Petra Kuijpers

Treatment of post-myocardial infarction depressive disorder: a randomized, placebo-controlled trial with mirtazapine.

Objective: To examine the antidepressant efficacy of a dual-acting antidepressant (mirtazapine) in patients with post-myocardial infarction (MI) depressive disorder. Antidepressants used in post MI trials with a randomized, double-blind, placebo-controlled design have been restricted to selective serotonin reuptake inhibitors (SSRIs). Antidepressant effects have been limited. Methods: In a prospective multicenter study, 2177 patients with MI were evaluated for depressive disorder during the first year post MI. Ninety-one patients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for major or minor depressive disorder were randomized to a 24-week, double-blind, placebo-controlled trial. Antidepressant efficacy was tested using last-observation-carried-forward procedure and repeated measurements analysis using the SPPS mixed models approach, with as primary outcome reduction in depressive symptomatology on the 17-item Hamilton-Depression Rating Scale (Ham-D), and secondary outcomes the Beck Depression Inventory (BDI) and depression subscale of the Symptom Check List 90 items (dSCL-90) as well as the Clinical Global Impression (CGI) scale. Results: Using the “last observation carried forward” (LOCF) method, mirtazapine did not show to be superior to placebo on the Ham-D, but did on the BDI, dSCL-90, and CGI scale over the acute treatment phase of 8 weeks (n = 91). Using mixed models analysis over the entire 24 weeks of treatment (n = 40), we did find a significant difference favoring mirtazapine to placebo on the Ham-D, BDI, and CGI, but on the dSCL-90, this difference was not significant. Conclusions: This trial shows efficacy of mirtazapine on primary and secondary depression measures. Mirtazapine seems to be safe in the treatment of post-MI depression. MI = myocardial infarction; RCT = randomized controlled trial; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders; CAD = coronary artery disease; SSRI = selective serotonin reuptake inhibitors; TCA = tricyclic antidepressant; Ham-D = Hamilton-Depression Rating Scale; BDI = Beck Depression Inventory; CGI = Clinical Global Impression; dSCL-90 = Symptom Check List 90 items, depression subscale; SES = standardized effect size.

Beta-thromboglobulin and platelet factor 4 levels in post-myocardial infarction patients with major depression

Platelet factor 4 (PF 4) and beta-thromboglobulin (beta-TG) were studied in 12 depressed post-myocardial infarction (MI) patients and 12 matched non-depressed post-MI patients. PF4 was significantly higher in the depressed group than in the non-depressed group. beta-TG was increased in the depressed subgroup, but the difference was not statistically significant.

The Impact of Differences in EQ-5D and SF-6D Utility Scores on the Acceptability of Cost-Utility Ratios: Results across Five Trial-Based Cost-Utility Studies

OBJECTIVE This article investigates whether differences in utility scores based on the EQ-5D and the SF-6D have impact on the incremental cost-utility ratios in five distinct patient groups. METHODS We used five empirical data sets of trial-based cost-utility studies that included patients with different disease conditions and severity (musculoskeletal disease, cardiovascular pulmonary disease, and psychological disorders) to calculate differences in quality-adjusted life-years (QALYs) based on EQ-5D and SF-6D utility scores. We compared incremental QALYs, incremental cost-utility ratios, and the probability that the incremental cost-utility ratio was acceptable within and across the data sets. RESULTS We observed small differences in incremental QALYs, but large differences in the incremental cost-utility ratios and in the probability that these ratios were acceptable at a given threshold, in the majority of the presented cost-utility analyses. More specifically, in the patient groups with relatively mild health conditions the probability of acceptance of the incremental cost-utility ratio was considerably larger when using the EQ-5D to estimate utility. While in the patient groups with worse health conditions the probability of acceptance of the incremental cost-utility ratio was considerably larger when using the SF-6D to estimate utility. CONCLUSIONS Much of the appeal in using QALYs as measure of effectiveness in economic evaluations is in the comparability across conditions and interventions. The incomparability of the results of cost-utility analyses using different instruments to estimate a single index value for health severely undermines this aspect and reduces the credibility of the use of incremental cost-utility ratios for decision-making.

Noncardiac chest pain in the emergency department: the role of cardiac history, anxiety or depression and Type D personality.

Background Noncardiac chest pain is common in patients presenting to emergency departments and is frequently associated with panic disorder. This can represent a major burden for patients and the healthcare system. Little is known about the patient characteristics that increase the risk of noncardiac chest pain. We examined whether cardiac history or Type D personality was associated with panic disorder and/or depression-driven noncardiac chest pain. Methods and results Patients presenting with noncardiac chest pain to the emergency department of the University Hospital Maastricht were screened using the Hospital Anxiety and Depression Scale (HADS). Patients scoring ≥8 on the HADS subscale were invited for a psychiatric interview; a consecutive sample of patients scoring <8 on the HADS was included as a reference group. Type D personality (tendency to experience emotional distress) was assessed with the DS14. Among the 304 HADS-positive patients, 89% were diagnosed with panic disorder/depression as compared with 8% of the 106 HADS-negative patients. Previous cardiac history was not associated with psychiatric diagnosis. Type D patients reported more anxiety symptoms (12.4 ± 4.0 vs. 8.1 ± 4.9) and depression symptoms on the HADS (10.2 ± 4.7 vs. 5.8 ± 4.9) and more often had comorbid panic disorder/depression (91/157 = 58% vs. 57/253 = 23%) than non-Type D patients (P<0.0001). Type D personality (odds ratio =8.67, 95% confidence interval 4.69–16.02), younger age and male sex were independently associated with increased risk of panic disorder or depression. Type D was independently associated with comorbid panic disorder/depression (odds ratio = 14.49). Conclusion Type D personality, but not cardiac history, is independently associated with the presence of psychopathology in noncardiac chest pain. Type D is associated with a substantially increased risk of co-occurring PD/depression in these patients.

