Excerpt A correlation between premenstrual-menstrual mood changes, weight changes, and alteration... more Excerpt A correlation between premenstrual-menstrual mood changes, weight changes, and alterations in the aldosterone-dependent urinary potassium-to-sodium ratio during the menstrual cycle was stud...
The purpose of this paper is to review the use of psychotropic drugs in the aged. Psychotropic ag... more The purpose of this paper is to review the use of psychotropic drugs in the aged. Psychotropic agents can be an effective tool in a physician’s armamentarium in treating mental disorders in the aged. However, these drugs can also be inappropriately used. The aged may be more susceptible to certain drug side effects. In addition, since they are more apt to have medical problems, there is more likelihood of drug-drug interactions occurring. Even physicians who may not be particularly interested in psychotropic drug use may need to be knowledgeable about this aspect of patient care since patients may suffer from toxicity due to psychotropic drugs administered by another physician or by the patients themselves. Psychotropic drugs are commonly taken by a large percentage of the population of the United States (Balter and Levine, 1971). Two hundred twenty million prescriptions are filled by patients for psychotropic drugs; 80 million for antianxiety agents; 40 million for hypnotics; 30 million for stimulants. Patients can often be taking several psychotropic drugs, sometimes administered by one physician, sometimes administered by several different physicians with the patient continuing to take one doctor’s prescription as well as a second psychotropic agent added by another doctor. To this cocktail can be added proprietary medications bought without prescription. Since sedative hypnotics do reduce mental function, it is not unusual to find elderly patients who are over-medicated who may do better when they discontinue the cocktail of sedative hypnotic drugs which they are taking. For that reason, the first problem in treating the aged with psychotropic drugs is for the clinician to consider whether the patient needs the psychotropic drugs he may be on. The discontinuance of current medication to get a drug-free baseline state is a useful strategy for the treatment of many patients. It is important to evaluate the patient’s medical status and use of the wide variety of drugs for treating his medical problems. This information is relevant to drug-drug interactions and side effects of possible psychotropic drugs. Having reviewed the patient’s baseline status and his medical problems, one may move on to consider which psychotropic drugs may be indicated for a given patient.
Reading crystal balls has always been difficult. Nevertheless, it may be a worthwhile exercise to... more Reading crystal balls has always been difficult. Nevertheless, it may be a worthwhile exercise to stop and make some educated guesses about where the field of psychopharmacology will stand 10 years from now--knowing full well that insights and discoveries we cannot predict or anticipate now may pop up to dramatically change the course and direction of clinical psychopharmacology.
Concern with the possibility that chemicals may be used in international conflicts has grown in t... more Concern with the possibility that chemicals may be used in international conflicts has grown in the past several years. Possible use of highly toxic and lethal chemical agents by Soviet forces in Afghanistan, by Soviet supported forces in Southeast Asia, and by Iraq in its war with Iran have been detailed (3, 4, 7, 10, 12, 13).
In a preceding manuscript, Janowsky and associates have reviewed the evidence implicating central... more In a preceding manuscript, Janowsky and associates have reviewed the evidence implicating central cholinergic mechanisms in the pathophysiology of affective disorders. In this manuscript we report that a subgroup of apparently normal subjects, with no personal or family history of affective disorder, are supersensitive, both behaviorally and neuroendocrinologically, to the effects of centrally active cholinomimetics. Although the functional significance of this finding is not yet apparent, it is conceivable that this cholinergic supersensitivity in a subgroup of normal subjects may represent a biological marker for vulnerability to affective illness. In addition, we speculate that a cholinergically mediated adrenocorticotropic (ACTH)/β-endorphin pathway may modulate mood and cognition in human subjects, and that affective disorder subjects and normal subjects sensitive to the dysphoric effects of centrally active cholinomimetics may exhibit hypersensitivity of this hypothalamic pituitary axis.
