Robert Elie

Temporal lobe abnormalities in panic disorder: An MRI study ☆

Brain mapping studies have shown abnormal changes in cerebral blood volume and oxygen consumption, or other neurophysiological abnormalities, in panic disorder (PD) patients. Because of these intriguing reports, we decided to assess the neuroanatomical aspects of patients with PD using magnetic resonance imaging (MRI). We included 31 consecutive cases with a diagnosis of PD according to the DSM-III criteria, and 20 controls. All subjects had to be right-handed and between 20 and 40 years of age. The usual exclusion criteria were applied. We carried out the MRI tests with a General Electric Signa Machine operating at 1.5 Tesla. Over 100 images were obtained per patient with an emphasis on assessing temporal lobe. There were no significant differences in age, gender, or weight between the patients and controls. We found a statistically significant higher number of abnormalities in PD patients (40%), as compared with the controls (10%). The most striking findings were focal abnormalities in the temporal lobes: areas of abnormal signal activity, and asymmetric atrophy of the temporal lobe occurred mostly on the right side. These results implicated the limbic system and may prove to be of particular relevance in panic and phobic disorders. However, the significance of our findings remains unknown and challenging. Further MRI studies in PD will be required for a better understanding of the illness.

The treatment of the restless legs syndrome with clonazepam: a prospective controlled study

The effect of clonazepam on the restless legs syndrome was studied in a group of 6 patients. Following a drug-free period, 3 patients received clonazepam for 4 weeks followed by placebo for 4 weeks thereafter and 3 patients received the same medication and for the same length of time but in reverse order. The effectiveness of the medication was evaluated by means of a self-rating system in which patients assigned a score daily to the degree of discomfort experienced in the previous 24 hours. Three patients improved on clonazepam but 2 of these also improved on placebo. Clonazepam was not shown to be significantly more effective than placebo in the treatment of RLS.

Quetiapine in patients with comorbid schizophrenia-spectrum and substance use disorders: an open-label trial.

ABSTRACT Background: Preliminary evidence suggests that clozapine relieves the craving for psychoactive substances in schizophrenia patients. Quetiapine shares crucial pharmacological properties with clozapine. Promising results have been described with quetiapine therapy in patients with psychosis and substance use disorder. Methods: Based on Diagnostic and Statistical Manual of Mental Disorders – fourth edition (DSM‐IV) criteria, patients were diagnosed with comorbid schizophrenia-spectrum and substance use disorders. Patients were switched to quetiapine for a 12‐week open-label trial. Craving, quantities used, days of consumption, and severity of substance abuse were assessed every 3 weeks. Alcohol and Drug Use Scales were administered on baseline and end-point. Psychiatric symptoms, depressive symptoms, extrapyramidal symptoms, and cognition were also assessed at baseline, week 6 and week 12. Results: Twenty-four schizophrenia-spectrum patients were included in the last observation carried forward (LOCF) analyses, responding to one or more of the following substance use disorders: cannabis (15 patients), alcohol (10 patients), and other psychoactive substances (nine patients). Overall, severity of substance abuse improved during the study. Less weekly days were spent on drugs of abuse. A decrease in the weekly Canadian dollars spent on psychoactive substances was also observed. Cognition, psychiatric, depressive, and extrapyramidal symptoms also significantly improved ( p < 0.05). Conclusions: In this open-label, uncontrolled trial, significant improvements were noted in substance abuse, psychiatric symptoms, extrapyramidal symptoms, and cognition during quetiapine therapy. The study suffered from three main limitations: (1) the open-label design of the study; (2) the patients’ poor compliance; and (3) the small sample size involved. Controlled studies on the use of quetiapine in dual diagnosis schizophrenia are warranted to confirm that the effects are drug-related.

Effects of chronic antidepressant treatments on 5-HT and NA transporters in rat brain: an autoradiographic study.

Tricyclic antidepressants and serotonin (5-HT) uptake inhibitors rapidly block uptake sites, or transporters; however, their therapeutic effects are only seen after 2-3 weeks of treatment. Thus, direct blockade of 5-HT and noradrenaline (NA) transporters cannot account entirely for their clinical efficacy, and other long-term changes may be involved. Adult Sprague-Dawley rats were treated for 21 days with daily injections of either desipramine, trimipramine, fluoxetine, or venlafaxine; a fifth group that was used as a control, received daily saline injections. Identified cortical areas, hippocampal divisions and nuclei raphe dorsalis, raphe medialis and locus coeruleus were examined by quantitative autoradiography using either [3H]citalopram to label 5-HT transporters, or [3H]nisoxetine for NA uptake sites. Increases in [3H]nisoxetine binding were found in the cingulate, frontal, parietal, agranular insular, entorhinal and perirhinal cortices as well as in the hippocampal divisions CA1, CA3, dentate gyrus and subiculum, and in nucleus raphe dorsalis of trimipramine-treated animals compared to the control rats. Also, densities of NA transporters decreased in temporal cortex, CA2 and nucleus raphe dorsalis in fluoxetine-treated rats as compared to the controls. Also, there was a decrease in NA transporters in the locus coeruleus of the desipramine-treated animals as compared to the densities measured in the control group. Chronic treatment with desipramine or trimipramine, which do not directly inhibit 5-HT uptake, compared to fluoxetine and venlafaxine, lead to increases in 5-HT transporter densities in cingulate, agranular insular and perirhinal cortices. The present study shows differential region-specific effects of antidepressants on 5-HT and NA transporters, leading to distinct consequences in forebrain areas.

