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A case is reported of toxic psychosis in a patient with a diagnosis of discoid lupus erythematosus treated with hydroxychloroquine. The dose slightly exceeded the maximum recommended dose for 10 days because of a pharmacy error. Since more antimalarials are being used for various diseases, attention is called to this possible complication with a subtle onset.
Study of the competition between hallucinogens and tranquilizers at cerebral synapses and on behavior in various species of animals indicates a continuum of effects from protection to dominance of tranquilizer toxicity as the dose of tranquilizer increases. Data on cat and monkey behavior, supplementing that on the rat, show that it is possible to arrive at a tranquilizer dose that can aggravate instead of protect, in accord with the competitive inhibitory nature of the interaction of hallucinogen and tranquilizer.
Aqueous procaine penicillin G therapy is frequently used in ambulatory care settings and clinicians have long been alerted to the potential allergic reactions that may occur with this therapy; however, the nonallergic toxic reaction has not been as widely publicized. A possible psychotic-like, pseudoanaphylactic reaction may occur within 60 seconds following an injection of aqueous procaine penicillin G. Two case reports and a review of the literature will be presented to alert clinicians to this reaction. Suggestions for management will also be offered.
Pathomorphologic examination of the brain in alcoholic delirium was carried out. Comparison was made between the changes in the brain of patients who died at the height of delirium and those of patients who died suddenly in the postdelirium state. The pathomorphologic picture of the brain in alcoholic delirium may be defined as chronic toxico-dyscirculatory encephalopathy aggravated by acute toxic and dyshemic changes. The latter were largely attributed to the delirium state per se. The characteristic features of the cases studied included considerable depletion of the cortical cells, chronic dystrophic changes in the neurons and gliocytes, and also chronic impairments of vascular wall permeability aggravated by marked acute pathologic phenomena in the microcirculatory vessels.
Over the last 10 years or so in Europe, there has been a development of the "ecstasy" phenomenon, which is the symbol of "recreational" drugs in general. Users, either alone or in private parties, are on the increase. The phenomenon is most frequent in England and in the Netherlands, with an estimated incidence of 13-18% amongst the 18-25 years old, which may reach 52% in "exposed populations", such as individuals who go to "techno" night clubs. In France, the prevalence is uncertain, but estimated at least 5% of males between 18 and 23 years old. Several substance, with more or less the same effects, are grouped together by the term "ecstasy", the best-known one being 3,4-methylenedioxymethamphetamine (MDMA), but there are also an N-demethylated derivative (MDA), methylenedioxyethylamphetamine (MDEA), N-methyl-benzodioxazolylbutanamine (MBDB) and 4-bromo-2,5-dimethoxyphenylethylamine (2-CB or Nexus). The psychopathological consequences of MDMA in man are relatively poorly understood. On the basis of series of cases reported in the literature, acute psychosis, chronic psychosis similar to paranoid delusions, flash-back phenomena similar to with LSD, anxiety/panic states and depressive mood disorders may occur. The case which we report is therefore that of an acute psychotic episode, with residual symptomatology 6 months later, which occurred suddenly following absorption of toxic substances (alcohol and ecstasy), at least 12 hours after taking the ecstasy tablet without his knowing it, in an individual without any previous psychopathology, other than moderate social phobia. Twelve cases of acute psychotic episodes after ecstasy have been reported in the literature. Two of them occurred after a single dose and one after 2 doses. No author was able to examined the previous history of the individuals accurately, nor any possible psychopathological history. Our patient did not have any previous history of psychosis, using a standardized validated interview, which his peers and family confirmed. He did however fulfil the criteria of "social phobia". Retrospectively, we noted the extent of his psychomotor disinhibition with ecstasy, which seemed to be proportional to the intensity of his previous social inhibition. This point does not explain the psychotic episode. From a neurobiologic point of view, acute psychotic disorders are often related to dysfunction of the mesolimbic dopaminergic system. During the first 3 hours, the effect of absorption of MDMA is a massive release of the serotonin, dopamine and noradrenaline stocks. Later, an acute hyposerotoninergic state is present. In our observation, the psychotic disorder appeared at least 12 hours after taking ecstasy, during the reduction phase of the intoxication. Toxicological analysis of the blood was negative (this detection is only positive for 24 hours). Like other authors, our hypothesis is that serotoninergic dysregulation affects the dopaminergic system. Sudden disappearance of serotoninergic feedback on the dopaminergic pathways, may contribute to an increase in the mesolimbic hyperdopaminergic state. In animals, it has been shown that serotonin depletion induced by MDMA, unmasks the effects of a hyperdopaminergic state. In addition, although it has not been mentioned much in the literature, MDMA disturbs dopaminergic function either directly, or through the peptidergic systems (neurotensin, substance P, dynorphines). A consistent series of arguments therefore suggest that there is a sudden central hyperdopaminergic state, which may be related to the appearance, sometimes de novo, of an acute psychotic disorder. From the published cases, psychotic disorders following absorption of ecstasy, appear to become chronic. Most of the cases occurred in individuals, who either abused multiple substances or were chronic ecstasy users. In a case like