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Previous research has demonstrated that psychological test results of newly admitted alcoholics are not stable due to lingering alcohol toxicity. The present study (N = 40) demonstrated that a 10-day delay in testing is sufficient to obtain stable results on some psychological tests.
UNLABELLED: The interferon alpha stands as a reference both in oncology and virology. But its efficiency is limited by frequent somatic as well as neuropsychic side effects. As a matter of fact, the reduction or the ending of a chemotherapy treatment come chiefly from the psychiatric complications caused by the use of interferon. For about 30% of patients, various psychic disorders are noticed: personality disorders, mood disorders, anxiety states, suicidal tendencies, manic and psychotic symptoms. We thus propose a review which shall be completed by a discussion on wether the interferon is responsible or not of the appearance of the described mental disorders. We shall conclude with a synthesis of the proposed practical management when confronted with such disorders. Psychiatric complications under interferon-Alpha. The appearance of psychiatric complications caused by interferon has been the subject of many publications. They have also raised the question of the toxicity mechanism which is still misunderstood today. This toxicity appears to be dose-dependent with variations depending on the daily dose given, the mode of administration, the combination with other chemotherapy treatments, the concomitance with a cerebral radiotherapy or a medical history of psychiatric disorders. Most of these effects occur after three weeks of treatment but non specific neuropsychic symptoms can be observed earlier. Non specific symptoms. They appear early but are difficult to detect, though they bring together a whole lot of clinical signs: asthenia, irritability, psychomotor slowdown, depressive mood or even a real "subsyndromic" depressive syndrome, anorexia, decline of the libido, concentration and attention problems, dizzy spells and headaches. Some authors have described intense and fluctuating of personality, mixing anxiety, irritability and disorder of drive control. Depression. Depression is the most frequently found psychiatric pathology in studies but the real frequency of clear cases of depressive problems is difficult to determine through lack of serious studies. So the incidence of depressive disorders usually varies from 5 to 15%. The depressive syndrome can settle as soon as the first week treatment, with a peak in the frequency during the first and third months. The seriousness and the incidence of this syndrome seem to be dose-dependent. The gravity of this complication lies in the suicidal risk, a risk all the more dreadful since there is not any identified risk factor. Suicides and suicidal behaviours. Serious complications, because they act directly on the vital prognosis. However fortunately, suicidal behaviours only represent a minority within all the side effects attributed to the interferon-alpha. These actions fit into three main clinical dimensions: complication of a severe depressive syndrome, confusional context and disorder of the impulses control. In practical terms, prevention proves to be difficult without identified predictive factors. Nevertheless, some authors point out the importance of aggravating comorbid disorders like alcoholism or the coinfection by the HIV. Manic syndrome. The appearance of a manic state under a chemotherapy treatment seems to be rare, given that there have been only a dozen cases published around the world. But these observations are interesting as far as both the study of imputability and the understanding of the toxicity mechanisms are concerned. Most of the cases deal with patients without a family or personal history of psychiatric disorders, and whose symptomatology disappears with the end of the treatment, which is an argument in favour of the imputation of the interferon in the appearance of manic disorders. In addition, some authors introduce the notion of tertiary mania: the appearance of an autoimmune hypothyroidism in relation with interferon and leading to athymic elation. Eventually, the appearance of manic problems at the end of the treatment makes it possible to speculate about the physiopathological mechanisms that are at issue. Anxiety disorders. These disorders are not much described: they generally are already existing disorders (like phobic or obsessive compulsive disorders), reactivated or aggravated by the interferon-alpha molecule. Adaptation disorders. It deals with adaptation disorders along with anxious temper coming at the beginning of the treatment. These problems are more concerned with the announcement of the diagnosis and its seriousness than with the toxicity of the interferon-alpha molecule. Psychotic states. There are less papers on the prevalence of psychotic disorders during the treatment, or at the end of it. But they can be found in both viral and malignant pathologies. A large retrospective study has shown ten cases of psychotic disorders and that in the absence of history of psychiatry or of a HIV co-infection. In every case the psychiatric aspect is stopped by the ending of the treatment or by an appropriated treatment. Usually, the few cases of paranoïd delusion described in papers seem to appear between one and three months of treatment, with patients having a history of psychiatric disorders. Aggravation of pre-existing mental disorders. Numerous authors have reported the recurrence of addictive behaviours (alcohol or other psychoactive matter) by weaned patients. Imputability to interferon-alpha in psychiatric disorders. It is difficult to draw the relationship between the chemotherapy with the interferon-alpha treatment and neuropsychiatric complications because there is a lack in specific studies. Nevertheless, it seems to be causal relations between the prescription of interferon and the appearance of psychic disorders. As a matter of fact, even if there is neither predictive criterion nor diagnosis of clinical type (set apart a dose effect), it is clear that there are diagnostic criteria of chronological kind: delay of appearance and disappearance of side effects compatible with the kinetics of the molecule and test of positive reintroduction. The