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Biomedical subjects

Erick H Turner

Publications and source records attributed to Erick H Turner.

7 recordsLinked to original sources

Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan.

This paper reviews the preclinical and clinical evidence regarding the use of the dietary supplement 5-hydroxytryptophan (5-HTP) for the treatment of depression. In the absence of supplementation with exogenous 5-HTP, the amount of endogenous 5-HTP available for serotonin synthesis depends on the availability of tryptophan and on the activity of various enzymes, especially tryptophan hydroxylase, indoleamine 2,3-dioxygenase, and tryptophan 2,3-dioxygenase (TDO). Factors affecting each of these are reviewed. The amount of 5-HTP reaching the central nervous system (CNS) is affected by the extent to which 5-HTP is converted to serotonin in the periphery. This conversion is controlled by the enzyme amino acid decarboxylase, which, in the periphery, can be blocked by peripheral decarboxylase inhibitors (PDIs) such as carbidopa. Preclinical and clinical evidence for the efficacy of 5-HTP for depression is reviewed, with emphasis on double-blind, placebo-controlled (DB-PC) trials. Safety issues with 5-HTP are also reviewed, with emphasis on eosinophilia myalgia syndrome (EMS) and serotonin syndrome.

5-Hydroxytryptophan↗

Is it always unethical to use a placebo in a clinical trial?

BACKGROUND TO THE DEBATE: Placebos are used in trials to conceal whether a treatment is being given or not and hence to control for the psychosomatic effects of offering treatment. Placebo-controlled trials are controversial. Critics of such trials argue that if a proven effective therapy exists, a placebo should not be used. But proponents argue that placebo trials are still crucial to prove the efficacy and safety of many treatments.

Ethics, Medical↗

5-Hydroxytryptophan plus SSRIs for interferon-induced depression: synergistic mechanisms for normalizing synaptic serotonin.

Interferon-alpha (IFN) is widely used in the treatment of certain cancers and viral infections, including hepatitis C (HCV). Unfortunately, depression is a common side effect of IFN therapy, affecting approximately a third of HCV patients receiving IFN therapy. Studies have shown that selective serotonin reuptake inhibitors (SSRIs) can effectively treat IFN-induced depression in only 63-75% of cases. For the remaining percentage, depression often necessitates dose reduction of or discontinuation from IFN therapy. Emerging evidence indicates that IFN may cause depression by affecting brain serotonin. IFN has been shown to increase serotonin reuptake and to decrease serotonin synthesis. We hypothesize that SSRIs are not fully effective because they affect only serotonin reuptake, not serotonin synthesis, and that effective treatment must address both uptake and synthesis. 5-Hydroxytryptophan (5-HTP) effectively increases central nervous system synthesis of serotonin. It is the immediate precursor of serotonin and is widely available as a dietary supplement, which is well absorbed after an oral dose. Several double-blind studies have shown 5-HTP to be effective in the treatment of nondrug-induced depression. We hypothesize that patients who become depressed on IFN will respond to the synergistic combination of SSRIs plus 5-HTP.

5-Hydroxytryptophan↗

Strategies to decrease costs of prescribing selective serotonin reuptake inhibitors at a VA Medical Center.

OBJECTIVE: The authors examined the efficacy of a multifaceted intervention designed to contain the cost of prescribing selective serotonin reuptake inhibitors (SSRIs) to inpatients and outpatients served by a Veterans Affairs (VA) medical center. METHODS: Elements of the intervention included identification of a preferred agent, tablet splitting, education and feedback for prescribers, and an electronic record and ordering system to facilitate changes in prescriber behaviors. VA databases were searched for information on use and costs of antidepressants. RESULTS: Over 35 months the number of patients treated with SSRIs and the amount spent on SSRIs increased. However, the mean monthly cost per patient decreased from $57.12 to $42.19. The projected cost savings over the 35 months was approximately $700,000; one-fourth of the savings was due to tablet splitting and three-fourths to changes in the proportions of the various SSRIs prescribed. A survey of the top 75 antidepressant prescribers showed that after the educational interventions, 91 percent were aware that citalopram was the medical center's preferred antidepressant, and 59 percent identified it as their own preferred first-line treatment. DISCUSSION AND CONCLUSIONS: The results suggest that multifaceted interventions can influence antidepressant costs through provider education and changes in pharmacy and computerized information processes, resulting in substantial cost savings for institutions.

Citalopram↗

Patients with seasonal affective disorder have lower odor detection thresholds than control subjects.

BACKGROUND: Behavioral changes in patients with seasonal affective disorder resemble seasonal changes in photoperiodic animals. Because the olfactory system has a modulatory role in seasonal photoperiodic responses in certain species, we hypothesized that olfactory function may differ between patients with seasonal affective disorder and healthy control subjects. METHODS: Fourteen patients who had winter seasonal affective disorder and 16 healthy volunteers were studied once in winter and once in the subsequent summer. We administered a phenyl ethyl alcohol detection threshold test to each side of the nose in a counterbalanced order, with the nostril contralateral to the tested site occluded. Patient and control data were compared using a 4-way repeated measure analysis of covariance (with group and gender as between-subjects factors, season and side-of-the-nose as within-subjects factors, and age as a covariate). RESULTS: The patients exhibited lower thresholds than did the controls (F(1,25) = 9.2; P =.006). There was no main effect of season. CONCLUSION: In humans, marked seasonal behavioral rhythms with recurrent winter depression may be associated with a more acute sense of smell.

Adult↗

Double-blind, placebo-controlled study of single-dose metergoline in depressed patients with seasonal affective disorder.

A role for serotonin in season affective disorder (SAD) has been explored with a variety of serotonergic pharmacologic agents. The authors initially hypothesized that metergoline, a nonspecific serotonin antagonist, would exacerbate depressive symptoms. In a small, open-label pilot study, the authors observed the opposite effect. They decided to follow up on this finding with this formal study. The study followed a double-blind, randomized cross-over design. Sixteen untreated, depressed patients with SAD received single oral doses of metergoline 8 mg and of placebo, spaced 1 week apart. Fourteen patients were restudied after 2 weeks of light treatment. Depression ratings using the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version were performed at baseline and at 3 and 6 days after each intervention. These data were analyzed by baseline-corrected repeated measures with analysis of variance. In the off-lights condition, severity of depression was diminished after metergoline compared with placebo administration (p = 0.001). Patient daily self-ratings suggested that the peak effect occurred 2 to 4 days after study drug administration. In contrast, after 2 weeks of treatment with bright artificial light, metergoline did not demonstrate a significant effect on mood. These data suggest that single doses of metergoline may have antidepressant effects that last several days. Possible mechanisms include 5-hydroxytryptamine(2) receptor downregulation and dopamine agonism.

Adult↗