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MECHANISMS OF ACTIONS OF ANTIDEPRESSANTS
Abstracts antisense technology in the treatment of mood disorders is discussed.
EMERGING PRACTICE OPPORTUNITIES IN GERIATRIC PSYCHIATRY: MANAGED CARE WORKSHOP. Gary S. Moak, M.D.; Paul Sorgi, M.D.; and Alan P. Siegal, M.D.
T
his session provides the attendee with the knowledge about how to effectively structure geriatric psychiatric practices within managed care systems. The way in which geriatric psychiatrists actually work within managed care systems is reviewed. Through an interactive approach, experienced faculty present primers on how to structure (including staffing and billing issues) your practice to effectively participate in managed care systems and outline survival strategies to maximize your role as a geriatric psychiatrist in such systems. Useful, targeted handouts are provided by each faculty member.
MEDICATION TREATMENT OUTCOMES IN DEPRESSION: DOES MECHANISM OF ACTION MAKE A DIFFERENCE? Chair: Andrew F. Leuchter, M.D.; Martha L. Bruce, Ph.D., M.P.H.; Alan Frazer, Ph.D.; Steven P. Roose, M.D.; Soo Borson, M.D.
T
here are heterogeneous treatment outcomes in late-life depression. Although 50%–70% of patients may respond to any single agent, there is increasing evidence that subgroups of patients may respond differentially to some types of antidepressant medication. Patients with melancholic features may respond preferentially to medications with more noradrenergic effects; those with obsessivecompulsive features may respond preferentially to more serotonergic medications; those with atypical features may have best outcomes with monoamine oxidase inhibitors; and finally, older adults may have preferential response to some classes of medications. Response should be examined not just with the criteria of mood improvement but also with criteria of functional outcome. Different medications may have distinct effects on functional outcome. In addition, patients with specific pretreatment patterns of brain function may have differential responses to serotonergic and noradrenergic antidepressants. The range of current medications in affecting serotonin and norepinephrine reuptake, and selectivity in blocking postsynaptic receptor sites, may make it possible to tailor medication selection to individual patient characteristics. This symposium reviews the current state of clinical and research knowledge relating antidepressant mechanism of action to treatment outcomes of depression. The range of mechanisms of action of antidepressant medications are discussed and studies relating mechanism of action to treat-
Am J Geriatr Psychiatry Supplement, Fall 1999
ment of symptoms and functional outcome are examined. In addition, research findings relating pretreatment differences in brain function to outcomes with different classes of antidepressant medication are presented.
MECHANISMS OF ACTIONS OF ANTIDEPRESSANTS. Alan Frazer, Ph.D.; and Audie L. Murphy
T
he advent of the selective serotonin (5-HT) reuptake inhibitors (SSRIs) has resulted, perhaps, in norepinephrine (NE) becoming the “forgotten” monoamine with respect to the mechanism of action of antidepressants. This is unfortunate as it has been clear for many years that drugs that acutely alter NE function selectively can be antidepressants (e.g., desipramine). This presentation focuses on the mechanisms of action of all types of antidepressants as well as the pharmacodynamic reasons for differences in their side-effect profile. For example, the improved side-effect and toxicity profile seen with the SSRIs, as well as newer drugs such as venlafaxine, is due, at least in part, to their inability to block muscarinic cholinergic, (1 adrenergic, or H1 histamine receptors, nor to inhibit myocardial conduction. With respect to mechanism of action, it is of interest that different types of antidepressants have comparable efficacy in treating heterogeneous groups of depressed patients. Drugs that selectively block the uptake of serotonin (e.g., fluoxetine, sertraline) or norepinephrine (desipramine, the investigational compound reboxetine) or both monoamines (imipramine, venlafaxine) cause a similar extent of improvement in nonselected depressed patients. Whether this holds true for subgroups of depressed patients is currently under investigation. Relevant to this issue is whether drugs that are selective in vitro retain their selectivity in vivo, especially under repeated administration. Both preclinical and clinical data will be presented that address this. For example, repeated administration of NE reuptake inhibitors to rats does not affect certain serotonergic parameters (e.g., 5-HT1A receptor sensitivity) in the same way as SSRIs. On the other hand, SSRIs do not downregulate b1 adrenergic receptors, but antidepressants that affect noradrenergic function do this. Also, the clinical efficacy of NE reuptake inhibitors does not seem to be dependent on the presence of 5-HT, nor is the efficacy of SSRIs dependent on the presence of NE. By contrast, new in vivo voltammetric data are presented demonstrating that NE reuptake inhibitors alter the clearance of 5-HT in certain brain areas. Also, treatment of depressed patients with desipramine causes, over time, a reduction of the content of 5-HT in their platelets. Thus, there is evidence for both selective and nonselective effects of various types of antidepressants on monoamine function in vivo.
