Esa Leinonen

Effects of S-ketamine as an anesthetic adjuvant to propofol on treatment response to electroconvulsive therapy in treatment-resistant depression: a randomized pilot study.

Objective Ketamine in electroconvulsive therapy (ECT) anesthesia has been reported to be associated with better seizure quality and longer duration compared with methohexital anesthesia. Furthermore, ketamine may enhance the efficacy of ECT while having rapid independent antidepressant properties itself. However, data on the effects of ketamine with ECT are inconsistent, and there are no reports of S-ketamine. The aim of the present pilot study was to explore the effects of S-ketamine as an adjuvant to propofol on the efficacy, seizure duration, and quality of electroencephalography in patients with treatment-resistant depression. Methods Thirty-two patients with a recurrent severe or psychotic major depressive disorder with treatment resistance to antidepressants were included in the study. For induction of anesthesia, the patients were randomized into 2 study groups. The S-ketamine group first received S-ketamine (0.4 mg/kg) as a bolus and then propofol. The treatment-as-usual group first received saline and then propofol. Results A statistically significant and clinically relevant reduction in the depression symptom scores was found in both study groups during ECT. There was no difference in the magnitude or speed of response between the study groups, nor was there any difference in the numbers of ECT treatments, seizure thresholds, seizure durations, and the electrical doses either. The patients recovered from anesthesia equally, but the degree of posttreatment disorientation and restlessness was more marked in the S-ketamine group. Conclusions In conclusion, a subanesthetic adjuvant dose of S-ketamine with propofol may not increase the effects of ECT in patients with treatment-resistant depression. However, S-ketamine was associated with increased posttreatment disorientation and restlessness.

Catechol-O-methyltransferase and monoamine oxidase A genotypes and drug response to conventional neuroleptics in schizophrenia.

Biogenic amine synthesis and degradation are involved in the pathogenesis of schizophrenia. Catechol-O-methyltransferase and monoamine oxidase enzymes are important agents in the metabolic inactivation of these neurotransmitters (ie, dopamine, serotonin, and norepinephrine). Functional polymorphism in the catechol-O-methyltransferase and monoamine oxidase A genes causes variation in enzyme activities. We investigated the relationship of catechol-O-methyltransferase Val158Met and monoamine oxidase A promoter repeat polymorphism with response to conventional neuroleptic treatment in schizophrenia. Ninety-four schizophrenic patients formed 2 different study populations. The responders had experienced a fair and steady response to conventional neuroleptics. The nonresponders had failed to achieve an acceptable response to conventional neuroleptics. We also used a control population of 94 age-matched and gender-matched blood donors. Genotyping of the catechol-O-methyltransferase and monoamine oxidase A genes was performed by polymerase chain reaction. Forty-three percent of the nonresponders had a low activity catechol-O-methyltransferase genotype compared with 16% of the responders (P = 0.009). Monoamine oxidase A genotype alone did not differ significantly between the groups. Moreover, the risk of having both low-activity catechol-O-methyltransferase and monoamine oxidase A genotypes was over 6 times more common (odds ratio = 6.16, P = 0.03) in the nonresponders compared with responders. The whole population of patients with schizophrenia did not differ from the controls. The low-activity catechol-O-methyltransferase genotype may be associated with unsatisfactory drug response to conventional neuroleptics or alternatively be involved in a subset of schizophrenics. The role of monoamine oxidase A genotype seems to be additive in this respect.

Fluvoxamine increases the clozapine serum levels significantly

In this case report we describe an interaction between clozapine and fluvoxamine in two physically healthy patients meeting the DSM-IIIR criteria for paranoid schizophrenia. The substantial rise of clozapine serum levels suggest that caution should be exercised when combining fluvoxamine with clozapine as the clozapine concentration may increase by a factor of 5-10.

Sleep in panic disorders.

Panic disorder is a common anxiety disorder, which has relatively often its onset during adolescence. Besides panic attacks and avoidance behavior the patients often have sleep disturbances. They suffer from insomnia, nocturnal panic attacks, fear of going to bed or falling asleep and drug- or alcohol-related symptoms such as withdrawal phenomena.

Interaction between NOTCH4 and catechol-O-methyltransferase genotypes in schizophrenia patients with poor response to typical neuroleptics.

OBJECTIVEnIn this study we attempted to show that the interaction between NOTCH4 and catechol-O-methyltransferase (COMT) polymorphism predicts the response to typical neuroleptics in schizophrenia. Our sample consisted of 94 Finnish patients with DSM-IV schizophrenia and 98 controls.nnnMETHODSnSeveral studies have connected COMT and NOTCH4 genes to schizophrenia. We have previously shown that COMT polymorphism is significantly associated with treatment response in schizophrenia. NOTCH4 SNP2 polymorphism has been associated with age of onset in schizophrenia, but there is also a trend that this polymorphism may predict response to typical neuroleptics. In the present sample, there is a strong gene-gene interaction between these genes (P = 0.003) and they have additive effect in treatment response.nnnRESULTSnPatients carrying both NOTCH4 C/C genotype and COMT low/low genotype, had more than ten times higher risk of being a non-responder than responder to treatment with typical neuroleptics [OR = 10.25 (95% CI 2.21-47.53), P < 0.001]. This combination of genotypes is also more common in patients considered non-responders than in controls [OR = 3.00 (95% CI 1.33-6.76), P = 0.007].nnnCONCLUSIONnOur results suggest that an interaction between COMT and NOTCH4 genotypes may predict the treatment response to typical neuroleptics in patients with schizophrenia.

