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)

Bupropion is widely used in the treatment of depression. There are, however, limited data on its long-term effects on monoaminergic neurons and therefore the mechanism of its delayed onset of action is at present not well understood. The present study was conducted to examine the effects of prolonged bupropion administration on the firing activity of dorsal raphe nucleus (DRN), locus coeruleus (LC), and ventral tegmental area (VTA) neurons. Spontaneously firing neurons were recorded extracellularly in rats anesthetized with chloral hydrate. Bupropion (30 mg/kg/day) was administered using subcutaneously implanted minipumps. In the DRN, the firing rate of serotonin (5-HT) neurons was significantly increased after 2, 7 and 14 days of administration. The suppressant effect of LSD was significantly diminished after the two-day regimen, indicating a desensitization of 5-HT1A autoreceptors. In the LC, the firing rate of norepinephrine (NE) neurons was significantly attenuated after a 2-day regimen, but recovered progressively over 14 days of administration. The suppressant effect of clonidine on NE neuronal firing was significantly attenuated in rats treated with bupropion for 14 days, indicating a desensitization of alpha2-adrenoceptors. In the VTA, neither 2 nor 14 days of bupropion administration altered the firing and burst activity of dopamine neurons. These results indicate that bupropion, unlike 5-HT reuptake inhibitors, promptly increased 5-HT neuronal activity, due to early desensitization of the 5-HT1A autoreceptor. The gradual recovery of neuronal firing of NE neurons, due to the desensitization of alpha2-adrenoceptors, in the presence of the sustained increase in 5-HT neuronal firing, may explain in part the delayed onset of action of bupropion in major depression.
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PMID:Sustained administration of bupropion alters the neuronal activity of serotonin, norepinephrine but not dopamine neurons in the rat brain. 1870 76

Clinical studies indicate that addition of bupropion to selective serotonin (5-HT) reuptake inhibitors (SSRIs) provides incremental benefit over SSRI monotherapy in depression. This study was designed to investigate the effects of co-administration of bupropion with escitalopram on the firing rate of 5-HT and norepinephrine (NE) neurons in anesthetized rats. Escitalopram (10 mg/kg/day x 2 days), given via subcutaneously (s.c.) implanted minipumps, decreased the firing of 5-HT and NE neurons by 70% and 55%, respectively. The firing of 5-HT neurons, unlike that of NE neurons, recovered after the 14-day escitalopram regimen. Bupropion, injected once daily (30 mg/kg/day, s.c. x 2 days), did not increase 5-HT firing but decreased that of NE by 55%. After 14 days of repeated bupropion administration, 5-HT firing was increased by 50%, and NE firing was back to baseline. Co-administration of escitalopram and bupropion doubled 5-HT firing after 2 and 14 days, whereas NE neurons were inhibited by 60% after 2 days, but partially recovered after 14 days. The responsiveness of 5-HT(1A) autoreceptors was significantly attenuated in the combination-treated rats after 2 days, indicating an early desensitization. These results provide support for contributions from 5-HT and NE mechanisms for enhanced effectiveness of combination of SSRI and bupropion treatment.
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PMID:Electrophysiological effects of the co-administration of escitalopram and bupropion on rat serotonin and norepinephrine neurons. 1871 44

Fatigue is a highly distressing symptom of cancer associated with significant psychological morbidity and reduced quality of life. Cancer-related fatigue (CRF) has been underreported, underdiagnosed, and undertreated. Fatigue and depression may coexist in patients with cancer, and considerable overlap of symptoms often occurs. This has led researchers to examine the role of psychotropic medications to treat fatigue. Psychostimulants, wakefulness-promoting agents, antidepressants, and cholinesterase inhibitors have been studied for CRF treatment. Methylphenidate has been studied most and is effective and well tolerated despite common side effects. Some preliminary data support using modafinil for patients with CRF. Antidepressant studies have shown mixed results. Paroxetine shows benefit for fatigue, primarily when it is a symptom of clinical depression. Bupropion sustained release may have psychostimulant-like effects and, therefore, may be beneficial in treating fatigue. Donepezil, a cholinesterase inhibitor, has shown benefit only in open-label trials. Randomized, placebo-controlled trials with specific agents are needed to further assess the efficacy and tolerability of psychotropic medications in CRF treatment.
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PMID:Pharmacologic treatment options for cancer-related fatigue: current state of clinical research. 1884 22

