Geriatric depression, antidepressant treatment, and healthcare utilization in a health maintenance organization.

Fischer LR, Wei F, Rolnick SJ, Jackson JM, Rush WA, Garrard JM, Nitz NM, Luepke LJ.

HealthPartners Research Foundation, University of Minnesota, Minneapolis 55440, USA. lucy.r.fischer healthpartners.com

OBJECTIVES: To assess the separate effects of depressive symptoms and antidepressant treatment on healthcare utilization and cost. SETTING: Social Health Maintenance Organization (HMO) at HealthPartners in Minnesota. PARTICIPANTS: Geriatric Social HMO enrollees were screened for depressive symptoms using the 30-item Geriatric Depression Scale. A stratified sample was created, composed of geriatric enrollees with depressive symptoms, with antidepressant prescriptions, or with neither (n = 516). DESIGN: Regression analyses were conducted with separate equations for utilization and charge outcome variables, both outpatient and inpatient (log-transformed). The Charlson Comorbidity Index, age, and gender served as covariates. MEASUREMENT: Depressive symptoms were identified through the Diagnostic Interview Schedule. Antidepressant treatment was determined from the HMO pharmacy database. RESULTS: Having depressive symptoms was associated with a 19 increase in the number of outpatient encounters and a 30 increase in total outpatient charges. Antidepressant treatment was associated with a 32 increase in total outpatient charges but was not significantly associated with number of outpatient encounters. Depressive symptoms and antidepressant therapy were not significantly associated with inpatient utilization or charges. CONCLUSION: This study found that patients with depressive symptoms generated more outpatient health care and higher charges but not necessarily more inpatient care. Our findings suggest that programs targeted to geriatric patients whose depression is comorbid with other chronic medical conditions might be cost-effective and particularly appropriate for geriatric care.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12028213&dopt=Abstract antidepressant




The management of depression in older nursing home residents.

Brown MN, Lapane KL, Luisi AF.

College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA.

OBJECTIVES: Depression remains underrecognized and undertreated in older people. We estimated the prevalence of depression in older nursing home (NH) residents and described its pharmacological management. DESIGN: Cross-sectional study. SETTING: Residents in 1,492 NHs in five states (Kansas, Maine, Mississippi, New York, South Dakota). PARTICIPANTS: Forty-two thousand nine hundred one residents aged 65 and older with depression documented as an active clinical condition on the Minimum Data Set (MDS) assessment. MEASUREMENTS: Data were from the Systematic Assessment of Geriatric drug use via Epidemiology database. We grouped antidepressant medications by class: tricyclic antidepressants (TCAs), tetracyclics, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors, and others. Logistic regression models revealed predictors of receipt of any antidepressant and, among those treated, predictors of receipt of an SSRI. RESULTS: Eleven percent of the residents were identified as depressed on the MDS. Of these, 55% received antidepressant therapy. Of depressed residents receiving antidepressant therapy, 32% received doses less than the manufacturers' recommended minimum effective dose for treating depression, with residents on TCAs more likely to receive less than the recommended dose for treating depression. The oldest-old (> or = 85 years) (odds ratio (OR) = 0.93, 95% confidence interval (CI) = 0.88-0.98), black residents (OR = 0.83, 95% CI = 0.75-0.92), and those with severe cognitive impairment (OR = 0.69, 95% CI = 0.64-0.75) were the least likely to receive an antidepressant. In those treated, cardiovascular diseases were associated with an increased likelihood of SSRI use. Despite control for comorbid conditions, women were less likely than men to receive an SSRI (OR = 0.77, 95% CI = 0.72-0.82). CONCLUSIONS: Although depression is a treatable illness, the majority of NH residents may be inadequately treated.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12028249&dopt=Abstract antidepressant




Induction of mania and cycle acceleration in bipolar disorder: effect of different classes of antidepressant.

Joffe RT, MacQueen GM, Marriott M, Robb J, Begin H, Young LT.

Regional Mood Disorders Program, Department of Psychiatry and Behavioral Neuroscience, McMaster University, Hamilton, Ontario, Canada. joffe umdnj.edu

OBJECTIVE: To assess the effect of different antidepressants on induction of mania and cycle acceleration, commonly accepted unwanted effects of antidepressant treatment for acute bipolar depression. There is, however, the suggestion that certain classes of antidepressants may be less likely than others to cause these unwanted effects. METHOD: We conducted a prospective, open, naturalistic, life charting study to assess the occurrence of onset of mania and cycle acceleration attributable to two antidepressant classes: selective serotonin reuptake inhibitors (SSRIs) and bupropion. RESULTS: No difference was found between the two drug classes for either antidepressant-induced mania or cycle acceleration. Antidepressant-induced mania was much more likely to occur in bipolar I rather than bipolar II patients. The overall occurrence of induction of mania and cycle acceleration was low across antidepressant classes. CONCLUSION: These findings suggest that there is probably no difference in the risk of antidepressant-induced mania or cycle acceleration across commonly used classes of antidepressants for the treatment of bipolar depression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12059846&dopt=Abstract antidepressant




An investigation of monoamine receptors involved in antinociceptive effects of antidepressants.

