Depression moclobemide

In a controlled multicenter study of 115 in-patients with relatively severe depression, moclobemide was better tolerated but had a weaker therapeutic effect than clomipramine. Nine of the patients taking moclobemide withdrew owing to worsening of depression and suicidality, although it is possible that the dosage of moclobemide (400 mg/day) was inadequate (SEDA-18, 15). 

Moclobemide in conventional doses (300-600 mg/day) does not significantly potentiate the pressor effects of oral tyramine, and special dietary restrictions are therefore not usually necessary. However, higher doses of moclobemide are sometimes used to treat patients with resistant depression. Moclobemide 900 mg/day and 1200 mg/day have been compared with placebo in 12 healthy volunteers (35). Neither dose of moclobemide significantly potentiated the pressor effect of 50 mg of... 

Fewer adverse effects were reported among moclobemide-treated patients compared with selective serotonin reuptake inhibitor (SSRI)-treated patients. Since moclobemide does not induce orthostatic hypotension, does not possess anticholinergic properties, and is not cardiotoxic, it is very well suited among the MAOIs for the treatment of depression. Moclobemide has limited potential to elicit a hypertensive crisis, because the pressor effect of tyramine from food is only marginally potentiated compared with tranylcypromine. The pressor effect of tyramine is normalized within 3 days of cessation of treatment with moclobemide. The combination of SSRIs and moclobemide has good efficacy in cases of refractory depression, but there is controversy as to whether toxic side-effects such as serotonin syndrome can result from this combination. Currently, more studies are needed before this combination can be recommended. Acute overdose with MAOIs causes agitation, hallucinations, hyperpyrexia, hyperreflexia, convulsions, and death. The most dangerous MAOIs in overdose are the irreversible non-selective MAOIs. T2s-27... 

Few data are available about paroxetine interactions with MAOIs, even though they might be similar to those of other selective serotonin reuptake inhibitors (SSRIs). Clinically significant or severe interactions have not been found to date. Administered together in patients with depression, moclobemide and paroxetine or fluoxetine appeared to produce adverse effects indicative of potentiated serotonergic activity. 

Maprotiline, Moclobemide, Mianserin, Fluoxetine (Prozac), Paroxetine, Sertraline, Fluvoxamine, Citalopram, Venlafaxin (generic IR formulation and the brand Venlafaxine XR), Mirtazapine, Flupentixol-melitracen (Deanxit), Tianeptine, Extract of St. John s Wort, Buspirone Depression and anxiety... 

Inside the cytoplasm of the presynaptic neuron the monoamines are exposed to the mitochondrial outer membrane-bound enzyme monoamine oxidase (MAO). MAO breaks the monoamines down into inactive metabolites before they are taken up into the vesicles. However, if MAO is inhibited, then the monoamines enter the vesicles and are available for release. MAO inhibitors, such as moclobemide, have been used in the treatment of depression, since they increase the availability of noradrenaline and serotonin. Selegiline is used for Parkinson s disease, since it raises dopamine levels. 

Larsen, J. K., Gjerris, A., Holm, P. etal. Moclobemide in depression a randomized, multicentre trial against isocar-boxazide and clomipramine emphasizing atypical depression. Acta Psychiatr. Scand. 84 564-570,1991. 

These mediators probably play significant roles in CNS functions consistent with the stimulant effects of MAO inhibitors on mood and psychomotor drive and their use as antidepressants in the treatment of depression (A). Tranylcypromine is used to treat particular forms of depressive illness as a covalently bound suicide substrate, it causes long-lasting inhibition of both MAO isozymes, (MAOa, MAOb). Moclobemide reversibly inhibits MAOa and is also used as an antidepressant. The MAOb inhibitor selegiline (deprenyl) retards the cat-obolism of dopamine, an effect used in the treatment of parkinsonism (p. 188). 

The pharmacological inhibition of the serotonin eliminating enzyme MAO is used in the therapy of depression and hypertension. Tranylcypromine is an irreversible unselective MAO inhibitor which displays numerous interactions with amine-containing food and monoamine-related drugs, resulting in evenmally fatal hypertensive crisis, cranial hemorrhage, arrhythmias and seizure can occur. The coadministration with speciflc serotonin reuptake inhibitors (SSRI) can result in similar effects and is therefore contraindicated. Moclobemide, on the other hand, is a reversible inhibitor of MAOa, one of the two enzyme subtyppes (MAOa, MAOb) which is void of most interactions see with tranylcypromine. 