Depression in mentally retarded individuals is not uncommon and usually is treatable. However, st... more Depression in mentally retarded individuals is not uncommon and usually is treatable. However, studies of the diagnosis and treatment of psychiatric illnesses in general and depression specifically in this population are relatively rare. Although Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria can be applied to mildly and moderately retarded individuals, the diagnosis of depression in those with
A growing body of data indicates that central neurotransmitters and neuromodulators, including no... more A growing body of data indicates that central neurotransmitters and neuromodulators, including norepinephrine, serotonin, GABA, dopamine, vasopressin, and the opioid polypeptides, are likely to have a major role in the regulation of stress (1). In the following paragraphs, we will review and present evidence suggesting that central acetylcholine may also have an important role in the regulation of stress. Supportive of this, Gilad et al. (7) have observed stress-induced increases in central nervous system acetylcholine turnover and neuronal choline uptake, and down-regulation of muscarinic receptors in rats; and these effects are exaggerated in stress-sensitive rats. Furthermore, there is evidence from a number of studies and from our own work that many of the manifestations of naturally occurring stress are mimicked by administration of centrally acting cholinomimetic agents in both animals and in man.
Considerable attention has focused recently on the possibility that endogenous peptides with opio... more Considerable attention has focused recently on the possibility that endogenous peptides with opioid-like activity (endorphins) may have a role in the regulation of normal and abnormal human behavior. Animal studies support the possibility that endorphins may have behavioral effects, apart from their known analgesic properties. Bloom et al. (1976) and Segal et al. (1977) noted that centrally administered s-endorphin induces rigidity and immobility in rats, and Bloom et al. (1976) noted that i.v.t. s-endorphin induces a ‘catatonic-like state, reminiscent of some aspects of schizophrenia, reversible with the relatively pure narcotic antagonist naloxone’. In addition, naloxone has been reported to inhibit apomorphine-induced stereotyped behavior in the rat (Cox et al. 1976); to enhance chlorpromazine’s effects on schedule-controlled behavior in pigeons (McMillan, 1971); to inhibit d-amphetamine-induced increases in locomotor activity (Holtzman, 1974; Segal et al. this volume) and continuous avoidance responding in rats (Holtzman, 1974); and to reverse the effect of morphine and d-amphetamine on intracranial self-stimulation in rats (Holtzman, 1974).
A wide variety of neuroendocrine abnormalities have been reported in affective disorder patients.... more A wide variety of neuroendocrine abnormalities have been reported in affective disorder patients. Probably the most extensively studied have been hypothalamic-pituitary-adrenal (HPA) activation and dexamethasone resistance. In addition, an elevated 24-h pituitary growth hormone secretion has been reported in depressed patients. Reduced pituitary growth hormone responses to central nervous system (CNS) probes have been reported in depressed patients, particularly in response to the noradrenergic agent clonidine. The sequencing and availability of corticotropin-releasing factor (CRF) and growth hormone-releasing factor (GRF) allow direct testing of pituitary responses to these neuropeptides in affective disorder patients. Our findings to date confirm the reports by Gold and colleagues1 and Holsboer and colleagues2 of an attenuated ACTH response to intravenously administered ovine CRF in depressed patients. In addition, we preliminarily report an attenuated growth hormone response to intravenous human GRF in depressed patients.
Catecholamines: Basic and Clinical Frontiers, 1979
ABSTRACT Intravenous methylphenidate (0.5 mg/kg) caused human serum growth hormone to be signific... more ABSTRACT Intravenous methylphenidate (0.5 mg/kg) caused human serum growth hormone to be significantly increased following methylphenidate infusion, an effect attenuated in schizophrenics, as contrasted to non-psychotic patients, and in antipsychotic drug treated individuals. Serum prolactin levels significantly decreased from baseline after methylphenidate infusion.
ABSTRACT Methylphenidate (0.5 mg/kg) and placebo were administered intravenously to twenty psychi... more ABSTRACT Methylphenidate (0.5 mg/kg) and placebo were administered intravenously to twenty psychiatric inpatients. Subjects engaged in one-hour dialogues with trained interviewers after infusion. The typical methylphenidate effects on mood and psychopathology were observed. Subjects also reported increases in their perception of regard from their interviewers. The prediction, concomitants, and implication of drug-induced changes in interpersonal perceptions are discussed.