imputability is thus most likely towards, given the reported clinical observations and signs of direct cerebral toxicity described for interferon: induction of neurophysiological changes among healthy volunteers, reversible EEG impairments the second week of treatment, direct vascular and neurological toxicity. Eventually, authors have shown that the psychiatric morbidity could be more important among patients under treatment than in a control group. In conclusion, the imputability of interferon appears to be very likely, more particularly in the appearance of mood disorders, mainly depressive ones, of manic syndromes and of certain psychotic episodes. MANAGEMENT: The most numerous therapeutic propositions naturally concern the depressive syndromes, because of their high frequency. In a recent article, the authors have detailed the pharmacological criteria of the ideal molecule: limited hepatic metabolism, low rate of proteinic fixation, long half-life and absence of active metabolite. So they advise not to prescribe imipraminic molecules and recommend the use of some SRI in first intention: citalopram and sertraline mainly, paroxetine to avoid given its pharmacological features that do not seem adapted. Only the minalcipram seems to show all the theoretical advantages described above. If there is an indication in the introduction of an anxiolytic medication, we shall prefer a benzodiazepine with short half-life like loxazepam and alprazolam. Besides, all the publications point out the importance of a specific clinical observation during the treatment as well as in the six months following its end. The agreement must bear full medical costs, above all including psychotherapic and social aspects. The proposed treatments for the other disorders are conventional: haloperidol and lithium for bipolar disorders, fluvoxamine for obsessive compulsive disorders and neuroleptics for psychotic disorders. CONCLUSION: The appearance of neuropsychiatric side effects during a chemotherapy using the interferon-alpha molecule is a frequent complication, the consequences of which can prove tragic: involvement of the vital prognosis, family and professional relation disturbances, compliance problems, risks of psychiatric morbidity at short and middle terms.... In spite of the absence of rigorous controlled studies, the imputability to the interferon of the appearance of psychological disorders appears very likely. So the role of the psychiatrist seems to be determining in the follow-up care of these patients who must be considered at high risk to develop a psychiatric pathology. The agreement to bear medical costs has to be made in narrow collaboration with clinical practitioners and must be part of a clinical continuity, from the pre-therapeutical evaluation to the remote follow-up care. Finally, it seems important to implement controlled studies, resting on a great diagnostic and methodological rigour, in order to clarify the toxicity mechanisms of interferon and to optimise the agreement to bear medical cost for the patients.
The general hospital emergency room has become the locus of care for many psychiatric patients. It has become essential for emergency department personnel to be able to manage the behavioral emergency. Critical to this management is the rational use of psychotropic drugs. The author offers guidelines for the use of antipsychotic drugs and minor tranquilizers. The importance of differential diagnosis and the correlation of drug use with patient variables are stressed. The section on anti-depressants addresses the issues of when, and under what conditions the treatment of a depressive disorder can be initiated in an emergency setting. An approach to the toxic-behavioral-confusional state is offered. The final section reviews the approach to the patient who is a diagnostic dilemma and/or mute.
In two patients with acute bromide toxicity, serum bromide levels rose during the period of observation, but this increase was not associated with clinical deterioration. In both, serum "chloride" levels were also high, but these values actually indicated elevated extracellular halide concentrations.
Bupropion hydrochloride is a phenylaminoketone antidepressant whose clinical pharmacology is poorly understood. Part of bupropion's action may be attributed to inhibition of dopamine reuptake that may induce organic mental disorders in certain susceptible patients. We report three cases of organic mental disorders in patients receiving bupropion hydrochloride for treatment of the depressed phase of their bipolar-type mood instability. The organic mental disorders that occurred in these patients were characterized largely by visual disturbances--visual hallucinations and visual illusions--although one patient also experienced auditory hallucinations. The patients' use of concomitant medications and potential drug interactions are carefully evaluated and the literature on bupropion's ability to induce organic mental disorders is reviewed. We suggest a number of possible mediating mechanisms for these syndromes including dose-related dopaminergic augmentation, accumulation of toxic metabolites, predisposition to psychosis, and drug interactions.
Parkinson's disease is an illness occurring in the third stage of life. At times, the patient suffers from arteriosclerosis as well. Reconstruction processes caused by aging are under way in the brain, which affect, among others, the synapses and transmitter substances. The biotransformation of medication may be changed in elderly persons. The tendency to multimorbidity leads to consumption of several drugs at the same time, possibly causing interference symptoms. Changes in transmitter balance and receptor excitability are, however, the main causes of the toxic side-effects of anti Parkinson therapy. The greater the nigrostriatal degeneration, the lower the tolerance level. Recently, in addition to basic therapy consisting of reduced doses of combined dopa preparations and/or Amantadine sulphate, dopaminergic agonists are used, which act on the receptors which have been maintained. This prevents some side-effects and stabilizes the patient's unpleasant daily fluctuations. Reducing the dosage prevents dyskinesia. pharmacotoxic psychoses require neuroleptics of the Thiaxanthen group or change-over to i.v. Amantadine sulphate infusions or Lisuride i.v.
