Mandies are not dandy: Another adverse drug interaction with methaqualone

There has been a steady increase in methaqualone abuse throughout the world. Phrases used to describe the drug or its effect include “mandies, Sopors, and luding out.” Dependence, attempted suicide, adverse interaction with alcohol, suicide, acute toxic states, and withdrawal epileptic seizures have all been well documented.¹ Epistaxis, menstrual disturbance, dry mouth, and depersonalization have occurred² with phenothiazine and or tricyclic antidepressants in combination with the hypnotic. A recent editorial³ suggests that methaqualone may cause neuropathy. Drug abusers have reported an elation with ataxia and paraesthesia of the extremities, lips, and tongue.⁴This report describes the side effects following a methaqualone-fluphenazine-nortriptyline combination.     

Central monoamine metabolism in depressions. II. Catecholamines and related compounds

CA research in depressions is reviewed. The present situation can be outlined as follows:Vital depressive patients may show central CA disorders that point in the direction of CA deficiency. In principle, this deficiency can be a primary phenomenon or a secondary development: the result of hypersensitivity of postsynaptic CA receptors. The former possibility is considered more plausible than the latter.The DA disorder seems to be related to motor retardation and loss of initiative and probably plays a role in their pathogenesis. There is no reason to assume that this disorder is a predisposing factor.The NA disorder is not related to motor symptoms. Its causative significance is still uncertain.An important byproduct of CA research in depressions is the momentum it gives to attempts to “translate” behavior disorders in terms of disturbed psychological functions. Such a functional psychopathology could be an important supplement to the traditional, more syndromal, and nosological classification of psychiatric conditions.     

Central monoamine metabolism in depressions. I. Serotonin and related compounds

This article reviews research into the possible significance of disorders of the central 5-HT metabolism in the pathogenesis of recurrent depressions. The available data would seem to warrant the tentative conclusion that such metabolic disorders are indeed involved in a certain subcategory of vital depressions and play a (possible predisposing) role in the pathogenesis of these depressions.The use of 5-HT precursors in depressions is regarded as a potential asset, although the conclusion that real substitution therapy can thus be given would be premature.     

A cytogenetic study of bipolar affective illness

Cytogenetic studies in psychiatry are important in view of the potential multiple etiologies of psychiatric syndromes, the strong genetic component of the functional psychoses, and the high incidence of chromosome abnormalities reported in diverse psychiatric populations. These studies, that suffered largely from heterogenous patient samples and lack of diagnostic criteria, involved mainly “gross” screening for sex chromosome defects (sex chromatin). As a result, the incidence of minor chromosome variants, as detected with new chromosome techniques, remains largely unknown in psychiatry. Bipolar affective disorder (manic-depressive) is a good place to start the more elaborate studies, since criteria for diagnosis is widely agreed upon and the illness has a predictable course and treatment response suggestive of a common etiology.Recent cytogenetic developments, such as the chromosome banding techniques, permit the exact identification of chromosomes through the differential staining of their segments. Evidence from the record of human chromosome imbalance indicates that banding patterns may also reflect the genetic constitution of a given chromosomal segment. The use of late prophase or early metaphase chromosomes instead of the customary midmetaphases considerably increases visual resolution. Late prophase chromosomes show over 1240 bands per haploid set, representing four times the number of bands observed on midmetaphase chromosomes. Since it is believed that man has approximately 30,000 genes per cell, the more elongated chromosomes would bring us relatively close to the gene level (around 23 genes per observed band) (Fig. 1).The present study was prompted by the observation of linkage of bipolar affective disorder to two genetically distant loci in the X chromosome in some informative families^2–4 and a recent report of familial X-linked mental retardation in connection with an X chromosome defect.⁵ The latter highlights the potential importance of studying chromosome structure in X-linked disorders.We began “standard” chromosome studies on a homogenous sample of bipolar patients diagnosed according to research diagnostic criteria. Subsequently, studies of chromosome banding and analyses of X chromosome structure using elongated chromosomes (late prophase/early metaphase) were performed in selected cases.     

