Showing papers in "Journal of Psychiatry & Neuroscience in 1998"

Use and abuse of over-the-counter analgesic agents.

Abstract: Pain and discomfort in everyday life are often treated with over-the-counter (OTC) analgesic medications. These drugs are remarkably safe, but serious side effects can occur. Up to 70% of the population in Western countries uses analgesics regularly, primarily for headaches, other specific pains and febrile illness. It is not known whether the patterns of use are consistent with good pain management practices. OTC analgesics are also widely used to treat dysphoric mood states and sleep disturbances, and high levels of OTC analgesic medication use are associated with psychiatric illness, particularly depressive symptoms, and the use of alcohol, nicotine and caffeine. More than 4 g per day of acetylsalicylic acid (ASA) or acetaminophen over long periods is considered abuse. People using excessive amounts of OTC analgesics may need more effective treatments for chronic pain, depression or dysthymia. The possibility that these drugs have subtle reinforcing properties needs to be investigated. Certainly phenacetin, which was taken off the market in the 1970s, had intoxicating effects. A better understanding of patterns of use is needed to determine the extent of problem use of OTC analgesics, and whether health could be improved by educating people about the appropriate use of these drugs.

Schizotypal thinking and associative processing: a response commonality analysis of verbal fluency

Abstract: OBJECTIVE: To determine whether people with high scores for schizotypal thinking generate more uncommon words in a letter fluency task than people with low scores. DESIGN: Prospective study. SETTING: University psychology department. PATIENTS: Forty healthy, right-handed students. INTERVENTIONS: Students were administered the Magical Ideation (MI) Scale and a 2-minute letter fluency task in which they named as many nouns as possible beginning with "A" or "F," in any order. OUTCOME MEASURES: Total number of words produced and percentage of unique, rare and common words (as determined by the responses of the whole group); scores on MI scale. RESULTS: Participants with high scores (above the median) on the MI scale generated as many words as those who had low scores. People in both groups also generated a comparable number of unique words (named by only 1 person) and common words (named by 6 or more people). As hypothesized, people with high scores on the MI scale generated more rare words (named by fewer than 6 people) than those with low scores. CONCLUSIONS: These findings support the view of a disinhibition of semantic network functioning as the neuropsychological basis of creative thought, magical ideation and thought disorder.

Valproic acid use in psychiatry: issues in treating women of reproductive age.

Abstract: Valproic acid, a well known anticonvulsant, is being used by psychiatrists increasingly to manage bipolar and other affective disorders. Because of the demographics of the population affected by such psychiatric conditions, more women of childbearing age are likely to be exposed to this teratogenic drug. Neural tube defects (NTD) are the most common of the major anomalies associated with in utero valproic acid exposure, and are estimated to occur in 1% to 2% of exposed fetuses. Other teratogenic effects include facial dysmorphism, congenital cardiac defects, limb reduction defects and other skeletal anomalies. Prenatal diagnosis, in particular maternal serum alpha-fetoprotein screening and targeted ultrasonography, should be offered to all pregnant women exposed to valproic acid and couples need to be aware of the prenatal diagnostic options available to them. Periconceptual prophylaxis with high doses of folic acid is recommended for all women on valproic acid and counselling should also emphasize planning pregnancy to optimize folic acid supplementation. Psychiatrists should be aware of the teratogenic potential of valproic acid and know how to counsel their patients of reproductive age.

Nicotine: abused substance and therapeutic agent.

Abstract: Tobacco dependence is a complex phenomenon that is not fully understood. Nicotine is the main alkaloid in tobacco and the addictive compound of tobacco. It can improve both mood and cognitive functioning; these positive effects are strong reinforcements for smokers and contribute to their addiction. Opposite results also have been reported, however, and the effects of nicotine remain controversial. Recent epidemiological and empirical studies have indicated that smoking or nicotine or both may have protective effects against certain diseases. These findings have suggested that nicotine may be used as a therapeutic agent. However, because a variety of nicotinic cholinergic receptors are present in the brain, new agonist compounds may prove to be more effective than nicotine for therapeutic purposes. Studies are reviewed and the suggestion made that nicotine may prove useful as a tool to help us understand normal and pathological brain functioning.

