Robert E. Strong

Treatment-Associated Suicidal Ideation and Adverse Effects in an Open, Multicenter Trial of Fluoxetine for Major Depressive Episodes

Background: Some reports suggest that a subset of depressed patients may experience suicidality – that is increase or emergence of suicidal ideation (SI) or behavior – after initiation of an antidepressant. The time course and clinical correlates of this phenomenon have not been characterized in detail. Method: We conducted a secondary analysis of a multicenter, prospective, open, 12-week trial of fluoxetine 20 mg in outpatients with nonpsychotic major depressive episodes. Adverse effects and other clinical features associated with the emergence of suicidality, defined using item 3 of the Hamilton Depression Rating Scale, were examined using Cox regression models. Results: Among 414 subjects without SI at baseline, 59 (14.3%) reported SI on at least 1 postbaseline visit. In a Cox regression, emergence of activation and worsening of depression severity were independently associated with emergence of SI, along with female gender, younger age and having thoughts that life was not worth living prior to treatment. Treatment response and remission were significantly less likely among subjects who developed SI. Conclusions: New SI was relatively common in this trial of fluoxetine and associated with the emergence of activation and overall symptomatic worsening. Whether prophylaxis against or aggressive treatment of adverse events can decrease emergence of SI merits further study.

Borderline personality disorder in patients with bipolar disorder and response to lamotrigine

BACKGROUND Recent reports suggesting lamotrigine as an effective treatment in bipolar disorder, and perhaps borderline personality disorder, a common comorbid personality disorder in bipolar patients, led us to retrospectively examine patients from two bipolar studies to investigate this pattern of comorbidity, and to determine whether lamotrigine effected the dimensions of borderline personality. METHODS Fifteen months following entry into either study, we retrospectively assessed DSM-IV dimensions of borderline personality disorder pre- and post-treatment with lamotrigine in 35 bipolar patients. RESULTS Forty percent met criteria for borderline personality disorder; this subgroup had a more frequent history of substance abuse and childhood symptoms of attention deficit hyperactivity disorder (ADHD). Dimensions of borderline personality improved significantly with treatment in both patient groups, and corresponded with response of bipolar symptoms. Six (43%) comorbid bipolar patients endorsed three or fewer criteria of borderline personality during treatment with lamotrigine. There was a trend for comorbid bipolar patients to require a second psychoactive medication in addition to lamotrigine during extended treatment. LIMITATIONS Criteria for borderline personality and improvement were assessed retrospectively in an open manner. CONCLUSIONS Dimensions of borderline personality disorder may respond to lamotrigine in comorbid bipolar patients; controlled studies appear warranted. Bipolar studies should assess and specify the number of patients with personality disorders in the trial.

Narrow-band blue-light treatment of seasonal affective disorder in adults and the influence of additional nonseasonal symptoms

Background: Bright visible‐spectrum light therapy has proven effective in the treatment of seasonal affective disorder (SAD) and recent basic research suggests that blue wavelengths ∼470 nm account for that effectiveness. To more stringently test the importance of these wavelengths, bright red‐light was used for the placebo (control) condition. Methods: Thirty subjects meeting DSM‐IV criteria for SAD were randomized to narrow‐band light‐emitting diode panels emitting blue‐ or red‐light in this 3‐week, parallel, double‐blind trial. Twenty‐five subjects participated in an open‐label blue‐light follow‐up. Subjects were divided in a blinded, post hoc manner into two groups: SAD only and those experiencing depression with seasonal intensification. The outcome was assessed using Hamilton Depression Rating Scale–17 item version (HAMD‐17) and the Structured Interview Guide for the Hamilton Depression Rating Scale—SAD version. Responders were defined by Clinical Global Impression—Improvement scale. Results: HAMD‐17 scores improved more under the blue‐light condition (51%) than under the red‐light condition (32%) (P=.05). Further, in the blue arm 60% of subjects responded compared with 13% in the red arm (P=.01). During the open‐label phase, subjects from both double‐blind arms improved over baseline. SAD alone patients responded numerically better to treatment than those experiencing depression with seasonal intensification during both treatment periods. Conclusions: Narrow bandwidth blue‐light therapy proved superior to red‐light therapy. Blue‐light therapy produced results similar to both previous 10,000 lux visible‐spectrum light studies and many medication studies. The use of bright red panels supported claims that wavelengths of ∼470 nm account for the documented effectiveness of light therapy. Depression and Anxiety, 2009.