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P.1.186 Drug treatment of depression in the elderly by family physicians in Germany
P.1 Affective disorders and antidepressants
S194
• S. Allard
Pharmacokinetic (PK) and pharmacodynamic (PD) interactions between zolpidem and sertraiine in healthy women
1, j.
Maclntyre
1, B. Roth-Schechter 2.1Lorex
Pharmaceuticals, Skokie, Illinois; Boston Research and Science Consulting, Dover, Massachusetts, USA Sertraline, a recently introduced SSRI, is used in the treatment of depression and can be associated with various degrees of insomnia. The use of a short-acting hypnotic, such as zolpidem, could have significant clinical benefits in patients suffering from insomnia. This single-center, open, fixed-treatment-sequence study was conducted in 27 healthy female volunteers (mean age 30.1 yrs) with the objective to evaluate potential PK and PD interactions of five consecutive doses of nighttime zolpidem 10 mg (Z) together with sertraline 50 mg (S) as a single morning dose following 13 days of S alone. PK and PD parameters were assessed after a single dose of Z (Day 2), after two weeks of S alone (Days 12-14), and during 5 days of co-administration of Z and S (Days 15-19). Steady-state plasma concentrations of S and its metabolite N-desmethylsertraline were not achieved after 14 days of treatment with S. Compared to PK results obtained after a single dose of Z, the mean Crn~.~ of Z was significantly increased (+43%) and the mean Tmax was significantly decreased (-54%: 1.9 hrs vs 0,9 hrs) when Z was co-administered for 5 consecutive doses with S. The bioavailability of Z was not affected by coadministration with S. The presence of Z resulted in changes of PK parameters of S: a decrease in mean AUC ( - 6 % ) of S and an increase of the m e a n Cma x of the metabolite of S (+13%). The bioavailability of S was not modified by the presence of Z. Nine hours after Z, PD tests (DSST and others) were unchanged during the co-administration of Z and S compared to after single-dose treatment of Z. The overall incidence of adverse events (AE) was 7%, 32%, and 27% during the Z, S, and Z plus S dosing periods, respectively. These incidence rates cannot be compared since the lengths of dosing periods were not equal. No unexpected or serious AE occurred. While there was no significant change in the overall AUC of Z in presence of S, across the different dosing periods of this study, the higher Cmax and shorter Tmax suggests a shift in the AUC after multiple doses of Z in presence of S, with possible clinical impact on the onset of action of Z. The changes in the metabolism of S were relatively minor, but the dose of S (50 mg) is at the lower end of the therapeutic spectrum of S. Together with the absence of any PD interactions or changes in adverse events and their incidence, the co-administration of Z 10 mg and S 50 mg appears to be safe, though the continuous use of a higher dose drug regimen would have to be monitored.
~ D r u g treatment of depression in the elderly by family physicians in Germany G. Stoppe, H. Sandholzer 1, p Aksari, C Muder, H. Duwe, J. Staedt.
University of Grttingen; 1Department of Psychiat~; 1Department of General Practice, Gi~ttingen, Germany With a prevalence of about 20% depression is the most common disorder in old age with a strong impact on quality of life and also on physical health. Previous studies revealed a striking underdiagnosis and undertreatment of depression in primary care (1,2). The following study was designed to investigate the influence of various factors (gender, severity, comorbidity) on disease recognition and treatment. We designed two written case histories describing mild depression (case 1, Hamilton Depression Rating Scale (HDRS): 9) and moderate to severe (delusionary) depression (case 2, HDRS: 23). For each case different versions were used: in case 1 the gender of the patients varied, in case 2 both the gender and the previous history (stroke/hypothyreosis). The different combinations of case l a/b and case 2a~l were randomly assigned and a pair of case 1 and 2 presented to family physicians (FP) by trained investigators in a face-to-face interview. A standardised interview was performed. 170 (77.6%) of all FPs in Kassel and rural surroundings were interviewed during summer 1995. Though the recognition of depression
was considerably good, for case 1 36.5% and for case 2 10.6% of all physicians prescribed antidepressive agents. Tricyclics and hypericum were most frequently chosen, the latter considerably less in case 2. Newer antidepressants were considered rarely. Overall there was a trend to low dosages. In conclusion our findings suggest that only a minority of FPs would treat old age depression with antidepressants. With increasing disease severity the probability of an appropriate drug treatment decreased. Newer antidepressants with a favourable side effect profile are rarely considered. The results arise major concerns as to the quality of psychopharmacological treatment in primary care.