Supra‐normal age‐linked retrograde amnesia: Lessons from an older amnesic (H.M.)

MacKay and James ( 2001 ) demonstrated greater‐than‐normal retrograde amnesia (RA) for lexical‐semantic information in amnesic H.M., a deficit that worsened with aging or represented supranormal age‐linked RA (SARA). The present experiments extend these earlier observations to new types of information. Experiment 1 participants (H.M. and carefully matched memory‐normal controls) named pictures on the Boston Naming Test and H.M. correctly named reliably fewer pictures with low frequency names, he produced unusual naming errors, and he benefited reliably less than the controls from phonological cues to the target word. Experiment 2 participants recalled irregularly‐spelled aspects of familiar words in a two‐choice recognition memory task and H.M. chose the correct spelling reliably less often than the controls. Experiment 3 participants read low frequency words aloud at age 73 and H.M. produced reliably more reading errors than the controls. Results of all three experiments indicate supranormal RA (SRA) for information once familiar to H.M. and comparisons with earlier studies using similar or identical stimuli indicated that H.M.'s SRA has worsened with aging from 1980 to 1999. In short, H.M. exhibits SARA for phonological and orthographic information, consistent with the MacKay and James results and with interactions between aging and amnesia predicted under binding theory. © 2008 Wiley‐Liss, Inc.     

Neuroleptics, extrapyramidal symptoms, and serum-calcium levels

A prospective study of 34 new admissions to a psychiatric center revealed an 80% incidence of extrapyramidal symptoms among patients receiving only neuroleptic drugs (N = 24) during the first 2 weeks of hospitalization. The occurrence of acute dystonic reactions and parkinsonian symptoms (but not akathisia) in this group was significantly associated with a decrease in serumcalcium levels. The findings suggest the need for (1) prophylactic use of antiparkinsonian drugs during the initial stages of neuroleptic treatment and (2) further research into the possible role of calcium metabolism in the production of extrapyramidal side effects.     

Medication use and mortality

A logistic regression analysis of the association among specific causes of mortality and indices of psychotropic medication use was carried out among 722 psychiatric inpatient deaths and age, sex, diagnosis, and length of stay matched controls. Overall findings revealed remarkably few significant associations between death and drug use. Of the significant findings, an increased proportion of dead patients in three categories were using piperidine phenothiazines at death while young male patients dying of heart disease tended to be receiving significantly higher average daily doses of medications with strong anticholinergic effects than controls, often in combination. On the positive side, elderly living patients tended to be receiving tricyclic antidepressants for longer durations than controls for several death categories, suggesting a possible beneficial effect of medication use.     

Neurological side effects of lithium: Organic brain syndrome,seizures, extrapyramidal side effects,and EEG changes

The precise mode of action of lithium carbonate on the central nervous system (CNS) is still far from clear. However, there have been some speculations based on the electroencephalogram (EEG) findings to suggest that lithium has both cortical and subcortical effect on the CNS.¹Rochford et al.² found that 36.8% of young adult psychiatric patients showed neurological abnormalities, but only 5% of normal controls showed such deficit. However, they found no neurological impairment, whether diffuse or localized, including EEG abnormalities, among patients with affective disorders. This investigation, which included 65 patients of both sexes and extended over a period of 1.5 yr was intended to examine the earlier claims^3–5 that CNS dysfunction plays an important role in the pathogenesis of functional psychiatric disorders.These findings have important implications in that one may anticipate a higher incidence of lithium-induced neurotoxicity in the treatment of psychiatric patients suffering from other than primary affective disorders.⁶ This article reviews the neurological complications arising from lithium carbonate treatment of primary affective disorders and schizoaffective disorders.     

