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Selective serotonin reuptake inhibitors: Discontinuation rates due to side effects
P I Affective disorders and antidepressants [2] MSssner R., Lesch K.-P. (1999): Role of serotonin in the immune system and in neuroimmune interactions. Brain, Behau lmmun. 1999 (in press)
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Buspiron and pindolol in augmentation therapy of treatment-resistant depression
A.S. Grniil, A. O~uz, I. Yabanoglu, S.S. Asian, T. Turan. Erciyes Uni-
versity School of Medicine, Department of Psychiatry, Kayseri, Turkey OHeetive: Although the number and variety of antidepressants have increased rapidly during the past decade, 20% to 30% of patients with major depression fail to respond an adequate trial of a particular antidepressant. In recent years augmentation strategies done with some drugs like pindolol and buspirone which have different effects on serotonergic system have been used successfully (1, 2). In this study we compare the efficacy of pindolol and buspirone in addition to ongoing therapy of treatment-resistant depressed patients. Methods: Fourteen patients (8 female, 6 male) with major depressive disorder who had failed several previous treatments for their current depressive episode were included in the study. They received either buspirone (30 mg/day) or pindolol 7.5 mg/day in addition to their serotonin reuptake inhibitor antidepressants for 3 weeks in a randomized manner. Six patients were on fluoxetine (40~0 mg/day) and the others were on paroxetine (40-60 mg/day) therapy. In the second phase of the study, patients who had not responded, had another trial with the other drug. Fifty percent decrease in Hamilton Depression Rating Scale scores was accepted as a response to the treatment. Results: Four of the 7 patients (57%) who received buspirone and SSRI had responded the treatment while just 2 patients (28%) responded in the pindolol group after 3 weeks in the first phase. In the second phase, 3 patients who did not respond the buspirone augmentation therapy did not respond pindolol augmentation therapy, either. But three patients of 5 (60%) who had not responded pindolol augmentation responded buspirone augmentation. No serious side effect was observed during the trial. Conclusion: Our results demonstrate that buspirone is more effective than pindolol as an augmenting drug in the treatment of resistant depression. The fact that these drugs affect basically different serotonergic receptors can explain this difference in their efficacy. Pre-synaptic and/or post-synaptic 5-HTIA stimulation as buspirone does might be essential for the augmentation of ongoing antidepressant therapy. But this result needs to be confirmed by further studies.
References [1] Artias, F., Perez, V., Alverez, E. 1994. Pindolol induces a rapid improvement of depressed patients with serotonln reuptake inhibitors. Arch Gen Psychiatry 51,248-251. [2] Dimitriou, E.C., Dimitriou, C.E. 1998. Buspirone augmentation of antidepressant therapy. J Clin Psychopharmacol 18, 465469.
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Selective serotonin reuptake inhibitors: discontinuation rates due to side effects
A.S. Grniil, I. Yabano~lu, M. Reyhancan, A. O~uz. Department of Psychiatry, Erciyes University School of Medicine, Kayseri, Turkey Objective: When the serotonin reuptake inhibitors were introduced, it was hoped that they would represent an advance in the treatment of depression compared with the traditional tricyclic antidepressants (TCAs). Although they are not superior in efficacy but they have better tolerability over the TCAs. Recently it has been understood that each SSRI has a different pharmacokinetic and pharmacodynamic property (1). These properties reflect themselves not only in treating depression but also in the side effects that they induce. In this study we try to compare the side effects and the discontinuation rates of SSRIs in depressed patients. Methods: One hundred-sixty (80 males, 80 female) patients who fully met DSM-IV criteria for major depression were included in the study.
$215
Neither of them had psychotic nor catatonic symptoms. Their mean age + SD was 35.6 + 11.8. Hamilton Depression Rating Scale score (HAM-D) of 12 was chosen for the lowest limit to be included in the study. In a single blind randomised manner patients received one of the SSRIs in advised antidepressant dose (20 mg/day fluoxetine, 20 mg/day paroxetine, 50 mg/day sertraline, 150 mg/day fluvoxamine). Every SSRI trial group had equal number of patient. Each patient scored the most common 18 side effects of SSRIs that were reported in literature with a capability of adding new items in 100 mm Visual Analogue Scale in days 0, 7, 14, 21 and 28. Twenty percent increase in a symptom analogue was accepted as drug side effect. At the 4 th week Fifty percent decrease in HAM-D scores were accepted as a response to the treatment. Results: One hundred fifty-seven patients could finish the study. Four patients (%10) from fluoxetine, 3 patients (%8) and 6 patients (%15) from sertraline and 6 patients (%15) from paroxetine group stopped taking their drugs due to the intolerance to side effects. Seventy-four (%54) patients reported at least one side-effect. 81% of reported side effects were noted in the first week of therapy. Although there was no significant difference between the drugs in term of drop-outs (X 2 = 0.89 p > 0.05), the side effect profile of each SSRI was different from each other. When the number of patients responding therapy was taken into account for the efficacy of each SSRI, we could not find any significant difference among them (X 2 = 0.28 p < 005). Conclusion: Although SSRIs have different pharmacokinetic and pharmacodynamic profiles, their efficacy and their discontinuation rates are not different from one SSRI to another. Different side effect profiles of SSRIs allow clinicians to advise another SSRI to a patient who is intolerant to a certain SSRI.
