Use of antidepressants among elderly subjects: trends and contributing factors.

Mamdani MM, Parikh SV, Austin PC, Upshur RE.

Institute for Clinical Evaluative Sciences, the Center for Addiction and Mental Health, Toronto, Canada. muhammad.mamdani ices.on.ca

OBJECTIVE: The authors assessed changes over time in antidepressant utilization among elderly subjects regarding the prevalence of antidepressant users, shifts in prescription patterns, and related financial implications. METHOD: The authors conducted a population-based study of more than 1.4 million Ontario residents aged 65 years or older. Cross-sectional data regarding annual antidepressant utilization were obtained from administrative databases for 1993 to 1997. Time series analysis was used to assess trends over time and to make future projections. RESULTS: The proportion of antidepressant users increased from 9.3% of the elderly population in 1993 to 11.5% in 1997. Prescriptions for selective serotonin reuptake inhibitors (SSRIs) accounted for 9.6% of antidepressant prescriptions dispensed in the first 30 days of 1993 and 45.1% of those dispensed by the last 30 days of 1997 and were projected to increase to approximately 56% by the end of 2000. Prescriptions for tricyclic antidepressants fell from 79.0% in the first 30 days of 1993 to 43.1% by the last 30 days of 1997 and were projected to decline to approximately 28% by the end of 2000. Annual antidepressant costs (in Canadian dollars) increased by 150%, from $10.8 million in 1993 to $27.0 million in 1997. Population shifts and an increase in the prevalence of antidepressant users accounted for at least 20% of this increase, whereas the prescribing transition from tricyclic antidepressants to SSRIs accounted for at least 61% of the increase. CONCLUSIONS: The introduction of SSRIs has had a substantial financial impact at the drug utilization level. Future research should address the appropriate balancing of the cost of newer agents versus their ostensible advantages.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10698810&dopt=Abstract antidepressant




Increased tonic activation of rat forebrain 5-HT(1A) receptors by lithium addition to antidepressant treatments.

Haddjeri N, Szabo ST, de Montigny C, Blier P.

Neurobiological Psychiatry Unit, McGill University, 1033 Pine Avenue West, Montreal, PQ, Canada.

The present study was undertaken to determine whether lithium addition to long-term treatment with different classes of antidepressant drugs could induce a greater effect on the serotonin (5-HT) system than the drugs given alone. Because 5-HT(1A) receptor activation hyperpolarizes and inhibits the firing activity of CA(3) pyramidal neurons in the dorsal hippocampus, the degree of disinhibition produced by the selective 5-HT(1A) receptor antagonist WAY 100635 was determined using in vivo extracellular recordings. In controls, as well as in rats receiving a lithium diet for 3 days, the administration of WAY 100635 (25-100 microg/kg, IV) did not modify the firing activity of dorsal hippocampus CA(3) pyramidal neurons. When the tricyclic antidepressant imipramine (10 mg/kg/day, SC), the monoamine oxidase inhibitor tranylcypromine (2.5 mg/kg/day, SC) and the selective 5-HT reuptake inhibitor paroxetine (10 mg/kg/day, SC) were administered alone for 21 days, a dose of 50 microg/kg of WAY 100635 was needed to increase significantly the firing activity of these neurons. On the other hand, WAY 100635, at a dose of only 25 microg/kg, increased significantly the firing rate of CA(3) pyramidal neurons in rats receiving both a long-term antidepressant treatment and a short-term lithium diet. It is concluded that the addition of lithium to antidepressant treatments produced a greater disinhibition of dorsal hippocampus CA(3) pyramidal neurons than any treatments given alone. The present results support the notion that the addition of lithium to antidepressants may produce a therapeutic response in treatment-resistant depression by enhancing 5-HT neurotransmission.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10700654&dopt=Abstract antidepressant




[Prescriptions for antidepressants in a population of psychiatrists and non-psychiatrists]

[Article in French]

Schuck S, Allain H, Lebeux P, Chaperon J.

Laboratoire de Pharmacologie experimentale et clinique, CHRU de Rennes.

OBJECTIVE: Much proof has been accumulated over the last decade demonstrating that depression is a major public health issue. Use of psychotropics and more precisely antidepressants is considered to be excessive. It is however paradoxical that prescribing antidepressants has become commonplace. The aim of this study was to better assess the process of prescribing antidepressants in the hospital setting. METHODS: An epidemiological study was carried out to examine prescribing practices used by psychiatrists and non psychiatrists working in the Rennes University Hospital. The psychiatrist population was used as the reference population for univariate and multivariate analysis designed to ascertain differences concerning prescription practices. RESULTS: Duration of the clinical examination (shortest for non-psychiatric physicians, p = 0.0001), use of a diagnostic scale (more frequently for psychiatrists, p = 0.0008), reasons for choosing an antidepressant (pharmacological considerations more frequent among psychiatrists, p = 0.0009), and co-therapies (neuroleptic association more frequent among psychiatrists, p = 0.0001) were found to be different between the two prescribing populations. CONCLUSION: All patients with signs of depression are not necessarily given optimal care. Errors in assessing antidepressants is probably a common problem.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10723468&dopt=Abstract antidepressant




Measuring antidepressant prescribing practice in a health care system using administrative data: implications for quality measurement and improvement.