the one we report, in an individual with good general health, who is not a drug user and who has an acute episode following a single dose, the prognosis should be good. Similarly, a team from Milan has described the experience of 3 friends who had a brief psychotic episode, following ingestion of substances containing ecstasy. These episodes resolved completely, after rehydration and anxiolytic treatment. However, after 6 months' follow-up, our patient still has psychotic symptoms, albeit mild, but which were not present before the intoxication. The patient and his psychiatrist do not envisage changing or stopping his antipsychotic treatment. Other authors have described a lesion in the serotoninergic neurons, by making a parallel with toxic effects described in animals, in particular in primates, with MDMA. Degradation of the serotoninergic cell bodies and nerve endings has been suggested to occur with high doses and/or repeated doses of MDMA. Other authors show the large variations in MDMA and MDA metabolism. (ABSTRACT TRUNCATED)
Five children, admitted with acute psychotic reactions after use of Scopolamine eye drops 0.2%, are presented. The predominant symptoms were visual hallucinations, strange behaviour, and restlessness. In one case peripheral symptoms were observed. Recovery was complete in 24 h. Prescription of Scopolamine eye drops should be followed by information of possible adverse effects. Cyclopentolate might be used instead.
Carbamazepine, mainly used as an anticonvulsant but also used for trigeminal neuralgias and other neuralgic pains, is now being used experimentally for affective disorders, nonresponsive psychoses, and dyscontrol. However, carbamazepine dosage must be carefully monitored because low initial doses are equivalent to higher later doses, and the drug's addition to a regimen of other drugs may increase carbamazepine's serum levels. Given alone to a pharmacologically naive inpatient, initial dosage of carbamazepine 200 mg/day can be increased by 100 mg every day or every second day; an outpatient can have the dosage increased by 100 mg every third day. Serum levels and side effects should be monitored. White cell counts usually decrease about 25%, but the decrease is not clinically related to the very rare occurrence of agranulocytosis. A side effect of concern is hepatic toxicity, but few such cases have been reported. The most common side effect is allergic rash, which occurs in about 5% of all patients receiving carbamazepine; antihistamines sometimes bring about a remission of the rash. Generic carbamazepine may cause more problems than Tegretol.
Marijuana seems firmly established as another social drug in Western countries, regardless of its current legal status. Patterns of use vary widely. As with other social drugs, the pattern of use is critical in determining adverse effects on health. Perhaps the major area of concern about marijuana use is among the very young. Using any drug on a regular basis that alters reality may be detrimental to the psychosocial maturation of young persons. Chronic use of marijuana may stunt the emotional growth of youngsters. Evidence for an amotivational syndrome is largely based on clinical reports; whether marijuana use is a cause or effect is uncertain. A marijuana psychosis, long rumored, has been difficult to prove. No one doubts that marijuana use may aggravate existing psychoses or other severe emotional disorders. Brain damage has not been proved. Physical dependence is rarely encountered in the usual patterns of social use, despite some degree of tolerance that may develop. The endocrine effects of the drug might be expected to delay puberty in prepubertal boys, but actual instances have been rare. As with any material that is smoked, chronic smoking of marijuana will produce bronchitis; emphysema or lung cancer have not yet been documented. Cardiovascular effects of the drug are harmful to those with preexisting heart disease; fortunately the number of users with such conditions is minimal. Fears that the drug might accumulate in the body to the point of toxicity have been groundless. The potential deleterious effects of marijuana use on driving ability seem to be self-evident; proof of such impairment has been more difficult. The drug is probably harmful when taken during pregnancy, but the risk is uncertain. One would be prudent to avoid marijuana during pregnancy, just as one would do with most other drugs not essential to life or well-being. No clinical consequences have been noted from the effects of the drug on immune response, chromosomes, or cell metabolites. Contamination of marijuana by spraying with defoliants has created the clearest danger to health; such attempts to control production should be abandoned. Therapeutic uses for marijuana, THC, or cannabinoid homologs are being actively explored. Only the synthetic homolog, nabilone, has been approved for use to control nausea and vomiting associated with cancer chemotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)
Adverse effects related to clozapine were assessed within a post-marketing drug surveillance program, the AMUP study, in two university psychiatric departments. In a randomly selected sample of patients (intensive drug monitoring) ADRs of any type were observed in 76% of clozapine-treated inpatients. Sedation, hypersalivation, increase in transaminases, and EEG changes were most frequently observed, but only rarely required changes in therapy. In 8.1% of 959 patients exposed to clozapine in the total inpatient population of the participating hospitals ADR led to withdrawal of clozapine; in 3.9% reactions judged as severe and potentially life-threatening occurred. Among these latter toxic delirium prevailed. In addition, four cases of severe cardiovascular and respiratory dysregulation were observed with the combination of clozapine and benzodiazepines. These cases and one case of sudden death under clozapine and haloperidol treatment are presented in some detail. The results obtained for clozapine are compared to data from this drug surveillance program for other neuroleptics.