Yokogawa F, Kiuchi Y, Ishikawa Y, Otsuka N, Masuda Y, Oguchi K, Hosoyamada A.

Department of Anesthesiology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan. yokogawa jz8.so-net.ne.jp

We attempted to determine which monoamine receptor subtypes are predominantly involved in antidepressant-induced antinociception. Antinociceptive effects were evaluated by using formalin tests with rats. Antidepressants acting as potent inhibitors of norepinephrine reuptake (nisoxetine, nortriptyline, and maprotiline) or inhibiting reuptake of both norepinephrine and serotonin (5-HT) (imipramine and milnacipran) induced dose-dependent antinociception. Simultaneous intraperitoneal administration of antidepressants and either prazosin (alpha(1) antagonist) or ketanserin (5-HT(2) antagonist) significantly antagonized antinociceptive effects. Fluvoxamine (selective serotonin reuptake inhibitor) induced antinociception less potently than other antidepressants and was significantly antagonized by ketanserin, but not prazosin. Ondansetron (5-HT(3) antagonist) significantly antagonized antinociception by 10 mg/kg of imipramine. In contrast, SDZ-205,557 (5-HT(4) antagonist) markedly enhanced antinociception by small-dose (2.5 mg/kg) imipramine. Imipramine-induced antinociception was significantly antagonized by intracerebroventricular administration of prazosin or ketanserin, but not by yohimbine (alpha(2) antagonist) or ondansetron, and was significantly enhanced by intracerebroventricularly administered SDZ-205,557. These findings suggest that alpha(1) adrenoceptors and 5-HT(2) receptors in the brain are involved in antidepressant-induced antinociception. In addition, the results suggested functional interactions between noradrenergic and serotonergic neurons as mechanisms for antidepressant-induced antinociception. IMPLICATIONS: Formalin tests of rats treated with antidepressants and antagonists of monoamine receptors indicate that alpha(1) adrenoceptors, serotonin (5-HT)(2) receptors, and 5-HT(3) receptors are involved in antidepressant-induced antinociception, suggesting functional interactions between noradrenergic and serotonergic neurons as mechanisms of antidepressant-induced antinociception.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12088962&dopt=Abstract antidepressant




Chronic substance P (NK1) receptor antagonist and conventional antidepressant treatment increases burst firing of monoamine neurones in the locus coeruleus.

Maubach KA, Martin K, Chicchi G, Harrison T, Wheeldon A, Swain CJ, Cumberbatch MJ, Rupniak NM, Seabrook GR.

Department of Pharmacology, Merck Sharp & Dohme Neuroscience Research Centre, Essex CM20 2QR, UK. karen_maubach merck.com

The mechanism of action of conventional antidepressants (e.g. imipramine) has been linked to modulation of central monoamine systems. Substance P (NK1) receptor antagonists may have antidepressant and anxiolytic effects in patients with major depressive disorder and high anxiety but, unlike conventional antidepressants, are independent of activity at monoamine reuptake sites, transporters, receptors, or monoamine oxidase. To investigate the possibility that substance P receptor antagonists influence central monoamine systems indirectly, we have compared the effects of chronic administration of imipramine with that of the substance P receptor antagonist L-760735 on the spontaneous firing activity of locus coeruleus neurones. Electrophysiological recordings were made from brain slices prepared from guinea-pigs that had been dosed orally every day for 4 weeks with either L-760735 (3 mg/kg), imipramine (10 mg/kg), or vehicle (water), or naive animals. Chronic, but not acute, treatment with the substance P receptor antagonist L-760735, induced burst firing of neurones in the locus coeruleus. This effect resembles that of the conventional antidepressant imipramine. However, their effects are dissociable since, in contrast to chronic imipramine treatment, chronic L-760735 treatment does not cause functional desensitisation of somatic alpha2 adrenoceptors.The mechanism by which chronic substance P receptor antagonist or conventional antidepressant treatment influences the pattern of firing activity of norepinephrine neurones remains to be elucidated. However, an indirect action in the periphery or distant brain nuclei has been excluded by the use of the in vitro slice preparation, suggesting a local site of action in the locus coeruleus.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11823070&dopt=Abstract antidepressant




Antidepressant medication and suicide in Sweden.

