Effect of bupropion on nocturnal urinary free cortisol and its association with antidepressant response.

Rao U, Ott GE, Lin KM, Gertsik L, Poland RE.

Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, USA.

The study examined the relationship between pre-treatment nocturnal hypothalamic-pituitary-adrenal (HPA) activity, as reflected by nocturnal urinary free cortisol (NUFC) response to a single-dose of sustained-release bupropion, and the antidepressant effect of the drug. NUFC changes in response to treatment with bupropion also were assessed. NUFC was measured in 20 patients with unipolar major depressive disorder before and after initiating treatment with sustained-release bupropion. Prior to treatment, subjects were studied on two separate sessions, one week apart. On the morning of each session, the participants received bupropion (150 mg, PO) or placebo using a randomized, double-blind procedure. Following the second session, subjects then received open-label treatment with bupropion for 8 weeks. NUFC sampling was repeated at the end of treatment. There was a significant interaction between NUFC concentration in response to single-dose bupropion and its antidepressant effect. Treatment non-responders showed a significant increase in NUFC in response to a single-dose of bupropion, whereas responders showed no such change. In addition, the NUFC response to bupropion challenge correlated significantly with the change in depression ratings as a result of treatment. In contrast to many other antidepressants, treatment with bupropion for 8 weeks did not reduce HPA activity in either responders or non-responders. These findings suggest that the NUFC response to a test-dose of bupropion might be helpful in predicting its antidepressant effect. One possible mechanism for the association between the NUFC response to acute bupropion challenge and antidepressant efficacy might be linked through dopaminergic and/or noradrenergic mechanisms.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15589567&dopt=Abstract antidepressant




Antidepressant effects of nicotine and fluoxetine in an animal model of depression induced by neonatal treatment with clomipramine.

Vazquez-Palacios G, Bonilla-Jaime H, Velazquez-Moctezuma J.

Neuroscience Laboratory, Department of Reproductive Biology, Universidad Autonoma Metropolitana-Iztapalapa, Mexico City C.P. 09340. Mexico. jvm xanum.uam.mx

The association between smoking and depression has been widely investigated. Most of these reports suggest that nicotine (NIC) may act as an antidepressant. To examine the suggested antidepressant effect of nicotine and its possible interaction with the serotonergic system, we assessed the effect of nicotine and fluoxetine (FLX) in an animal model of depression induced by neonatal treatment with clomipramine (CLI) and submitted to the forced swim test (FST). Results corroborated that CLI-treated rats displayed higher levels of immobility. After the administration of nicotine (0.4 mg/kg sc) acutely (1 day), subchonically (7 days), and chronically (14 days), CLI-treated rats significantly reduced the immobility and increased swimming without affecting climbing. These effects were similar to the effects induced for subchronic and chronic administration of the antidepressant fluoxetine (5 mg/kg sc), a selective serotonin re-uptake inhibitor. However, fluoxetine failed to affect immobility when it was administered acutely. No synergism was observed when both drugs were administered simultaneously. The present results further corroborate the antidepressant action of nicotine and fluoxetine. The increase of swimming during the FST has been linked to an increase of serotonergic activity. Thus, it could be possible that the antidepressant action of nicotine is mediated by the serotonergic system.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15610943&dopt=Abstract antidepressant




Association between mortality from suicide in England and antidepressant prescribing: an ecological study.

Morgan OW, Griffiths C, Majeed A.

Health and Care Division, Office for National Statistics, 1 Drummond Gate, London, United Kingdom. omorgan bigfoot.com

BACKGROUND: Antidepressant prescribing has been increasing in England. Studies in other countries suggest that while this may be associated with reduced suicide rates, it may also be associated with increased fatal poisoning from antidepressant drugs. We therefore conducted an ecological study to assess the association between prescription rates for antidepressants and suicide or fatal antidepressant-related poisoning in England. METHODS: The Office for National Statistics provided information on the number of suicides, antidepressant-related poisoning deaths and populations for England between 1993 and 2002. The Department of Health supplied data on prescriptions for all antidepressants dispensed in England. Associations between prescriptions and deaths were assessed using Spearman's rank correlation coefficient. RESULTS: There were 46,747 suicides, 3,987 deaths involving tricyclic antidepressants and 430 involving selective serotonin re-uptake inhibitors and other antidepressants. Increased antidepressant prescribing was statistically associated with a fall in suicide rates (Spearman's rs = -0.73, p = 0.02) and fatal poisoning involving tricyclic antidepressants (rs = -0.64, p = 0.05). In contrast, increased prescribing of selective serotonin re-uptake inhibitors and other antidepressants was statistically associated with an increase in fatal poisoning involving these drugs (rs = 0.99, p < 0.001). CONCLUSION: Increased prescribing of antidepressants may indicate improved diagnosis and treatment of depression in primary care. Our analysis suggests that this was accompanied by lower suicide rates. A decrease in poisoning deaths involving tricyclic antidepressants may suggest a change in preference for using serotonin reuptake inhibitors and other antidepressant drugs for high-risk patients. This may also partially explain the increase in deaths involving these drugs. Due to the ecological nature of the design, we cannot say conclusively whether reduced suicide rates are a direct consequence of increased antidepressant prescribing rates. To confirm these associations, individual level data on prescribing and suicide is needed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15613234&dopt=Abstract antidepressant




Breast cancer risk among users of antidepressant medications.