OBJECTIVE: To describe a patient with increased tacrolimus concentrations due to a diltiazem drug interaction. CASE SUMMARY: A 68-year-old white man, four months following orthotopic liver transplantation secondary to hepatitis C and Laënnec's cirrhosis, was admitted to the intensive care unit for diarrhea, dehydration, and atrial fibrillation. He was stabilized on oral tacrolimus 8 mg twice daily, with a whole blood tacrolimus trough concentration of 12.9 ng/mL on admission. He was started on a continuous infusion of diltiazem for one day, followed by 30 mg orally every eight hours. Three days after admission, the patient became delirious, confused, and agitated; he was found to have a whole blood tacrolimus trough concentration of 55 ng/mL. The tacrolimus was withheld and diltiazem was discontinued. The tacrolimus concentrations fell over the next three days to 6.7 ng/mL, with a corresponding improvement in his mental status. The oral tacrolimus was restarted at 3 mg twice daily and increased gradually to 5 mg twice daily over the next four days; this produced tacrolimus trough concentrations between 9 and 10 ng/mL. DISCUSSION: Tacrolimus is known to be a substrate for P-glycoprotein and metabolized by CYP3A. Diltiazem inhibits CYP3A, P-glycoprotein, and tacrolimus metabolism in vitro. Although this interaction may have been predictable, this is the first detailed case report describing this clinically significant drug interaction. CONCLUSIONS: Diltiazem can dramatically increase tacrolimus concentrations and result in tacrolimus toxicity. Avoidance of this interaction or careful monitoring of tacrolimus concentrations along with tacrolimus dose reduction is recommended if diltiazem therapy cannot be avoided.
The question of toxic interactions resulting from combinations of lithium and neuroleptic drugs is largely based on anecdotal reports. We replicated the methods of Miller and Menninger (1987) who reported that 27% of manic patients on treatment with lithium and neuroleptics developed toxicity. We found no cases of neurotoxicity as defined in the earlier report. Pharmacologic mechanisms and differences in the clinical findings of the two studies are discussed.
Central pontine myelinolysis (CPM) is a rare, acute, and uniformly fatal demyelinative process that involves the pons almost exclusively. Three cases diagnosed at autopsy illustrate the characteristic clinical course and pathologic features of CPM. A unique extrapontine location of a similar process is noted in the medulla of a 6-year-old girl. The term "medullary myelinolysis" is a descriptive designation for demyelination that occurs predominantly in this area. The clinical and pathologic features of CPM are reviewed in detail, together with a brief review of theories of metabolic, nutritional, vascular, and endogenous and exogenous toxic factors that act either singly or in concert in the cause and pathogenesis of CPM.
We reviewed the use of physostigmine in the diagnosis and management of acute toxic psychosis due to drugs with anticholinergic properties. The syndrome of agitation and toxic confusional psychosis associated with peripheral signs of cholinergic blockade is produced by several plant toxins, antispasmodics, ophthalmic preparations, and certain proprietary sedatives, as well as antiparkinson medications, antidepressants, and some antipsychotic drugs. Physostigmine, uniquely among the available reversible anticholinesterase agents, can pass the blood-brain barrier to exert central as well as peripheral cholinomimetic actions to reverse this syndrome. Psychiatrists should make more use of this safe, specific, rapid, and effective treatment for anticholinergic drug toxicity, and should particularly be alert to reversible anticholinergic brain syndromes associated with antidepressants and antiparkinson medications, and even with antipsychotic medications.
Sleep disruption is a common complaint in levodopa-treated parkinsonian patients. A survey of 100 parkinsonian patients revealed prominent sleep complaints in 74%. Sleep complaints were unrelated to patient age and the duration of disease but increased in prevalence with longer periods of levodopa therapy. Sleep abnormalities tended to increase in severity with continued treatment and insomnia tended to be followed by daytime somnolence, altered dream events, and episodic nocturnal vocalization and myoclonus. While dyskinetic side effects and on-off syndrome were encountered in patients with and without sleep complaints, 98% of patients experiencing psychiatric side effects also reported sleep disruption. It is suggested that sleep-related symptoms constitute an early stage of levodopa-induced dopaminergic psychiatric toxicity in the parkinsonian population. Clinical and experimental observations suggest that serotonergic mechanisms are important in this symptom complex.
