Relapse Prevention in Major Depressive Disorder After Successful Acute Electroconvulsive Treatment: a 6-month Double-blind Comparison of Three Fixed Dosages of Escitalopram and a Fixed Dose of Nortriptyline - Lessons from a Failed Randomised Trial of the Danish University Antidepressant Group (DUAG-7).

INTRODUCTION: Electroconvulsive treatment (ECT) is an effective treatment for severe depression but carries a risk of relapse in the following months. METHODS: Major depressive disorder patients in a current episode attaining remission from ECT (17-item Hamilton Depression Rating Scale (HAM-D17) score≤9) received randomly escitalopram 10 mg, 20 mg, 30 mg or nortriptyline 100 mg as monotherapies and were followed for 6 months in a multicentre double-blind set-up. Primary endpoint was relapse (HAM-D17≥16). RESULTS: As inclusion rate was low the study was prematurely stopped with only 47 patients randomised (20% of the planned sample size). No statistically significant between-group differences could be detected. When all patients receiving escitalopram were compared with those receiving nortriptyline, a marginal superiority of nortriptyline was found (p=0.08). One third of patients relapsed during the study period, and one third completed. DISCUSSION: Due to small sample size, no valid efficacy inferences could be made. The outcome was poor, probably due to tapering off of non-study psychotropic drugs after randomisation; this has implications for future study designs. ClinicalTrials.gov Identifier: NCT00660062.

Relationship between mood and TSH response to TRH stimulation in bipolar affective disorder.

Moderate to severe depression and mania are associated with a reduced thyroid stimulating hormone (TSH) response to TSH releasing hormone (TRH). Continued reduction of this response after clinical recovery seems indicative of early relapse. The aim of the present study was to test the relationship between mild changes in mood and the TSH response to TRH stimulation in patients with bipolar affective disorder. Nineteen outpatients with bipolar affective disorder were followed prospectively for three years. Every third month, mood symptoms were rated using the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Bech-Rafaelsen Mania Scale (BRMS). A TRH test was performed in connection with each rating session (IV injection of 200 microg TRH), and serum TSH was measured at 0, 20, and 60 min. The maximum TSH response (D-max TSH) and the temporal change in D-max TSH between succeeding rating sessions (DD-max TSH) were determined. Psychometric rating and TRH data were obtained for a total of 198 examinations. The temporal change in mood symptom rating score was negatively correlated with the temporal change in D-max TSH, thus suggesting that increasing severity of mood symptoms was related to a reduced TSH response to TRH stimulation. The temporal change in TSH response to TRH stimulation correlated with the actual score on an overall index of symptom severity. In conclusion, milder fluctuations in mood in bipolar affective disorder seem to correlate with the TSH response to TRH stimulation: Increasing severity of mood symptoms seems to be associated with reduced TSH response.

[Abnormal neurological findings at first admission in patients with schizophrenia or schizophreniform disorders. Results of computer tomography and measurement of regional cerebral blood flow]. / Neurologiske abnormfund hos førstegangsindlagte patienter med skizofreni eller skizofreniform forstyrrelse. Sammenhoeng med resultater af computertomografi og måling af regional cerebral blodgennemstrømning.

Forty-five patients with schizophrenia or schizophreniform disorder admitted to hospital for the first time had a neurological examination, including integrative sensory and complex motor acts, by a trained neurologist. The patients were studied by CT and regional cerebral blood flow as well. A control group of 24 healthy volunteers was included. The patients had significantly more neurological abnormalities (NA) than the healthy volunteers. Medication did not explain the discrepancy. The NA were associated with sulcal enlargement and smaller brains as visualized by CT but not with ventricular enlargement. There was no association between the regional flow values and NA.

Neurological abnormalities in patients with schizophrenia or schizophreniform disorder at first admission to hospital: correlations with computerized tomography and regional cerebral blood flow findings.

Forty-five patients with schizophrenia or schizophreniform disorder admitted to hospital for the first time had a neurological examination, including integrative sensory and complex motor acts, by a trained neurologist. The patients were studied by CT (computerized tomography) and rCBF (regional cerebral blood flow) as well. A control group of 24 healthy volunteers was included. The patients had significantly more neurological abnormalities (NA) than the healthy volunteers. Medication did not explain the discrepancy. The NA were associated with sulcal enlargement and smaller brains as visualized by CT but not with ventricular enlargement. There was no association between the regional flow values and NA.

Regional cerebral blood flow distribution in newly diagnosed schizophrenia and schizophreniform disorder.

