only one article with descriptions of two patients who developed stuttering as a dose-dependent side effect of treatment with three different phenothiazine antipsychotics (chlorpromazine, trifluoperazine, and fluphenazine). However, a case of stuttering associated with the use of levomepromazine (also known as mepromazine or methotrimeprazine) has so far not been reported. Levomepromazine is a low-potency aliphatic phenothiazine antipsychotic characterized by strong sedative abilities and 5-HT2A:D2 affinity ratio 5:15.
We present a case in which levomepromazine was implicated as a potential cause of stuttering.