Muller DJ, Schulze TG, Macciardi F, et al (2002) Moclobemide response in depressed patients association study with a functional polymorphism in the monoamine oxidase A promoter. Pharmacopsychiatry 35 157-158... 

Therapeutic efficacy by selective MAO-A inhibitors (such as clorgyline or moclobemide) in major depressions strongly suggests that MAO inhibition at central serotonin or norepinephrine synapses or both is responsible for the antidepressant properties of these agents. However, since complete MAO-A inhibition is achieved clinically within a few days of treatment, while the antidepressant effects of these drugs are not observed for 2 to 3 weeks, suggests that additional actions must be involved. 

Versiani, M., Amrein, R., and Stahl, M. (1997) Moclobemide and imiptamine in chtonic depression (dysthymia) an international double-blind, placebo-controlled trial. International Collaborative Study Gtoup. Int Clin Psychopharmacol 12 183-193. 

Those patients presenting with atypical symptoms of depression (i.e., rejection-sensitivity, hypersomnia, hyperphagia, and hysteroid personality types] were confirmed as a unique subgroup responsive to MAOls including phenelzine (Liebowitz et al. 1988]. There are indications that atypical symptomatology may also be responsive to the RlMAs such as moclobemide (Lonnqvist et al. 1994 Paykel 1995] however, results are preliminary. 

London E, Fanelh RJ, Kimes A, et al Effects of chronic nicotine on cerebral glucose utilization in the rat. Brain Res 520 208-214, 1990 Lonnqvist J, Sihvo S, Syvalahti E, et al Moclobemide and fluoxetine in atypical depression a double-blind trial. J Affect Disord 32 169-177, 1994 Loo H, Malka R, Defance R, et al Tianeptine and amitriptyline controlled double-blind trial in depressed alcoholic patients. Neuropsychobiology 19 79-85, 1988... 

Montgomery SA, Brown RE, Clark M Economic analysis of treating depression with nefazodone v. imipramine. Br J Psychiatry 168 768-771, 1996 Monti JM Effect of a reversible monoamine oxidase-A inhibitor (moclobemide) on sleep of depressed patients. Br J Psychiatry Suppl 155 61-65, 1989 Monti JM, Alterwain P, Monti D The effects of moclobemide on nocturnal sleep of depressed patients. J Affect Disord 20 201-208, 1990 Montkowski A, Holsboer F Absence of cognitive and memory deficits in transgenic mice with heterozygous disrupt of the brain-derived neurotrophic factor gene. J Psychiatr Res [in press)... 

Stassen HH, Angst J, DeHni-Stula A Severity of baseline and onset of improvement in depression metanalysis of imipramine and moclobemide versus placebo. European Psychiatry 9 (suppl 3) 129-136, 1994... 

The side effects of antidepressants, sometimes very unpleasant, olten lead patients to interrupt their treatment or to reduce the drug dose, which involves a great risk in view of the high relapse rate and danger of suicide in depression. The newer antidepressants, such as trazodone, fluoxetine and other SSRIs and moclobemide, are characterized by better tolerability and lower toxicity and are therefore preferred in the treatment of outpatients and elderly patients (Rudorfer and Potter, 1989). A detailed list of general and specific common side effects associated with the newer generation of antidepressants is seen in Table 1.7. 

In depression, serotoninergic and/or noradrenergic neurotransmission is assumed to be deficient. One of the approaches to increase the availability of these neurotransmitters is to inhibit the activity of MAO, the enzyme involved in the degradation of serotonin and noradrenaline. Older drugs such as phenelzine and recently also moclobemide are representatives of this therapeutic approach used in some forms of depression. 

Results of crossover studies indicate that lithium is efficacious in treating acute depression in bipolar subjects unequivocally (36%, 29/80) and partially (43%. 34/80). respectively (Xomberg and Pope, 1993 Keck and McElroy, 2002). Various antidepressants have shown variable rates of efficacy in the treatment of acute bipolar depression, i.e. desipramine (50%), maprotiline (67%), imipra-mine (40 60%), tranylcypromine (87%), moclobemide (53%) and fluoxetine (60%) (Keck and McElroy, 2002). Among the anticonvulsants, valproic add and lamotrigine appear to have some potential efficacy in the treatment of acute bipolar depression (Calabrese et al., 1992, 1999 Fatemi et al., 1997). 

Gattaz WF, Vogel P, Kick H, et al. Moclobemide versus fluoxetine in the treatment of inpatients with major depression. J din Psychopharmacoi 1995 15[Suppl 2] 35S-40S. 