A case of risperidone overdose in early schizophrenia: a review of potential complications.

Abstract: Deliberate drug overdose is a frequent occurrence in patients with schizophrenia. Typical antipsychotic medications can be lethal at doses 5 times the recommended therapeutic range. Clozapine, an atypical antipsychotic, can be toxic at doses 4 times a moderate dose. Little is known about the lethal effects of the novel antipsychotic risperidone, despite the fact that it is now one of the most widely prescribed antipsychotics in North America. To date, only 1 death attributable to risperidone overdose has been reported. The case presented here documents adverse cardiac effects in a 28-year-old man who intentionally ingested 24 mg of risperidone--4 times the recommended dose. A potential drug interaction with fluvoxamine and the role of active metabolites are discussed.

Olfactory identification and Stroop interference converge in schizophrenia.

Abstract: OBJECTIVE: To test the discriminant validity of a model predicting a dissociation between measures of right and left frontal lobe function in people with schizophrenia. PARTICIPANTS: Twenty-one clinically stable outpatients with schizophrenia. INTERVENTIONS: Patients were administered the University of Pennsylvania Smell Identification Test (UPSIT), the Stroop Color-Word Test (Stroop), and the Positive and Negative Syndrome Scale (PANSS). OUTCOME MEASURES: Scores on these tests and relation among scores. RESULTS: There was a convergence of UPSII and Stroop interference scores consistent with a common cerebral basis for limitations in olfactory identification and inhibition of distraction. There was also a divergence of UPSIT and Stroop reading scores suggesting that the olfactory identification limitation is distinct from a general limitation of attention or a dysfunction of the left dorsolateral prefrontal cortex. Most notable was the 81% classification convergence between the UPSIT and Stroop incongruous colour naming scores compared with the near-random 57% classification convergence of the UPSIT and Stroop reading scores. CONCLUSIONS: These data are consistent with a right orbitofrontal dysfunction in a subgroup of patients with schizophrenia, although the involvement of mesial temporal structures in both tasks must be ruled out with further study. A multifactorial model depicting contributions from diverse cerebral structures is required to describe the pathophysiology of schizophrenia. Valid behavioural methods for classifying suspected subgroups of patients with particular cerebral dysfunction would be of value in the construction of this model.

Chronic depression: a case series of 203 outpatients treated at a private practice.

Abstract: Objectif: Determiner la prevalence de la depression chronique chez les patients en service externe qui consultent pour une depression. Conception : Serie de cas. Contexte : Pratique privee. Patients : Deux cent trois patients en service externe qui avaient des troubles thymiques, sauf les patients qui avaient des troubles comorbides decoulant de l'abus de substances et de graves troubles de la personnalite. Mesures de resultats : Taux de prevalence et variables des patients (diagnostic, âge a la ligne de base, âge au debut, sexe, nombre d'episodes anterieurs de depressions, caracteristiques atypiques, co-morbidite psychiatrique, psychose, duree de la maladie et gravite a la ligne de base). Resultats : La prevalence de la depression chronique s'est etablie a 46.7 %, ce qui est plus eleve que les niveaux indiques auparavant. Le nombre d'episodes de depression etait plus eleve, les symptomes psychotiques etaient plus frequents et la duree de la maladie etait plus longue chez les patients atteints de depression chronique que chez ceux qui etaient aux prises avec une depression non chronique. Conclusions : La depression chronique est plus grave que la depression non chronique et est une affection prevalente chez les patients en service externe qui consultent pour une depression en pratique privee.

Event-related potentials during a selective attention task with short interstimulus intervals in patients with schizophrenia.