Regional cerebral blood flow distribution (rCBF) in 24 first admissions with schizophrenia or schizophreniform disorder and in 17 healthy volunteers was examined. Single photon emission computed tomography with a brain-retained tracer, technetium-99m-d,l-hexamethyl-propylene amine oxime, was used to study subjects under resting conditions and during performance of the Wisconsin Card Sorting Test. The study is a replication of a previous investigation in an independent series of patients and healthy volunteers. The patients had significantly lower relative blood flow in prefrontal regions during activation than did the healthy volunteers. An earlier series of 19 patients and 7 healthy volunteers was studied using exactly the same procedure. Analyses of the combined samples from the two studies (43 patients and 24 healthy volunteers) showed the patients to have significantly lower relative flow in prefrontal regions both at rest and during activation and higher flow in the left striatum during activation. The same finding emerged when analyses were confined to drug-naive patients and patients educationally matched to the healthy volunteers. The study suggests a defective frontostriatal interrelationship in schizophrenia and schizophreniform disorder.

Post-stroke depression: combined treatment with imipramine or desipramine and mianserin. A controlled clinical study.

In a 6-week study the efficacy of combined treatment of imipramine plus mianserin was compared to combined treatment of desipramine plus mianserin in patients with post-stroke depression. Patients were required to have a minimum baseline total score of 15 on the 17-item Hamilton Depression Scale (HAMD). The Melancholia Scale (MES) was also used to measure severity of depressive states to show that somatic symptoms had little influence on the evaluation of depression. Out of 120 stroke patients screened, 20 patients fulfilled the inclusion criteria. The doses of the drugs were flexible, using side-effects as a guide during treatment. Both intention to treat analysis and efficacy data (excluding patients who had dropped out during the first 2 weeks of treatment) showed that imipramine (mean dose 75 mg daily) plus mianserin (mean dose 25 mg daily) was superior to desipramine (mean dose 66 mg daily) plus mianserin (27 mg daily). The MES was found to be more sensitive than the HAMD for measuring change in depressive states during treatment. The assessment of side-effects using the UKU scale showed good tolerance in general. The only difference between the two treatment groups was seen in micturition disturbances, where the imipramine treated patients had most complaints after 14 days of treatment, but the symptoms disappeared despite continuous treatment.

Altered modulation of prefrontal and subcortical brain activity in newly diagnosed schizophrenia and schizophreniform disorder. A regional cerebral blood flow study.

To measure prefrontal and subcortical activity during a cognitive task, we examined 19 newly diagnosed schizophrenics and patients with schizophreniform psychosis. Seven healthy volunteers served as controls. The patients were drug naive or had received neuroleptics for a few days only. Cerebral blood flow distribution was depicted by single photon emission computed tomography at rest and during activation with the Wisconsin Card Sorting Test. A significant relative activation deficit in the left inferior-prefrontal region was revealed during the Wisconsin Card Sorting Test in the patient group. Furthermore, the patients had impaired striatal suppression on the left side during the cognitive task. The test performance was significantly impaired in the patients. The inability to reduce striatal activity may be due to a lack of corticostriatal feedback during prefrontal activation.

[Chronic subdural hematoma. A frequently suspected diagnosis]. / Kronisk subduralt haematom. En hyppigt mistaenkt diagnose.

A retrospective investigation was undertaken in which the clinical picture in 43 patients in whom chronic subdural haematoma (CSH) was diagnosed during a period of 11 years in a large central hospital were compared with the clinical picture in 97 patients referred for neurological assessment on account of suspected CSH during a period of three years. Thirteen out of the 97 patients referred with suspected CSH had the disease. All of the patients with CSH had focal neurological symptoms or complained of headache. None presented only mental symptoms and/or impaired consciousness. On this basis, the diagnosis could have been repudiated in 30% of the patients referred who presented neither focal neurological symptoms nor complained of headache. Information about previous head-injury was not found to be of any significant value for the diagnosis. Probably, no or only few cases of CHS are overlooked.

Effect rates of different modalities for treatment of prolactin adenomas.

Results of treatment of 963 patients with prolactin adenomas described in the literature were reviewed. The patient population was stratified into four subgroups: women and men with serum prolactin levels above and below 100 ng/ml for each of the treatment modalities: transsphenoidal surgery, bromocriptine, heavy ion radiation, conventional radiation, and transsphenoidal surgery plus conventional radiation. The five largest series within each subgroup were included. Success rates and recurrence rates were calculated for: (1) reduction of tumor size, (2) normalization of serum prolactin levels, and (3) normalization of other pituitary functions. Complication rates were calculated for procedural impairment of other pituitary functions. Transsphenoidal surgery was found to be the most effective treatment for lasting control, and bromocriptine for temporary control, of prolactin adenomas. Recurrent adenomas were most effectively treated by transsphenoidal surgery if serum prolactin levels were below 100 ng/ml. If serum prolactin levels were above 100 ng/ml, bromocriptine was the most effective treatment. Heavy ion radiation, with success rates comparable to those of transsphenoidal surgery and bromocriptine, but with lower recurrence rates, may eventually prove the most effective treatment of all.