Depression human studies

There are several herbs with CNS depressant effects that have been used mostly for anxiolytic and sedative effects historically. This has been supported by neuropharmacological, animal, and human studies (table 6.1). In some cases, the herbs meet Class I criteria for therapeutic treatment (table 6.4). Much work remains to be done in further testing the efficacy of these drugs and more firmly delineating their biochemical mechanisms. 

A proposed explanation for the discrepant findings on the role of neurotrophic factors in depression is that there are polymorphisms for BDNF that may yield very different effects. Mutations in the BDNF gene have been found to be associated with altered anxiety and depressive behavior in both animal and human studies. 

Toluene (methylbenzene) does not possess the myelotoxic properties of benzene, nor has it been associated with leukemia. It is, however, a central nervous system depressant and a skin and eye irritant. It is also fetotoxic. See Table 56-1 for the TLVs. Exposure to 800 ppm can lead to severe fatigue and ataxia 10,000 ppm can produce rapid loss of consciousness. Chronic effects of long-term toluene exposure are unclear because human studies indicating behavioral effects usually concern exposures to several solvents. In limited occupational studies, however, metabolic interactions and modification of toluene s effects have not been observed in workers also exposed to other solvents. Less refined grades of toluene contain benzene. 

Psychological effects have been associated with 2,3,7,8-TCDD exposure in some human studies. Personality changes were reported following acute exposure (Oliver 1975). Depression (Levy 1988 ... 

The NE system mediates various autonomic, neuroendocrine, emotional and cognitive functions. One of the central roles of NE is response to stress and aversion. This role can be summarized as an activation of response to the acute stress and aversion, followed by decreased reaction to repeated or chronic aversion. Since the response to stress and aversion is a basic part in pathology of mood disorder, NE should play an important role in anxiety, depression and mania. Indeed, this role has been demonstrated in numerous animal and human studies. Majority of antidepressant drugs and mood stabilizers affect NE system as their direct or indirect target. Various medications have different effects on NE neuronal activity. The majority of antidepressants, Li and benzodiazepines suppress NE transmission. Other medications, such as AADs, activate NE neuronal firing activity and NE release. Appropriate combination of different medications, based on the consideration of their effect on NE system, might be critical to obtain good treatment outcome. The combination of SSRIs... 

The Army s interim RfD of 6 x 10 mg/kg per day for VX was based on an oral toxicity study in sheep, in which depression in blood-ChE activity was observed. After evaluating that study, the subcommittee concludes that uncertainties about the relevance of this animal model to humans and weaknesses in the study design undermine the use of the study for deriving the RfD. Instead, the subcommittee recommends using a 1964 study of human volunteers in whom depression in RBC ChE was observed after oral exposure to low concentrations of VX. Although that study also has weaknesses and involves a biomarker of exposure rather than an adverse effect, the subcommittee believes it is preferable to use human data rather than data from a questionable animal model, because the uncertainty associated with extrapolating from animals to humans is avoided. On the basis of the human study, the subcommittee concludes that the data on VX support an RfD of 5 x 10 mg/kg per day, which is slightly lower than the Army s interim RfD of 6 x 10 mg/kg per day. 

Effect of Phosphorus on the Metabolism of Iron and Zinc by Animals. These differences in the effects of phosphorus on zinc and iron metabolism are not peculiar to human studies. The differences can certainly be observed in studies with animals. Hegsted, et al. (31) and Buttner Muhler (41) found that the addition of sodium and potassium orthophosphate salts to diets depressed the utilization of iron by rats, but several groups of investigators have observed that these salts had no effect on iron metabolism by rats (29. 42, 43, 44). Other investigators have observed that the addition of sodium and potassium orthophosphate... 

It is equally important to clearly define the term low-level exposure. This term has seen many different usages in the papers reviewed by these authors. These appear to range from any nonlethal exposure through subtoxic (defined by DeMenti [1999] as no clinical signs) to subclinical (defined by DeMenti [ibid.] as no clinical signs and no significant depression of ChE). Exposure, then, is any contact with a chemical that may induce a biochemical effect. Each definition suffers from arbitrariness and we see no way around this. For the purposes of this review, we will attempt to characterize each paper in terms of presence/absence of either clinical signs or symptoms (in the case of human studies) and level and type of ChE inhibition. 

St. ]ohn s wort Hypericumperforatum), the most popular herbal remedy for mild depression, was reported to have efficacy in randomized, controlled trials and in one open-label PMS trial. For the treatment of menopausal symptoms, only one observational study has reported that women had substantial improvement in physical and psychological symptoms. The usual dose recommended for mild depression is 300 mg three times daily of a standardized product (hypericum 0.3%). Several in vitro and human studies suggest that St. John s wort induces the hepatic cytochrome P450 3A4 enzymes and may decrease the efficacy of OCs and should not be combined with SRIs because of the potential risk of a 5-HT syndrome. ... 

Human Toxicity Causes severe and prolonged bone marrow depression. Toxicity studies Wilson et aL, Antlbiot. 

Because it markedly lowers cerebral metabolism, thiopental has been used as a protectant against cerebral ischemia. At least one human study suggests that thiopental may be efficacious in ameliorating ischemic damage in the perioperative setting. Thiopental also reduces intraocular pressure. Perhaps due to their CNS depressant activity, barbiturates are effective anticonvulsants thiopental in particular is effective in the treatment of status epilepticus. 

Segrave R, Nathan PJ. Pindolol augmentation of selective serotonin reuptake inhibitors accounting for the variability of results of placebo-controlled double-blind studies in patients with major depression. Human Psychopharmacol 2005 20 163-174. 

Acute and chronic administration of alcohol can inhibit the biotransformation or detoxification of many drugs, such as barbiturates, meprobamate, and amphetamines by liver enzymes. The effect can occur in two opposite ways. Alcohol and cannabinoids effects are additive. Both are CNS depressants. Animal studies indicate that simultaneous administration of alcohol and tetrahydrocannabinol (THC), the psychoactive component of marijuana, increased the tolerance and physical dependence to alcohol. Human studies show that alcohol and THC combination enhanced the impairment of physical and mental performance only, and there is no evidence of any interaction between both drugs. With barbiturates. 

Malnutrition is a complex disease, rarely characterized ty a well defined deficit of specific nutrients. For example, the protein composition of the diet often influences the trace element content. Differences between animal models, in which protein deficiency often stimulates cell-mediated immunity, and human studies, which have often indicated depressed cel 1-mediated immunity in protein restriction, can be rationalized by deficiencies of zinc which occur in protein-poor human diets. Consistent with this picture, most amino acid deficiencies exert less influence on the immune response than on overall growth rate (Hill, 1982). 

For example, increase in sleep latency, sleep fragmentation and decreased slow-wave sleep with reduced sleep efficiency and increased daytime sleepiness are observed during nicotine consumption. Nicotine-induced rapid eye movement (REM) sleep suppression is also known. Some researchers have not detected any effect of nicotine on sleep [217]. In contrast, when administered intravenously [218], subcutaneously [219], or into the medial pontine reticular formation [220], nicotine is reported to increase REM sleep in cats. Moreover, some human studies employing transdermal nicotine report a decreased total sleep time, sleep efficiency, and REM sleep and an increase in wakefulness [221, 222]. On the other hand, depressive nonsmokers experience a mood improvement under nicotine administration comparable to the effect of antidepressants. Actually, transdermal... 

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