Comparison of moclobemide with selective serotonin reuptake inhibitors (SSRIs) on sexual function in depressed adults. The Australian and German Study Groups.

OBJECTIVE: To compare the emergent sexual effects of moclobemide and selective serotonin reuptake inhibitors (SSRIs) during acute and maintenance therapy in routine practice. METHOD: 268 patients were evaluated for sexual function at baseline, 6 weeks, 3 and 6 months of treatment using physician ratings and self-rating questionnaires. Patients received moclobemide, an reversible monoamine oxidase A inhibitor (RIMA), or a SSRI (fluoxetine, fluvoxamine, paroxetine, sertraline). RESULTS: Baseline values were similar in all groups. Incidences of impairments of sexual functioning with treatment, whether clinically relevant or not, were 24.3% with moclobemide and 61.5% with SSRIs (physician ratings), with no significant tolerance to these effects. There was a suggestion of differences between the SSRIs in their specific dysfunctions they cause. SSRIs (21.6% of patients) had about ten times the moclobemide rate (1.9%) of sexual dysfunction reported as adverse events. Antidepressant efficacy was comparable between treatments. CONCLUSION: In patients for whom sexual function is important or sexual dysfunction is present, moclobemide should be considered a first line antidepressant.     

A double-blind comparison of moclobemide and toloxatone in out-patients presenting a major depressive disorder

A double-blind comparison of moclobemide and toloxatone was performed in adult out-patients diagnosed as suffering from a major depressive disorder. Parallel groups of patients received moclobemide, 450 mg/day (n=135) or toloxatone, 1000 mg/day (n=133) for 28 days. Both groups showed a significant clinical improvement while on therapy; the response was most marked and rapid in those receiving moclobemide treatment. Improvement was greatest in those patients with the most severe depression at the time of trial onset. A significantly higher number of patients returned to normal sleep patterns following moclobemide treatment than following toloxatone. Overall, tolerance was rated as good or very good in more than 80% of patients. The most frequent complaints in the moclobemide-treated group were hot flushes, dry mouth, constipation and headache, while an increase in anxiety was associated with toloxatone usage. Moclobemide was found to be as effective as toloxatone in the treatment of major depressive episodes, but with the advantages of improved sleep patterns and reduced anxiety.     

Moclobemide: therapeutic use and clinical studies

Moclobemide is a reversible inhibitor of monoamine-oxidase-A (RIMA) and has been extensively evaluated in the treatment of a wide spectrum of depressive disorders and less extensively studied in anxiety disorders. Nearly all meta-analyses and most comparative studies indicated that in the acute management of depression this drug is more efficacious than placebo and as efficacious as tricyclic (or some heterocyclic) antidepressants or selective serotonin reuptake inhibitors (SSRIs). There is a growing evidence that moclobemide is not inferior to other antidepressants in the treatment of subtypes of depression, such as dysthymia, endogenous (unipolar and bipolar), reactive, atypical, agitated, and retarded depression as with other antidepressants limited evidence suggests that moclobemide has consistent long-term efficacy. However, more controlled studies addressing this issue are needed. For patients with bipolar depression the risk of developing mania seems to be not higher with moclobemide than with other antidepressants. The effective therapeutic dose range for moclobemide in most acute phase trials was 300 to 600 mg, divided in 2 to 3 doses. While one controlled trial and one long-term open-label study found moclobemide to be efficacious in social phobia, three controlled trials subsequently revealed either no effect or less robust effects with the tendency of higher doses (600 - 900 mg/d) to be more efficacious. Two comparative trials demonstrated moclobemide to be as efficacious as fluoxetine or clomipramine in patients suffering from panic disorder. Placebo-controlled trials in this indication are, however, still lacking. A relationship between the plasma concentration of moclobemide and its therapeutic efficacy is not apparent but a positive correlation with adverse events has been found. Dizziness, nausea and insomnia occurred more frequently on moclobemide than on placebo. Due to negligible anticholinergic and antihistaminic actions, moclobemide has been better tolerated than tri- or heterocyclic antidepressants. Gastrointestinal side effects and, especially, sexual dysfunction were much less frequent with moclobemide than with SSRIs. Unlike irreversible MAO-inhibitors, moclobemide has a negligible propensity to induce hypertensive crisis after ingestion of tyramine-rich food ("cheese-reaction"). Therefore, dietary restrictions are not as strict. However, with moclobemide doses above 900 mg/d the risk of interaction with ingested tyramine might become clinically relevant. After multiple dosing the oral bioavailability of moclobemide reaches almost 100%. At therapeutic doses, moclobemide lacks significant negative effects on psychomotor performance, cognitive function or cardiovascular system. Due to the relative freedom from these side effects, moclobemide is particularly attractive in the treatment of elderly patients. Moclobemide is a substrate of CYP2C19. Although it acts as an inhibitor of CYP1A2, CYP2C19, and CYP2D6, relatively few clinically important drug interactions involving moclobemide have been reported. It is relatively safe even in overdose. The drug has a short plasma elimination half-life that allows switching to an alternative agent within 24 h. Since it is well tolerated, therapeutic doses can often be reached rapidly upon onset of treatment. Steady-state plasma levels are reached approximately at one week following dose adjustment. Patients with renal dysfunction require no dose reduction in contrast to patients with severe hepatic impairment. Cases of refractory depression might improve with a combination of moclobemide with other antidepressants, such as clomipramine or a SSRI. Since this combination has rarely been associated with a potentially lethal serotonin syndrome, it requires lower entry doses, a slower dose titration and a more careful monitoring of patients. Combination therapy with moclobemide and other serotonergic agents, or opioids, should be undertaken with caution, although no serious adverse events have been published with therapeutic doses of moclobemide to date. On the basis of animal data the combined use of moclobemide with pethidine or dextropropoxyphene should be avoided. There is no evidence that moclobemide would increase body weight or produce seizures. Some preclinical data suggest that moclobemide may have anticonvulsant property.     

Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity

AIMS: To investigate the spectrum of toxicity of moclobemide overdose, the occurrence of serotonin toxicity, and to estimate toxicokinetic parameters. METHODS: All moclobemide overdoses presenting over a 10-year period to the Hunter Area Toxicology Service were reviewed. Clinical features, complications, length of stay (LOS) and intensive care (ICU) admission rate were extracted from a standardized, prospectively collected database. Comparisons were made between moclobemide alone and moclobemide with a serotonergic coingestant poisoning. Serotonin toxicity was defined by a combination of Sternbach's criteria and a clinical toxicologist's diagnosis. In five patients serial moclobemide concentrations were measured. Time to maximal plasma concentration (Tmax), peak plasma concentration (Cmax) and terminal elimination half-lives were estimated. RESULTS: Of 106 included patients, 33 ingested moclobemide alone, 21 ingested moclobemide with another serotonergic agent (in some cases in therapeutic doses) and 52 ingested moclobemide with a nonserotonergic agent. Eleven (55%) of 21 patients coingesting a serotonergic drug developed serotonin toxicity, which was significantly more than one (3%) of 33 moclobemide-alone overdoses (odds ratio 35, 95% confidence interval 4, 307; P < 0.0001). In six of these 21 cases severe serotonin toxicity developed with temperature >38.5 degrees C and muscle rigidity requiring intubation and paralysis. The 21 patients had a significantly increased LOS (34 h) compared with moclobemide alone overdoses (12 h) (P < 0.0001) and a significantly increased ICU admission rate of 57% vs. 3% (P < 0.0001). Time to peak plasma concentration was delayed in two patients where prepeak samples were obtained. Cmax increased slightly with dose, but all three patients ingesting > or = 6 g vomited or had charcoal. The mean elimination half-life of moclobemide in the five patients in whom serial moclobemide concentrations were measured was 6.3 h and elimination was first order in all cases. There was no evidence of a dose-dependent increase in half-life. CONCLUSIONS: The effects of moclobemide alone in overdose are minor, even with massive ingestions. However, moclobemide overdose in combination with a serotonergic agent (even in normal therapeutic doses) can cause severe serotonin toxicity. The elimination half-life is prolonged by two to four times in overdose, compared with that found in healthy volunteers given therapeutic doses. This may be a result of wide interindividual variation in overall elimination, also seen with therapeutic doses, but appears not to be due to saturation of normal elimination pathways.     

Use of moclobemide in children with attention deficit hyperactivity disorder

A monoamine oxidase hypothesis for the cause of attention deficit hyperactivity disorder has recently been established (Shekim et al. 1986). To test this, moclobemide, a new and reversible inhibitor of monoamine oxidase-A, was administered to 12 children between the ages of 6 and 13 years, diagnosed as attention deficit hyperactive according to DSM III-R, in a 4-week study. All had previously discontinued treatment with methylphenidate due to side-effects. A 40% improvement in parental assessment of children's behaviour occurred among those who received moclobemide as outpatients, and a 31% improvement among the five in-patients. There was a general increase in concentration and attention span at the end of the trial, but mood changes and explosive behaviour continued to be present at a low level. Brain mapping after moclobemide treatment showed an overall reduction in frontal lobe delta activity. Moclobemide was well tolerated by these patients, although two complained of mild gastrointestinal disturbances during the first week of therapy.     