Kerr EA, McGlynn EA, Van Vorst KA, Wickstrom SL.

Veterans Affairs (VA) Center for Practice Management and Outcomes Research, Ann Arbor VA Healthcare System, USA. ekerr umich.edu

BACKGROUND: Up to one in eight Americans experiences an episode of depression that requires treatment in his or her lifetime. The direct and indirect costs associated with major depression are high but may be reduced with appropriate treatment. To decrease the probability of relapse, guidelines specify that treatment with antidepressant medications should continue for at least 4 months after symptom remission and that adequate doses of antidepressants be used. A study was conducted in 1997-1999 to examine how different specifications in the construction of quality of care measures for depression treatment influence conclusions about the adequacy of antidepressant prescribing practices. METHODS: Subjects were all adult members of two United Healthcare plans who each had at least one outpatient or inpatient claim with a diagnosis of depression during the years 1993-1995 and were continuously enrolled for 12 months. Pharmacy claims data were used to construct measures of duration of treatment, dose, and type of antidepressant. The effects of two different definitions of a new episode (4-month versus 9-month clean period) and two different ways of identifying an episode of depression (one visit versus two visits with a code for depression) were examined on conclusions about adequacy of antidepressant prescribing practices (dose and duration). Whether antidepressant type was related to the likelihood that antidepressants were prescribed at therapeutic doses was also examined. RESULTS: Patients with two or more visits with depression diagnosis codes were significantly more likely to receive antidepressants than those with only one visit, and were more likely to receive therapeutic doses at each time period (1-5 months). The duration of the clean period was not related to conclusions about therapeutic dosing. Among persons receiving antidepressants, those receiving selective serotonin reuptake inhibitors (SSRIs) were more likely to receive therapeutic doses and to continue treatment for at least 5 months than were those prescribed other classes of antidepressants. In multivariate analysis, being prescribed an SSRI versus another class of antidepressants was significantly associated with receiving both 1 month (OR = 7.3 [5.7-9.3]) and 5 months (OR = 2.0 [1.6-2.5]) of therapeutic treatment. DISCUSSION: Conclusions regarding the appropriateness of antidepressant prescribing can vary markedly, depending on how the quality measure is specified. Given that administrative data are and will continue to be used for both monitoring and quality improvement purposes in the short run, it is critical that we understand how variations in measurement specifications influence the conclusions that are drawn about treatment of depression in health plans.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10749005&dopt=Abstract antidepressant




Effect of subchronic antidepressant treatments on behavioral, neurochemical, and endocrine changes in the forced-swim test.

Connor TJ, Kelliher P, Shen Y, Harkin A, Kelly JP, Leonard BE.

Department of Pharmacology, National University of Ireland, Galway, Ireland.

The purpose of the present study was to examine the effect of subchronic treatment (24 days) with antidepressants displaying differential effects on noradrenaline and serotonin reuptake, on behavior, neurochemistry, and hypothalamic-pituitary-adrenal (HPA) axis activity following FST exposure in the rat. Desipramine (7.5 mg/kg, IP) significantly decreased immobility in the FST, whilst paroxetine (7.5 mg/kg IP) and venlafaxine (10 mg/kg, IP) were without effect. Nonetheless, treatment with all three antidepressants significantly attenuated stress-related increases in amygdaloid and cortical serotonin turnover. Of the three antidepressants examined, only desipramine attenuated the stress-associated elevation in serum corticosterone. In conclusion, although FST-induced increases in serotonin turnover in the frontal cortex and amygdala were attenuated following treatment with all three antidepressants, FST-induced behavioral changes and increased HPA axis activity were normalized only following desipramine treatment. In addition, these results suggest that neurochemical mechanisms independent of increased serotonergic activity subserve the normalization of behavior and HPA axis responses in the FST. These data also add to our understanding of the interactions between antidepressants and stress-induced behavioral, neurochemical, and endocrine alterations, and illustrates important differences between classes of antidepressants.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10764911&dopt=Abstract antidepressant




Regulation of GRK 2 and 6, beta-arrestin-2 and associated proteins in the prefrontal cortex of drug-free and antidepressant drug-treated subjects with major depression.

Grange-Midroit M, Garcia-Sevilla JA, Ferrer-Alcon M, La Harpe R, Huguelet P, Guimon J.

Clinical Research Unit, Department of Psychiatry, University of Geneva, H.U.G., Belle-Idee (Les Voirons), CH-1225 Chene-Bourg, Geneva, Switzerland.

