Only Severely Depressed Affected by Anti-Depressants

A recent study found that common anti-depressants only helped the severely depressed, while people with milder forms of depression on the anti-depressants exhibited little to no difference compared to those on a placebo regimen.

The meta-analysis included six studies, which included 434 patients given anti-depressant regimen and 284 on a placebo regimen. The patients were rated on the Hamilton depression rating scale, with the lowest score among the trials being 10 and the highest a 39. Three studies used paroxetine, a serotonin reuptake inhibitor, and the remaining used imipramine, a tricyclic antidepressant. The study suggests that other popular, similar anti-depressants, such as Lexipro and Prozac, would show similar results. This analysis concerned patients older than 18 and did not perform a placebo washout period.

The studies all concluded that the presentation of true drug effects was a function of the severity of depres- sion. Patients with a score of 25 or lower (mild to moderate depression) showed no difference between the placebo and anti-depressant groups. Conversely, those with a score of 25 or higher (severe depression) responded to the anti-depressant medication with increasing efficacy as their HDRS num- ber increased.

Reference: JAMA. 2010;303(1):47-53.

Catheter Ablation as a First Line Arrhythmia Defense

A recent study found atrial fibrillation, a heart rhythm disorder, could be controlled by a procedure called catheter ablation more effectively than traditional antiarrhythmic drug therapy (ADT). Catheter ablation is a process that cauterizes muscles surrounding the pulmonary veins in an effort to destroy the tissue causing the abnormal electrical pulses.

The trial was conducted at 19 hospitals and included 167 patients that had had at least 3 atrial fibrillation episodes during the last six months. 106 patients were randomly given the procedure, while 61 were given a new form of ADT. Researchers found that 66% of catheter ablation patients were free of episodes nine months later, while only 16% of the ADT patients were episode free.

Five patients out of the catheter ablation group suffered from major treatment-related negative effects (4.9% of the catheter ablation group). Five patients from the ADT group suffered from ADT-related adverse effects (8.8% of ADT group).

Traditional ADT has re-occurrences on average of 50%, so catheter ablation is likely to be seen as an alternative first line defense against many cases of atrial fibrillation. Biosense Webster, the company that produces the catheters used in the procedure, funded the study.

Reference: JAMA. 2010;303(4):333-340.

Reduced Salt Intake Could Lead to Decreases in Medical Costs and Heart Disease

The New England Journal of Medicine published a study stating a decrease in 3g of salt per day for every individual in the US could lead to a drastic decrease in the prevalence of Coronary Heart Disease (CHD), stroke, myocardial infraction and death from these causes.

The study used a computer model, CHD Policy Model, to study the prevalence and mortality of CHD of a variety of ages and demographics within the US. Using the data from multiple studies correlating the effect of salt on systolic blood pressure, researchers were able to compare the impact of salt intake to a variety of health effects. They determined that a reduction in salt intake by 3 grams daily was a more effective way to prevent CHD, stroke and myocardial infraction than would a 50% reduction in smoking, a 5% decrease in body mass index and some treatments of hypertension. The study showed that a decrease in salt intake would affect both white and non-white men and women.

A salt intake reduction of 3 grams would save an estimated $10 billion and $24 billion in yearly healthcare costs and would reduce the number of new cases of CHD by 60,000 to 120,000, stroke by 32,000 to 66,000, and myocardial infarction by 54,000 to 99,000 annually. Deaths from these three sources would be reduced by 44,000 to 92,000 a year. Researchers suggest that the cost-effectiveness of a state wide initiative to lower salt intake would save money in comparison to the medical costs that the US’s salt dense culture creates.

Reference: NEJM. January 20, 2010 (10.1056/ NEJMoa0907355)

Morphine May Lower Risk of Developing PTSD

A new research study found that the use of morphine directly following a traumatic experience significantly lowers the chances of developing Post Trau matic Stress Disorder (PTSD). The study examined soldiers who were admitted to navy-marine corps care during opera- tion Iraqi Freedom.

Researchers examined 696 patients from the Navy–Marine Corps Combat Trauma Registry Expeditionary Medical Encounter Database. Soldiers who suffered traumatic brain injuries or lacked complete records were excluded from the study. Of the 243 participants who developed PTSD, only 61 were administered morphine. Of the 453 patients who did not develop PTSD, 76% received morphine. Even taking into account other variables such as age, injury severity, and amputation status, the correlation remained significant.

This research shadows a previous study that linked the use of morphine and other opiates to reduce the chance of developing PTSD in pediatric burn victims.

Researchers suggest that pharmacotherapeutic intervention may be amethod of second line of defense against PTSD not only in soldiers but rape vic- tims, burn victims and others. While this was an observational study, and therefore causal inferences cannot be made, many doctors believe that opiates would block memory consolidation and subsequent fear responses after a traumatic event. Researchers were unable to fully develop a dose-response relationship because of the nature of the research.