The literature on denatured alcohol drinking includes substantial reports on the toxicological aspects of the experimental studies and on acute poisoning of denatured alcohol. However, there is scant mention of the alcoholic's use of denatured alcohol as an alternate source to sustain his addictive habit. We have been repeatedly impressed by reports of consumption of denatured alcohol in histories given by chronic alcoholics. By definition, a drinker of denatured alcohol is a person who, over a period of time, drinks any preparation of rectified spirits which has been denatured for domestic, industrial, or medical use (see Table I). Common denaturants used are methyl alcohol, gasoline, benzene, chloroform, pyridine, and naphthalene, in combination or individually. (see Table I-Glossary). This study was lndertaken to explore the damage, mainly to the central nervous system, caused by the denaturants. Ten cases were studied for neuropsychiatric pathology resulting from drinking denatured alcohol. The duration of their drinking this substance varied from two months to eighteen months. From the clinical data, a personality profile is drawn of these individuals. There is a high incidence of toxicity to the central nervous system of an irreversible nature as well as to the respiratory system. Psychometric tests can be helpful in early detection (with prophylaxis) of damage caused to the higher cerebral process.
Phencyclidine is now one of the most frequently used main ingredients of "street drug" preparations. Its effects are highly dose dependent and three varieties of acute intoxication have been seen clinically associated with different dosages and routes of administration. Most persons using phencyclidine smoke it sprinkled on parsley in low doses. The presence of horizontal and vertical nystagmus associated with hypertension in a patient who is agitated or comatose are diagnostic of a phencyclidine intoxicated state. Sensory isolation and intravenous administration of diazepam in the event of seizure activity have proved effective in the treatment of acute intoxicated states. Phencyclidine has pronounced behavioral toxicity and several deaths due to this agent have now been documented. It is unknown whether seizure activity or respiratory depression is the primary cause of death in pharmacological overdoses.
Five cases of poisoning by indigenous mushroom Hikageshibiretake (Psilocybe argentipes) are reported. As this mushroom contains psilocybin, in general, clinical features were similar to those seen by pure psilocybin. Acute toxic stuporous state with complete amnesia in the culminating period occurred in one case, psychedelic state with dreamy consciousness in one case and psychotic adverse reactions with vivid visual hallucinations with consciousness in three cases. There were accompanied with anxiety and panic reactions to subjective experiences. Though these toxic effects were usually short-lived, for management of such patients it is important to recognize that horrible emotional reactions and other harmful behavioral problems can also occur.
Phencyclidine (PCP) is a popular illicit drug often misrepresented as some other hallucinogenic substance and distributed in widely varying dosage forms and strengths. Users of hallucinogenic drugs may present with unintentional PCP overdoses. Toxicological laboratory analyses are essential to establish the diagnosis. In nine admitted overdose patients, the consciousness level ranged from alert to comatose on presentation, and all showed a prolonged recovery phase with agitation and toxic psychosis. Severe behavior disorder, paranoid ideation, and amnesia for the entire period of in-hospital stay are characteristic. In very high dose patients, shallow respiratory excursions and periods of apnoea and cyanosis coincided with generalized extensor spasm and spasm of neck muscles. Excessive bronchial secretions, gross ataxia, opisthotonic posturing, and grimacing occur. PCP toxic psychosis should be considered in drug-abusing patients presenting with schizophrenic-like symptoms, psychosis, or other bizarre behavior, whether or not they admit to taking PCP.
The management of sleep disorders in elderly patients with internal diseases consists in the first line in rectifying pathophysiological disregulations. Only in the second line, proper hypnotics are to be prescribed. When considered as indispensable, these medicaments are selected according to their toxicity and side effects. In present time, Benzodiazepines are definitely preferred, whereas neuroleptic, anti-depressant and the older drugs are to be taken secondarly in account.
Some aspects of drug management of acute behavioural disorder are discussed. Drug management aims at the amelioration of the patient's ineraction with his environment; it is used as a diagnostic procedure, and to facilitate further definitive diagnosis and investigation, as a form of psychotherapeutic contact, to facilitate further psychotherapy, and to initiate a treatment programme aimed at returning the patient to being a useful and health member of society. Some methods of rapid tranquillisation are described and the drug management of the following specific behavioural disturbances are discussed: schizophrenic distrubance, acute mania, depressive behavioural disturbance, acute anxiety states, acting-out psychopathic behaviour, toxic states, epileptic furore and dyscontrol syndrome, behavioural disturbances of the elderly, and behavioural disturbances in organic conditions.
We report on the present views on disturbances regarding spermatogenesis caused by chronic abuse of alcohol which still are partly based on findings from the year 1910. We are also presenting results of semen analysis in alcoholics. There is some evidence that alcohol-toxic damage of the testes may occur immediately. Regarding alcohol-toxic effects, we discuss some biochemical conceptions as there are the metabolism of Vitamin A and possible effects on the steroid reductases in particular. Our own studies have revealed some disturbances with regard to the gestagen metabolism of chronic alcoholics.