Cascade screening of familial hypercholesterolemia must go on.

PURPOSE: This study assesses the success of the recently terminated Dutch nationwide cascade screening by examining whether children with familial hypercholesterolemia (FH) were identified through family screening or due to cardiovascular (CVD) events in the FH parent. METHODS: We collected clinical information of all children (0-18 years) with FH with a pathogenic variant at our outpatient lipid clinic between 1992 and 2014 and their FH parents and FH grandparents. RESULTS: We analysed 292 FH children from 205 parents with FH. A history of premature CVD was present in 20% of the parents (29% of the fathers, 9% of the mothers) and 49% of the FH grandparents. CONCLUSION: The fact that CVD is still a presenting event of FH in especially fathers shows that nationwide screening might have been terminated too early. Therefore we recommend to proceed the cascade screening.

Treatment of unipolar psychotic depression: a randomized, double-blind study comparing imipramine, venlafaxine, and venlafaxine plus quetiapine.

OBJECTIVE: It remains unclear whether unipolar psychotic depression should be treated with an antidepressant and an antipsychotic or with an antidepressant alone. METHOD: In a multi-center RCT, 122 patients (18-65 years) with DSM-IV-TR psychotic major depression and HAM-D-17 > or = 18 were randomized to 7 weeks imipramine (plasma-levels 200-300 microg/l), venlafaxine (375 mg/day) or venlafaxine-quetiapine (375 mg/day, 600 mg/day). Primary outcome was response on HAM-D-17. Secondary outcomes were response on CGI and remission (HAM-D-17). RESULTS: Venlafaxine-quetiapine was more effective than venlafaxine with no significant differences between venlafaxine-quetiapine and imipramine, or between imipramine and venlafaxine. Secondary outcomes followed the same pattern. CONCLUSION: That unipolar psychotic depression should be treated with a combination of an antidepressant and an antipsychotic and not with an antidepressant alone, can be considered evidence based with regard to venlafaxine-quetiapine vs. venlafaxine monotherapy. Whether this is also the case for imipramine monotherapy is likely, but cannot be concluded from the data.

Pharmacological treatment for psychotic depression.

BACKGROUND: Regarding the pharmacological treatment of psychotic depression there is uncertainty about the effectiveness of an antidepressant alone compared to the combination of an antidepressant and an antipsychotic. OBJECTIVES: To compare the clinical effectiveness of pharmacological treatments for patients with a psychotic depression: antidepressant monotherapy, antipsychotic monotherapy, and the combination of an antidepressant and an antipsychotic, compared with each other and/or with placebo. SEARCH STRATEGY: (1) The Cochrane Central Register of Controlled Trials (CENTRAL) was screened with the terms depressive disorder and drug treatment (April 2004). (2) MEDLINE (1966 to April 2004) and EMBASE (1980 to April 2004) were searched using terms with regard to treatment of unipolar psychotic depression.(3) Reference lists of related reviews and reference lists of all identified studies were searched.(4) Personal communications. SELECTION CRITERIA: All randomised controlled trials (RCTs) with patients with major depression with psychotic features as well as RCTs with patients with major depression with or without psychotic features which reported on the subgroup of patients with psychotic features separately. DATA COLLECTION AND ANALYSIS: Two reviewers assessed the methodological quality of the included studies, according to the Cochrane Handbook criteria. Data were entered into RevMan 4.2.5. We used intention-to-treat data. For dichotomous efficacy outcomes, the relative risk with 95% confidence intervals (CI) was calculated. For continuously distributed outcomes, it was not possible to extract data from the RCTs. Regarding the primary harm outcome, only overall drop-out rates were available for all studies. MAIN RESULTS: The search identified 3333 abstracts, but only 10 RCTs with a total of 548 patients could be included in the review. Due to clinical heterogeneity, few meta-analyses were possible. We found no conclusive evidence that the combination of an antidepressant and an antipsychotic is more effective than an antidepressant alone (two RCTs; RR 1.44, 95% CI 0.86 to 2.41), but a combination is more effective than an antipsychotic alone (three RCTs; RR 1.92, 95% CI 1.32 to 2.80). There were no statistically significant differences in the overall drop-out rates between any of the treatments, neither in individual studies nor after pooling of studies. AUTHORS' CONCLUSIONS: Treatment with an antipsychotic alone is not a good option. Starting with an antidepressant alone and adding an antipsychotic if the patient does not respond or starting with the combination of an antidepressant and an antipsychotic both appear appropriate options for patients with psychotic depression. In clinical practice the balance between risks and benefits suggests that initial antidepressive monotherapy and adding an antipsychotic if there is inadequate response should be the preferred treatment strategy for many patients. The general lack of available data limits confidence in the conclusions drawn.

Relapse prevention in major depressive disorder after successful ECT: a literature review and a naturalistic case series.

OBJECTIVE: Medication-resistance in major depressive disorder (MDD) may be related to high relapse rates after successful ECT when continued medication (C-MED) is used to prevent relapse. An alternative could be to continue ECT (C-ECT). METHOD: Patients with medication-resistant MDD responding to ECT were offered C-ECT without medication. Follow-up was 6 months. Publications from a literature search were screened against prespecified criteria. RESULTS: With C-ECT the 6-month relapse-rate was 50% (6/12, 95% CI:21-79) in our medication-resistant group. In the review we found with C-ECT 29% (7/24,CI:13-51) in 'unknown' medication resistance and no data about medication-resistant depression. With C-MED at 6 months: no data were found concerning medication-resistant depression, 28% (35/124,CI:20-36) in 'unknown' resistance and 13% (2/15,CI:2-41) in non-resistance. With C-MED at 12 months, 73% (16/22,CI:50-90), 50% (16/32,CI:32-68) and 27% (8/30,CI:12-46) were found, respectively. CONCLUSION: The efficacy of C-MED is related negatively to medication resistance before ECT. This may also be the case for C-ECT. Further studies with C-ECT are urgently needed.