Tyramine pressor sensitivity in healthy subjects during combined treatment with moclobemide and selegiline

Objective: The objectives of this double-blind study were to assess the tolerability and i.v. tyramine pressor response during combined treatment with moclobemide and selegiline. Subjects: Two parallel groups of 12 healthy male and female subjects were treated with 200 mg moclobemide or 5 mg selegiline b.d. for 14 days. On Day 7, selegiline or moclobemide was added to the other treatment. IV tyramine pressor tests were conducted at baseline and at steady state during mono- and combined treatment. Results: Treatment with moclobemide and selegiline alone was well tolerated, whereas combined treatment led to a slight increase in adverse events. Tyramine pressor sensitivity during moclobemide, selegiline and moclobemide + selegiline treatment was enhanced, on average, by 2.4-, 1.3- and 8.4-times, respectively. Conclusion: Although combined treatment with moclobemide and selegiline was well tolerated, the supra-additive potentiation of the tyramine pressor effects means that dietary restriction of tyramine intake will be necessary during such combination therapy.     

Moclobemide,a new reversible MAO inhibitor — interaction with tyramine and tricyclic antidepressants in healthy volunteers and depressive patients

Moclobemide is a new, short-acting, reversible MAOI, preferentially affecting type A MAO. We have studied the interaction of moclobemide with tyramine and tricyclic antidepressants in healthy volunteers and depressive patients.Neither tyramine capsules (50 mg) nor cheese and wine meals (65 mg tyramine) produced a significant change in blood pressure and heart rate after single or repeated doses of moclobemide in volunteers. In contrast, after 1 weeks' treatment with tranylcypromine pressure response to cheese and wine meals was severe. Blood pressure sensitivity to IV tyramine was slightly increased (1.5–2 fold;P<0.05 versus predrug) during moclobemide treatment in patients and volunteers. This increase was neutralised by concomitant administration of desipramine in volunteers. Amitriptyline was well tolerated when given to patients after or together with moclobemide.In conclusion, moclobemide appears relatively safe with respect to tyramine sensitivity and interaction with tricyclics.     

Effects of moclobemide on sexual performance and nocturnal erections in psychogenic erectile dysfunction

RATIONALE AND OBJECTIVES: We tested the hypothesis that the selective reversible MAO-A inhibitor moclobemide has a specific therapeutic effect on erectile dysfunction independent of its antidepressive properties. METHODS: In a double-blind placebo controlled study, 12 male outpatients suffering from psychogenic erectile dysfunction without any other psychiatric disorder were investigated. Based on comprehensive diagnosis before the beginning of the study, organic factors relevant for sexual function were excluded. The treatment period was 8 weeks. Half the patients received 450 mg moclobemide during the first week, and 600 mg afterwards; the others received placebo. Apart from assessment of erectile function by means of the Clinical Global Impression (CGI) scale, nocturnal erections were measured under polysomnographic control at baseline and at the end of the treatment period. RESULTS: The evaluation of the CGI scale revealed a clearly stronger improvement under moclobemide compared to placebo during the study period. The therapeutic efficacy found on the subjective level had no clear correlate on the neurophysiological level. No alterations of nocturnal erectile parameters were obvious under treatment, neither were clinically relevant alterations found regarding sleep EEG parameters. The medication was well tolerated without serious adverse events. CONCLUSIONS: The findings support the hypothesis that moclobemide has a specific effect on erectile dysfunction. Thus, patients suffering from psychogenic erectile dysfunction who are not depressed might benefit from moclobemide without relevant side effects.     

A double-blind comparison of moclobemide and amineptine in the treatment of depressed out-patients

A randomised, double-blind, multicentre study was performed to compare the effects of moclobemide and amineptine in the treatment of endogenous depression in out-patients. Ninety patients received moclobemide, 450 mg/day and 94 received amineptine 200 mg/day in two parallel groups, over a trial period of 8 weeks. At the end of 4 weeks doses could be reduced to 300 mg/day, moclobemide and 100 mg/day, amineptine if required. All evaluated patients showed a significant clinical improvement during treatment, but no significant difference occurred between the groups. When patients were asked to assess the benefit of their treatment, 76% thought their condition had improved following moclobemide therapy, compared to 53% of those receiving amineptine. Both drugs were well tolerated, and over 60% of patients reported no side-effects. Moclobemide appeared to be as effective as amineptine in the treatment of these patients, and was significantly better tolerated.     