G protein-coupled receptor kinases (GRKs) and beta-arrestin-2 play a crucial role in the regulation of neurotransmitter receptors in brain. In this study, GRK 2, GRK 6, beta-arrestin-2 and associated proteins (Gbeta proteins and protein phosphatase (PP)-2A) were quantitated in parallel (immunodensity with specific antibodies) in brains of depressed subjects (drug-free and antidepressant-treated) to investigate the effect of major depression and antidepressant drugs on these receptor regulatory proteins. Specimens of the prefrontal cortex (Brodmann's area 9) were collected from 19 suicide and non-suicide depressed subjects and 13 control subjects. In drug-free (n=9), but not in antidepressant-treated (n=10), depressed subjects an increase in the density of membrane-associated GRK 2 (30%, n=9, P=0.005) was found compared with that in sex-, age-, and PMD-matched controls. Comparison between drug-free and antidepressant-treated depressed subjects showed that GRK 2 was reduced in membrane (39%, n=10, P=0.008) and cytosolic (44%, n=10, P=0.09) preparations after antidepressant drug treatment. In contrast, membrane-associated GRK 6 (drug-free and antidepressant-treated depressed subjects) was found unchanged when compared with that in matched controls. Similarly, the densities of beta-arrestin-2, PP-2A, and Gbeta proteins were not significantly different from those in matched controls. There was a positive correlation between the immunodensities of GRK 2 and beta-arrestin-2 in membrane preparations (r=0.48, n=19, P=0.04), suggesting that both proteins are regulated in a coordinated manner in brains of depressed subjects. The results of this study indicate that major depression is associated with upregulation of brain GRK 2, but not GRK 6, and that antidepressant drug treatment appears to induce downregulation of GRK 2 protein.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12654503&dopt=Abstract antidepressant




Differential effects of beta-carbolines and antidepressants on rat exploratory activity in the elevated zero-maze.

Pahkla R, Kask A, Rago L.

Department of Pharmacology, University of Tartu, Ravila 19, 50411, Tartu, Estonia.

Present experiments were designed to compare the effects of antidepressants desipramine (10 and 20 mg/kg IP) and fluoxetine (5 and 10 mg/kg IP) with anxiogenic beta-carboline DMCM (0.5 and 1.0 mg/kg IP) in the elevated zero-maze test in rats. The second aim of this study was to assess the effects of pinoline (6-methoxy-1,2,3, 4-tetrahydro-beta-carboline) in the rat elevated zero-maze test in comparison with structurally unrelated beta-carboline DMCM and antidepressants. The time spent in the open part of the elevated zero-maze was not significantly affected by antidepressants, but was decreased by beta-carbolines pinoline and DMCM. The number of line crossings in the open parts and the number of head dips were also decreased more by beta-carbolines in comparison with antidepressants. Latency to enter the open part was statistically significantly increased only by DMCM. Measurement of locomotor activity in a separate experiment indicated that activity of the rats' time moving, distance traveled, and number of rearings were reduced by all four drugs studied. These results demonstrate that the effects of antidepressants in the elevated zero-maze test differ from the effects of the reference anxiogenic compound DMCM. The effects of pinoline and DMCM in the zero-maze test were similar, which suggests the involvement of mechanisms other than serotoninergic in the action of pinoline.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10764931&dopt=Abstract antidepressant




Antidepressant use in the elderly population in Canada: results from a national survey.

Newman SC, Hassan AI.

Department of Psychiatry, University of Alberta, Edmonton, Canada. stephen.newman ualberta.ca

BACKGROUND: There are few epidemiologic studies of the rate of antidepressant use in the elderly population, especially for community residents. We report findings on antidepressant use in the elderly population using data from a national survey in Canada which drew samples from both the community and institutional settings. METHODS: Data for the present study came from the Canadian Study of Health and Aging (CSHA), a national prevalence study of dementia in which information was collected from 2914 elderly subjects on current drug use, place of residence (community, institution), depression, dementia, and self-reported health. Survey weights were constructed to reflect the national population and data were analyzed using the SUDAAN statistical software package. RESULTS: The rate of antidepressant use was 4.1% (community 3.1%, institution 16.5%). Of those who were depressed, 9.4% were taking an antidepressant (community 4.2%, institution 36.0%). A logistic regression analysis showed that female gender, living in an institution, the presence of dementia, and the presence of a chronic physical disease, but not depression, were associated with increased antidepressant use. CONCLUSIONS: Our findings on the rate of antidepressant use in the elderly population are consistent with and extend previously published reports. We found evidence of underutilization of antidepressants in the treatment of geriatric depression, especially for community residents. However, this evidence needs to be interpreted with caution as the CSHA data on depressive symptoms were incomplete.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10568536&dopt=Abstract antidepressant