Excerpt A correlation between premenstrual-menstrual mood changes, weight changes, and alteration... more Excerpt A correlation between premenstrual-menstrual mood changes, weight changes, and alterations in the aldosterone-dependent urinary potassium-to-sodium ratio during the menstrual cycle was stud...
The purpose of this paper is to review the use of psychotropic drugs in the aged. Psychotropic ag... more The purpose of this paper is to review the use of psychotropic drugs in the aged. Psychotropic agents can be an effective tool in a physician’s armamentarium in treating mental disorders in the aged. However, these drugs can also be inappropriately used. The aged may be more susceptible to certain drug side effects. In addition, since they are more apt to have medical problems, there is more likelihood of drug-drug interactions occurring. Even physicians who may not be particularly interested in psychotropic drug use may need to be knowledgeable about this aspect of patient care since patients may suffer from toxicity due to psychotropic drugs administered by another physician or by the patients themselves. Psychotropic drugs are commonly taken by a large percentage of the population of the United States (Balter and Levine, 1971). Two hundred twenty million prescriptions are filled by patients for psychotropic drugs; 80 million for antianxiety agents; 40 million for hypnotics; 30 million for stimulants. Patients can often be taking several psychotropic drugs, sometimes administered by one physician, sometimes administered by several different physicians with the patient continuing to take one doctor’s prescription as well as a second psychotropic agent added by another doctor. To this cocktail can be added proprietary medications bought without prescription. Since sedative hypnotics do reduce mental function, it is not unusual to find elderly patients who are over-medicated who may do better when they discontinue the cocktail of sedative hypnotic drugs which they are taking. For that reason, the first problem in treating the aged with psychotropic drugs is for the clinician to consider whether the patient needs the psychotropic drugs he may be on. The discontinuance of current medication to get a drug-free baseline state is a useful strategy for the treatment of many patients. It is important to evaluate the patient’s medical status and use of the wide variety of drugs for treating his medical problems. This information is relevant to drug-drug interactions and side effects of possible psychotropic drugs. Having reviewed the patient’s baseline status and his medical problems, one may move on to consider which psychotropic drugs may be indicated for a given patient.
Reading crystal balls has always been difficult. Nevertheless, it may be a worthwhile exercise to... more Reading crystal balls has always been difficult. Nevertheless, it may be a worthwhile exercise to stop and make some educated guesses about where the field of psychopharmacology will stand 10 years from now--knowing full well that insights and discoveries we cannot predict or anticipate now may pop up to dramatically change the course and direction of clinical psychopharmacology.
Concern with the possibility that chemicals may be used in international conflicts has grown in t... more Concern with the possibility that chemicals may be used in international conflicts has grown in the past several years. Possible use of highly toxic and lethal chemical agents by Soviet forces in Afghanistan, by Soviet supported forces in Southeast Asia, and by Iraq in its war with Iran have been detailed (3, 4, 7, 10, 12, 13).
In a preceding manuscript, Janowsky and associates have reviewed the evidence implicating central... more In a preceding manuscript, Janowsky and associates have reviewed the evidence implicating central cholinergic mechanisms in the pathophysiology of affective disorders. In this manuscript we report that a subgroup of apparently normal subjects, with no personal or family history of affective disorder, are supersensitive, both behaviorally and neuroendocrinologically, to the effects of centrally active cholinomimetics. Although the functional significance of this finding is not yet apparent, it is conceivable that this cholinergic supersensitivity in a subgroup of normal subjects may represent a biological marker for vulnerability to affective illness. In addition, we speculate that a cholinergically mediated adrenocorticotropic (ACTH)/β-endorphin pathway may modulate mood and cognition in human subjects, and that affective disorder subjects and normal subjects sensitive to the dysphoric effects of centrally active cholinomimetics may exhibit hypersensitivity of this hypothalamic pituitary axis.