Moclobemide treatment causes a substantial rise in the sparteine metabolic ratio. Danish University Antidepressant Group.

A sparteine test was carried out immediately before (n = 37) and during (n = 33) moclobemide treatment (200 mg twice daily) in 37 patients participating in a controlled clinical trial. The sparteine metabolic ratio (MR) did not correlate with the plasma concentration of moclobemide and/or its oxidized metabolite Ro 12-8095, and four sparteine poor metabolisers (PM, MR > 20) had plasma moclobemide concentrations similar to those in extensive metabolisers (EM, MR < 20). The Ro 12-8095/moclobemide ratio tended to correlate negatively with the sparteine MR before and during treatment (rs = -0.32, -0.37). During moclobemide treatment the sparteine MR rose substantially by a factor of 1-103 (median 4.7), and two EM became phenotypically PM. In the PM subjects as well as in one EM patient on cimetidine during both tests, no change in sparteine MR occurred.     

Moclobemide is effective and well tolerated in the long-term pharmacotherapy of social anxiety disorder with or without comorbid anxiety disorder

Social phobia (social anxiety disorder) is a highly prevalent and chronic disorder that is associated with significant comorbidity and disability. Despite recent advances in the pharmacotherapy of the disorder, there is a paucity of randomized controlled trials on patients with comorbid disorders and on maintenance treatment. A randomized placebo-controlled, double-blind multi-site trial of moclobemide, a reversible inhibitor of monoamine oxidase A, was undertaken with 390 subjects. After an initial 12 weeks, there was the option of continuing for an additional 6 months of treatment. The primary efficacy parameter chosen was responder status as defined by the Clinical Global Impression scale change item. From week 4 onwards, there was a significantly higher response rate on moclobemide than on placebo. Superiority of medication over placebo was similar in patients with comorbid anxiety disorders (33% of subjects) and without, as well as in patients with different subtypes of social anxiety disorder; indeed, treatment with moclobemide rather than placebo was the strongest predictor of response. Adverse events were similar across treatment groups, and were typically mild and transient. In the extension phase, response rates remained higher in the moclobemide group, and ratings of tolerability were equally high in both groups. Thus, in a large sample of social anxiety disorder patients with and without comorbid anxiety disorders, moclobemide was both effective and well-tolerated in the short as well as long-term. These data confirm and extend previous findings on the value of moclobemide in the treatment of social anxiety disorder, and strengthen the range of therapeutic options for managing this important disorder.     

A 12-week study comparing moclobemide and sertraline in the treatment of outpatients with atypical depression

One hundred and ninety-seven outpatients with atypical depression [Atypical Depression Diagnostic Scale (ADDS) score=4] were randomized to 12 weeks of double-blind treatment with sertraline or moclobemide in a multicentre, parallel-group clinical trial. Patients were started on either 50 mg/day sertraline or 300 mg/day moclobemide. If the therapeutic response was not satisfactory after 4 weeks, the dose could be increased to either 100 mg/day sertraline or 450 mg/day moclobemide. Primary efficacy evaluations were the 29-item Hamilton Psychiatric Rating Scale for Depression (HAM-D) and the Clinical Global Impression of Improvement (CGI-I) response rate (much or very much improved) at study endpoint. Secondary efficacy evaluations included the ADDS, the Hamilton Anxiety Scale (HAMA), the Leeds Sleep Scale, and the Battelle Quality of Life Battery (BQOLB). In the analysis of the 172 patient efficacy-evaluable population, there was significant baseline to endpoint improvement in all primary and secondary efficacy assessments after treatment with either sertraline or moclobemide. At the endpoint, the proportion of responders on CGI-I, was 77.5% in the sertraline group and 67.5% in the moclobemide group (p=0.052). The baseline to endpoint mean 29-item HAM-D score decreased from 35.9 to 14.5 in the sertraline group and from 36.3 to 16.1 in the moclobemide group. Sertraline also resulted in a significantly (p < 0.05) greater degree of improvement at the endpoint, compared with moclobemide, in the proportion of remitters on the HAMA (total score < or = 7), ADDS Category IID (Rejection Sensitivity), Leeds Sleep Factor 4 (Integrity of Behaviour Following Awakening), and on three dimensions of the BQOLB (Energy/Vitality, Social Interaction and Life Satisfaction). There were no other significant differences between treatment groups. Overall, both medications were well tolerated. In this study, both sertraline and moclobemide improved the symptoms of atypical depression.     

