Carbamazepine prevents imipramine-induced behavioural sensitization to the dopamine D(2)-like receptor agonist quinpirole.

D'Aquila PS, Peana AT, Tanda O, Serra G.

Dipartimento di Scienze del Farmaco, Universita di Sassari, via Muroni 23/a, 07100, Sassari, Italy. dsfpaolo ssmain.uniss.it

Chronic treatment with antidepressants potentiates the behavioural sensitivity to the administration of dopamine receptor agonists. Such supersensitivity might be involved in the mechanism of action of antidepressant drugs, but it has also been suggested to play a role in the mechanisms underlying antidepressant treatment-related mania (i.e. antidepressant-induced mood switch and rapid cycling). Consistently to this hypothesis, we have recently shown that lithium salts, which are poorly effective in antidepressant-related mania, fail to prevent the development of imipramine-induced supersensitivity to the locomotor effect of the dopamine D(2)-like receptor agonist quinpirole. In the present paper, we report the ability of carbamazepine, an anticonvulsant with antimanic and mood stabiliser properties, to prevent the development of supersensitivity to the locomotor response to quinpirole induced by chronic treatment with imipramine. The present results, together with the results of our previous study, might contribute to explain the different responsiveness to lithium and carbamazepine observed in some manic patients, and are consistent with the clinical data suggesting that carbamazepine might be more effective than lithium in antidepressant-related mania.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11282119&dopt=Abstract antidepressant




Sociological influences on antidepressant prescribing.

Sleath B, Shih YC.

School of Pharmacy and Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Beard Hall CB #7360, Chapel Hill, NC 27599-7360, USA. betsy_sleath unc.edu

This study examined how patient characteristics, physician characteristics, the physician's interaction with the health care system, and the physician's interaction with the patient influenced whether patients with a depression diagnosis received an antidepressant prescription and whether they received a SSRI antidepressant, a non-SSRI antidepressant, or both.The 1998 National Ambulatory Medical Care Survey (NAMCS), in the USA, was used for the analysis. Logistic regression was used to examine what characteristics influenced whether a patient with a depression diagnosis received an antidepressant prescription. Next, a multinomial logistic regression model was applied to examine the relative risk of using one type of antidepressant versus another among antidepressant users while correcting for possible sample selections using the Heckman selection model. Sixty-seven percent of patients with a depression diagnosis received an antidepressant. Patients who were seeing providers who were not primary care physicians or psychiatrists, self-paying patients, and patients with neurotic depression were significantly less likely to receive an antidepressant prescription. Patients with depression listed as their first diagnosis were significantly more likely to receive an antidepressant prescription. Patients seeing a psychiatrist were more likely than patients seeing a primary care physician to receive a non-SSRI antidepressant than a SSRI antidepressant. Patients belonging to an HMO that had capitated visits were over four times more likely to receive non-SSRI antidepressants than SSRI antidepressants. Patients with major depression were significantly more likely to receive a non-SSRI antidepressant. Patients with depression as their primary diagnosis and patients who saw psychiatrists were significantly more likely to receive both SSRI and non-SSRI antidepressants rather than just SSRI antidepressants. Patient characteristics, physician characteristics, the physician's interaction with the health care system, and the physician's interaction with the patient all influenced antidepressant prescribing. An especially important finding was that insurance status influenced whether patients received an antidepressant. Health care providers need to take the time to help patients without insurance obtain antidepressant medication if it is needed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12600369&dopt=Abstract antidepressant




Chronic treatment with the atypical antidepressant tianeptine attenuates sickness behavior induced by peripheral but not central lipopolysaccharide and interleukin-1beta in the rat.

Castanon N, Bluthe RM, Dantzer R.

