Multifunctional drugs are those with more than one therapeutic mechanism. Trazodone is a multifunctional drug with dose-dependent pharmacologic actions. That is, it has hypnotic actions at low doses due to blockade of 5-HT2A receptors, as well as H1 histamine receptors and α1 adrenergic receptors. Higher doses recruit the blockade of the serotonin transporter (SERT) and turn trazodone into an antidepressant. Although trazodone has traditionally been used as a low dose hypnotic, a new controlled release formulation that has the potential to improve the tolerability of high doses may provide an opportunity to revisit this multifunctional drug as an antidepressant as well.

Introduction: We studied the relationship between obsessive-compulsive disorder (OCD) and lifetime history of any traumatic events among methadone maintenance treatment (MMT) patients.

Methods: In a cross-sectional sample of 167 patients, we clinically assessed for OCD using the Yale-Brown Obsessive Compulsive Scale and interviewed for their lifetime history of traumas.

Results: OCD was defined among 40.1% patients. Sixteen percent of patients reported having been victims of sexual abuse or rape, 21.6% had self-inflicted physical injuries, 34.1% attempted suicide, 44.9% sustained other physical violence or abuse, 28.7% were involved in a car accident as drivers and 6% as passengers, and 16.8% had significant falls. Patients with OCD compared with patients without OCD included more rape victims (28.4% vs. 9%), had more self-inflicted physical injuries (31.3% vs. 15%), and had more suicide attempts (46.3% vs. 26%), with no differences in other traumatic events exposure. The OCD group was characterized as being female (OR=4.0 [95% CI 1.7-9.3]), having a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text-Revision Axis I psychiatric disorder (OR=2.6 [95% CI 1.2-5.5]), being Israeli born (OR=2.9 [95% CI 1.2-6.9]), abusing benzodiazepines (OR=2.2 [95% CI 1.02-4.6]), having attempted suicide (OR=2.5 [95% CI 1.1-5.4]), and having longer duration of opiate abuse before admission to MMT (OR=1.06 [95% CI 1.01-1.1]).

Background: Exposure-based therapy for anxiety disorders is believed to operate on the basis of fear extinction. Studies have shown acute administration of D-cycloserine (DCS) enhances fear extinction in animals and facilitates exposure therapy in humans, but the neural mechanisms are not completely understood. To date, no study has examined neural effects of acute DCS in anxiety-disordered populations.

Methods: Two hours prior to functional magnetic resonance imaging scanning, 23 spider-phobic and 23 non-phobic participants were randomized to receive DCS 100 mg or placebo. During scanning, participants viewed spider, butterfly, and Gaussian-blurred baseline images in a block-design paradigm. Diagnostic and treatment groups were compared regarding differential activations to spider versus butterfly stimuli.

Results: In the phobic group, DCS enhanced prefrontal (PFC), dorsal anterior cingulate (ACC), and insula activations. For controls, DCS enhanced ventral ACC and caudate activations. There was a positive correlation between lateral PFC and amygdala activation for the placebo-phobic group. Reported distress during symptom provocation was correlated with amygdala activation in the placebo-phobic group and orbitofrontal cortex activation in the DCS-phobic group.

Conclusions: Results suggest that during initial phobic symptom provocation DCS enhances activation in regions involved in cognitive control and interoceptive integration, including the PFC, ACC, and insular cortices for phobic participants.

Objective: To evaluate the long-term safety and effectiveness of lisdexamfetamine dimesylate (LDX) in the treatment of adults with attention-deficit/hyperactivity disorder (ADHD).

Methods: Following a 4-week, placebo-controlled, double-blind trial, 349 adults with ADHD were enrolled into an open-label, single-arm study for up to 12 months. Treatment was initiated at 30 mg/day and titrated up to 70 mg/day at subsequent visits to achieve optimal effectiveness and tolerability. Safety assessments included adverse events inquiries, vital signs, and electrocardiograms while the primary effectiveness assessment was the ADHD Rating Scale (ADHD-RS) total score.

Results: A total of 191 (54.7%) subjects completed the study. The most common treatment-emergent adverse events (TEAEs) were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%). Most TEAEs were mild to moderate in severity. At endpoint, small but statistically significant increases in pulse and blood pressure were noted. Significant improvements in mean ADHD-RS total scores were observed at week 1 and sustained throughout the study (P<.0001 at all postbaseline visits). At endpoint, the mean improvement from baseline ADHD-RS total score was 24.8 (P<.0001).

Conclusions: LDX demonstrated a safety profile consistent with long-acting stimulant use and provided continued effectiveness in adults with ADHD for up to 12 months.