Effects of imipramine, fluvoxamine and depressive mood on autonomic cardiac functioning in major depressive disorder

OBJECTIVE: Diminished HR variability is considered to be associated with depression and the increased risk of cardiovascular disease. The pharmacological effects of antidepressants and depressive mood itself may contribute to alterations in autonomic cardiac functioning, but a limited amount of data is available. We studied the effects of two different types of antidepressant treatments (imipramine and fluvoxamine), in addition to the effect of depressive mood, on the cardiovascular system in depressed patients. METHODS: Depressed inpatients were studied during a drug-free period and after 4 weeks of adequate treatment with imipramine (n = 17) or fluvoxamine (n = 24). Heart rate variability, blood pressure variability, and a baroreflex sensitivity index during supine rest and orthostatic challenge were analyzed by means of spectral techniques to obtain noninvasive parameters of sympathetic and parasympathetic activity. RESULTS: Both imipramine and fluvoxamine reduced sympathetic and parasympathetic activity, although the effects of imipramine were much more pronounced. Severity of depression was positively related to mean levels of heart rate and blood pressure in the total patient group. There was no convincing evidence that these relationships differed between depressed patients treated with imipramine and those treated with fluvoxamine. CONCLUSION: Our findings suggest that alterations in mean heart rate and blood pressure in depressed patients after antidepressant treatment are the result of a combined effect of pharmacological actions of antidepressants and improvement of depressive mood state. The present study did not confirm the relationship between clinical state and cardiovascular variability or baroreflex sensitivity.     

Effect of electroconvulsive therapy on biopterin and large neutral amino acids in severe, medication-resistant depression.

Biopterin, neopterin and the large neutral amino acids (LNAA), i.e. phenylalanine, tyrosine, tryptophan, isoleucine, leucine and valine were measured in plasma of 20 severely depressed inpatients before and after a course of electroconvulsive therapy (ECT). These patients showed a significantly lower plasma biopterin concentration at baseline in comparison with healthy controls. After treatment an increase in biopterin was found, which was statistically significant in the depressed patients with psychotic features. The plasma phenylalanine-tyrosine ratio, which previously increased, normalised after ECT. Mean tryptophan concentration was lower in depressed patients than in normal controls. The patients who responded to ECT showed an increase in the tryptophan concentration and its ratio (tryptophan/LNAA) after treatment. Our results suggest that ECT increases biopterin, which probably results in synthesis of amino acids, especially tyrosine. Furthermore, ECT seems to increase cerebral tryptophan availability because of less tryptophan catabolism parallel with biopterin activation. More research is required to see if biopterin could be useful as a biological marker for the depressive state in this subgroup of patients, because this compound seems to play an important role in the etiology and treatment of depression.     

24-Hour motor activity after treatment with imipramine or fluvoxamine in major depressive disorder.

Psychomotor dysfunction in depression is related to alterations in the 24-h pattern of motor activity. After antidepressant treatment the diurnal pattern may be changed due to improvement of clinical state or pharmacological actions. The purpose of this study was to evaluate in 52 depressed in-patients the effects of imipramine (tricyclic antidepressant) and fluvoxamine (SSRI) on the 24-h motor activity. Motor activity was monitored by wrist-actigraphy during a medication-free period and after 4 weeks of treatment. Clinical improvement was not different after imipramine or fluvoxamine treatment. The Hamilton depression score decreased in patients treated with imipramine, as well as in patients treated with fluvoxamine. The clinical retardation score was also reduced in both treatment groups. However, patients treated with imipramine showed higher motor activity levels during the wake period in comparison to the medication-free period, and more fragmentation of motor activity during sleep. Treatment with fluvoxamine did not result in alterations in the 24-h pattern of motor activity. The improvement of depressive mood and retardation seems to play a minor role in the change of the pattern of motor activity after imipramine.     