INRA-INSERM U394, Neurobiologie Integrative, Institut Francois Magendie, Bordeau, France. nathalie.castanon bordeaux.inserm.fr

RATIONALE: The hypothesis that proinflammatory cytokines play a causative role in the pathophysiology of depression has been recently tested by studying the effect of antidepressants on production of endogenous cytokines, and on sickness behavior induced by exogenous cytokines. In this last case, however, the effect of antidepressants has been only studied on the effect of peripherally administered cytokines. OBJECTIVES: The aim of the present study was to determine whether the antidepressant tianeptine can attenuate both peripheral and central cytokine actions. METHODS: Rats were injected IP with acute (10 mg/kg) or chronic (10 mg/kg, 2 times/day, 17 days) tianeptine. The effects of this treatment were assessed on the behavioral (social exploration, locomotion) and metabolic (food intake, body weight) alterations induced by peripheral or central administration of the cytokine inducer lipopolysaccharide (LPS) (250 microg/kg IP; 100 ng/rat ICV) or the prototypical proinflammatory cytokine interleukin-1 (IL-1)beta (15 microg/rat IP; 90 ng/rat ICV). RESULTS: Chronic, but not acute, treatment with tianeptine attenuated the behavioral signs of sickness behavior induced by peripheral, but not central, LPS or IL-1beta. CONCLUSIONS: This work, which is the first in vivo study assessing the effect of an antidepressant on centrally induced immune activation, shows a clear dissociation between peripheral and central cytokine effects, and suggests a peripheral site of action of tianeptine. It also provides the first evidence that the protective effects of classical antidepressants on LPS-induced sickness behavior extend to an atypical antidepressant, and that the protective effect of antidepressants also applies to IL-1beta.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11292006&dopt=Abstract antidepressant




Treatment process and outcomes for managed care patients receiving new antidepressant prescriptions from psychiatrists and primary care physicians.

Simon GE, Von Korff M, Rutter CM, Peterson DA.

Center for Health Studies, Group Health Cooperative, 1730 Minor Ave, Suite 1600, Seattle, WA 98101-1448, USA. simon.g ghc.org

BACKGROUND: While many studies describe deficiencies in primary care antidepressant treatment, little research has applied similar standards to psychiatric practice. This study compares baseline characteristics, process of care, and outcomes for managed care patients who received new antidepressant prescriptions from psychiatrists and primary care physicians. METHODS: At a prepaid health plan in Washington State, patients receiving initial antidepressant prescriptions from psychiatrists (n = 165) and primary care physicians (n = 204) completed a baseline assessment, including the Structured Clinical Interview for DSM-IV depression module, a 20-item depression assessment from the Symptom Checklist-90, and the Medical Outcomes Survey 36-Item Short-Form Health Survey functional status questionnaire. All measures were repeated after 2 and 6 months. Computerized data were used to assess antidepressant refills and follow-up visits over 6 months. RESULTS: At baseline, psychiatrists' patients reported slightly higher levels of functional impairment and greater prior use of specialty mental health care. During follow-up, psychiatrists' patients made more frequent follow-up visits, and the proportion making 3 or more visits in 90 days was 57% vs 26% for primary care physicians' patients. The proportion receiving antidepressant medication at an adequate dose for 90 days or more was similar (49% vs 48%). The 2 groups showed similar rates of improvement in all measures of symptom severity and functioning. CONCLUSIONS: In this sample, clinical differences between patients treated by psychiatrists and primary care physicians were modest. Shortcomings in depression treatment frequently noted in primary care (inadequate follow-up care and high rates of inadequate antidepressant treatment) were also common in specialty practice. Possible selection bias limits any conclusions about relative effectiveness or cost-effectiveness.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11296101&dopt=Abstract antidepressant




Antidepressant prescribing to Hispanic and non-Hispanic white patients in primary care.

Sleath BL, Rubin RH, Huston SA.