Carlsten A, Waern M, Ekedahl A, Ranstam J.

Department of Social Medicine, University of Goteborg, Sweden. anders.carlsten telia.com

OBJECTIVE: To explore a possible temporal association between changes in antidepressant sales and suicide rates in different age groups. METHODS: A time series analysis using a two-slope model to compare suicide rates in Sweden before and after introduction of the selective serotonin reuptake inhibitors, SSRIs. RESULTS: Antidepressant sales increased between 1977-1979 and 1995-1997 in men from 4.2 defined daily doses per 1000 inhabitants and day (DDD/t.i.d) to 21.8 and in women from 8.8 to 42.4. Antidepressant sales were twice as high in the elderly as in the 25-44-year-olds and eight times that in the 15-24-year-olds. During the same time period suicide rates decreased in men from 48.2 to 33.3 per 10(5) inhabitants/year and in women from 20.3 to 13.4. There was significant change in the slope in suicide rates after the introduction of the SSRI, for both men and women, which corresponds to approximately 348 fewer suicides during 1990-1997. Half of these 'saved lives' occurred among young adults. CONCLUSION: We demonstrate a statistically significant change in slope in suicide rates in men and women that coincided with the introduction of the SSRI antidepressants in Sweden. This change preceded the exponential increase in antidepressant sales.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11828835&dopt=Abstract antidepressant




Effects of pharmacist monitoring on patient satisfaction with antidepressant medication therapy.

Bultman DC, Svarstad BL.

Medical Education Institute, Madison, Wis, USA. communitypharmacy tds.net

OBJECTIVE: To examine the effects of pharmacist monitoring on patient satisfaction with and adherence to antidepressant medication therapy. DESIGN: In this prospective field study, we interviewed patients starting an antidepressant after a new prescription was dispensed and again 2 months later. The first interview assessed patients' characteristics, antidepressant medication history, knowledge of antidepresant medications and their use, and beliefs about antidepressant medications. The second interview focused on pharmacist monitoring behavior and satisfaction with the antidepressant medication. SETTING AND PARTICIPANTS: From 23 community pharmacies, we enrolled 100 patients, 59 of whom were taking an antidepressant for the first time. MAIN OUTCOME MEASURES: Patient satisfaction with and reported adherence to their antidepressant medication regimen. RESULTS: Pharmacist monitoring of patients' antidepressant medication use varied. More than 70% of patients reported that pharmacists asked about medication concerns; 53% and 54% of patients, respectively, said pharmacists encouraged their questions and listened to their concerns; and 32% found pharmacists helpful in solving problems related to the antidepressant. Fifty-seven percent of patients reported feeling better a lot of the time since taking the antidepressant, 40% said the antidepressant did not bother them, and 83% reported missing doses, adding doses, or stopping the antidepressant during the study period. Initial beliefs about antidepressants were a strong predictor of patient outcomes. Pharmacist monitoring was predictive of satisfaction and adherence for individuals taking an antidepressant for the first time. CONCLUSION: Pharmacists can play a critical role in monitoring medication concerns at the beginning of use, allowing for problem solving, reinforcement, and greater patient satisfaction with and adherence to medication therapy. Obstacles to effective pharmacist monitoring and follow-up need to be identified and addressed in future improvement efforts.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11833513&dopt=Abstract antidepressant




The effects of tricyclic antidepressants on breast cancer risk.

Sharpe CR, Collet JP, Belzile E, Hanley JA, Boivin JF.

Centre for Clinical Epidemiology and Community Studies, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Chemin de la Cote Ste Catherine, Montreal, Quebec, Canada. csharp dsuper.net

To test the hypothesis that tricyclic antidepressant use increases invasive female breast cancer incidence, we carried out a case-control study within the population of female beneficiaries of the Saskatchewan Prescription Drug Plan aged 35 years from 1981-995 with no history of cancer since 1970. This agency has provided full or partial coverage for outpatient prescriptions to Saskatchewan residents since 1975. We accrued 5882 histologically proven cases and 23,517 controls, randomly selected from the source population and individually matched on age and sampling time. Heavy exposure to any tricyclic antidepressants was associated with an elevated rate ratio for breast cancer 11-15 years later (2.02, 95% confidence interval: 1.34-3.04). Post hoc analyses based on the results of genotoxicity studies carried out using Drosophila melanogaster suggested that the increased risk could be attributed to the use of the six genotoxic tricyclic antidepressants, and not to the use of the four nongenotoxic tricyclic antidepressants. However, our results may have been confounded by the effects of other determinants of breast cancer associated with tricyclic antidepressant use.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11857018&dopt=Abstract antidepressant