References [l] Collins E, Katona C, Orrell M.: Management of depression in the elderly by general practitioners: II. Attitudes to ageing and factors affecting practice. Fam Pract 1995; 12:12-17 [2] NIH consensus Development Panel on Depression in Late Life. Diagnosis and treatment of depression in late life. J Am Med Assoc 1992; 168:1018-1024
~ 8 ~
Thyroidal hormone profile in bipolar patients who were in short and long-term lithium treatment
Seher Sofuo~lu, Ahmet Tutus, Ali Saffet G~niil, Mustafa Ba~tiJrk, Kader KOse, Ertu~rul E~el. Erciyes University School qf Medicine,
Departments of Psychiat~; Nuclear Medicine and Biochemistry Kayseri, Turkey Objective: It is known that lithium carbonate treatment may frequently lead to thyroidal hormone abnormalities (1.2, 3). Our hypothesis in this study is that thyrnidal hormone abnormalities in patients in the short-term lithium treatment may differ from those of in the long-term. Methods: Seventeen (7 females, 10 males; mean ± SD age: 29.41 ± 7.33) patients with bipolar affective disorder according to DSM IIIR criteria ~md who were canditate for the lithium treatment and 22 (9 females, 13 males; mean ± SD age: 32.13 4. 7.72) bipolar patients who were in the long-term lithium treatment were included in the study (mean 4. SD duration of lithium treatment: 34.04 ± 6.09 months). All patients were euthymic and medication-free except lithium. The control group consisted of 19 (9 females, 10 males; mean -t-: SD age: 29.68 49.15) healthy volunteers. All of the subjects had a normal thyroidal size and clinically euthyroid at the time of assessment. Thyroidal hormone concentrations were measured in duplicate by commercially available RIA kits. Hormone assay was repeated in the fourth week of lithium treatment after baseline values were obtained in the short-term group. ResulL,;: We found significantly lower baseline FT4 values in the short-term group compared to those of the controls (t = 3.71 p < 0.001). The values obtained in the 4th week of lithium administration were significantly lower compared to their baseline values (t = 2.13 p < 0.05). However, FT3 values of the long-term group tend to be higher than those of the short-term group but not statistically significant. Pre-lithium TSH values of the patients who were candidate for lithium treatment also tend to be higher but not statistically significant. The values of the 4th week of lithium treatment of them were significantly higher than those of the controls (t = 2.03 p < 0.05). Conclusion: Our data suggest that both short and long-term lithium treatment may change thyroidal hormone profile with a decrease in FF4, an increase in TSH and probably a compensatory increase in FT3 concentrations, and the last change tend to be more prominent in the long-term lithium treatment.
References [1] Barclay ME, Brownlie EW. Turner JG et al (i994) Lithium-associated thyrotoxicosis: a report of 14 cases with statistical analysis of incidence. Clin Endocfinol 40: 759-764. [2] G~,niil AS, Tutu~ A, Sofuo~lu S, et al (1996) Effects of lithium treatment on thyroid functions in remitted bipolar patients. Euro Neurnpsychopharmacol 6 (Suppb: PI2. [3] Lee S, Chow CC, Wing YK, Sheck CC (1992) Thyroid abnormalities during chronic lithium treatment in Hong-KongChinese: a controlled study. J Affect Disord 26: 173-178.
S194
• S. Allard
Pharmacokinetic (PK) and pharmacodynamic (PD) interactions between zolpidem and sertraiine in healthy women
1, j.
Maclntyre
1, B. Roth-Schechter 2.1Lorex
Pharmaceuticals, Skokie, Illinois; Boston Research and Science Consulting, Dover, Massachusetts, USA Sertraline, a recently introduced SSRI, is used in the treatment of depression and can be associated with various degrees of insomnia. The use of a short-acting hypnotic, such as zolpidem, could have significant clinical benefits in patients suffering from insomnia. This single-center, open, fixed-treatment-sequence study was conducted in 27 healthy female volunteers (mean age 30.1 yrs) with the objective to evaluate potential PK and PD interactions of five consecutive doses of nighttime zolpidem 10 mg (Z) together with sertraline 50 mg (S) as a single morning dose following 13 days of S alone. PK and PD parameters were assessed after a single dose of Z (Day 2), after two weeks of S alone (Days 12-14), and during 5 days of co-administration of Z and S (Days 15-19). Steady-state plasma concentrations of S and its metabolite N-desmethylsertraline were not achieved after 14 days of treatment with S. Compared to PK results obtained after a single dose of Z, the mean Crn~.~ of Z was significantly increased (+43%) and the mean Tmax was significantly decreased (-54%: 1.9 hrs vs 0,9 hrs) when Z was co-administered for 5 consecutive doses with S. The bioavailability of Z was not affected by coadministration with S. The presence of Z resulted in changes of PK parameters of S: a decrease in mean AUC ( - 6 % ) of S and an increase of the m e a n Cma x of the metabolite of S (+13%). The bioavailability of S was not modified by the presence of Z. Nine hours after Z, PD tests (DSST and others) were unchanged during the co-administration of Z and S compared to after single-dose treatment of Z. The overall incidence of adverse events (AE) was 7%, 32%, and 27% during the Z, S, and Z plus S dosing periods, respectively. These incidence rates cannot be compared since the lengths of dosing periods were not equal. No unexpected or serious AE occurred. While there was no significant change in the overall AUC of Z in presence of S, across the different dosing periods of this study, the higher Cmax and shorter Tmax suggests a shift in the AUC after multiple doses of Z in presence of S, with possible clinical impact on the onset of action of Z. The changes in the metabolism of S were relatively minor, but the dose of S (50 mg) is at the lower end of the therapeutic spectrum of S. Together with the absence of any PD interactions or changes in adverse events and their incidence, the co-administration of Z 10 mg and S 50 mg appears to be safe, though the continuous use of a higher dose drug regimen would have to be monitored.