School of Pharmacy and Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, 27599-7360, USA. betsy_sleath unc.edu

OBJECTIVE: To examine whether there was a difference in the prescribing of selective serotonin-reuptake inhibitors (SSRIs) and non-SSRI antidepressants to Hispanic and non-Hispanic white patients in primary care. METHODS: Twenty-seven family practice and internal medicine resident physicians and 407 of their Hispanic and non-Hispanic white patients who were fluent in English or Spanish participated in the study The medical records of all patients were reviewed and information about patient diagnoses and antidepressant prescriptions was abstracted. Logistic regression was used to examine whether Hispanic ethnicity influenced physician prescribing of SSRI and non-SSRI antidepressants while controlling for other patient characteristics and diagnoses. For patients with a diagnosis of depression, logistic regression was used to examine whether Hispanic ethnicity influenced whether patients received antidepressant treatment while controlling for other patient characteristics RESULTS: Twenty-seven percent of patients received a prescription for one or more antidepressants. Hispanic and non-Hispanic white patients were equally likely to be prescribed SSRI and non-SSRI antidepressant medications. Having a diagnosis of depression and having a diagnosis of chronic pain was significantly correlated with the prescribing of a non-SSRI antidepressant (p < 0.001, p < 0.01, respectively). Having a diagnosis of depression was significantly correlated with the prescribing of an SSRI antidepressant (p < 0.001). Hispanic and non-Hispanic white patients with a diagnosis of depression were equally likely to be prescribed antidepressant treatment. Patients with a diagnosis of depression in the general medicine clinic were significantly less likely to receive antidepressant therapy than patients in the family practice clinic. CONCLUSIONS: Hispanic ethnicity did not influence antidepressant prescribing. Future research in other settings is needed to further determine whether Hispanic ethnicity influences antidepressant prescribing.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11302403&dopt=Abstract antidepressant




Antidepressant drug-induced alterations in neuron-localized tumor necrosis factor-alpha mRNA and alpha(2)-adrenergic receptor sensitivity.

Nickola TJ, Ignatowski TA, Reynolds JL, Spengler RN.

State University of New York at Buffalo, Department of Pathology, School of Medicine and Biomedical Sciences, Buffalo, New York 14214, USA.

The pleiotropic cytokine tumor necrosis factor-alpha (TNF) and alpha(2)-adrenergic receptor activation regulate norepinephrine (NE) release from neurons in the central nervous system. The present study substantiates the role of TNF as a neuromodulator and demonstrates a reciprocally permissive relationship between the biological effects of TNF and alpha(2)-adrenergic receptor activation as a mechanism of action of antidepressant drugs. Immunohistochemical analysis and in situ hybridization reveal that administration of the antidepressant drug desipramine decreases the accumulation of constitutively expressed TNF mRNA in neurons of the rat brain. Superfusion and electrical field stimulation were applied to a series of rat hippocampal brain slices to study the regulation of [(3)H]NE release. Superfusion of hippocampal slices obtained from rats chronically administered the antidepressant drug zimelidine demonstrates that TNF-mediated inhibition of [(3)H]NE release is transformed, such that [(3)H]NE release is potentiated in the presence of TNF, an effect that occurs in association with alpha(2)-adrenergic receptor activation. However, chronic zimelidine administration does not alter stimulation-evoked [(3)H]NE release, whereas chronic desipramine administration increases stimulation-evoked [(3)H]NE release and concomitantly decreases alpha(2)-adrenergic autoreceptor sensitivity. Collectively, these data support the hypothesis that chronic antidepressant drug administration alters alpha(2)-adrenergic receptor-dependent regulation of NE release. Additionally, these data demonstrate that administration of dissimilar antidepressant drugs similarly transform alpha(2)-adrenergic autoreceptors that are functionally associated with the neuromodulatory effects of TNF, suggesting a possible mechanism of action of antidepressant drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11303058&dopt=Abstract antidepressant




Antidepressant-like effects in various mice strains in the forced swimming test.

David DJ, Renard CE, Jolliet P, Hascoet M, Bourin M.