Abstract: Objective: Tostudy selective attention inschizophrenia byexamining event-related potentials during a dichotic listening taskwithshort interstimulus intervals (ISIs). Design: Prospective study. Participants: Twelve patients withschizophrenia inremission and12age-matched controls withno history ofpsychiatric or neurological illness. Interventions: Participants were asked topush a button inresponsetotargetstimuli ineither ear.Outcomemeasures: Reaction time, correctresponserateandresults ofelectroencephalography recorded at3regions: mean segmental amplitudes between0 and200ms and between 200and400ms after stimuli andprocessing negativity (Nd), measured bythenegative areaduringthese periods. Results: Distinct slow-positive potentials forunattended stimuli, which were elicited in a taskwithlongISIs ina previous report,didnotemerge ineither groupinthisstudy. Although the2 groupsdidnotdiffer significantly intermsofNd area,inthecontrols themean segmental amplitude for attended standard stimuli was significantly greaterthanthatinthepatients withschizophrenia. Conclusions: Impairment ofselective attention inpatients withschizophrenia isrelated toa lackofability tofocusattention on attended task-relevant stimuli during aselective attention taskwithshort ISI. Objectif: Etudier I'attention selective dansles casdeschizophrenie en examinant lespotentiels liesaux evenementsau coursd'une tached'ecoute dichotique comportantdebrefs intervalles interstimuli. Concept:Etudeprospective. Participants: Douzepatients atteints deschizophrenie en remission et12temoinsjumeles selon I'age sansantecedents detroubles psychiatriques ou neurologiques. Interventions: On a demande aux participants d'appuyer surun bouton pourrepondre aun stimulus cible dansl'une ou l'autre oreille. Mesuresderesultats :Tempsdereaction, tauxdebonnes reponses etresultats electroencephalographiques

Light therapy to treat winter depression in adolescents in Iceland.

Abstract: OBJECTIVE: To determine whether light therapy during winter is beneficial to adolescents with symptoms of seasonal affective disorder (SAD). SETTING: The 3 largest colleges in Reykjavik, Iceland. PARTICIPANTS: Eighteen college students, 18 and 19 years old, suffering from symptoms of SAD. OUTCOME MEASURES: School attendance and self-reported change in indicators (concentration, ability to awaken in the morning, and frequency of breakfast). RESULTS: Light therapy helped some of the students concentrate and wake up in the morning, usually only to a mild degree, but did not improve school attendance. CONCLUSIONS: The lack of effect of light therapy on school attendance in a group of students with symptoms of SAD indicates that school attendance is influenced by several complex factors, of which seasonal disorders are not a major determinant, even in those most at risk.

Efficacy and tolerability of venlafaxine in the treatment of primary dysthymia.

Abstract: OBJECTIVE: Currently, there is no documentation of the efficacy of venlafaxine (a serotonin norepinephrine reuptake inhibitor) in the treatment of dysthymia. This open-label pilot investigation examined the efficacy and tolerability of venlafaxine in patients with primary dysthymia without concomitant major depression. METHODS: Fifteen patients were treated with venlafaxine for 12 weeks, with a dose range of 75 mg to 225 mg daily (taken orally), and symptom changes were measured using standard instruments including the Hamilton Depression Rating Scale (HAM-D). RESULTS: Significant changes from pretreatment to posttreatment were observed (p < 0.001). Using the standard criteria of a 50% reduction in HAM-D scores, 73.3% of patients were rated as responders. About two-thirds of the patients reported adverse events, which were mostly mild and brief in duration. CONCLUSION: Venlafaxine may be useful in the treatment of primary dysthymia but placebo-controlled studies are required for confirmation.

