All-cause and cause-specific mortality among people with bipolar disorder: a large-scale systematic review and meta-analysis.

OBJECTIVE: Bipolar disorder (BD) is associated with premature mortality. All-cause and specific mortality risks in this population remain unclear, and more studies are still needed to further understand this issue and guide individual and public strategies to prevent mortality in bipolar disorder Thus, a systematic review and meta-analysis of studies assessing mortality risk in people with BD versus the general population was conducted. The primary outcome was all-cause mortality, whilst secondary outcomes were mortality due to suicide, natural, unnatural, and specific-causes mortality. RESULTS: Fifty-seven studies were included (BD; n = 678,353). All-cause mortality was increased in people with BD (RR = 2.02, 95% CI: 1.89-2.16, k = 39). Specific-cause mortality was highest for suicide (RR = 11.69, 95% CI: 9.22-14.81, k = 25). Risk of death due to unnatural causes (RR = 7.29, 95% CI: 6.41-8.28, k = 17) and natural causes (RR = 1.90, 95% CI: 1.75-2.06, k = 17) were also increased. Among specific natural causes analyzed, infectious causes had the higher RR (RR = 4,38, 95%CI: 1.5-12.69, k = 3), but the analysis was limited by the inclusion of few studies. Mortality risk due to respiratory (RR = 3.18, 95% CI: 2.55-3.96, k = 6), cardiovascular (RR = 1.76, 95% CI: 1.53-2.01, k = 27), and cerebrovascular (RR = 1.57, 95% CI: 1.34-1.84, k = 13) causes were increased as well. No difference was identified in mortality by cancer (RR = 0.99, 95% CI: 0.88-1.11, k = 16). Subgroup analyses and meta-regression did not affect the findings. CONCLUSION: Results presented in this meta-analysis show that risk of premature death in BD is not only due to suicide and unnatural causes, but somatic comorbidities are also implicated. Not only the prevention of suicide, but also the promotion of physical health and the prevention of physical conditions in individuals with BD may mitigate the premature mortality in this population. Notwithstanding this is to our knowledge the largest synthesis of evidence on BD-related mortality, further well-designed studies are still warranted to inform this field.

Gamma ventral capsulotomy for obsessive-compulsive disorder: a randomized clinical trial.

IMPORTANCE: Select cases of intractable obsessive-compulsive disorder (OCD) have undergone neurosurgical ablation for more than half a century. However, to our knowledge, there have been no randomized clinical trials of such procedures for the treatment of any psychiatric disorder. OBJECTIVE: To determine the efficacy and safety of a radiosurgery (gamma ventral capsulotomy [GVC]) for intractable OCD. DESIGN, SETTING, AND PARTICIPANTS: In a double-blind, placebo-controlled, randomized clinical trial, 16 patients with intractable OCD were randomized to active (n = 8) or sham (n = 8) GVC. Blinding was maintained for 12 months. After unblinding, sham-group patients were offered active GVC. INTERVENTIONS: Patients randomized to active GVC had 2 distinct isocenters on each side irradiated at the ventral border of the anterior limb of the internal capsule. The patients randomized to sham GVC received simulated radiosurgery using the same equipment. MAIN OUTCOMES AND MEASURES: Scores on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Clinical Global Impression-Improvement (CGI-I) Scale. Response was defined as a 35% or greater reduction in Y-BOCS severity and "improved" or "much improved" CGI-I ratings. RESULTS: Three of 8 patients randomized to active treatment responded at 12 months, while none of the 8 sham-GVC patients responded (absolute risk reduction, 0.375; 95% CI, 0.04-0.71). At 12 months, OCD symptom improvement was significantly higher in the active-GVC group than in the sham group (Y-BOCS, P = .046; Dimensional Y-BOCS, P = .01). At 54 months, 2 additional patients in the active group had become responders. Of the 4 sham-GVC patients who later received active GVC, 2 responded by post-GVC month 12. The most serious adverse event was an asymptomatic radiation-induced cyst in 1 patient. CONCLUSIONS AND RELEVANCE: Gamma ventral capsulotomy benefitted patients with otherwise intractable OCD and thus appears to be an alternative to deep-brain stimulation in selected cases. Given the risks inherent in any psychiatric neurosurgery, such procedures should be conducted at specialized centers. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01004302.