Changes in thought content following sleep deprivation in depression

This article examines the relationship between elements of the self-concepts of depressed persons and changes in mood which are stimulated by a biological intervention (sleep deprivation). In a pilot study, seven depressed patients were tested before and after sleep deprivation to rate their thinking about their personal life issues or themes. The changes in thought content were then compared and contrasted with changes noted on the Beck, Hamilton, and POMS. As in previous studies, we found that sleep deprivation in the short-term alleviates depressed mood. While there is overall change in the direction of alleviation of depressive thought content, patients showed very individualized patterns of change in the ways they thought about their problems. These are differences in the way individual thought content changes which are not addressed by standardized tests.     

Tablets and talking—A spurious contrast in psychiatry

Pharmacotherapy and psychotherapy of psychiatric patients are not given equal appreciation. Particularly in syndromes with marked psychogenic or psychosocial overtones, psychotherapy is regarded as the causal therapy par excellence. In these cases (the vast majority), psychotropic drugs are believed to have at best a symptomatic importance and to entail the risk of effacing the true causes. I consider this view to be as unfelicitous as it is wrong, because: (1) Psychosocially determined behavior disorders, too, have a neurochemical substrate; (2) It is by all means sensible to make an attempt to normalize behavior by correction of this substrate; (3) Normalization of the cerebral substrate with the aid of pharmacotherapy is no less a causal type of therapy than is reduction of the pathogenic input with the aid of psychotherapy; (4) This means that pharmacotherapy and psychotherapy are complementary, and that each separately is an incomplete therapy.This argument is valid where psychotropic drugs with a relatively specific effect are available, as they are for the vital depressions and psychoses of the schizophrenic type. In these groups of patients, empirical findings confirm the theoretical expectation formulated (4) above. It is postulated that, for the treatment of neuroses which has so far been based entirely on psychotherapeutic intervention, much is yet to be expected of future developments in psychopharmacology.     

A mathematical model of cerebrospinal fluid dynamics.

The ability to solve systems of simultaneous non-linear differential equations by a combination of analytical and computational techniques has encouraged the development of valid mathematical models of biological phenomena. The dynamics of the cerebrospinal fluid (CSF) system has been the subject of closer scrutiny in recent years since the recognition of symptomatic low-pressure hydrocephalic states in man. A mathematical model has been derived from 7 assumptions: (1) That the brain is a spherical shell. (2) That CSF is secreted at a constant rate. (3) That CSF absorption is linearly dependent on pressure. (4) That flow between the CSF compartments is proportional to the pressure difference. (5) That Laplace's Law holds for the visco-elastic properties of the brain. (6) That there is compliance in the spinal compartment of the CSF system. (7) That vascular pulsations in the cranial and spinal compartments are capacitatively coupled. Using known data (and estimates of as yet unknown values) for the several parameters, the validity of the model has been successfully tested against 3 clinical conditions. This model extends our understanding of derangements of CSF dynamics and suggest where further research may yield data at present lacking.     

Relationships between psychological factors and cardiac rhythm and electrical disturbances

The paper explores some relationships between psychological state and cardiac electrical and arrhythmic abnormalities. Prior studies of large clinic populations have disclosed an association between such disorders and hospitalizable mental illness. Conversely, some series of cardiology patients have commonly manifested severe psychological symptoms in the setting of even mild or transient cardiac symptoms. Frequently no cardiac disease was found. Careful studies of individual patients demonstrate that emotional arousal, sometimes related to a specific emotion in a given patient, can trigger episodes of serious arrhythmias.Seven patients with severe, symptomatic, intractable EKG-documented cardiac arrhythmias were interviewed. Recent changes in job status occurred in 5 patients prior to the first onset of arrhythmias. The immediate precipitants of arrhythmic crises included some emotional experiences, such as a patient's son hugging him, and some emotionally trivial experiences, such as awakening in the morning or standing up. Severe and unusual fatigue was present in 3 of the patients prior to their first arrhythmic crisis. It was concluded that important events with relatively long-term consequences in an individual's life may tonically lower the threshold to arrhythmias, and that the short-term effects of a diversity of physiological events (e.g., effort, emotional arousal, relaxation) may interact with the lowered threshold to precipitate and arrhythmic crisis.