Treatment of depression in HIV-infected patients

Abstract: Contexte : On a constate que le traitement pharmacologique de la depression chez les patients infectes par le VIH est efficace. Dans le cadre de cette etude, on evalue l'efficacite et la faisabilite d'un traitement a la fluoxetine et la meilleure facon d'administrer le medicament aux patients infectes par le VIH. Methodes : On a etudie 16 patients seropositifs et 16 autres seronegatifs, jumeles egalement en fonction de l'âge et du sexe, qui ont obtenu un resultat d'au moins 16 a l'echelle d'evaluation de la depression de Hamilton et qui ont recu au moins 20 mg/j de fluoxetine pendant huit semaines. Resultats : La depression a ete soulagee chez les deux groupes, mais l'amelioration chez les patients seropositifs s'est produite plus tard. Interpretation : Le resultat confirme l'efficacite de la fluoxetine comme traitement de la depression chez les personnes infectees par le VIH. Comme il n'a pas d'effet indesirable, ce traitement convient particulierement, surtout parce que les personnes seronegatives prennent plus de temps a y reagir.

Effects of electroconvulsive therapy and desipramine on neuroendocrine responses to the clonidine challenge test.

Abstract: OBJECTIVE: To investigate responses to the clonidine challenge test in depression, and after electroconvulsive therapy (ECT) or desipramine treatment for depression, in order to determine the usefulness of noradrenergic responses to clonidine as a state or trait marker in depression. PATIENTS: Twenty-six patients with depression and 15 control subjects. SETTING: The psychiatric ward of St. Joseph's Hospital in Hamilton. INTERVENTIONS: In the patients with depression: clonidine challenge pre- and post-treatment with ECT or desipramine. In the controls: 2 clonidine challenge tests 4 to 8 weeks apart. OUTCOME MEASURES: The primary measure was the growth hormone response to the clonidine challenge. Plasma norepinephrine, 3-methoxy-4-hydroxyphenylglycol (MHPG), cortisol, blood pressure, pulse and sedation levels were examined in subgroups of participants as secondary measures. RESULTS: The pre-treatment growth hormone response to clonidine was significantly more blunted in patients than in controls (p = 0.02). This response improved in both treatment groups after therapy and, although it remained decreased, there was no longer a significant difference in response between the patients and the controls. In the patients, a decreased growth hormone response to clonidine at baseline was correlated with response to treatment. Of the secondary measures, patient baseline norepinephrine levels were significantly elevated pre- and post-treatment, although there were no significant group-by-time challenge effects. MHPG levels were not significantly different pre- and post-treatment between patients and controls. Baseline blood pressure and pulse were elevated in the patients pre- and post-treatment. These differences were not statistically significant and did not change after treatment. Sedation levels were not significantly different among the groups at baseline. Clonidine-induced sedation occurred significantly earlier in the patients pretreatment and improved to the range of the controls after treatment. Pretreatment cortisol response was significantly more blunted in the patients who received ECT than in the controls; however, the group-by-time effect post-treatment was no longer significant. DISCUSSION: Treatment with either desipramine or ECT modified noradrenergic functioning in patients with depression, as assessed by growth hormone response to the clonidine challenge. In the patients, a decreased growth hormone response at baseline was correlated with clinical response. Changes between pre- and post-treatment measures suggest that this challenge test may not be sensitive enough to serve as a trait marker but may correlate with the state of depression in a subpopulation of these patients.

Calcitonin and bipolar disorder: a hypothesis revisited.

Abstract: Double-blind trials conducted in the early 1980s showed that subcutaneous injections of salmon calcitonin in patients suffering from mania resulted in significant decreases in irritability, euphoria and hyperactivity. Although these results were promising, there were no follow-up studies in this area. A MEDLINE search into the effect of calcitonin on neuronal tissues revealed that calcitonin affects neuronal tissues in a manner similar to that of the currently accepted mood-stabilizing agents--namely by modulating intracellular second messenger signalling mechanisms, stabilizing neuronal membranes and inhibiting neuronal calcium influx. We suggest that these effects of calcitonin on neuronal tissues, combined with earlier clinical research showing its efficacy in treating the acute symptoms of mania, make calcitonin a candidate for further research in the treatment of bipolar disorder.