Managing complex patients on a medical psychiatric unit: An observational study of university hospital costs associated with medical service use, length of stay, and psychiatric intervention

OBJECTIVE Although there is a suggestion that the medical psychiatric unit (MPU) may reduce length of hospital stay (LOS), little is known about costs in terms of medical service use and psychiatric interventions in MPU care. METHOD A record linkage study was conducted, linking cost data of hospital medical service use, LOS, and hospital psychiatric interventions to patients admitted to the MPU of the Maastricht University Medical Centre (MUMC) between 1998 and 2004. The data set was analyzed to enable comparison between cost changes of the same complex patient population following either MPU index admission or index admissions to reference MUMC medical wards. RESULTS Comparisons revealed lower costs of medical service use in favor of the MPU (-euro104; 95% CI -euro174 to -euro35; P<.01). However, cost of psychiatric intervention and cost of LOS were higher after MPU admission (respectively, +euro165; 95% CI +euro25 to +euro305; P<.05; and +euro202; 95% CI +euro170 to +euro235; P<.001). Total costs were higher after MPU admission compared to medical ward admission (+euro263; 95% CI +euro68 to +euro458; P<.05). These differences were not moderated by somatic diagnosis or previous pattern of admissions. CONCLUSION The findings suggest that patients at the interface of psychiatric and somatic morbidity are diagnosed and treated adequately at the MPU, leading to a decrease in medical service use and an appropriate increase in exposure to psychiatric interventions. These results are specifically generalizable to MPUs with a focus on psychosomatic conditions, for instance, somatoform disorders or affective disorders with comorbid somatic diseases. However, failure to show cost savings in terms of LOS compared to medical wards outweighs cost-benefit derived from lower medical service use, suggesting that MPU activities may gain in cost-effectiveness if shifted more to outpatient psychosomatic care solutions.

Role of Cytochrome P450 Polymorphisms in the Development of Pulmonary Drug Toxicity A Case-Control Study in the Netherlands

AbstractBackground: Drug-induced pulmonary toxicity is a serious and expanding problem with often unknown aetiology. Many drugs are metabolized by cytochrome P450 (CYP) enzymes. Objective: To establish whether allelic variation in CYP polymorphic genes contributes to variability in drug response and unexpected toxicity. Methods: A case-control study was conducted. The cases consisted of patients with drug-induced interstitial lung disease (DI-ILD; n = 59). Two control groups were used: one group of healthy volunteers (n = 173) and one group of patients with idiopathic pulmonary fibrosis (IPF; n = 110). Results: Of the patients with DI-ILD 91.5% (54/59) had at least one of the studied variant genes compared with 70.5% (122/173, p < 0.001) of the healthy volunteers and 69.1% (76/110, p < 0.001) of the IPF patients. The percentage of individuals with one or more variant CYP genes was higher in the DI-ILD group. Odds ratios were significantly increased and ranged from 3.25 to 40.8, indicating a significant association between the development of DI-ILD and the presence of one or more variant CYP genes. Conclusion: DI-ILD appeared to be associated with the presence of at least one variant CYP allele. This study supports the potential usefulness of personalized medicine by genotyping aiming to improve efficacy, tolerability and drug safety.

Depressive effect of an antidepressant: therapeutic failure of venlafaxine in a case lacking CYP2D6 activity

Understanding the mechanisms of drug metabolism and interactions can help to prevent side-effects. Not only drug interactions, environmental factors, disease processes and ageing are factors in the inter-individual metabolic capacity variance but also genetic factors probably play an important role, as is illustrated in the case presented. Besides therapeutic drug monitoring, genotyping some important cytochrome P450 (CYP450) enzymes was of additional value in explaining why the patient developed severe adverse effects and, moreover, did not experience any therapeutical effect of venlafaxine. Results indicated that the patient was a poor metabolizer for CYP2D6, the most important phase I enzyme to metabolize venlafaxine. This corroborates that polymorphisms in the CYP450 gene influence the metabolic activity of the corresponding enzymes, thus affecting the subsequent serum drug levels and their metabolites. This case highlights the potential benefit of both clinical and genetic risk stratification (pharmacogenetics) prior to treatment, either for setting the individual dose or for making a decision about using a particular drug.

Lactate: panicking doctor or panicking patient?

We report a case of a 51-year-old man with a first panic attack associated with high serum lactate due to hyperventilation induced alkalosis. Hyperlactataemia may trigger somatically oriented tests and divert attention from diagnosing panic disorder (PD). Factors associated with underdiagnosis of PD as well as pathophysiology of hyperlactataemia will be discussed.

Multidisciplinaire zorg voor gecombineerde somatische en psychiatrische problemen

De organisatie van de somatische en van de psychiatrische gezondheidszorg zijn over het algemeen strikt gescheiden. Dit staat haaks op de vaak voorkomende verwevenheid van somatische en psychiatrische stoornissen.