IMPORTANCECombining antidepressants is frequently done in the treatment of acute depression, but studies have yielded conflicting results.OBJECTIVE To conduct a systematic review and meta-analysis assessing efficacy and tolerability of combination therapy. Combinations using presynaptic α2-autoreceptor antagonists or bupropion were investigated separately.DATA SOURCES MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials were systematically searched from each database inception through January 2020.STUDY SELECTION Randomized clinical trials (RCTs) comparing combinations of antidepressants with antidepressant monotherapy in adult patients with acute depression were included.DATA EXTRACTION AND SYNTHESIS Following guidelines from Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and recommendations from the Cochrane Handbook, 2 reviewers independently performed a literature search, study selection, data extraction, and evaluation of risk of bias. Data were pooled in random-effects analyses.MAIN OUTCOMES AND MEASURES Primary outcome was efficacy measured as standardized mean difference (SMD); secondary outcomes were response, remission, change from baseline in rating scale scores, number of dropouts, and number of dropouts due to adverse events. RESULTS Thirty-nine RCTs including 6751 patients were eligible. Combination treatment was statistically significantly associated with superior treatment outcomes relative to monotherapy (SMD = 0.31; 95% CI, 0.19-0.44). Combining a reuptake inhibitor with an antagonist of presynaptic α2-autoreceptors was superior to other combinations (SMD = 0.37; 95% CI, 0.19-0.55). Bupropion combinations were not superior to monotherapy (SMD = 0.10; 95% CI, −0.07 to 0.27). Numbers of dropouts and dropouts due to adverse events did not differ between treatments. Studies were heterogeneous, and there was indication of publication bias (Egger test result was positive; P = .007, df = 36), but results remained robust across prespecified secondary outcomes and sensitivity and subgroup analyses, including analyses restricted to studies with low risk of bias. CONCLUSIONS AND RELEVANCEIn this meta-analysis of RCTs comparing combinations of antidepressants with antidepressant monotherapy, combining antidepressants was associated with superior treatment outcomes but not with more patients dropping out of treatment. Combinations using an antagonist of presynaptic α2-autoreceptors may be preferable and may be applied as a first-line treatment in severe cases of depression and for patients considered nonresponders.

This article examines various sides of the recent discussion about establishing a medical category within the “moral injury” discourse. Essential differences between the nature and development of moral injury among physicians and combat veterans are acknowledged. Essential similarities are also explored. Case notes from a 3-year encounter between a clinical chaplain and a disoriented physician are offered as an illustration of how moral injury interventions with veteran populations can inform care for physicians experiencing burnout.

the Italian government published Decree Law No. 195, which dealt with the management of two contingencies: toxic waste in the Campania region and recovery from the earthquake of 6 April 2009 in Abruzzo. 1 Article 16 of this legislative instrument was rather different from the other 18 articles, in that it mandated the privatization of civil protection in the form of a holding company entitled Protezione Civile Servizi SpA. The prime minister was named as the only shareholder, and start-up capital of 1 million euros was to be supplied by the public purse. For the preceding six weeks, rumors about this law had been circulating, but the head of the national Department of Civil Protection (DPC) from 1991-2010, Guido Bertolaso, had repeatedly denied that any such action was going to be taken. 2 As Article 14 of this decree law authorized the DPC to appoint an unspecified number of new employees to permanent posts, a large amount of unsupervised hiring took place. At the same time, a third of the employees of the DPC were formally transferred to the private sector. Trade unions, notably CGIL, protested, but the level of public interest in the matter was minimal.Decree Law No. 195 was approved by the Italian Senate, but in February 2010, while it was being discussed in the Chamber of Deputies, the scandal broke. Over the course of eight years, from 2002 to 2009, more than 600 ordinances had been issued by the DPC. 3 In contrast, during the period from 1994 to 2001, there had been only one or two Notes for this chapter begin on page 195.

Although great efforts have been made in recent decades to bring attention to the moral injury discourse as a complementary paradigm to psychiatry in understanding and treating severe forms of combat veteran disorientation, and although a number of treatments for moral injury how now been developed and are under assessment, the discourse is still often ignored, underappreciated, and misunderstood by many professional caregivers. The author contends that this underappreciation can be partly attributed to a poorly-developed internal nosology. This article offers a suggestion for strengthening the development of key, differentiated features within the moral injury discourse, beginning with the author's own experience and categorization of unusual veteran features which cannot be cleanly categorized within the existing spectra of the Diagnostic and Statistical Manual of Mental Disorders.

No abstract