Psychotropic medications may produce a toxic confusional state, especially in elderly patients. Tricylcic antidepressants particularly, and the phenothiazines to a lesser extent, may induce these behavioral changes by their anticholinergic activity. The situation may be compounded by the use of more than one psychotropic drug or the addition of an antihistamine or a belladonna alkaloid. Physostigmine can reverse the anticholinergic effects and clear the mental state.
The definition of resistant depression is imprecise and variable according to the different authors. In most cases, the definition concerns depressed patients who have received well managed treatment with optimal doses of a thymoanaleptic over a sufficiently long period of time. The distinction of manic-depressive psychoses (MDP) with a rapid cycle also raises the problem of resistance to the prophylactic effect of mood regulators in MDP. The inefficacy of treatment in at least 20% of cases of depression has led a number of authors to propose original drug combinations with the aim of potentiating the action of previous treatments. Most of the studies published report isolated cases in which the therapeutic approach is often empirical and rarely explained. The most frequently reported combination is that of 2 drugs, generally including one antidepressant. Such combinations can induce pharmacodynamic or pharmacokinetic interactions resulting in either a potentiation or a reduction of the effects of one of the 2 drugs or to the induction of toxicity. These last two possibilities illustrate what the authors describe as "bad combinations". Various drug combinations are reviewed and critically analysed. The most interesting and best documented combinations involve the addition of lithium, MAOI and thyroid hormones to tricyclic treatment in non-responding patients. Other combinations with tricyclics have been reported less frequently: ECT, neuroleptics, reserpine, carbamazepine, 5 HTP, tryptophan, amphetamines, oestrogens, sleep deprivations.(ABSTRACT TRUNCATED AT 250 WORDS)
A young woman presented with podophyllin intoxication following topical application of podophyllin resin to genital condylomata acuminata. The disorder was marked by hallucinatory psychosis, bone marrow depression, and mild hepatic dysfunction. The psychosis and systemic disturbances resolved within 3 weeks, but were followed by autonomic and sensorimotor peripheral neuropathy. This case illustrates the transient central neurotoxicity and persistent peripheral neurotoxicity of podophyllin.
The author compared the neurotoxic effects of disulfiram with those of carbon disulfide, a disulfiram metabolite. The results suggest that carbon disulfide is responsible for the behavioral and neurological side effects of disulfiram. If this is so, then some other toxic effects of carbon disulfide, including parkinsonism, choreoathetosis, and thalamic syndrome may follow the ingestion of more than 5 g of disulfiram by adults, and individuals receiving as little as 125 mg of disulfiram per day may be at a three- to four-fold greater risk for arteriosclerotic cardiovascular disease than a comparable population not receiving the drug.
Toxic psychosis due to Chloroquine is a relatively uncommon occurrence in childhood. This entity must be kept in differential diagnosis in a case of unexplained psychosis, before resorting to a sophisticated array of detailed investigations. The purpose of this is to familiarize pediatricians with this relatively uncommon entity. The authors encountered four cases of psychosis with a wide variety of symptomatology over a period of the past 18 months.