References [1] Goodnick, P.J.and Goldstein, B.J. 1998. Selectiveserotonin reuptake inhibitors in affective disorders-I. Basic pharmacology. J Psychopharmaeol; 12 (3 Suppl B): $5-20.
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Kidney functioning during short and long-term lithium treatment in bipolar patients
S. Sofuo~lu, C. Uta~ 1, S.S. Asian, C. Yalqinda~1, M. Ba~tfirk, A.S. Grniil. I Departments of Psychiatry and Nephrology; Erciyes University
School of Medicine, Kayseri, Turkey Objective: Patients with bipolar affective disorder on lithium (Li) treatment may develop functional changes in the kidneys. It has been suggested that functionally Li-induced affection is characterized by a reduced renal concentration ability, and the occurrence of this deficit could be related to the duration of Li treatment (1, 2). In this study, we hypothesized that long-term administration of Li might be the primary determinant of the changes in renal functioning. Methods: 29 patients fully meeting DSM-IV criteria for bipolar affective disorder were included in the study. Their mean age + SD was 34.48 + 8.31, and the mean duration of illness + SD was 6 97.52 + 66.03 months. 10 of them were lithium-naive but Li-candidate, 9 of them were on short-term (mean duration + SD: 15.83 + 10.92 months) Li maintenance therapy and 10 of them were on long-term (mean duration + SD: 79.55 + 25.41 months) Li maintenance therapy. All patients were in a euthymic stable mood state during the study. Determination of urine osmolality both before and after 12-h water deprivation and also after ADH (2 [xg) injection was carried out as renal concentrating ability tests. Comparisons were made with ANOVA. Results: Serum Li levels were 0.71 + 0.13 mmol/L in the short-term Li-treated group and 0.68 + 0.21 in the long-term Li-treated group and no significant difference was found between them. Creatinine clearance of the long-term Li-treated group was significantly lower than both that of the Li-naive group and that of the sbort-term Li-treated group (F = 14.10 p < 0.01). Urine osmolality measured before 12-h water deprivation of the long-term Li-treated group was significantly lower than both that of the Li-naive group and that of the short-term Li-treated group indicating some degree of tubular damage (F = 4.31 p < 0.05). When each patient was evaluated individually in terms of their renal concentration ability,
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Buspiron and pindolol in augmentation therapy of treatment-resistant depression
A.S. Grniil, A. O~uz, I. Yabanoglu, S.S. Asian, T. Turan. Erciyes Uni-
versity School of Medicine, Department of Psychiatry, Kayseri, Turkey OHeetive: Although the number and variety of antidepressants have increased rapidly during the past decade, 20% to 30% of patients with major depression fail to respond an adequate trial of a particular antidepressant. In recent years augmentation strategies done with some drugs like pindolol and buspirone which have different effects on serotonergic system have been used successfully (1, 2). In this study we compare the efficacy of pindolol and buspirone in addition to ongoing therapy of treatment-resistant depressed patients. Methods: Fourteen patients (8 female, 6 male) with major depressive disorder who had failed several previous treatments for their current depressive episode were included in the study. They received either buspirone (30 mg/day) or pindolol 7.5 mg/day in addition to their serotonin reuptake inhibitor antidepressants for 3 weeks in a randomized manner. Six patients were on fluoxetine (40~0 mg/day) and the others were on paroxetine (40-60 mg/day) therapy. In the second phase of the study, patients who had not responded, had another trial with the other drug. Fifty percent decrease in Hamilton Depression Rating Scale scores was accepted as a response to the treatment. Results: Four of the 7 patients (57%) who received buspirone and SSRI had responded the treatment while just 2 patients (28%) responded in the pindolol group after 3 weeks in the first phase. In the second phase, 3 patients who did not respond the buspirone augmentation therapy did not respond pindolol augmentation therapy, either. But three patients of 5 (60%) who had not responded pindolol augmentation responded buspirone augmentation. No serious side effect was observed during the trial. Conclusion: Our results demonstrate that buspirone is more effective than pindolol as an augmenting drug in the treatment of resistant depression. The fact that these drugs affect basically different serotonergic receptors can explain this difference in their efficacy. Pre-synaptic and/or post-synaptic 5-HTIA stimulation as buspirone does might be essential for the augmentation of ongoing antidepressant therapy. But this result needs to be confirmed by further studies.
References [1] Artias, F., Perez, V., Alverez, E. 1994. Pindolol induces a rapid improvement of depressed patients with serotonln reuptake inhibitors. Arch Gen Psychiatry 51,248-251. [2] Dimitriou, E.C., Dimitriou, C.E. 1998. Buspirone augmentation of antidepressant therapy. J Clin Psychopharmacol 18, 465469.
