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Typical vs. Atypical antipsychotics in late-life psychosis
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S-12 Pharmacology ofAtypical Neuroleptics in the Elderly The 15 year prevalence rates of affective disorders were: hypomania or mania 5.5%; major depression 16.1%: dysthymia 1.8%; brief hypomania 2%; recurrent brief depression 14.6%; and minor depression 10%. Approximately 40% of the sample reported suffering from nonspecific headache, and 12% met the diagnostic criteria of the International Headache Society for migraine. Migraine was associated primarily with major depression (odds ratio 1.8), whereas non-specific headache was associated with dysthymia (odds ratio = 2.1). The bipolar subtype was associated with aura, irrespective of whether the subjects met diagnostic criteria for migraine type headache. These findings will be further investigated with respect to the order of onset of headache syndromes and affective disorders, sex differences, and comorbid anxiety disorders. The implications of these findings for the treatment and course of the affective disorders will be described.
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18-11-31 Pleomorphic Expressions of Bipolarity Hagop S. Akiska!. University of California at San Diego This communication will summarize the author's research that supports the existence of a broad bipolar spectrum, that at the one extreme merges with severe psychotic disorders and at the other with temperamental dysregulation. Phenomenologic probing will reveal that apparently mood-incongruent psychotic experiences among schizoaffectives are often affective in origin, or else explained by comorbid substance abuse, alcoholism, and/or cerebral pathology especially cerebral dysrhythmia or migraine. Recurrent major depressions with hypomanic episodes (bipolar II) represent the most common clinical expression of bipolarity. Hypomania could be mobilized by antidepressant treatment, or it could be spontaneous; in others it forms part of a recurrent pattern of cyclothymia. Seasonality is a common characteristic of these bipolar II patients and it is not uncommon for bipolar II disorder to manifest as a recurrent rheumatological problem or fatigue states. Artistic creativity has been reported among cyclothymic individuals; however, many more cyclothymics lead tempestuous lives. Bipolar II patents with suicide attempts are likely to be misdiagnosed as borderline states. There is also a more "stable" life-long form of hypomania expressed at the temperamental level known as hyperthymia; these individuals are cheerful, over-confident and energetic and are often in leadership positions but are liable to depressive episodes. Mixed states are common in all varieties of bipolar disorder. The availability of new thymoregulators which are effective in reducing the amplitude of pleomorphic mood instabilities dictates accurate diagnosis and an individualized treatment approach.
I8-11-41
Valproate in Migraine Prophylaxis
Ninan T. Mathew. Baylor College of Medicine Valproate is a GABA mimetic agent which has been shown to increase the GABA levels in the brain, influence biologic rhythms and alter the firing rates of serotonergic cells in the dorsal raphe nuclei. Recent data indicate that apart from its central effect on GABA, valproate also blocks the neurogenic plasma extroversion through a GABA receptor mechanism and reduces C-Fos expression in trigeminal caudalis nuclei after meningeal stimulation. These mechanisms are common to many recently discovered antimigraine agents. Because of both central and peripheral effects of valproate, it is logical to use it in the treatment of migraine. Four double-blind placebo controlled studies published between 1992 and 1995 indicate that valproate is an effective prophylactic agent in migraine. Uncontrolled studies also indicate its usefulness in cluster headache and chronic daily headache of the transformed migraine type. Clinical experience has shown that the efficacy of valproate is greatest for frequent migraine, least for chronic tension-type headache, and intermediate for transformed migraine. A comparative study of propranolol and valproate reported equal efficacy and side-effect potentia!. Although beta-blockers are still considered the first line treatment of migraine, valproate may be used as a first line drug among patients with contraindications to beta-blockers; comorbid epilepsy; comorbid bipolar illness; or cardiac vascular disease.
I8-11-51
TheBipolar Nature of Migrainous Psychopathology
1. Himmelhoch, K.R. Merikangas. University of Pittsburgh School of Medicine, Yale University School of Medicine The association between migraine and affective disorders has been investigated in clinical and epidemiologic samples. Migraine is particularly associated with depression of the atypical variety and neurasthenia, as well as mood swings, and anxiety. This paper describes an investigation of the manifestations of migraine among adolescent bipolar patients in an outpatient specialty clinic for mood disorders. Thirty percent of a consecutive series of adolescent bipolar patients had a history of migraine, the majority of which had migraine with aura, rather than "common" migraine, or migraine without aura. Mood disorders in this group were characterized by anergic, neurasthenic depressive phases and mixed dysphoric rather than euphoric hypomanic episodes. The mood disorders in this sample were also frequently accompanied by panic attacks and social phobia. Treatment response to monoamine oxidase inhibitors, lithium salts, and/or anticonvulsants in these subjects was generally quite favorable, leading to a diminution of migraine as well as affective episodes. These findings suggest that migraine is associated with a specific atypical bipolar syndrome, particularly among patients with early onset of mood disturbances. Implications for the pathophysiology of mood disturbances with concomitant migraine will be discussed.