Double-blind study of mirtazapine and placebo in hospitalized patients with major depression

The purpose of the present 6-week multicenter dose finding study was to compare the efficacy and tolerability of mirtazapine (preferentially presynaptic alpha 2-adrenergic receptor blocker) to placebo in hospitalized patients with major depression. The clinical efficacy was evaluated with the Hamilton Depression Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), Beck Self-Rating Depression Scale, Global Assessment Scale (GAS), and Brief Psychiatric Rating Scale (BPRS). The side effects were recorded on a checklist of emergent symptoms (ROSE) and physical examinations, ECG, clinical chemistry, and hematology tests were carried out. The dosages of mirtazapine were gradually raised from 15 mg to 50 mg. One hundred and fourteen patients were included. Twenty-two patients (37%) in mirtazapine group and 24 (44%) in the placebo group were prematurely withdrawn from the study mainly due to inadequate efficacy. The decrease in HAM-D and MADRS was generally more pronounced in the mirtazapine group than in the placebo group. Minor side effects were reported in less than 15% of the patients in both groups. Only fatigue and faintness were slightly more pronounced in the mirtazapine group than in the placebo group. No significant changes were found in laboratory parameters. Because of methodological flaws like combining a dose finding study with a placebo controlled study, further conclusions should not be made on the efficacy of mirtazapine when treating depressive patients.

Mortality and causes of death in older patients with schizophrenia

The aim of this study was to evaluate mortality and causes of death in older patients with schizophrenia in comparison with the general population. The mortality of patients experiencing relapse was also compared with those in remission.

Delusional parasitosis in the elderly: a review and report of six cases from northern Finland.

A patient with delusional parasitosis has a strong conviction of being infested with parasites: for example, lice or worms. Such a patient is not satisfied with assurances or test results that no parasites are present, but is so convinced that he or she will go as far as to bring the parasites in matchboxes to a physician. Subjectively worried, the patient may try to pick the parasites out of the skin, causing cutaneous lesions and even ulcerations. The condition is classified as a delusional/paranoid disorder, somatic type according to DSM-III-R. Not much is known epidemiologically of this rare disorder, which usually affects older women who often are isolated socially. Therapy is regarded as difficult, and a wide variety of treatment methods have been attempted. In this article six female cases are presented, showing that a typical patient is an elderly woman who has suffered losses or is socially isolated. These patients lack deeper psychiatric insight into their problem, so they are mostly in the care of nonpsychiatric physicians. Treatment with a low dose of high-potency neuroleptics combined sometimes with antidepressants appears to be effective. Reducing social isolation is also important.

Meta-Analysis of Anxiety Disorders and Temperament

Background: The aims of the present study were to explore whether symptoms in different anxiety disorders are associated with Cloningers model temperament dimensions novelty seeking (NS), harm avoidance (HA), reward dependence and persistence compared with control subjects in clinical samples of adults or late adolescents. Method: Literature search in the following databases: Cochrane Library, PubMed (Medline), Web of Science, Psycinfo and PsycArticles. Systematic review, grading the level of evidence and meta-analysis for each disorder by comparing the temperament dimension scores between patient and control samples in single studies. Results: A total of 40 papers fulfilled the inclusion criteria. Meta-analyses were conducted on a total of 24 studies focusing on panic disorder (PD), social anxiety disorder (SAD) and obsessive-compulsive disorder (OCD). The primary finding was a constant and clinically marked positive association between the HA temperament dimension and symptoms of PD, SAD and OCD, with a most marked effect in SAD, and a moderate effect in OCD and PD. Second, less marked and clinically marginal associations between NS score and SAD and OCD (negative associations), but no associations with PD were observed. The meta-analyses revealed heterogeneity between the results of individual studies, especially in the analyses including SAD and OCD. Conclusions: PD, SAD and OCD share a marked and state-dependent avoidant behavioral pattern, which is common for all anxiety disorders. However, PD showed a different pattern of arousal to novel stimuli from that of SAD and OCD. The findings are state dependent and based on cross-sectional studies.

Delirium During Fluoxetine Treatment A Case Report

The correlation between high serum tricyclic antidepressant concentrations and central nervous system side effects has been well established. Only a few reports exist, however, on the relationship between the serum concentrations of selective serotonin reuptake inhibitors (SSRIs) and their toxic effects. In some cases, a high serum concentration of citalopram (> 600 nmol/L) in elderly patients has been associated with increased somnolence and movement difficulties. Widespread cognitive disorders, such as delirium, have not been previously linked with high blood levels of SSRIs. In this report, we describe a patient with acute hyperkinetic delirium connected with a high serum total fluoxetine (fluoxetine plus desmethylfluoxetine) concentration.