The AMUP study (AMUP = Arzneimittelüberwachung in der Psychiatrie (Drug Monitoring in Psychiatry)) was conducted from 1979 to 1989 in order to provide for a systematic and standardized assessment of all adverse reactions to psychotropic drugs under the conditions of routine clinical treatment at two psychiatric hospitals. This paper presents data from the AMUP study on the type and frequency of adverse psychic reactions to psychotropic drug groups and relevant single drugs. Psychic ADR leading to drug discontinuation were observed in 4.5% of 15,264 inpatients monitored over an eight-year period. Only neurological ADR were more frequent (4.9%). Neuroleptics and antidepressants were involved with similar frequencies in ADR that were at least "probably" drug-related (3.3 and 3.5%). Lithium salts and benzodiazepines were only rarely involved in psychic ADR. Toxic delirium (1.0%), agitation (0.9%), and sedation (0.8%) were the most frequent single events, usually rated as "probably" drug-related. Depression and psychotic states were next in frequency, but judged as only "possibly" drug-related in a considerable proportion of cases. Haloperidol, the most common high-potency neuroleptic, was imputed mainly for depression, sedation, agitation, and (malignant) neuroleptic syndrome; with medium-potency perazine, toxic delirium and sedation prevailed; among the most common antidepressants, amitriptyline was above all connected with toxic delirium, while with clomipramine agitation predominated. The paper discusses the particular difficulties encountered in the field of psychic ADR in psychiatric patients regarding causality assessment, and emphasizes the need for continuous ADR assessment studies including state hospitals.
Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in CNS can elevate level of neuronal excitability by the mechanisms of hyperpolarization. Gabaergic hypothesis of epileptogenesis influenced development of a group of gabamimetic antiepileptic drugs (AEDs). Powerful conventional AEDs barbiturates and benzodiazepines can directly activate GABA-A receptor but their usefulness is limited by development of dependence and tolerance to antiseizure activity. The second generation AEDs have been achieved by a rationale synthesis of compounds that could mimic or augment the activity of endogenous GABA. Vigabatrin (VGB) irreversibly inhibits GABA-T activity, tiagabine (TGB) inhibits GABA-reuptake system (GAT-1) and gabapentin (GPT) enhances GABA turnover in CNS. New drugs with selective and specific influence on GABA neurotransmission are non-toxic and well-tolerated, but some side-effects (aggravation of seizures, visual field deficit and psychotic reactions) seems to be strictly connected with their pharmacodynamic properties. Absence and probably myoclonic seizures noted in about 10% of patients under VGB seems to be the result of disturbed GABA inhibition in thalamic interneurons and non-controlled hyperactivity of excitatory neocortex-thalamus-neocotrex circuits. Perimetric examination might reveal peripheral, persistent binasal visual field deficit in about 30% of patients treated with VGB. This is probably the effect of cytotoxic influence of enormous accumulation of GABA in retinal neurons. Barbiturates and benzodiazepines can exacerbate intellectual functioning and behaviour. Some emotional and reactive disturbances are more characteristic for newer drugs. Serious depressive reactions and psychoses were observed respectively in 12.5 and 2.5% epileptics under VGB and anecdotically after TGB or GPT therapy. Newer selective and specific gabamimetic AEDs play an essential role as add-on therapy of pharmaco-resistant epilepsy, but they did not bring significant qualitive change in the possibilities of pharmacotherapy.
A case reported of a 27-year-old white woman who developed systemic toxicity after the local instillation of one drop of 2% cyclopentolate solution in each eye. The usefulness and toxic reactions of this very valuable drug are discussed. It is recommended that every ophthalmologist should warn not only the parents of the children, but also the adult patients about the possibility of systemic reaction before this drug is used and where possible the lowest concentration of solution be used. It is also suggested that a sufficient amount of injectable physostigmine salicylate be kept handy in the office emergency kit.
At least four distinct cerebral diseases--Wernicke-Korsakoff, Marchiafava-Bignami, pellagrous encephalopathy, and acquired hepatocerebral degeneration--have a close association with chronic alcoholism. Each is characterized by a distinctive pathologic change and a reasonably well-established pathogenesis; in each the role of alcohol in the causation is secondary. The question posed in this review is whether there is, in addition to the established types of dementia associated with alcoholism, a persistent dementia attributable to the direct toxic effects of alcohol on the brain--i.e., a primary alcoholic dementia. The clinical, psychologic, radiologic, and pathologic evidence bearing on this question is critically reviewed. None of the evidence permits the clear delineation of such an entity. The most serious flaw in the argument for a primary alcoholic dementia is that it lacks a distinctive, well-defined pathology, and it must remain ambiguous until such time as its morphologic basis is established.