Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pregabalin is a structural analogue of gamma-aminobutyric acid (GABA), one of the key inhibitory neurotransmitters in the brain. Its mode of action is believed to be mediated by the alpha-2-delta-1 subunit protein of voltage-gated calcium channels to bring about its anxiolytic, anticonvulsant and antinociceptive effects. Pregabalin has linear pharmacokinetics, undergoes minimal metabolism and is excreted largely unchanged. It has a mean elimination half-life of 6.3 hours. Pregabalin's anxiolytic activity in generalized anxiety disorder has been demonstrated in seven acute randomized, double-blind, placebo-controlled trials of four to eight weeks duration, and in one six-month relapse-prevention study at doses of 150-600 mg/day using twice-daily or three-times-daily regimes. The magnitude of pregabalin's anxiolytic effects was similar to that of alprazolam, lorazepam or venlafaxine. However, pregabalin had a more consistent effect on psychic and somatic anxiety factors than the active comparators. Its speed of onset was apparent within one week - similar to the benzodiazepines, but faster than that of venlafaxine. Moreover, pregabalin's anxiolytic effect was apparent in patients with moderate or severe baseline anxiety and high or low baseline severity of sub-syndromic depression. A long-term, 26-week, open-label study showed that pregabalin's anxiolytic effects were maintained, although the fixed-dose design may have contributed to a high attrition rate. Pregabalin showed less cognitive and psychomotor impairment than alprazolam, and it showed different effects on sleep architecture to the latter in terms of REM sleep latency and slow wave stage 3/4 sleep. The most frequently reported adverse events were dizziness and somnolence, although tolerance to these developed within a few weeks. Withdrawal symptoms during a one-week taper phase were mild and were similar after both acute and chronic administration.
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PMID:Pregabalin: its efficacy, safety and tolerability profile in generalized anxiety. 1794 Jun 37

Doxepin is a tricyclic antidepressant with a subnanomolar affinity for the histamine H(1) (H(1)) receptor. It has a long history of use for depression at doses higher than those needed for antagonism of H(1) receptors. Recent work has focused on its use at low doses (1, 3 and 6 mg) in patients with chronic primary insomnia. Two phase II studies and four phase III studies have investigated its efficacy on both objective and subjective sleep measures in both adults and elderly patients. It was effective on a variety of sleep onset, maintenance and early awakening outcomes and had minimal effects on sleep architecture. There was no signal for tolerance, psychomotor impairment, residual sedation, rebound insomnia or discontinuation symptoms in trials of up to 3 months duration. Doxepin was well tolerated; sedation/sleepiness and headache were the most common adverse events but these were mainly at placebo level or less. Further work is required to establish doxepin's low-dose effect on hypnotic activity.
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PMID:Selective histamine H(1) antagonism: a novel approach to insomnia using low-dose doxepin. 1949 91

While benzodiazepine intoxication alone may elicit sedative and antianxiety effects, alcohol coingestion greatly amplifies this central nervous system depression. As a result, this drug combination gained notoriety for its role in cases of facilitated sexual assault and fatal overdose. We previously validated the ability of the novel antiflunitrazepam monoclonal antibody (mAb) RCA3A3 to bind flunitrazepam (FLU) in vivo and block FLU-induced impairment of locomotion and memory. A therapeutically relevant application of this high affinity mAb (K(d,app) = 200 nM), however, is to the more tenuous indication of flunitrazepam (FLU) and alcohol cointoxication. Employing a murine behavioral model, passive immunization with mAb RCA3A3 before injection of ethanol (EtOH: low-dose, 1 g/kg, or high-dose, 1.5 g/kg), FLU (0.06 mg/kg), or a cocktail of both drugs offered partial to full restoration of motor activity levels in co-drug treated and FLU-treated mouse groups (n = 12), respectively. Whereas all drug treatments left contextual learning intact, auditory cued learning was severely disrupted. Prophylactic administration of mAb RCA3A3 prevented this deficit in cued learning in FLU-treated mice but not in the FLU- and EtOH-treated mice, in which co-drug exposure exacerbated the impairment in cued fear conditioning. To substantiate this finding, a dose-response study was performed, and the changes in locomotor activity incurred by different FLU (low-dose, 0.06 mg/kg, or high-dose, 0.09 mg/kg), EtOH (1.0 g/kg, 1.5 g/kg), and mAb RCA3A3 (14.5 mg/kg, 21.8 mg/kg) dose combinations illustrated the potentiation in motor effects by concomitant exposure to FLU and EtOH. Thus, motor activity and fear conditioning results demonstrated that both the amount of FLU left unbound by antibody and the pharmacological additivity between FLU and EtOH, a GABA mimetic, were limiting factors in the therapeutic efficacy of mAb RCA3A3. In sum, our study highlights the complex nature of psychomotor impairment upon co-drug versus singular drug exposure, which may pose a unique challenge to therapeutic treatment.
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PMID:Superadditive effects of ethanol and flunitrazepam: implications of using immunopharmacotherapy as a therapeutic. 2084 17