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Selective serotonin reuptake inhibitors: discontinuation rates due to side effects
A.S. Grniil, I. Yabano~lu, M. Reyhancan, A. O~uz. Department of Psychiatry, Erciyes University School of Medicine, Kayseri, Turkey Objective: When the serotonin reuptake inhibitors were introduced, it was hoped that they would represent an advance in the treatment of depression compared with the traditional tricyclic antidepressants (TCAs). Although they are not superior in efficacy but they have better tolerability over the TCAs. Recently it has been understood that each SSRI has a different pharmacokinetic and pharmacodynamic property (1). These properties reflect themselves not only in treating depression but also in the side effects that they induce. In this study we try to compare the side effects and the discontinuation rates of SSRIs in depressed patients. Methods: One hundred-sixty (80 males, 80 female) patients who fully met DSM-IV criteria for major depression were included in the study.
$215
Neither of them had psychotic nor catatonic symptoms. Their mean age + SD was 35.6 + 11.8. Hamilton Depression Rating Scale score (HAM-D) of 12 was chosen for the lowest limit to be included in the study. In a single blind randomised manner patients received one of the SSRIs in advised antidepressant dose (20 mg/day fluoxetine, 20 mg/day paroxetine, 50 mg/day sertraline, 150 mg/day fluvoxamine). Every SSRI trial group had equal number of patient. Each patient scored the most common 18 side effects of SSRIs that were reported in literature with a capability of adding new items in 100 mm Visual Analogue Scale in days 0, 7, 14, 21 and 28. Twenty percent increase in a symptom analogue was accepted as drug side effect. At the 4 th week Fifty percent decrease in HAM-D scores were accepted as a response to the treatment. Results: One hundred fifty-seven patients could finish the study. Four patients (%10) from fluoxetine, 3 patients (%8) and 6 patients (%15) from sertraline and 6 patients (%15) from paroxetine group stopped taking their drugs due to the intolerance to side effects. Seventy-four (%54) patients reported at least one side-effect. 81% of reported side effects were noted in the first week of therapy. Although there was no significant difference between the drugs in term of drop-outs (X 2 = 0.89 p > 0.05), the side effect profile of each SSRI was different from each other. When the number of patients responding therapy was taken into account for the efficacy of each SSRI, we could not find any significant difference among them (X 2 = 0.28 p < 005). Conclusion: Although SSRIs have different pharmacokinetic and pharmacodynamic profiles, their efficacy and their discontinuation rates are not different from one SSRI to another. Different side effect profiles of SSRIs allow clinicians to advise another SSRI to a patient who is intolerant to a certain SSRI.
References [1] Goodnick, P.J.and Goldstein, B.J. 1998. Selectiveserotonin reuptake inhibitors in affective disorders-I. Basic pharmacology. J Psychopharmaeol; 12 (3 Suppl B): $5-20.
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Kidney functioning during short and long-term lithium treatment in bipolar patients
S. Sofuo~lu, C. Uta~ 1, S.S. Asian, C. Yalqinda~1, M. Ba~tfirk, A.S. Grniil. I Departments of Psychiatry and Nephrology; Erciyes University
School of Medicine, Kayseri, Turkey Objective: Patients with bipolar affective disorder on lithium (Li) treatment may develop functional changes in the kidneys. It has been suggested that functionally Li-induced affection is characterized by a reduced renal concentration ability, and the occurrence of this deficit could be related to the duration of Li treatment (1, 2). In this study, we hypothesized that long-term administration of Li might be the primary determinant of the changes in renal functioning. Methods: 29 patients fully meeting DSM-IV criteria for bipolar affective disorder were included in the study. Their mean age + SD was 34.48 + 8.31, and the mean duration of illness + SD was 6 97.52 + 66.03 months. 10 of them were lithium-naive but Li-candidate, 9 of them were on short-term (mean duration + SD: 15.83 + 10.92 months) Li maintenance therapy and 10 of them were on long-term (mean duration + SD: 79.55 + 25.41 months) Li maintenance therapy. All patients were in a euthymic stable mood state during the study. Determination of urine osmolality both before and after 12-h water deprivation and also after ADH (2 [xg) injection was carried out as renal concentrating ability tests. Comparisons were made with ANOVA. Results: Serum Li levels were 0.71 + 0.13 mmol/L in the short-term Li-treated group and 0.68 + 0.21 in the long-term Li-treated group and no significant difference was found between them. Creatinine clearance of the long-term Li-treated group was significantly lower than both that of the Li-naive group and that of the sbort-term Li-treated group (F = 14.10 p < 0.01). Urine osmolality measured before 12-h water deprivation of the long-term Li-treated group was significantly lower than both that of the Li-naive group and that of the short-term Li-treated group indicating some degree of tubular damage (F = 4.31 p < 0.05). When each patient was evaluated individually in terms of their renal concentration ability,