Enhancer antidepressant effect

The combination of traditional antidepressant drugs (e.g., imipramine) and uncompetitive NMDA receptor antagonists (e.g., memantine) may produce enhanced antidepressive effects as a result of synergism. This observation may be of particular importance for the treatment of antidepressant-resistant patients. Most interesting was the observation that fluoxetine, which was inactive in the forced swimming test in rats when given alone, showed a positive effect when combined with memantine (2.5 and 5 mg/kg). 

Modulation of second-messenger pathways is also an attractive target upon which to base novel antidepressants. Rolipram [61413-54-5] an antidepressant in the preregistration phase, enhances the effects of noradrenaline though selective inhibition of central phosphodiesterase, an enzyme which degrades cycHc adenosiae monophosphate (cAMP). Modulation of the phosphatidyl iaositol second-messenger system coupled to, for example, 5-HT,, 5-HT,3, or 5-HT2( receptors might also lead to novel antidepressants, as well as to alternatives to lithium for treatment of mania. Novel compounds such as inhibitors of A-adenosyl-methionine or central catechol-0-methyltransferase also warrant attention. 

You might find some of this material tough going, and if you are willing to take my word for the significance of these factors, you could just skip over these parts. But I thought it important to document my claims about how placebos work. Just as I have documented my claim that most of the antidepressant drug response is a placebo effect and that the remainder is in all likelihood an enhanced placebo effect, so here, too, I present the details of the research upon which my conclusions about the way placebos work are based. 

Mechanism of Action A tetracyclic compound that blocks reuptake norepi nephri ne by CNS presynaptic neuronal membranes, increasing availability at postsynaptic neuronal receptor sites, and enhances synaptic activity. Therapeutic Effect Produces antidepressant effect, with prominent sedative effects and low anticholinergic activity. Pharmacokinetics Slowly and completely absorbed after PO administration. Protein binding 88%. Metabolized in liver by hydroxylation and oxidative modification. Excreted in urine. Unknown if removed by hemodialysis. Half-life 27-58 hr. 

Similar to the discovery of other psychiatric medications, the mood-enhancing effects of monoamine oxidase inhibitors (MAOIs) were identified serendipi-tously mood improvements were observed in patients with tuberculosis treated with iproniazid (Bloch et ah, 1954) The early enthusiasm for the MAOIs was based on significant and unprecedented antidepressant effects and the link between antidepressant efficacy and their... 

The role of dopamine is discussed more thoroughly in Finder, Chapter 14, in this volume. Several antidepressants are thought to have enhanced antidepressant action attributed to extra effects on the dopamine system. Bupropion, which is available as an antidepressant in the United States only, has an indirect effect on dopamine. An appropriate minimum effective dose was not established in the early clinical trial development program, and the rather high doses used in clinical practice may have contributed to the number of reports of convulsions. The rate, which is acceptable at lower doses of 450 mg/day, rises to unacceptable levels at higher doses [J. A. Johnston et al. 1991). 

A body of literature indicates that thyroid hormones are effective as adjuncts to antidepressants and that they enhance antidepressant activity, accelerate rate of response, and decrease treatment resistance. The accumulated literature is convincing that 25-50 mg of T3 is very effective as an adjunct to TGA when added to TGA nonresponders [Aronson et al. 1996]. Of special interest is the short period, 1 week, that is necessary for the T3... 

The antidepressant effect of agents that enhance dopamine transmission... 

The abiiity of various ciasses of antidepressants and ECS to enhance dopamine effects in animal models Interactional Theories of Depression... 

ECT enhances the production and reiease of severai neuropeptides (including insulin), some of which have demonstrated transient antidepressant effects (e.g., thyrotropin-releasing hormone). 

Stimulants should not be mixed with antidepressants, which may enhance the effects of a stimulant or with OTC cold medicines containing decongestants, which may cause blood pressure to become dangerously high or may lead to irregular heart rhythms. 

Marek, G. J., Martin-Ruiz, R., Abo, A. Artigas, F. (2005). The selective 5-HT2A receptor antagonist Ml00907 enhances antidepressant-like behavioral effects of the SSRI fluoxetine. Neuropsychopharmacology, 30, 2205-2215. 

Correct answer = D. MAO inhibitors and aspirin can be taken concurrently. Hypertensive crisis may result from use (concurrently or within 2 weeks) of MAO inhibitors and indirect sympathomimetic amines, such as ephedrine. Concomitant use of MAO inhibitors and tricyclic antidepressants may result in mutual enhancement of effects with the possibility of hyperpyrexia, hypertension, seizures and death. Tyramine-containing foods, such as aged cheeses and beer, may precipitate a hypertensive crisis because of the accumulation and release of stored catecholamines from nerve endings. MAO inhibitors may lead to an exaggerated response to dopamine. 

Treatment with bright light is used for mood disorders, and it has been suggested that antidepressants, which may act as photosensitizers, could enhance the effect of bright light on the eye, giving rise to adverse effects (SEDA-18, 17). 

Reduced effect of sublingual nitrates Increased plasma concentrations of tricyclic drugs Possible potentiation and/or increased speed of onset of antidepressant effect Enhanced cardiotoxic effects with thioridazine... 

There is a great deal of evidence that deficiency of serotonin (5-hydroxytryptamine) is a factor in depressive illness, and many antidepressant drugs act to decrease its catabolism or enhance its interaction with receptors. A key enzyme involved in the synthesis of serotonin (and the catecholamines) is aromatic amino acid decarboxylase, which is pyridoxal phosphate-dependent. Therefore, it has been suggested that vitamin Be deficiency may result in reduced formation of the neurotransmitters and thus be a factor in the etiology of depression. Conversely, it has been suggested that supplements of vitamin Be may increase aromatic amino acid decarboxylase activity, and increase amine synthesis and have a mood-elevating or antidepressant effect. There is little evidence that vitamin Be deficiency affects the activity of aromatic amino acid decarboxylase. In patients with kidney failure, undergoing renal dialysis, the brain concentration of pyridoxal phosphate falls to about 50% of normal, with no effect on serotonin, catecholamines, or their metabolites (Perry etal., 1985). 

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