Although there is a strong relationship between depression and smoking, most nicotine dependence treatment trials exclude depressed smokers. Our objective was to determine whether bupropion improves abstinence rates and abstinence-associated depressive symptoms when added to transdermal nicotine replacement therapy (NRT) and group cognitive behavioral therapy (CBT) in smokers with unipolar depressive disorder (UDD). Adult smokers with current (n = 90) or past (n = 109) UDD were randomly assigned to receive bupropion or placebo added to NRT and CBT for 13 weeks. In the primary analysis, with dropouts considered smokers, 36% (35/97) of those on bupropion and 31% (32/102) on placebo attained biochemically validated 7-day point prevalence abstinence at end of treatment (not significant). Because of a high dropout rate (50%) and a significant difference in abstinence status at dropout by treatment group, a traditional intent-to-treat analysis with last observation carried forward imputation of abstinence status was performed. In this secondary analysis, 56% (54/97) of those on bupropion and 41% (42/102) on placebo met criteria for abstinence at end of trial, chi2 = 4.18, P = 0.04. Nicotine replacement therapy usage and absence of a comorbid anxiety disorder predicted abstinence. Abstinence was associated with increased depressive symptoms, regardless of bupropion treatment. Thus, in the primary analysis, bupropion neither increased the efficacy of intensive group CBT and NRT for smoking cessation in smokers with UDD nor prevented abstinence-associated depressive symptoms. Bupropion seemed to provide an advantage for smoking cessation for those who remained in the trial. The dropout rate was high and was characterized by a higher prevalence of current comorbid anxiety disorder. Given the high abstinence rate achieved with CBT plus NRT, a ceiling effect related to the high level of intervention received by all subjects may have prevented an adequate test of bupropion.
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PMID:A controlled trial of bupropion added to nicotine patch and behavioral therapy for smoking cessation in adults with unipolar depressive disorders. 1901 35

In 2008 there is no major breakthrough in the field of psychopharmacology. Paliperidone, (Invega), or 9-hydroxyrisperidone, the main hydroxylated metabolite of risperidone, is now available in Switzerland. It has the same pharmacodynamic profile and a different pharmacokinetic profile, linked to an extended release preparation. Bupropion, an antidepressant with noradrenergic and dopaminergic activity, is now accepted on the Swiss market for the treatment of depression under the name of Wellbutrin. Until now, its indication was limited to tobacco withdrawal (under the name of Zyban). The article also includes new data issued from the STAR*D study (concerning the efficacy of cognitive behavioural therapy) and a few remarks about the recent debate in the media about the efficacy of antidepressants.
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PMID:[Psychiatry]. 1923 34

The pathophysiology of depression has been assigned to the noradrenalin and serotonin system. Results of different studies also support a role of the dopaminergic system in depression: In particular, psychomotor retarded depressive patients exhibited lower levels of homovanillic acid (metabolite of dopamine). While the moodimproving effect of methylphenidat, D-amphetamine and cocaine is also supportive for an involvement of the dopaminergic system, reserpine leads to diminished dopamine levels and may induce a depressive syndrome as well as dopamine receptor-blockers. Dopamine-mediated motor disturbances and accompanying changes in mood in Parkinson's disease likewise support pathophysiological similarities of depression and Parkinson's disease. Psychomotor inhibition, reduced facial expression and decreased speech production in depression are in line with a hypodopaminergic state of the respective motor areas. There is evidence from open studies for the ergotalkaloids bromocriptine and pergolide to have anti-depressive effects. Controlled studies for the selective dopamine D2/D3-agonists pramipexole and ropinirole are existing. Bupropion, a selective dopamine and noradrenaline reuptake inhibitor (DNRI), has proven antidepressant efficacy in controlled studies and has been licensed for the treatment of depression.
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PMID:[The relevance of dopamine agonists in the treatment of depression]. 1927 88

Various pharmacological strategies have been developed to treat such refractory depression, of which combination therapies with antidepressants are one of the most important. This article reviews both benefits and risks of all known antidepressant combination strategies. The relevant literature was identified by means of a computerized MEDLINE research on the years 1990-2006 and scanning of review articles. The use of antidepressant combinations to overcome refractory depression is a common strategy in practice. Many antidepressants can be usefully combined especially if they engage separate mechanisms of action--like SSRIs with Reboxetine, Bupropion, Mirtazapine and Tricyclics--or on the other hand--Tricyclics with MAO-Inhibitiors. Combination strategies are effective treatment options, however they do have potential safety risks due to pharmacokinetic and pharmacodynamic interactions. Combinations including MAOIs can cause serotonin syndrome, and some SSRIs like Fluoxetine may elevate tricyclic plasma levels with the consequence of an increased risk of toxicity. The distinct knowledge of available antidepressant combination strategies may help to increase response--as well as remission rates in therapy resistant depression. However, further research is urgently needed to determine relative efficacy.
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PMID:[Combining antidepressants: a useful strategy for therapy resistant depression?]. 1941 84