Plasma concentrations of endogenous benzodiazepine-receptor ligands in patients with hepatic encephalopathy: a comparative study.

Abstract: Objectif : L'encephalopathie hepatique est un trouble neuropsychiatrique complexe secondaire a une insuffisance hepatique aigue ou chronique. Meme si l'on n'a pas encore precise les causes exactes de l'encephalopathie hepatique, on a evoque une inhibition accrue du systeme nerveux central au complexe acide γ-aminobutyrique (GABA)-recepteurs des benzodiazepines, cause par des taux accrus de ligands recepteurs endogenes des benzodiazepines. Des recherches sur cette hypothese ont produit des resultats contradictoires. Dans le cadre de cette etude, on a evalue la presence et les taux de ligands recepteurs endogenes des benzodiazepines dans le plasma d'un patient atteint d'encephalopathie hepatique et de 3 groupes temoins. Conception: Etude transversale. Patients: Vingt-quatre patients d'atteints d'encephalopathie hepatique. 10 patients atteints de cirrhose du foie sans encephalopathie, 4 patients atteints d'encephalopathie uremique et 9 sujets en bonne sante. Interventions: Titrage de radiorecepteurs d'echantillons de plasma provenant de patients et de temoins. Principales mesures de resultats: Taux plasmatiques de ligands recepteurs endogenes des benzodiazepines. Resultats: Les patients atteints d'encephalopathie hepatique presentaient des taux plasmatiques de ligands recepteurs endogenes des benzodiazepines beaucoup plus eleves que les patients atteints d'encephalopathie uremique et les sujets en bonne sante, mais pas plus eleves que les sujets atteints de cirrhose du foie sans encephalopathie chez lesquels on a aussi detecte des concentrations importantes de ces composes. Lorsqu'on a classe les patients selon la gravite de l'encephalopathie hepatique, les taux plasmatiques de ligands recepteurs endogenes des benzodiazepines ont indique un lien modeste avec la gravite de l'encephalopathie (r = 0,37). Le tiers des patients atteints d'encephalopathie hepatique ne presentaient pas de niveau detectable de ligands recepteurs endogenes des benzodiazepines, ce qui est interessant Conclusion: Les ligands recepteurs endogenes des benzodiazepines peuvent jouer un role dans la pathogenese de l'encephalopathie hepatique, meme si les symptomes neuropsychiatriques de l'encephalopathie hepatique sont difficiles a expliquer en fonction de ces composes seulement.

The Canadian experience with risperidone for the treatment of schizophrenia: an overview.

Abstract: Objectif : Resumer des donnees publiees jusqu'a maintenant par des auteurs canadiens et tirees de sources canadiennes sur la risperidone, nouveau neuroleptique indique dans le traitement de la schizophrenie et des troubles psychotiques connexes. Ce medicament a ete lance au Canada en 1993. Sources de donnees : On a effectue une recherche dans MEDLINE en utilisant «risperidone» comme mot cle, et une recherche manuelle dans 3 journaux canadiens. Selection d'etudes : Articles publies entre janvier 1991 et juin 1996 par des auteurs canadiens ou portant sur des patients canadiens. Extraction de donnees : Les articles extraits ont ete classes en fonction des donnees sur l'efficacite, la surete, l'utilisation des ressources et l'economie, ainsi que d'autres aspects divers. Les articles ont ete abreges et resumes. On a utilise quelques sources non canadiennes a des fins de comparaison. Synthese des donnees : A la suite de la premiere etude multicentrique realisee au Canada, on a constate que la risperidone (6 mg par jour) est superieure a l'haloperidol (20 mg par jour) pour ce qui est de reduire les symptomes positifs et negatifs et entraine moins d'effets secondaires extrapyramidaux. Diverses etudes de cas ont etendu a la fois l'utilisation clinique et le profil de surete de la risperidone tandis que des etudes de neuro-imagerie visaient a clarifier son mode d'action. Des etudes economiques indiquent que la prevention des hospitalisations et l'amelioration de la qualite de vie entrainent des avantages importants au plan des couts. Conclusions : La recherche canadienne a contribue enormement aux connaissances actuelles sur la risperidone. D'autres etudes, tant controlees que naturalistes, devront porter avant tout sur des comparaisons avec les divers composes nouveaux maintenant disponibles.

