No abstract

Context Previous studies have found that few chronically depressed patients remit with antidepressant medications alone. Objective To determine the role of adjunctive psychotherapy in the treatment of chronically depressed patients with less than complete response to an initial medication trial. Design This trial compared 12 weeks of (1) continued pharmacotherapy and augmentation with cognitive behavioral analysis system of psychotherapy (CBASP), (2) continued pharmacotherapy and augmentation with brief supportive psychotherapy (BSP), and (3) continued optimized pharmacotherapy (MEDS) alone. We hypothesized that adding CBASP would produce higher rates of response and remission than adding BSP or continuing MEDS alone. Setting Eight academic sites. Participants Chronically depressed patients with a current DSM-IV–defined major depressive episode and persistent depressive symptoms for more than 2 years. Interventions Phase 1 consisted of open-label, algorithm-guided treatment for 12 weeks based on a history of antidepressant response. Patients not achieving remission received next-step pharmacotherapy options with or without adjunctive psychotherapy (phase 2). Individuals undergoing psychotherapy were randomized to receive either CBASP or BSP stratified by phase 1 response, ie, as nonresponders (NRs) or partial responders (PRs). Main Outcome Measures Proportions of remitters, PRs, and NRs and change on Hamilton Scale for Depression (HAM-D) scores. Results In all, 808 participants entered phase 1, of which 491 were classified as NRs or PRs and entered phase 2 (200 received CBASP and MEDS, 195 received BSP and MEDS, and 96 received MEDS only). Mean HAM-D scores dropped from 25.9 to 17.7 in NRs and from 15.2 to 9.9 in PRs. No statistically significant differences emerged among the 3 treatment groups in the proportions of phase 2 remission (15.0%), partial response (22.5%), and non-response (62.5%) or in changes on HAM-D scores. Conclusions Although 37.5% of the participants experienced partial response or remitted in phase 2, neither form of adjunctive psychotherapy significantly improved outcomes over that of a flexible, individualized pharmacotherapy regimen alone. A longitudinal assessment of later-emerging benefits is ongoing. Trial Registration clinicaltrials.gov Identifier: NCT00057551

No abstract

No abstract

The lack of biomarkers to identify target populations greatly limits the promise of precision medicine for major depressive disorder (MDD), a primary cause of ill health and disability. The endogenously produced molecule acetyl-l-carnitine (LAC) is critical for hippocampal function and several behavioral domains. In rodents with depressive-like traits, LAC levels are markedly decreased and signal abnormal hippocampal glutamatergic function and dendritic plasticity. LAC supplementation induces rapid and lasting antidepressant-like effects via epigenetic mechanisms of histone acetylation. This mechanistic model led us to evaluate LAC levels in humans. We found that LAC levels, and not those of free carnitine, were decreased in patients with MDD compared with age- and sex-matched healthy controls in two independent study centers. Secondary exploratory analyses showed that the degree of LAC deficiency reflected both the severity and age of onset of MDD. Moreover, these analyses showed that the decrease in LAC was larger in patients with a history of treatment-resistant depression (TRD), among whom childhood trauma and, specifically, a history of emotional neglect and being female, predicted the decreased LAC. These findings suggest that LAC may serve as a candidate biomarker to help diagnose a clinical endophenotype of MDD characterized by decreased LAC, greater severity, and earlier onset as well as a history of childhood trauma in patients with TRD. Together with studies in rodents, these translational findings support further exploration of LAC as a therapeutic target that may help to define individualized treatments in biologically based depression subtype consistent with the spirit of precision medicine.

Background There is growing evidence suggesting that early adversity may be a marker for a distinct pathway to major depressive disorder (MDD). We examined associations between childhood adversity and a broad variety of clinical characteristics and response to pharmacotherapy in a large sample of patients with chronic forms of MDD. Methods Subjects included 808 patients with chronic forms of MDD (chronic MDD, double depression, or recurrent MDD with incomplete recovery between episodes and a total continuous duration of >2 years) who were enrolled in a 12-week open-label trial of algorithm-guided pharmacotherapy. Baseline assessments included a semi-structured diagnostic interview, and clinician- and self-rated measures of depressive symptoms, social functioning, depressotypic cognitions, and personality traits, and childhood adversity. Patients were re-evaluated every 2 weeks. Results A longer duration of illness; earlier onset; greater number of episodes, symptom severity, self-rated functional impairment, suicidality, and comorbid anxiety disorder; and higher levels of dysfunctional attitudes and self-criticism were each associated with multiple forms of childhood adversity. A history of maternal overcontrol, paternal abuse, paternal indifference, sexual abuse, and an index of clinically significant abuse each predicted a lower probability of remission. Among patients completing the 12-week trial, 32% with a history of clinically significant abuse, compared to 44% without such a history, achieved remission. Conclusions These findings indicate that a history of childhood adversity is associated with an especially chronic form of MDD that is less responsive to antidepressant pharmacotherapy.

Depressive symptoms appear treatable in HIV-positive patients. Interpersonal psychotherapy may have particular advantages as a psychotherapy for patients who have experienced the significant life events of HIV infection.

Pharmacotherapy provides considerable relief from the symptoms of dysthymia in patients suffering from this chronic affective disorder, with both sertraline and imipramine being more effective than placebo. The greater tolerability of sertraline is an important consideration because of the chronicity of dysthymia, which may require prolonged treatment with antidepressant medication.