Depression and antidepressant therapy have been associated with sexual dysfunction. Studies report wide discrepancies with regard to frequency, gender, and quality of sexual dysfunction. Although sexual side effects are a common reason for non-compliance with medication, information on impairment of sexuality in psychiatric patients is rare. The impact of antidepressant- induced sexual dysfunction is substantial and negatively affects quality of life, self-esteem, mood, and relationship with partner. Sexual side effects resulting from serotonin specific reuptake inhibitors use may be mediated by a number of central and peripheral mechanisms. Some antidepressants such as Bupropion, mirtazapine, and moclobemide have a sexual tolerability profile significantly better than SSRIs, especially escitalopram, paroxetine, venlafaxine, sertraline, or fluoxetine. There are some possibilities for treatment of anti-depressant induced sexual dysfunctions such as waiting for spontaneous remission, reducing the dosage level, substituting the offending drug with other antidepressants, drug holidays, or administration of a phosphodiesterase- 5-inhibitor. These side-effects are increasingly used therapeutically in the context of the common male sexual dysfunction ejaculatio praecox. For this indication short-acting SSRI;s are available.
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PMID:[Major depressive disorder, antidepressants and sexual dysfunction]. 1957 5

In the medication of depression, the antidepressants such as selective 5-HT reuptake inhibitors (SSRIs) and a 5-HT and NA reuptake inhibitor (SNRI) are mainly in use in Japan. However, remission rates for SSRI or SNRI are 60% or less. This means that there are still many patients with treatment-resistant depression (TRD). Meanwhile it is considered that the DA nerve system plays an important role for recovery from troublesome feelings and a sense of aimlessness in life in patients with TRD. Recently, new generation antidepressants under development in Japan (escitalopram, duloxetine, mirtazapine, and bupropion) are expected as an option in the medical treatment of TRD. We introduce the pharmacological (focusing on the DA nerve system) and clinical data on these new antidepressants and their putative positioning of each antidepressant. Escitalopram is a stronger and safer SSRI with an earlier onset of action. The antidepressant effect of duloxetine is considered stronger than that of other SNRIs. Mirtazapine is an antagonist of alpha2, 5-HT2A, and 5-HT2C receptors and promotes releases of NA, 5-HT, and DA. Clinically, mirtazapine shows an earlier onset of action and a sedative effect. Bupropion is a DA and NA reuptake inhibitor, and is considered useful to activate DA neurons.
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PMID:[Mechanism of action of new generation antidepressants under development in Japan: focusing on dopamine neurotransmission]. 1966 59

The aim of the present study was to review the sexual side-effects of contemporary antidepressants in Australia, comparing the selective serotonin re-uptake inhibitors (SSRIs) with venlafaxine, reboxetine, mirtazepine, duloxetine, bupropion, desvenlafaxine and agomelatine. Double-blind, randomized comparative studies of these antidepressants that included assessment of sexual dysfunction with validated rating scales in patients with major depressive disorder were identified from the literature using MEDLINE, EMBASE and PsychINFO databases. Bupropion and duloxetine caused significantly less sexual dysfunction than the SSRIs in short-term studies and reboxetine significantly less in both short- and longer term studies. Bupropion and agomelatine caused significantly less sexual dysfunction than venlafaxine. The evidence for mirtazepine having an advantage over the SSRIs is lacking and there are currently insufficient data for desvenlafaxine. Well-designed comparative studies of contemporary antidepressants with direct assessment of sexual side-effects as the primary outcome measure are scarce. Future studies should be randomized, double-blind, active controlled trials in sexually active subjects with major depressive disorder. There should be direct assessment of sexual function and depression using reliable, validated rating scales before and during treatment. Studies should assess treatment-emergent effects in patients with normal function and resolution of baseline dysfunction over treatment, in both the short and long term. Further research should compare available instruments for measuring sexual function, and include separate analyses of both remitters/non-remitters and male/female subjects.
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PMID:Sexual side-effects of contemporary antidepressants: review. 1967 52


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