The use of psychotropic (mood or behaviour-altering) drugs is common among older people. Age-related changes in the way drugs work cause adverse effects such as hypotension, orthostatic hypotension, memory loss, drowsiness, cognitive and psychomotor impairment. All psychotropics increase the risk of falls and fractures. Long-term use may also lead to increased tolerance, dependency, poor sleep or depression. Benzodiazepine use should be limited to short-term relief of severe anxiety or primary insomnia.
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PMID:Effects of age on drug action. 2774 55

Depression is the most common comorbidity and neuropsychiatric complication in HIV. Estimates suggest that the prevalence rate for depression among HIV-infected individuals is three times that of the general population. The association between HIV and clinical depression is complex; however, chronic activation of inflammatory mechanisms, which disrupt central nervous system (CNS) function, may contribute to this association. Disruptions in CNS function can result in cognitive disorders, social withdrawal, fatigue, apathy, psychomotor impairment, and sleep disturbances, which are common manifestations in depression and HIV alike. Interestingly, the parasympathetic system-associated vagus nerve (VN) has primary homeostatic properties that restore CNS function following a stress or inflammatory response. Unfortunately, about 30% of adults with HIV are resistant to standard psychotherapeutic and psychopharmacological treatments for depression, thus suggesting the need for alternative treatment approaches. VN stimulation (VNS) and its benefits as a treatment for depression have been well documented, but remain unexplored in the HIV population. Historically, VNS has been delivered using a surgically implanted device; however, transcutanous VNS (tVNS) with nonsurgical auricular technology is now available. Although it currently lacks Food and Drug Administration approval in the US, evidence suggests several advantages of tVNS, including a reduced side-effect profile when compared to standard treatments and comparable results to implantable VNS in treating depression. Therefore, tVNS could offer an alternative for managing depression in HIV via regulating CNS function; moreover, tVNS may be useful for treatment of other symptoms common in HIV. From this, implications for nursing research and practice are provided.
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PMID:The potential role of vagus-nerve stimulation in the treatment of HIV-associated depression: a review of literature. 2872 Oct 49

Cotard's syndrome is often described as the delusional belief that one is dead or non-existent. However, Jules Cotard's initial description (1880) of the "delusion of negations" was much richer and also involved delusions and claims of immortality and enormity, feelings of damnation, and illusions of bodily dissolution and transformation. Alternatively conceived as an extreme case of depression, hypochondria, or psychosis, the condition is considered rare and remains poorly understood. Cotard himself provided a taxonomy and several explanations for the condition, focusing on its distinction from classical persecutory delusions and suggesting that it could be a kind of reversed grandiosity. He proposed a psychosensory basis in the dissolution of mental imagery, which he then extended to a more general psychomotor impairment of volition. Other early authors highlighted a disorder of the bodily self, and more recent theories postulated an impairment of right hemispheric functions, leading to perceptual and somatosensory feelings of unreality, which coupled with reasoning impairments and an internalized attributional style led in turn to beliefs of non-existence. However, despite its striking presentation and its relevance to our understanding of self-awareness, Cotard's syndrome remains an elusive condition, rarely reported and poorly researched.
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PMID:Cotard Syndrome. 2915 Oct 88


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