Reference: NEJM. 2010; 362:110-117

Most Effective HIV and TB Treatment

A study found that individuals who underwent combined-integrated therapy for both Tuberculosis and HIV survived remarkably better than individuals who received sequential therapy. Concomitant therapy is encouraged by the World Health Organizations, however many clinicians worry about drug interactions and the pragmatics of taking so many pills for patients. This randomized study was designed to find the most opportune time for patients with both TB and HIV to start antiretroviral therapy.

The study was conducted in Durban, South Africa and included 642 patients that had a positive diagnosis of tuberculosis and an HIV infection with a CD4+ cell count < 500 per ml3. The combined-integrated therapy group included 429 patients which received a standard tuberculosis treatment, prophylaxis with trimethoprim–sulfamethoxazole, and a once daily antiretroviral treatment of didanosine, lamivudine, and efavirenz.

The sequential therapy group was designed to first be treated for Tuberculosis, using the same TB treatment plan, and start antiretroviral therapy upon completion of the TB regimen.

Researchers found that in the combined-integrated therapy group, the incidence of death was 5.4 for every 100 person-years of observation. The sequential therapy group saw an incidence of death of 12.1 for every 100 person-years of observation. After adjustment for various confounding factors, researchers found that patients in the combined-integrated therapy group had a relative risk reduction of 54%. Two and a half years into the study, the data and safety monitoring committee recommended all patients be put onto the combined-integrated therapy regimen for the remainder of the study. The combined-integrated therapy group saw nearly three times the cases of immune reconstitution inflammatory syndrome. However, there were no deaths resulting from this syndrome.

Researchers concluded that antiretroviral therapy should be started during TB therapy to improve rates of survival in individuals with both an active diagnosis of TB and HIV. Even after controlling for complications resulting from drug interactions and regimen compliance, the risk ratio remains lower for combined-integrated therapy. This evidence further supports WHO’s recommendation.

Reference: NEJM Volume 362:697-706

Serotonin and Tryptophan Hydroxylase Deficiency Found in SIDS Infants

A Harvard based research group found that victims of Sudden Infant Death Syndrome (SIDS) are most likely to have a decreased level of serotonin and its biosynthetic enzyme TPH2, tryptophan hydroxylase, when compared to control children. These lower levels would normally lead to a diagnosis of medullary 5-HT (serotonin) deficiency disorder, if caught before death.

Previous hypothesis of SIDS speculated that death was due to the inability of a baby to self-arouse after a life threatening event, such as asphyxia. The study aimed to find whether the inability to return to homeostasis was due to an elevated or decreased serotonin production. The study included post-mortem evaluations of serotonin and tissue from 41 infants. Seven infants, who had died from known causes other than SIDS were used as controls, as well as five infants who were hospitalized with chronic hypoxiaischemia.

Researchers found that serotonin levels were 26% lower in babies who had died of SIDS. Tissue collection from the raphé obscurus showed levels of TPH2 were 22% lower in SIDS cases than in controls. The ratio between serotonin and TPH2 was consistent throughout both the SIDS cases and control cases.

From these results researchers extrapolated that SIDS death most likely due to the insufficient amount of serotonin, due to the decreased levels of TPH2, to self-arouse during asphyxia. Authors of the study hypothesize that the low levels of TPH2 result from some unknown developmental reason, probably in the first or second trimester, that leads to the production of immature serotonin receptor binding sites and decreased levels of serotonin. Further animal testing might divulge how decreased levels of TPH2 arise during embryonic development and how this deficiency leads to sudden death during sleep.

Reference: JAMA. 2010;303(5):430-437.

Vitamins Ineffective in Lowering Pregnancy Related Hypertension

The New England Journal of Medicine published a study investigating the effect of supplemental vitamins in pregnant women who were at risk of hyperten- sion. Researchers performed a double-blind, randomized test to test the efficacy of supplemental vitamin C and E in preventing pregnancy-associated hypertension. They found that the supplements did not significantly decrease the risk of hypertension or negative perinatal/ maternal outcomes.

The data was calculated from 9,969 women without previous symptoms of hypertension and who were fewer than 16 weeks pregnant. The women were randomly assigned to receive 1000 mg of Vitamin C and 400 IU of Vitamin E or a placebo. The outcomes investigated were pregnancy related hypertension, eclamptic seizure, preterm birth and maternal or perinatal death. Results confirmed that vitamins C and E did not significantly reduce the risk of hyper- tension; the relative risk of the vitamin group was 1.07.

While other studies had previously suggested the role of vitamin C and E in lowering rates of hypertension in pregnant women, recent studies have not been able to reproduce this result. Most of the women in the trial were already taking prenatal vitamins, so many researchers suggested that the extra supplements were superfluous to normal levels of vitamin C and E.

Reference: NEJM Volume 362:1282-1291