Quetiapine augmentation of treatment-resistant depression: a comparison with lithium

ABSTRACT Objective: The prevalence of and morbidity associated with treatment-resistant depression has motivated the exploration of treatment alternatives. In this study, quetiapine was compared with lithium in the augmentation of treatment-resistant depression. Research design and methods: Open-label, comparative study in 20 patients with major depression who had failed to respond after 4 weeks of treatment with an antidepressant at the maximal recommended dose. Patients were randomised to either lithium or quetiapine in addition to the maximally dosed antidepressant and any other concurrent medications. Lithium was initiated at 600 mg/day; quetiapine was titrated to 400 mg by day 7. Results: Depression, measured by the Hamilton Depression Rating Scale (HAM‑D), significantly improved from baseline in both quetiapine (F1,90 = 25.11, p < 0.0001) and lithium (F1,90 = 34.54, p < 0.0001). The difference in improvement between the two groups began at day 14 and was seen at all timepoints thereafter ( p < 0.05), with the quetiapine group showing greater improvement than the lithium group. In the Montgomery–Asberg Depression Rating Scale (MADRS) analysis, the difference between the quetiapine and lithium group was significant from day 28 onwards ( p < 0.05), with subjects improving more in the quetiapine group than the lithium group. The treatment by week interaction showed a significant difference overall between the two groups ( p < 0.0001). The severity of psychomotor retardation showed a significant decrease in the Widlocher Psychomotor Retardation Scale scores in the quetiapine ( p < 0.0001) and lithium ( p < 0.0001) groups. Conclusions: In this pilot study, quetiapine was an effective augmenting agent in treatment-resistant depression.

Captopril in infants for congestive heart failure secondary to a large ventricular left-to-right shunt

Abstract Vasodilators have been used for many years in the treatment of cardiac failure of adult patients with cardiomyopathy, mitral regurgitation or coronary artery disease. More recently, they have been used in children with similar problems.1,2 Their use in infants with ventricular left-to-right shunts was suggested a few years ago3 but did not gain wide acceptance. One of the reasons could be the difficulty of finding a safe and reliable systemic vasodilator that could be administered orally in infants. This study investigates the ability of captopril, a selective systemic vasodilator, to reduce ventricular leftto-right shunting and assesses the global hemodynamic status of infants receiving the drug.

Refractory depression: the addition of lithium to fluoxetine or desipramine.

We carried out an open clinical study with 60 consecutive patients suffering from major depression with melancholia who were resistant to anti‐depressants. After at least 6 weeks of desipramine (DMI) or fluoxetine (FX) without improvement, lithium carbonate was added to the anti‐depressant. Semistructured clinical interviews using the 7‐point Clinical Global Impression Scale and 90‐item Symptom Checklist were done at baseline and weeks 1, 6 and 14. Following the addition of lithium, more patients on FX improved within the first week than those on DMI. However, with FX, 6 relapses occurred during the 2 months of follow‐up and none with DMI. The unified serotonergic and noradrenergic hypothesis for the antidepressant action could be relevant in drug‐refractory depression and should be studied further.

The Treatment of Avoidant Personality Disorder by Social Skills Training in the Clinic or in Real-Life Settings

Twenty-eight outpatients who met DSM-III diagnostic criteria for avoidant personality disorder completed 14 one and a half hour sessions of social skills training in the clinic only or a combination of four sessions in the clinic, four sessions in real-life and six follow-up sessions in the clinic. Subjects were assessed before treatment began, after four sessions, at the end of treatment and at three month follow-up points. Training in real-life did not enhance social skills training; no significant difference between the groups at any assessment points was found. In both groups improvement in time was significant and clinically worthwhile. The treatment effects were maintained up to the three month follow-up, where available. Social skills training appears to be a useful and promising intervention for avoidant personality disorder but its long term impact remains to be investigated.

Zopiclone versus Flurazepam in Insomnia: Prolonged Administration and Withdrawal

Zopiclone (7·5 mg), a cyclopyrrolone derivative with a 6·5 h half-life, and flurazepam (30 mg) were compared to placebo in a randomized double-blind study involving 36 adult patients suffering from insomnia. All previous psychotropic drugs were discontinued 1 week prior to the study. During 4 weeks, 12 patients received zopiclone, 12 flurazepam and the others placebo. Thereafter, all patients received single-blind placebo for 3 nights. Rapidity of sleep onset, sleep duration, frequency of nocturnal awakenings, psychomotor coordination and side-effects were assessed daily with a questionnaire and a symptom checklist. The results of the study suggest that zopiclone 7·5 mg was at least as potent as flurazepam 30 mg in inducing and maintaining sleep. Both drugs maintained their efficacy during the 4 weeks of treatment. However, the two drugs differed in that flurazepam impaired psychomotor coordination whereas zopiclone did not demonstrate daytime protracted effects on psycho-motor performance. Upon discontinuation of drug treatment, score values of the different sleep parameters under study returned to the baseline values. Side-effects were mild and consistent with earlier studies.

Thought-stopping for Delusions and Hallucinations: A Pilot Study

A pilot controlled study was designed to evaluate the efficacy of the thought-stopping technique (T.S.) as a treatment for persecutory delusions and auditory hallucinations with chronic schizophrenics already treated with neuroleptics and to compare this combination with patients only treated with antipsychotic drugs. Medication was standardized for each patient and psychological measurements were recorded before and after treatment and during a 6-month follow-up. Results show significant differences in favor of the T.S. group mainly after treatment. Although T.S. was beneficial for chronic psychotics, other studies should be conducted with patients whose illness would be less severe and less chronic. The length of treatment as well as the cues that would serve to stop delusions and hallucinations also merit further investigation.