Safety of high-intensity treatment with the irreversible monoamine oxidase inhibitor tranylcypromine in patients with treatment-resistant depression.

INTRODUCTION: Because the irreversible monoamine oxidase inhibitor tranylcypromine (TCP) was introduced nearly 50 years ago, only few studies exist on today's clinical prescribing practice together with 2nd and 3rd generation psychotropic drugs. METHODS: We performed a practice-based observational study of patients with depression treated with TCP in two psychiatric departments in Berlin to assess side effects, effectiveness, comedication and acceptance of the low-tyramine diet. RESULTS: We identified thirty-two patients treated with TCP at a mean dose of 51.9 mg/day after an average of 3.3 pre-treatments in the current episode. Dosing of TCP and the use of multiple psychotropic comedications indicate a high-intensity treatment. The most frequent side effects resulted from arterial hypotonia (28%). Dietary restrictions were mainly rated as moderate. 59% of patients remitted (HAMD- (21)<9 or CGI-I=1) and 22% responded (HAMD- (21) reduction >50% or CGI-I=2). DISCUSSION: A high-intensity treatment of inpatients with TCP is clinically feasible, i.e., the use of high doses and multiple comedications with a good benefit-risk-ratio. Prospective data aiming at comparisons with modern antidepressants and clarifying further safety issues are warranted.

Lithium augmentation in treatment-resistant depression: clinical evidence, serotonergic and endocrine mechanisms.

For now more than 50 years, lithium has been the gold standard for the pharmacologic treatment of bipolar disorder. However, its utility is not restricted to acute mania and prophylactic treatment of bipolar disorder. A relatively new indication for its use is the addition to an antidepressant in the acute treatment phase of unipolar major depression. To date, this treatment approach called lithium augmentation is the best-documented approach in the treatment of refractory depression. In international treatment guidelines and algorithms, lithium augmentation is considered a first-line treatment strategy for patients with a major depressive episode who do not adequately respond to standard antidepressant treatment. In a recent double-blind, placebo-controlled trial, lithium augmentation has demonstrated to also be effective in the continuation treatment phase to prevent early relapses. From animal studies there is robust evidence that lithium augmentation increases serotonin (5-HT) neurotransmission, possibly by a synergistic action of lithium and the antidepressant on brain 5-HT pathways. In contrast to the established decline of HPA system activity during treatment with tricyclic antidepressants, neuroendocrine studies on the effects of lithium augmentation on the HPA system showed an unexpected and marked increase in the ACTH and cortisol response in the combined DEX/CRH test. Here we review new data on the efficacy and mechanism of action of lithium augmentation.

Influence on serum lipids, lipoproteins and blood pressure of mackerel and herring diet in patients with type IV and V hyperlipoproteinemia.

Eight patients with type IV and V hyperlipoproteinemia were put on a mackerel and herring diet of an isocaloric regimen for 2 weeks, in a cross-over design. At the end of the dietary periods a predominant increase of eicosapentaenoic acid (EPA - C20:5, n-3) in cholesterol esters and of docosahexaenoic acid (DHA - C22:6, n-3) in serum triglycerides, being more pronounced after mackerel as compared to herring diet, could be confirmed. After mackerel diet serum triglycerides and total cholesterol were significantly lower, returning to basal levels 3 months later. High density lipoprotein (HDL) cholesterol appeared slightly increased after mackerel diet and decreased to initial values thereafter. After herring diet, which contained half as much EPA as compared to mackerel diet, the differences were minor. The decline of free fatty acids (FFA) and insulin at the end of the mackerel period reached the level of significance 60 min and 120 min, respectively, after glucose load. A significantly lower systolic blood pressure in recumbent and upright position after the mackerel period could be found, whereas diastolic pressure and blood pressure after herring diet remained unchanged.