Open-label, randomized, parallel-group controlled clinical trial of massage for treatment of depression in HIV-infected subjects.

ObjectivesThe study objectives were to determine whether massage therapy reduces symptoms of depression in subjects with human immunodeficiency virus (HIV) disease.DesignSubjects were randomized non-blinded into one of three parallel groups to receive Swedish massage or to one of two control groups, touch or no intervention for eight weeks.Settings/locationThe study was conducted at the Department of Psychiatry and Behavioral Neurosciences at Cedars-Sinai Medical Center in Los Angeles, California, which provided primary clinical care in an institutional setting.SubjectsStudy inclusion required being at least 16 years of age, HIV-seropositive, with a diagnosis of major depressive disorder. Subjects had to be on a stable neuropsychiatric, analgesic, and antiretroviral regimen for >30 days with no plans to modify therapy for the duration of the study. Approximately 40% of the subjects were currently taking antidepressants. All subjects were medically stable. Fifty-four (54) subjects were randomized, 50 completed at least 1 week (intent-to-treat; ITT), and 37 completed the study (completers).InterventionsSwedish massage and touch subjects visited the massage therapist for 1 hour twice per week. The touch group had a massage therapist place both hands on the subject with slight pressure, but no massage, in a uniform distribution in the same pattern used for the massage subjects.Outcome measuresThe primary outcome measure was the Hamilton Rating Scale for Depression score, with the secondary outcome measure being the Beck Depression Inventory.ResultsFor both the ITT and completers analyses, massage significantly reduced the severity of depression beginning at week 4 (p ≤ 0.04) and continuing at weeks 6 (p ≤ 0.03) and 8 (p ≤ 0.005) compared to no intervention and/or touch.ConclusionsThe results indicate that massage therapy can reduce symptoms of depression in subjects with HIV disease. The durability of the response, optimal "dose" of massage, and mechanisms by which massage exerts its antidepressant effects remain to be determined

Phase 1 randomized study on the safety, tolerability, and pharmacodynamic cognitive and electrophysiological effects of a dopamine D1 receptor positive allosteric modulator in patients with schizophrenia.

ASP4345, a novel dopamine D1 receptor positive allosteric modulator, is being evaluated for the treatment of cognitive impairment associated with schizophrenia (CIAS). This phase 1 multiple ascending-dose study (NCT02720263) assessed the safety, tolerability, and pharmacodynamics of ASP4345 in patients with schizophrenia/schizoaffective disorder. Pharmacodynamic assessments were Cogstate cognitive tests and electrophysiological biomarkers, including gamma-band power and phase synchronization in response to 40-Hz auditory steady-state stimulation, as well as mismatch negativity (MMN) and P3a event-related potentials. The sample size determination was based on standard practice in assessing safety and tolerability of a new chemical entity. Data were summarized by conversion of this data into effect sizes using descriptive and inferential statistics. A total of 36 randomized patients received ASP4345 (3, 15, 50, and 150 mg; n = 9 each dose) and 12 patients received placebo. Patients in the ASP4345 group experienced 73 treatment-emergent adverse events (TEAEs) and 34 TEAEs were reported for the placebo group. The most common TEAEs were headache and somnolence and nearly all TEAEs were mild in severity. No changes in mood or self-reports of suicidal ideation/behavior were observed. Improvements in performance on cognitive tests were noted, which suggests a potential improvement in psychomotor function and visual attention. Furthermore, positive changes in neurophysiological biomarkers (auditory steady-state response [ASSR] and MMN) suggest improvement in information processing. The findings need to be confirmed in studies with a larger patient population. Nonetheless, the trends in safety and pharmacodynamic data support further clinical development of ASP4345 for the treatment of CIAS

Proof-of-Mechanism Study of the Phosphodiesterase 10 Inhibitor RG7203 in Patients With Schizophrenia and Negative Symptoms

BACKGROUND:Reduced activation of dopamine D1receptor signaling may be implicated in reward functioning as apotential driver of negative symptoms in schizophrenia. Phosphodiesterase 10A (PDE10A), an enzyme that is highlyexpressed in the striatum, modulates both dopamine D2- and D1-dependent signaling.METHODS:We assessed whether augmentation of D1signaling by the PDE10 inhibitor RG7203 enhances imagingand behavioral markers of reward functions in patients with schizophrenia and negative symptoms. In a 3-period,double-blind, crossover study, we investigated the effects of RG7203 (5 mg and 15 mg doses) and placebo asadjunctive treatment to stable background antipsychotic treatment in patients with chronic schizophrenia withmoderate levels of negative symptoms. Effects on reward functioning and reward-based effortful behavior wereevaluated using the monetary incentive delay task during functional magnetic resonance imaging and the effort-cost-benefit and working memory reinforcement learning tasks.RESULTS:Patients (N= 33; 30 male, mean age6SD 36.667.0 years; Positive and Negative Syndrome Scalenegative symptom factor score 23.063.5 at screening) were assessed at three study centers in the United States; 24patients completed the study. RG7203 at 5 mg significantly increased reward expectation–related activity in themonetary incentive delay task, but in the context of significantly decreased overall activity across all task conditions.CONCLUSIONS:In contrast to our expectations, RG7203 significantly worsened reward-based effortful behavior andindices of reward learning. The results do not support the utility of RG7203 as adjunctive treatment for negativesymptoms in patients with schizophrenia