EA 3256 Neurobiologie de l'anxiete et de la depression, Faculte de Medecine, 1 rue Gaston Veil, BP 53508, 44035, Nantes Cedex 01, France.

RATIONALE: Strain differences in mice have been reported in response to drugs in the mouse forced swimming test (FST), even if few antidepressants were examined. OBJECTIVES: The aim of the present study was to investigate the influence of genetic factors, using five antidepressants (imipramine, desipramine, citalopram, paroxetine and bupropion) in the mouse FST, in outbred strains (Swiss, NMRI) and inbred strains (DBA/2, C57BL/6J Rj). Moreover, whole brain levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT) in vehicle treated animals, which were or were not subjected to the FST, were measured by HPLC analysis in an attempt to explain behavioural differences. METHODS: For each antidepressant, a dose range (1-16 mg/kg) was tested in the locomotor apparatus and only non-psychostimulant doses were then tested in the FST in order to detect antidepressant-like activity. RESULTS: No baseline differences among Swiss, NMRI, DBA/2 and C57BL/6J Rj strains were observed in our experiments, allowing the comparison of different antidepressants in each strain. Imipramine (16 mg/kg), desipramine, citalopram (4-16 mg/kg) and paroxetine (8 and 16 mg/kg) treatment decreased the immobility time in the Swiss strain and the size of the effect reached more than 20% for each of these antidepressants. C57BL/6J Rj was the only strain sensitive to bupropion (2 and 4 mg/kg). In the NMRI strain, only paroxetine treatment decreased the immobility time (16 mg/kg). CONCLUSION: Our study showed that drug sensitivity is genotype dependent. FST results have shown that Swiss mice are the most sensitive strain to detect 5-HT and/or NA treatment. The use of DBA/2 inbred mice may be limited, as an absence of antidepressant-like response was observed in the FST. The lack of sensitivity to antidepressant treatment in DBA/2 strains could be due to high DA, NA and 5-HT whole brain concentrations.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12601501&dopt=Abstract antidepressant




Involvement of 5-HT(2C) receptors in the anti-immobility effects of antidepressants in the forced swimming test in mice.

Clenet F, De Vos A, Bourin M.

Faculte de Medecine et GIS Medicament, JE 2029 Neurobiologie de l'Anxiete, Faculte de Medecine, BP 53508, 1 rue Gaston Veil, F44035 Cedex 01, Nantes, France.

Several recent studies have demonstrated that 5-HT(1A), 5-HT(1B) and 5-HT(3) receptors were implicated in the mechanism of action of antidepressants in the mouse forced swimming test. Despite extensive evidence for a role of 5-HT(2C) receptors in depression, the precise role of these receptors in the effects of clinically established antidepressants was not directly investigated in the mouse forced swimming test. This work was aimed at exploring interactions between several doses of Ro 60-0175, a recently available, full and selective 5-HT(2C) agonist, and antidepressant drugs in the mouse forced swimming test. Spontaneous locomotor activity was measured as an index of intact sensorimotor functions and the dose-effect of Ro 60-0175 alone, as well as interactions with several antidepressants, such as tricyclic antidepressants (imipramine, desipramine and maprotiline) and selective serotonin reuptake inhibitors (paroxetine, citalopram, fluoxetine, fluvoxamine and sertraline), were studied in the mouse forced swimming test. There was no intrinsic antidepressant-like effect of Ro 60-0175, but an impairment in locomotor function was detected when using doses higher than 4 mg/kg in the mouse. There was a synergistic effect of low doses of Ro 60-0175 with sub-active doses of imipramine, paroxetine, citalopram and fluvoxamine; an antagonism between the highest dose of Ro 60-0175 and the active doses of paroxetine and fluoxetine was also detected. There is evidence that 5-HT(2C) receptors may be involved in the action of antidepressants which are able to boost the concentration of serotonin in the synapse, i.e. SSRIs and imipramine

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11313160&dopt=Abstract antidepressant