Depression in mentally retarded individuals is not uncommon and usually is treatable. However, st... more Depression in mentally retarded individuals is not uncommon and usually is treatable. However, studies of the diagnosis and treatment of psychiatric illnesses in general and depression specifically in this population are relatively rare. Although Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria can be applied to mildly and moderately retarded individuals, the diagnosis of depression in those with
A growing body of data indicates that central neurotransmitters and neuromodulators, including no... more A growing body of data indicates that central neurotransmitters and neuromodulators, including norepinephrine, serotonin, GABA, dopamine, vasopressin, and the opioid polypeptides, are likely to have a major role in the regulation of stress (1). In the following paragraphs, we will review and present evidence suggesting that central acetylcholine may also have an important role in the regulation of stress. Supportive of this, Gilad et al. (7) have observed stress-induced increases in central nervous system acetylcholine turnover and neuronal choline uptake, and down-regulation of muscarinic receptors in rats; and these effects are exaggerated in stress-sensitive rats. Furthermore, there is evidence from a number of studies and from our own work that many of the manifestations of naturally occurring stress are mimicked by administration of centrally acting cholinomimetic agents in both animals and in man.
Considerable attention has focused recently on the possibility that endogenous peptides with opio... more Considerable attention has focused recently on the possibility that endogenous peptides with opioid-like activity (endorphins) may have a role in the regulation of normal and abnormal human behavior. Animal studies support the possibility that endorphins may have behavioral effects, apart from their known analgesic properties. Bloom et al. (1976) and Segal et al. (1977) noted that centrally administered s-endorphin induces rigidity and immobility in rats, and Bloom et al. (1976) noted that i.v.t. s-endorphin induces a ‘catatonic-like state, reminiscent of some aspects of schizophrenia, reversible with the relatively pure narcotic antagonist naloxone’. In addition, naloxone has been reported to inhibit apomorphine-induced stereotyped behavior in the rat (Cox et al. 1976); to enhance chlorpromazine’s effects on schedule-controlled behavior in pigeons (McMillan, 1971); to inhibit d-amphetamine-induced increases in locomotor activity (Holtzman, 1974; Segal et al. this volume) and continuous avoidance responding in rats (Holtzman, 1974); and to reverse the effect of morphine and d-amphetamine on intracranial self-stimulation in rats (Holtzman, 1974).
A wide variety of neuroendocrine abnormalities have been reported in affective disorder patients.... more A wide variety of neuroendocrine abnormalities have been reported in affective disorder patients. Probably the most extensively studied have been hypothalamic-pituitary-adrenal (HPA) activation and dexamethasone resistance. In addition, an elevated 24-h pituitary growth hormone secretion has been reported in depressed patients. Reduced pituitary growth hormone responses to central nervous system (CNS) probes have been reported in depressed patients, particularly in response to the noradrenergic agent clonidine. The sequencing and availability of corticotropin-releasing factor (CRF) and growth hormone-releasing factor (GRF) allow direct testing of pituitary responses to these neuropeptides in affective disorder patients. Our findings to date confirm the reports by Gold and colleagues1 and Holsboer and colleagues2 of an attenuated ACTH response to intravenously administered ovine CRF in depressed patients. In addition, we preliminarily report an attenuated growth hormone response to intravenous human GRF in depressed patients.
Catecholamines: Basic and Clinical Frontiers, 1979
ABSTRACT Intravenous methylphenidate (0.5 mg/kg) caused human serum growth hormone to be signific... more ABSTRACT Intravenous methylphenidate (0.5 mg/kg) caused human serum growth hormone to be significantly increased following methylphenidate infusion, an effect attenuated in schizophrenics, as contrasted to non-psychotic patients, and in antipsychotic drug treated individuals. Serum prolactin levels significantly decreased from baseline after methylphenidate infusion.
ABSTRACT Methylphenidate (0.5 mg/kg) and placebo were administered intravenously to twenty psychi... more ABSTRACT Methylphenidate (0.5 mg/kg) and placebo were administered intravenously to twenty psychiatric inpatients. Subjects engaged in one-hour dialogues with trained interviewers after infusion. The typical methylphenidate effects on mood and psychopathology were observed. Subjects also reported increases in their perception of regard from their interviewers. The prediction, concomitants, and implication of drug-induced changes in interpersonal perceptions are discussed.
Uploads
Papers by David Janowsky