Gonzalez-Perez A, Garcia Rodriguez LA.

Centro Espanol de Investigacion Farmacoepidemiologica (CEIFE), Madrid, Spain. agonzalez ceife.es

BACKGROUND: Breast cancer is the most common cancer in women. Laboratory studies suggest that antidepressants may promote breast cancer tumor growth. Several epidemiologic studies have evaluated this association with conflicting results. METHODS: We conducted a cohort study with a secondary nested case-control analysis based on the General Practice Research Database. Our goal was to assess the association between the risk of breast cancer and use of serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and other antidepressants. We calculated adjusted estimates controlling for breast cancer risk factors using unconditional logistic regression. RESULTS: A total of 3708 cases of breast cancer were ascertained. Overall, antidepressant use was not associated with an increased risk of breast cancer. Current users of SSRIs had an odds ratio (OR) of 0.98 (95% confidence interval=0.81-1.19), whereas current users of TCAs had an OR of 0.86 (0.73-1.00). When only use for longer than 1 year was considered, the corresponding estimates for SSRIs and TCAs were 0.76 (0.53-1.09) and 0.87 (0.70-1.09), respectively. None of the individual drugs was associated with breast cancer risk. CONCLUSIONS: Use of antidepressants was not associated with an increased risk of breast cancer regardless of duration of use, daily dose, or specific drug being used. These results, together with evidence from prior studies, support the lack of a clinically meaningful association between breast cancer risk and antidepressants.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15613952&dopt=Abstract antidepressant




Antidepressant-like properties of some serotonin receptor ligands and calcium channel antagonists measured with the forced swimming test in mice.

Biala G.

Department of Pharmacodynamics, Medical Academy, Lublin, Poland.

This study has examined the effects of 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), buspirone, nifedipine and verapamil on duration of immobility in the forced swimming test in mice. The 5-HT1A agonist-8-OH-DPAT (0.25, 0.5, 1 mg/kg) and dihydropyridine calcium channel antagonist-nifedipine (10 mg/kg) produced decreases in immobility time. These effects were similar to those of the tricyclic antidepressant-imipramine (5 and 10 mg/kg). Non-dihydropyridine calcium channel antagonist-verapamil (10 and 20 mg/kg) had no effect on immobility time. The non-benzodiazepine anxiolytic and 5-HT1A agonist-buspirone (1 mg/kg) when given in a single injection or as repeated treatment, did not exert antidepressant-like activity in the forced swimming test. Pretreatment with dopamine antagonist-haloperidol (0.5 mg/kg) significantly antagonized the effects of 8-OH-DPAT (1 mg/kg), imipramine (10 mg/kg) and nifedipine (10 mg/kg). Pretreatment with benzodiazepine anxiolytic-diazepam (2 mg/kg) antagonized the effect of imipramine (10 mg/kg) but not that of 8-OH-DPAT (1 mg/kg) or nifedipine (10 mg/kg). Neither haloperidol nor diazepam produced any effects in this test. Single or repeated administration of buspirone (1 mg/kg) did not alter the reduction of immobility time produced by imipramine (10 mg/kg). These results suggest that 5-HT1A agonists and dihydropyridine calcium channel blockers may have antidepressant efficacy in the forced swimming test, but the effects of buspirone and 8-OH-DPAT may be mediated via different mechanisms. These results also indicate that the relationship between serotonin and dopamine neurons may play a role in the action of antidepressant drugs. In addition, the interactions involving both GABAergic and serotoninergic processes exist between benzodiazepine anxiolytics and some antidepressants.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9798263&dopt=Abstract antidepressant




Antidepressant prescribing in nursing homes: is there a place for tricyclics?

Borson S, Scanlan JM, Doane K, Gray S.

Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, USA. soob u.washington.edu

OBJECTIVE: To deduce a model describing physicians' choice of antidepressants for treating elderly nursing home patients. METHODS: Subjects were geriatric residents of 137 skilled nursing facilities who regularly received an antidepressant medication for at least one month (n = 3,440, 28% of all residents). Reasons for prescribing antidepressants and physicians' diagnoses of depression and dementia were identified by medical record audit. Residents were grouped by dementia and antidepressant target symptoms (depression, or one or more non-psychiatric symptoms, i.e. insomnia, pain, incontinence, itching). RESULTS: Selective serotonin reuptake inhibitors (SSRIs) were prescribed preferentially over tricyclic antidepressants (TCAs) for treating depression in both demented and non-demented residents, but TCAs were nine times more likely to be prescribed for treating non-psychiatric target symptoms alone. When non-psychiatric target symptoms were present without depression or dementia, both amitriptyline and nortriptyline prescribing was increased, but amitriptyline appeared to be the antidepressant of choice. In all subgroups examined, its use was two to five times more prevalent when such symptoms were present. In patients with dementia, amitriptyline prescribing declined whether or not non-psychiatric target symptoms were present, but nortriptyline prescribing did not; nortriptyline was three times more likely than amitriptyline to be prescribed in the presence of dementia. CONCLUSIONS: Physicians prescribe anticholinergic TCAs principally to treat common non-depressive symptoms in nursing home residents, preferring SSRIs for uncomplicated depression and depression with dementia. They tend to avoid prescribing anticholinergic TCAs other than nortriptyline when they recognize a patient as demented. The data suggest that physicians employ a decision model for antidepressant prescribing that simultaneously recognizes the utility of TCAs in treating non-psychiatric symptoms and the anticholinergic vulnerability of older, especially demented, patients. Whether or not this model leads to optimal patient management requires further study. Copyright 2002 John Wiley & Sons, Ltd.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12461763&dopt=Abstract antidepressant




[Risk factors associated with the consumption of antidepressant agents]

[Article in Spanish]

Rispau Falgas A, Soler Vila M, Garcia Bayo I, Carames Duran E, Espin Martinez A, Garcia Pulido C.

Centro de Salud Gava II, Barcelona.

OBJECTIVES: To find the profile of the consumer of anti-depressants, identify risk factors and calculate the prevalence of the under-diagnosis of depression in our milieu. DESIGN: Case-control study. SETTING: Gava II Health Centre, Barcelona. PARTICIPANTS AND METHODS: The study covered 134 consumers of anti-depressants and 274 controls with no treatment (one group from the Centre, the other from the community) paired for sex, age and general practitioner. The Zung-Conde self-applied depression) scale was administered. MEASUREMENTS AND MAIN RESULTS: 88% of those surveyed were women, with an average age of 50. The prescribing doctor was, in 55% of cases, their general practitioner. The anti-depressants prescribed were mainly (70.9%) from the group of selective inhibitors of serotonin uptake. There were more divorced and widowed people among the cases (p < 0.05). The pathology most often associated with the cases was digestive (31%, p < 0.02). 63% of cases had suffered some event they thought important in the 6 months before prescription. Average score on the Zung test was 51.5% in the cases, and 40% in the controls (p < 0.0001). Using 50 on the Zung scale as the cut-off point, we classified 56% of the cases and 17% of the controls as depressed. CONCLUSIONS: The profile of the consumer of anti-depressants is a women of about 50, living as one of a couple, house-wife, with primary education only, and medium to low social and economic level. The prevalence in the controls of depressive illness neither detected nor treated is similar to that found in other studies. We need to find some instrument to measure attitude, in order to reduce the number of patients who are underdiagnosed in the consulting room.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9842082&dopt=Abstract antidepressant




Antidepressants and suicide mortality.

Ohberg A, Vuori E, Klaukka T, Lonnqvist J.

Department of Forensic Medicine, University of Helsinki, Finland. annakatri.ohberg helsinki.fi

BACKGROUND: This paper presents a nationwide analysis of suicide mortality in Finland from 1990 to 1995, when the total use of antidepressants, especially that by selective serotonin reuptake inhibitors (SSRIs) expanded in the country. METHODS: Suicide rate was analysed by various methods including that by intake of antidepressants. Various antidepressants were compared by calculating fatal toxicity indices (FTI) by relating number of fatal poisonings by a drug to its consumption. RESULTS: The expanded use of antidepressants coincided with an increased number of deaths caused by these drugs. The proportion of suicides committed by use of antidepressants among all suicides increased from 5.6% to 8.4%. The total suicide rate, however, declined significantly. This was mainly accounted for by the reduced suicide rates by hanging and carbomonoxide poisoning, which outnumbered the increased figures of suicides by poisoning. On the whole, 82% of suicides by antidepressants were committed by use of tricyclics. Use of doxepin and amitriptyline remained steady, and their FTIs were constantly high. The lowest FTIs were associated with fluoxetine, citalopram, mianserin and moclobemide. LIMITATIONS: The method ignores causality between the increased use of SSRIs and suicide mortality. Various factors affecting risk of suicide or choice of a method remain outside the scope of the data. CONCLUSION: The increased use of SSRIs coincided with a significant decline in suicide mortality. However, suicides by use of antidepressants showed an upward trend. Therefore, in suicide prevention, risks and benefits of antidepressants should be considered in choosing treatment for depressive patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9858081&dopt=Abstract antidepressant