1
5-121 Pharmacology of Atypical Neuroleptics in the Elderly
18-12-1 I Typical YS. Atypical Antipsychotics in Late-Life Psychosis
D.V. Jeste, J.H. Eastham, J.P. Lacro, D. Naimark, E. Rockwell. University ofCalifornia, San Diego and San Diego Va Medical Center Antipsychotic drugs are the most effective symptomatic treatment of late-life schizophrenia and other psychoses. Pharmacotherapy in older patients is, however, complicated by alterations in pharmacokinetics and pharmacodynamics. The risk of many adverse effects is considerably higher in the elderly. We found the cumulative annual incidence of tardive dyskinesia with typical neuroleptics among patients over age 45 to be 26%, which was five to six times greater than that reported in younger patients. Studies suggest that a majority of patients with schizophrenia relapse without neuroleptic maintenance therapy, exemplifying the need for improved pharmacological regimens. Data concerning the use of the new serotonin-dopamine antagonists in patients with late-life psychoses are relatively scanty. Initial studies suggest that clozapine is efficacious but its use is limited by side effects. We examined the use of risperidone in 39 older patients. Risperidone was clinically effective in a majority of patients and was generally well-tolerated, but needed to be prescribed. in lower dosages than those recommended for younger adults. Our preliminary data also suggested a mild but significant cognitive enhancing effect of low-dose risperidone in older psychotic patients.
I 8-12-21 Atypical Neuroleptics: Pharmacologic Considerations R.A. Sweet, B.G. Pollock, B.H. Mulsant, J. Rosen, R. Henteleff. Geriatric Psychopharmacology Program, Department of Psychiatry, University of Pittsburgh School ofMedicine, Pittsburgh. PA, USA Development of atypical neuroleptics for use in the elderly needs to derive from an understanding of the pharmacokinetic and pharmacodynamic changes associated with age or disease. Both reduced metabolic capacity due to drug interactions and decline in creatinine clearance can lead to accumulation of parent drug or active metabolites, altering neuroleptic therapeutics. We have found, for example, that neuroleptic-induced parkinsonism after treatment with perphenazine is increased in elderly patients who are phenotypically poor metabolizers at the cytochrome P450 2d6 isozyme. Similarly, target doses ofrisperidone (RIS) need to be reduced by 2/3 in the elderly due to the accumulation of the active metabolite, 9-0H-RIS.
S-12 Pharmacology ofAtypical Neuroleptics in the Elderly The 15 year prevalence rates of affective disorders were: hypomania or mania 5.5%; major depression 16.1%: dysthymia 1.8%; brief hypomania 2%; recurrent brief depression 14.6%; and minor depression 10%. Approximately 40% of the sample reported suffering from nonspecific headache, and 12% met the diagnostic criteria of the International Headache Society for migraine. Migraine was associated primarily with major depression (odds ratio 1.8), whereas non-specific headache was associated with dysthymia (odds ratio = 2.1). The bipolar subtype was associated with aura, irrespective of whether the subjects met diagnostic criteria for migraine type headache. These findings will be further investigated with respect to the order of onset of headache syndromes and affective disorders, sex differences, and comorbid anxiety disorders. The implications of these findings for the treatment and course of the affective disorders will be described.
=
18-11-31 Pleomorphic Expressions of Bipolarity Hagop S. Akiska!. University of California at San Diego This communication will summarize the author's research that supports the existence of a broad bipolar spectrum, that at the one extreme merges with severe psychotic disorders and at the other with temperamental dysregulation. Phenomenologic probing will reveal that apparently mood-incongruent psychotic experiences among schizoaffectives are often affective in origin, or else explained by comorbid substance abuse, alcoholism, and/or cerebral pathology especially cerebral dysrhythmia or migraine. Recurrent major depressions with hypomanic episodes (bipolar II) represent the most common clinical expression of bipolarity. Hypomania could be mobilized by antidepressant treatment, or it could be spontaneous; in others it forms part of a recurrent pattern of cyclothymia. Seasonality is a common characteristic of these bipolar II patients and it is not uncommon for bipolar II disorder to manifest as a recurrent rheumatological problem or fatigue states. Artistic creativity has been reported among cyclothymic individuals; however, many more cyclothymics lead tempestuous lives. Bipolar II patents with suicide attempts are likely to be misdiagnosed as borderline states. There is also a more "stable" life-long form of hypomania expressed at the temperamental level known as hyperthymia; these individuals are cheerful, over-confident and energetic and are often in leadership positions but are liable to depressive episodes. Mixed states are common in all varieties of bipolar disorder. The availability of new thymoregulators which are effective in reducing the amplitude of pleomorphic mood instabilities dictates accurate diagnosis and an individualized treatment approach.
