Introduction: The safety and tolerability profiles of antidepressants can often influence the treatment choices of clinicians treating major depressive disorder. The purpose of this investigation was to characterize the safety and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) in treating depression.

Methods: An integrated analysis of all short-term, randomized, double-blind, placebo-controlled registration studies for major depressive disorder (four flexible-dose and five fixed-dose studies) was performed. Adult outpatients with major depressive disorder received desvenla-faxine doses ranging from 50–400 mg/day or placebo for 8 weeks. Treatment-emergent adverse events, laboratory values, vital signs, and discontinuation symptoms were evaluated. In the subset of fixed-dose studies, dose-related effects were analyzed.

Results: In the overall population (placebo: n=1,116; desvenlafaxine: n=1,834), adverse events resulted in discontinuations in 3% of placebo-treated patients and 12% of desvenla-faxine-treated patients; in the subset of fixed-dose studies, the rates were 4% with placebo and increased with desvenlafaxine dose (50 mg/ day: 4%; 400 mg/day: 18%). The most common treatment-emergent adverse event was transient nausea that was generally mild to moderate. The most common sexual dysfunction associated with desvenlafaxine treatment was erectile dysfunction in men (7% vs 1% with placebo) and anorgasmia in women (1% and 0%). One desvenlafaxine-treated patient died of a completed suicide; there were four suicide attempts (three desvenlafaxine, one placebo) and eight cases of suicidal ideation (five desvenlafaxine, three placebo) during the on-therapy period. Small but statistically significant changes in mean blood pressure occurred at all desvenlafaxine doses; clinically meaningful changes were observed in 1% of placebo-treated patients and 2% of desvenlafaxine-treated patients. Desvenlafaxine was associated with small but statistically significant mean changes in laboratory assessments, particularly lipid and liver enzyme elevations, and electrocardiograms; few cases of these changes were clinically relevant.

Conclusion: Desvenlafaxine in the treatment of major depressive disorder exhibited a safety and tolerability profile generally consistent with the serotonin-norepinephrine reuptake inhibitor class. The most common adverse event was transient nausea. At the recommended therapeutic dose of 50 mg/day, discontinuation due to adverse events was similar to placebo.

Introduction: Effective management of major depressive disorder (MDD) continues to be a challenging task for psychiatrists and primary care physicians. This trial evaluated the efficacy and safety of adjunctive aripiprazole versus antidepressant monotherapy in patients with MDD and independently replicated the positive findings of two similar trials.

Methods: Patients (N=1, 147) with MDD experiencing a major depressive episode and a history of inadequate response to antidepressant monotherapy were enrolled (week 0); 827 received single-blind adjunctive placebo plus open-label antidepressant (escitalopram, fluoxetine, paroxetine controlled release, sertraline, or venlafaxine extended release) for 8 weeks to confirm inadequate response to antidepressants; 349 patients with inadequate response were randomized (1:1) to double-blind, adjunctive placebo (n=172) or adjunctive aripiprazole (n=177; 2–20 mg/day). Primary outcome was the mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total score from baseline (week 8) to endpoint (week 14).

Results: Clinically significant improvements in depressive symptoms as assessed by decreases in the MADRS Total score were greater with adjunctive aripiprazole (−10.1) than placebo (−6.4; P<.001). Remission rates were greater for adjunctive aripiprazole than for adjunctive placebo (week 14, 36.8% vs 18.9%; P<.001). Completion rates with adjunctive aripiprazole and placebo were high (83% vs. 87%) and discontinuations due to adverse events were low (6.2% vs 1.7%).

Conclusion: For some patients with MDD who do not obtain adequate symptom relief with antidepressant monotherapy, adjunctive therapies can significantly improve depressive symptoms. As reported, adjunctive aripiprazole was associated with a two-fold higher remission rate than adjunctive placebo. This, and previous studies, have shown that discontinuations due to adverse events were low and completion rates were high, and has indicated that both antidepressant and aripiprazole in combination were relatively well-tolerated and safe. This is the third consecutive clinical trial, in the absence of a failed trial, to demonstrate that aripiprazole augmentation to antidepressants is an efficacious and well-tolerated treatment for patients with MDD who do not respond adequately to standard antidepressant monotherapy (ClinicalTrials.gov study NCT00105196).

This case report describes the use of transcranial magnetic theta burst stimulation (TBS) in the treatment of incapacitating tinnitus accompanied by symptoms of severe depression. Tinnitus is known to be associated with hyperactivity and maladaptive cortical reorganization of the central auditory system. Combined with anxiety and depression, it can occasionally constitute a psychiatric emergency. Recently, it has been demonstrated that tinnitus can be temporarily suppressed by non-invasive transcranial magnetic stimulation. TBS is a newly developed technique for rapid and lasting modulation of cortical excitability. Herein, we present a case of a 54-year-old woman with incapacitating tinnitus that has significantly decreased after three cycles of 1-week treatment with continuous TBS to the temporo-parietal auditory association cortex. According to the Tinnitus Questionnaire, tinnitus intensity decreased from 84 points before to 59 points after treatment. Hamilton Rating Scale for Depression score dropped from 44 to 23 points. TBS showed to be efficient, well-tolerated, and practical in the management of distressing tinnitus accompanied by symptoms of severe depression.

This case report describes a patient with reportedly new onset of tics, beginning at 21 years of age, in the context of posttraumatic stress disorder (PTSD) and comorbid alcohol abuse, with no known head injury. The setting is an American Society of Addiction Medicine intensive outpatient substance abuse rehabilitation program in an United States Army Medical Center. The patient is a 22-year-old male diagnosed with alcohol abuse and delayed PTSD who presented to the program's medical officer due to insomnia. We discovered he had a reportedly new ocular tic of ∼9 months duration, which he claimed developed at 21 years of age soon after returning from 1 year of combat duty. The patient was thoroughly evaluated, and we surmised the tic was a symptom of PTSD. After achieving full remission from alcohol, the tic persisted. However, as his PTSD symptoms remitted, so did his tic symptoms. At 6-month follow-up, the patient reported he was essentially free from PTSD symptoms, and his tic was significantly reduced.