The side effects and cardiotoxicity of the tricyclic antidepressants have been discussed in detail elsewhere in this volume and, while there is ample evidence of their therapeutic efficacy, it seems difficult to justify their use, particularly in a group of patients who are most vulnerable to their detrimental side effects. Of the newer antidepressants, the reversible inhibitors of monoamine oxidase type A such as moclobemide may also be of value in the elderly depressed patient, particularly in those patients who fail to respond to the amine uptake inhibitor type of antidepressant. 

Angst, J., Scheidegger, P., Stabl, M. 1993, Efficacy of moclobemide in different patient groups. Results of new subscales of the Hamilton Depression Rating Scale, Clin.Neuropharmacol., vol. 16, suppl. 2, pp. S55-S62. 

Inhibitors of monoamine oxidase A (thy-meretics). Moclobemide is the only representative of this group. It produces a reversible inhibition of MAOa, which is responsible for inactivation of the amines norepinephrine, dopamine, and serotonin (A). Enzyme inhibition results in an increased concentration of these neurotransmitters in the synaptic cleft. Moclobemide is less effective as an antidepressant than as a psychomotor stimulant. It is indicated only in depressions with extreme psychomotor slowing and is contraindicated in patients at risk of suicide. 

Fitton A, Faulds D, Goa KL. Moclobemide. A review of its pharmacological properties and therapeutic use in depressive illness. Drugs 1992 43(4) 561-96. 

In a multicenter comparison of moclobemide, amitriptyline, and placebo, gastrointestinal discomfort, headache, and dizziness occurred in over 20% of moclobemide-treated patients insomnia was also common (10). In healthy volunteers there were no effects of moclobemide on psychomotor performance. Acute confusion and agitation was reported in one patient who dropped out of a clinical trial owing to this adverse effect (SEDA-16, 7). Hypomania was attributed to moclobemide in two cases (SEDA-17, 16). Aggressive behavior and mild manic symptoms were described in severely depressed patients, refractory to other treatments, who took moclobemide (SEDA-18, 15). 

Versiani M, Oggero U, Alterwain P, Capponi R, Dajas F, Heinze-Martin G, Marquez CA, Poleo MA, Rivero-Almanzor LE, Rossel L, et al. A double-blind comparative trial of moclobemide v. imipramine and placebo in major depressive episodes. Br J Psychiatry Suppl 1989 6 72-7. 

Realini R, Mascetti R, Calanchini C. Efficacite et tolerance du moclobemide (Ro 11-1163 Aurorix) en comparaison avec la maprotiline chez des patients ambulatoires presen-tant un episode depressif majeur. [Effectiveness and tolerance of moclobemide (Ro 11-1163 Aurorix) in comparison with maprotiline in ambulatory patients presenting with a major depressive episode.] Psychol Med 1989 21 1689. 

Laux G. Moclobemid in der Depressionsbehandlung - eine Ubersicht. [Moclobemide in the treatment of depression -an overview.] Psychiatr Prax 1989 16(Suppl 1 ) 37—40. 

Koczkas C, Holm P, Karlsson A, Nagy A, Ose E, Petursson H, Ulveras L, Wenedikter O. Moclobemide and clomipramine in endogenous depression. A randomized clinical trial. Acta Psychiatr Scand 1989 79(6) 523-9. 

Baumhackl U, Biziere K, Fischbach R, Geretsegger C, Hebenstreit G, Radmayr E, Stabl M. Efficacy and tolerability of moclobemide compared with imipramine in depressive disorder (DSM-III) an Austrian double-blind, multicentre study. Br J Psychiatry Suppl 1989 6 78-83. 

Bakish D, Bradwejn J, Nair N, McClure J, Remick R, Bulger L. A comparison of moclobemide, amitriptyline and placebo in depression a Canadian multicentre study. Psychopharmacology (Berl) 1992 106(Suppl) S98-S101. 

Amrein R, Martin JR, Cameron AM. Moclobemide in patients with dementia and depression. Adv Neurol 1999 80 509-19. 

Monoamine oxidase (MAO) enzymes have an important function in modulating the intraneuronal content of neurotransmitter. The enzymes exist in two principal forms, A and B, defined by specific substrates some of which cannot be metabolised by the other form (Table 20.3). The therapeutic importance of recognising these two forms arises because they are to some extent present in different tissues, and the enzyme at these different locations can be selectively inhibited by the individual inhibitors moclobemide for MAO-A (used for depression, p. 379) and selegiline for MAO-B (Table 20.3). 

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