Safety of ipsapirone treatment compared with lorazepam: discontinuation effects.

Abstract: OBJECTIVE: To determine discontinuation effects of ipsapirone, a novel azapirone and partial 5-HTIA agonist that has anxiolytic effects clinically and has not caused dependence or withdrawal symptoms in animals, and to compare these effects with those of the benzodiazepine lorazepam, owing to concern about dependence or withdrawal symptoms following use of these drugs. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Outpatient and inpatient treatment. PARTICIPANTS: Sixty-five healthy male volunteers who had experience with sedative-hypnotics or anxiolytics and did not meet DSM-III-R criteria for abuse or dependence. INTERVENTIONS: Participants were randomized to receive ipsapirone 15 mg per day (n = 17), ipsapirone 22.5 mg per day (n = 16), lorazepam 3 mg per day (n = 16), or placebo (n = 16) as outpatients for 36 days (treatment) followed by single-blind placebo as inpatients for 3 days and as outpatients for 6 days (withdrawal). OUTCOME MEASURES: Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Scale (HAM-D), Spielberger State Anxiety Scale, Sleep Quality Questionnaire, General Symptom Checklist, self-rated intoxication, Clinical Institute Withdrawal Assessment--Benzodiazepines (CIWA-Benzo), psychomotor testing and urine drug screen. RESULTS: Only 45 subjects completed the study; discontinuation rates did not significantly differ among treatment groups. At day 39, fewer and less severe symptoms (e.g., insomnia and fatigue) were found on the CIWA-Benzo scale after treatment with ipsapirone or placebo than after treatment with lorazepam (p < 0.05). Subjects reported longer sleep latency and poorer sleep quality after receiving lorazepam than after receiving ipsapirone or placebo. Scores on the HAM-D, Spielberger State Anxiety and HAM-A scales did not change from baseline. CONCLUSIONS: Withdrawal symptoms were detected after discontinuation of therapeutic doses of lorazepam. Significantly fewer symptoms were observed after withdrawal from anxiolytic doses of ipsapirone.

In vivo occupation of dopamine D1, D2 and serotonin (5-HT)2A receptors by sertindole in the rat brain.

Abstract: OBJECTIVE: To determine the in vivo occupation of dopamine D1, D2 and serotonin (5-HT)2A receptors by novel antipsychotic agent sertindole using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), an irreversible antagonist at these receptor sites. DESIGN: Animal study. INTERVENTIONS: Intraperitoneal administration to Wistar rats of 1 of 4 test compounds: a control compound of 0.15% tartaric acid, or a compound of either sertindole (0.5 mg/kg or 2.0 mg/kg) or clozapine (20 mg/kg) dissolved in 0.15% tartaric acid 1 hour before intraperitoneal administration of EEDQ (8 mg/kg) or ethanol/water solution. RESULTS: Sertindole exhibited little or no effect on D1 and D2 binding sites in vivo. On the other hand, sertindole occupied 5-HT2A receptors more extensively and firmly than EEDQ. This study indicates that sertindole is characterized by high occupancy of 5-HT2A receptors and by low or minimum occupancy of D1 and D2 receptors. CONCLUSIONS: These characteristics are very similar to atypical antipsychotic agents such as clozapine. Sertindole's low liability to cause extrapyramidal side effects (EPS) may be related to greater long-term binding for 5-HT2A receptors relative to D2 receptors.