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EMERGING PRACTICE OPPORTUNITIES IN GERIATRIC PSYCHIATRY: MANAGED CARE WORKSHOP. Gary S. Moak, M.D.; Paul Sorgi, M.D.; and Alan P. Siegal, M.D.
T
his session provides the attendee with the knowledge about how to effectively structure geriatric psychiatric practices within managed care systems. The way in which geriatric psychiatrists actually work within managed care systems is reviewed. Through an interactive approach, experienced faculty present primers on how to structure (including staffing and billing issues) your practice to effectively participate in managed care systems and outline survival strategies to maximize your role as a geriatric psychiatrist in such systems. Useful, targeted handouts are provided by each faculty member.
MEDICATION TREATMENT OUTCOMES IN DEPRESSION: DOES MECHANISM OF ACTION MAKE A DIFFERENCE? Chair: Andrew F. Leuchter, M.D.; Martha L. Bruce, Ph.D., M.P.H.; Alan Frazer, Ph.D.; Steven P. Roose, M.D.; Soo Borson, M.D.
T
here are heterogeneous treatment outcomes in late-life depression. Although 50%–70% of patients may respond to any single agent, there is increasing evidence that subgroups of patients may respond differentially to some types of antidepressant medication. Patients with melancholic features may respond preferentially to medications with more noradrenergic effects; those with obsessivecompulsive features may respond preferentially to more serotonergic medications; those with atypical features may have best outcomes with monoamine oxidase inhibitors; and finally, older adults may have preferential response to some classes of medications. Response should be examined not just with the criteria of mood improvement but also with criteria of functional outcome. Different medications may have distinct effects on functional outcome. In addition, patients with specific pretreatment patterns of brain function may have differential responses to serotonergic and noradrenergic antidepressants. The range of current medications in affecting serotonin and norepinephrine reuptake, and selectivity in blocking postsynaptic receptor sites, may make it possible to tailor medication selection to individual patient characteristics. This symposium reviews the current state of clinical and research knowledge relating antidepressant mechanism of action to treatment outcomes of depression. The range of mechanisms of action of antidepressant medications are discussed and studies relating mechanism of action to treat-
Am J Geriatr Psychiatry Supplement, Fall 1999
ment of symptoms and functional outcome are examined. In addition, research findings relating pretreatment differences in brain function to outcomes with different classes of antidepressant medication are presented.
MECHANISMS OF ACTIONS OF ANTIDEPRESSANTS. Alan Frazer, Ph.D.; and Audie L. Murphy
T
he advent of the selective serotonin (5-HT) reuptake inhibitors (SSRIs) has resulted, perhaps, in norepinephrine (NE) becoming the “forgotten” monoamine with respect to the mechanism of action of antidepressants. This is unfortunate as it has been clear for many years that drugs that acutely alter NE function selectively can be antidepressants (e.g., desipramine). This presentation focuses on the mechanisms of action of all types of antidepressants as well as the pharmacodynamic reasons for differences in their side-effect profile. For example, the improved side-effect and toxicity profile seen with the SSRIs, as well as newer drugs such as venlafaxine, is due, at least in part, to their inability to block muscarinic cholinergic, (1 adrenergic, or H1 histamine receptors, nor to inhibit myocardial conduction. With respect to mechanism of action, it is of interest that different types of antidepressants have comparable efficacy in treating heterogeneous groups of depressed patients. Drugs that selectively block the uptake of serotonin (e.g., fluoxetine, sertraline) or norepinephrine (desipramine, the investigational compound reboxetine) or both monoamines (imipramine, venlafaxine) cause a similar extent of improvement in nonselected depressed patients. Whether this holds true for subgroups of depressed patients is currently under investigation. Relevant to this issue is whether drugs that are selective in vitro retain their selectivity in vivo, especially under repeated administration. Both preclinical and clinical data will be presented that address this. For example, repeated administration of NE reuptake inhibitors to rats does not affect certain serotonergic parameters (e.g., 5-HT1A receptor sensitivity) in the same way as SSRIs. On the other hand, SSRIs do not downregulate b1 adrenergic receptors, but antidepressants that affect noradrenergic function do this. Also, the clinical efficacy of NE reuptake inhibitors does not seem to be dependent on the presence of 5-HT, nor is the efficacy of SSRIs dependent on the presence of NE. By contrast, new in vivo voltammetric data are presented demonstrating that NE reuptake inhibitors alter the clearance of 5-HT in certain brain areas. Also, treatment of depressed patients with desipramine causes, over time, a reduction of the content of 5-HT in their platelets. Thus, there is evidence for both selective and nonselective effects of various types of antidepressants on monoamine function in vivo.
9