I8-11-41
Valproate in Migraine Prophylaxis
Ninan T. Mathew. Baylor College of Medicine Valproate is a GABA mimetic agent which has been shown to increase the GABA levels in the brain, influence biologic rhythms and alter the firing rates of serotonergic cells in the dorsal raphe nuclei. Recent data indicate that apart from its central effect on GABA, valproate also blocks the neurogenic plasma extroversion through a GABA receptor mechanism and reduces C-Fos expression in trigeminal caudalis nuclei after meningeal stimulation. These mechanisms are common to many recently discovered antimigraine agents. Because of both central and peripheral effects of valproate, it is logical to use it in the treatment of migraine. Four double-blind placebo controlled studies published between 1992 and 1995 indicate that valproate is an effective prophylactic agent in migraine. Uncontrolled studies also indicate its usefulness in cluster headache and chronic daily headache of the transformed migraine type. Clinical experience has shown that the efficacy of valproate is greatest for frequent migraine, least for chronic tension-type headache, and intermediate for transformed migraine. A comparative study of propranolol and valproate reported equal efficacy and side-effect potentia!. Although beta-blockers are still considered the first line treatment of migraine, valproate may be used as a first line drug among patients with contraindications to beta-blockers; comorbid epilepsy; comorbid bipolar illness; or cardiac vascular disease.
I8-11-51
TheBipolar Nature of Migrainous Psychopathology
1. Himmelhoch, K.R. Merikangas. University of Pittsburgh School of Medicine, Yale University School of Medicine The association between migraine and affective disorders has been investigated in clinical and epidemiologic samples. Migraine is particularly associated with depression of the atypical variety and neurasthenia, as well as mood swings, and anxiety. This paper describes an investigation of the manifestations of migraine among adolescent bipolar patients in an outpatient specialty clinic for mood disorders. Thirty percent of a consecutive series of adolescent bipolar patients had a history of migraine, the majority of which had migraine with aura, rather than "common" migraine, or migraine without aura. Mood disorders in this group were characterized by anergic, neurasthenic depressive phases and mixed dysphoric rather than euphoric hypomanic episodes. The mood disorders in this sample were also frequently accompanied by panic attacks and social phobia. Treatment response to monoamine oxidase inhibitors, lithium salts, and/or anticonvulsants in these subjects was generally quite favorable, leading to a diminution of migraine as well as affective episodes. These findings suggest that migraine is associated with a specific atypical bipolar syndrome, particularly among patients with early onset of mood disturbances. Implications for the pathophysiology of mood disturbances with concomitant migraine will be discussed.
1
5-121 Pharmacology of Atypical Neuroleptics in the Elderly
18-12-1 I Typical YS. Atypical Antipsychotics in Late-Life Psychosis
D.V. Jeste, J.H. Eastham, J.P. Lacro, D. Naimark, E. Rockwell. University ofCalifornia, San Diego and San Diego Va Medical Center Antipsychotic drugs are the most effective symptomatic treatment of late-life schizophrenia and other psychoses. Pharmacotherapy in older patients is, however, complicated by alterations in pharmacokinetics and pharmacodynamics. The risk of many adverse effects is considerably higher in the elderly. We found the cumulative annual incidence of tardive dyskinesia with typical neuroleptics among patients over age 45 to be 26%, which was five to six times greater than that reported in younger patients. Studies suggest that a majority of patients with schizophrenia relapse without neuroleptic maintenance therapy, exemplifying the need for improved pharmacological regimens. Data concerning the use of the new serotonin-dopamine antagonists in patients with late-life psychoses are relatively scanty. Initial studies suggest that clozapine is efficacious but its use is limited by side effects. We examined the use of risperidone in 39 older patients. Risperidone was clinically effective in a majority of patients and was generally well-tolerated, but needed to be prescribed. in lower dosages than those recommended for younger adults. Our preliminary data also suggested a mild but significant cognitive enhancing effect of low-dose risperidone in older psychotic patients.
I 8-12-21 Atypical Neuroleptics: Pharmacologic Considerations R.A. Sweet, B.G. Pollock, B.H. Mulsant, J. Rosen, R. Henteleff. Geriatric Psychopharmacology Program, Department of Psychiatry, University of Pittsburgh School ofMedicine, Pittsburgh. PA, USA Development of atypical neuroleptics for use in the elderly needs to derive from an understanding of the pharmacokinetic and pharmacodynamic changes associated with age or disease. Both reduced metabolic capacity due to drug interactions and decline in creatinine clearance can lead to accumulation of parent drug or active metabolites, altering neuroleptic therapeutics. We have found, for example, that neuroleptic-induced parkinsonism after treatment with perphenazine is increased in elderly patients who are phenotypically poor metabolizers at the cytochrome P450 2d6 isozyme. Similarly, target doses ofrisperidone (RIS) need to be reduced by 2/3 in the elderly due to the accumulation of the active metabolite, 9-0H-RIS.