Towards an objective quantitative assessment of daily functioning in migraine: a feasibility study

Migraine is a chronic disabling disorder, with migraine episodes significantly reducing quality of life and leading to impaired functioning (physically, socially, emotionally) both at home and at work. We explored whether ambulatory accelerometry can be used as an objective method to quantify the behavioral aspects of migraine-related disability. Four body mounted uni-axial piezo-resistive accelerometers were used to quantify the time spent in different body postures (lying, sitting, standing), physical activities (walking, cycling) and a general index of body motility during eight migraine attacks and subsequent recovery periods of six patients in their habitual environment. The migraine attacks and recovery periods could be monitored after about 1 h, which was the time required for the investigator to travel to the patient and for the sensors to be attached. In order to quantify the influence of a migraine episode on daily activities, we also performed measurements during a headache-free baseline period of the same patients. Overall, the procedures functioned well, indicating that ambulatory accelerometry measurements before, during and after a migraine attack are feasible to perform. Furthermore, our quantitative data revealed that migraine always influenced behavior by reducing overall body motility and that, dependent upon the severity of the attack, the effectiveness of acute treatment and the time of day, the time spent in various body positions, dynamic activities, and the number of postural transitions were affected. This feasibility study showed that ambulatory accelerometry can provide the objective behavioral effect parameters for the evaluation of migraine and its treatment on daily functioning in the habitual environment of migraine patients.     

The number of admissions to Dutch hospitals for barbiturate poisoning from 1981-1989 and those for poisoning with sedatives and hypnotics,and benzodiazepines]

Over the period 1981 to 1989, the number of admissions to Dutch general hospitals for barbiturate poisoning has dropped sharply and steadily, due to a more restrictive policy in prescribing regarding these sedatives. This trend is also present concerning poisoning with sedatives and hypnotics in general (ICD-code 967), but not concerning those with benzodiazepines (ICD-code 969.4). The female-male ratio was nearly 2:1. This difference is possibly due to the fact that females take more medication than males.     

Impaired glycine-serine conversion and increased plasma taurine levels in episodic psychotic patients with psychedelic symptoms

A disturbance of serine-glycine metabolism has been demonstrated in patients suffering from episodic acute psychosis, characterized by sensory perceptual distortions in whom oral loading with either serine or glycine induced psychedelic symptoms. Fasting plasma amino acid levels in oral serine-responsive patients were compared with those in glycine-responsive and manic-depressive patients. Only serine-responsive patients had a decreased plasma serine and increased plasma taurine concentration, while glycine responsive patients showed decreased alanine and manic-depressive patients an increased plasma glycine level. Amino acid analyses of plasma samples obtained after serine loading in patients and controls suggest that serine-responsive patients had an impaired conversion of glycine into serine. The results suggest that the higher plasma taurine level in serine-responsive patients is caused by an increased synthesis of taurine from homocysteine and serine. The limiting capacity of methyltetrahydrofolate-homocysteine methyltransferase coupled to increased formation of taurine may be responsible for the serine-evoked psychotic syndrome.     

Nitric oxide and neopterin in bipolar affective disorder

BACKGROUND: There is an increasing interest in the role of nitric oxide (NO) and pterines in the pathophysiology of neuropsychiatric disorders. The results so far show an inconsistent pattern. METHODS: In the present study, neopterin and a measure of NO synthesis in plasma of symptomatic and euthymic bipolar affective patients were compared to those of patients with a major depression and healthy controls. As an index of NO synthesis, the ratio of the amino acids citrulline and arginine (Cit-Arg ratio) was calculated. Neopterin is a bypass product in the synthesis of tetrahydrobiopterin, which is a cofactor of NO synthase. RESULTS: The results indicate that both neopterin and the Cit-Arg ratio are decreased in bipolar affective patients, irrespective of their symptomatic status. In addition, an association between the values of the Cit-Arg ratio and the neopterin level was observed, which is suggestive for a low tetrahydrobiopterin activity. CONCLUSION: NO formation may be endangered in bipolar affective disorder.