~ D r u g treatment of depression in the elderly by family physicians in Germany G. Stoppe, H. Sandholzer 1, p Aksari, C Muder, H. Duwe, J. Staedt.
University of Grttingen; 1Department of Psychiat~; 1Department of General Practice, Gi~ttingen, Germany With a prevalence of about 20% depression is the most common disorder in old age with a strong impact on quality of life and also on physical health. Previous studies revealed a striking underdiagnosis and undertreatment of depression in primary care (1,2). The following study was designed to investigate the influence of various factors (gender, severity, comorbidity) on disease recognition and treatment. We designed two written case histories describing mild depression (case 1, Hamilton Depression Rating Scale (HDRS): 9) and moderate to severe (delusionary) depression (case 2, HDRS: 23). For each case different versions were used: in case 1 the gender of the patients varied, in case 2 both the gender and the previous history (stroke/hypothyreosis). The different combinations of case l a/b and case 2a~l were randomly assigned and a pair of case 1 and 2 presented to family physicians (FP) by trained investigators in a face-to-face interview. A standardised interview was performed. 170 (77.6%) of all FPs in Kassel and rural surroundings were interviewed during summer 1995. Though the recognition of depression
was considerably good, for case 1 36.5% and for case 2 10.6% of all physicians prescribed antidepressive agents. Tricyclics and hypericum were most frequently chosen, the latter considerably less in case 2. Newer antidepressants were considered rarely. Overall there was a trend to low dosages. In conclusion our findings suggest that only a minority of FPs would treat old age depression with antidepressants. With increasing disease severity the probability of an appropriate drug treatment decreased. Newer antidepressants with a favourable side effect profile are rarely considered. The results arise major concerns as to the quality of psychopharmacological treatment in primary care.
References [l] Collins E, Katona C, Orrell M.: Management of depression in the elderly by general practitioners: II. Attitudes to ageing and factors affecting practice. Fam Pract 1995; 12:12-17 [2] NIH consensus Development Panel on Depression in Late Life. Diagnosis and treatment of depression in late life. J Am Med Assoc 1992; 168:1018-1024
~ 8 ~
Thyroidal hormone profile in bipolar patients who were in short and long-term lithium treatment
Seher Sofuo~lu, Ahmet Tutus, Ali Saffet G~niil, Mustafa Ba~tiJrk, Kader KOse, Ertu~rul E~el. Erciyes University School qf Medicine,
Departments of Psychiat~; Nuclear Medicine and Biochemistry Kayseri, Turkey Objective: It is known that lithium carbonate treatment may frequently lead to thyroidal hormone abnormalities (1.2, 3). Our hypothesis in this study is that thyrnidal hormone abnormalities in patients in the short-term lithium treatment may differ from those of in the long-term. Methods: Seventeen (7 females, 10 males; mean ± SD age: 29.41 ± 7.33) patients with bipolar affective disorder according to DSM IIIR criteria ~md who were canditate for the lithium treatment and 22 (9 females, 13 males; mean ± SD age: 32.13 4. 7.72) bipolar patients who were in the long-term lithium treatment were included in the study (mean 4. SD duration of lithium treatment: 34.04 ± 6.09 months). All patients were euthymic and medication-free except lithium. The control group consisted of 19 (9 females, 10 males; mean -t-: SD age: 29.68 49.15) healthy volunteers. All of the subjects had a normal thyroidal size and clinically euthyroid at the time of assessment. Thyroidal hormone concentrations were measured in duplicate by commercially available RIA kits. Hormone assay was repeated in the fourth week of lithium treatment after baseline values were obtained in the short-term group. ResulL,;: We found significantly lower baseline FT4 values in the short-term group compared to those of the controls (t = 3.71 p < 0.001). The values obtained in the 4th week of lithium administration were significantly lower compared to their baseline values (t = 2.13 p < 0.05). However, FT3 values of the long-term group tend to be higher than those of the short-term group but not statistically significant. Pre-lithium TSH values of the patients who were candidate for lithium treatment also tend to be higher but not statistically significant. The values of the 4th week of lithium treatment of them were significantly higher than those of the controls (t = 2.03 p < 0.05). Conclusion: Our data suggest that both short and long-term lithium treatment may change thyroidal hormone profile with a decrease in FF4, an increase in TSH and probably a compensatory increase in FT3 concentrations, and the last change tend to be more prominent in the long-term lithium treatment.
References [1] Barclay ME, Brownlie EW. Turner JG et al (i994) Lithium-associated thyrotoxicosis: a report of 14 cases with statistical analysis of incidence. Clin Endocfinol 40: 759-764. [2] G~,niil AS, Tutu~ A, Sofuo~lu S, et al (1996) Effects of lithium treatment on thyroid functions in remitted bipolar patients. Euro Neurnpsychopharmacol 6 (Suppb: PI2. [3] Lee S, Chow CC, Wing YK, Sheck CC (1992) Thyroid abnormalities during chronic lithium treatment in Hong-KongChinese: a controlled study. J Affect Disord 26: 173-178.