Effect of a novel monoamine-oxidase inhibitor, moclobemide on the sensitivity to intravenous tyramine and norepinephrine in humans

This study compared the effects of moclobemide (Ro11-1163), a selective and reversible inhibitor of monoamine-oxidase (MAOI) type A and phenelzine, an irreversible non-selective MAOI, on the pressor responses to IV tyramine and norepinephrine. Because of the reversibility of this inhibition, the pressor effect of tyramine was expected to be minimal. Twelve healthy men participated in this randomized double-blind, placebo-controlled, crossover study. Volunteers began with oral treatment of moclobemide (100 mg TID) or phenelzine (15 mg TID) for 1 week followed by placebo treatment for 2 weeks and then moclobemide or phenelzine treatment for another week. The tyramine and norepinephrine challenge tests were conducted at baseline and then at weekly intervals, for a total of five challenges. The average tyramine dose that was required to increase systolic blood pressure by 25 mm Hg (PD25) was 1.6 +/- 0.2 mg after moclobemide treatment, which was lower (P less than .01) than the baseline value of 3.6 +/- 0.7 mg and that after phenelzine (3.0 +/- 0.5 mg) treatment. Moclobemide did not influence norepinephrine sensitivity. In conclusion, moclobemide mildly decreased the sensitivity to IV tyramine as compared with placebo and phenelzine.     

A comparison of moclobemide, amitriptyline and placebo in depression: a Canadian multicentre study

In a 7-week prospective multicentre study, the efficacy, tolerability and safety of moclobemide were compared to those of amitriptyline and placebo in parallel groups of out-patients (n=173) fulfilling the DSM III-R criteria for a major depressive episode. Participants were required to have a minimum baseline total score of 18 on the 17-item Hamilton Depression Rating Scale (HAMD). After a 1-week placebo washout, patients were randomly allocated to the three treatment groups. Assessment of efficacy, as judged by the number of responders achieving a 50% reduction in HAMD score by the end of treatment, showed that both moclobemide and amitriptyline were significantly superior to placebo, but that they were not significantly different from each other. Both treatments differed significantly from placebo with respect to the Physician's Global Assessment of Efficacy (very good or good response: moclobemide 57%, amitriptyline 60% and placebo 35%). Assessment of tolerance as judged by the spontaneous reporting of adverse events showed a significant superiority of moclobemide over amitriptyline, but there was no significant difference between moclobemide and placebo. At termination of the study, amitriptyline patients showed a significant elevation of heart rate both supine (10.8 beats/min) and standing (15.5 beats/min), as well as significant weight gain (1.7 kg), but no changes were seen in the moclobemide or placebo groups. In conclusion, both moclobemide and amitriptyline were found to be more effective than placebo in the treatment of depression, while moclobemide had fewer side effects.     

Treatment of depression with comorbid anxiety disorders: differential efficacy of paroxetine versus moclobemide

To compare the efficacy and tolerability of moclobemide versus paroxetine for the treatment of depression with comorbid anxiety disorders. Outpatients fulfilling DSM-III-R criteria for major depression or dysthymia and for a co-occurring comorbid anxiety disorder (panic disorder, generalized anxiety disorder or obsessive-compulsive disorder) after a 1-week run-in phase were randomly assigned to open-label moclobemide (300-600 mg/day) or paroxetine (20-40 mg/day) for 4 months. Primary criterion for response was a 50% score reduction from baseline on Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scores. Mean changes in Clinical Global Impressions Severity of Illness and Improvement Scales (CGI-I) were also used to evaluate treatment response. Of the 123 patients included in the study, 65 were randomly assigned to moclobemide and 58 to paroxetine. At study end, the two treatment groups did not differ significantly in terms of proportion of responders. Treatment group differences emerged when comorbid anxiety diagnoses were considered. In patients with comorbid panic disorder, paroxetine was superior to moclobemide in improving both anxiety and depression (five patients out of 18 in the moclobemide group and nine out of 14 in the paroxetine group were rated as responders according to CGI-I, P = 0.04). Neither medication was superior in treating comorbid generalized anxiety disorder. These findings indicate that both moclobemide and paroxetine are effective for treatment of depression with comorbid anxiety disorders. However, in the subgroup with comorbid panic disorder, paroxetine is more effective than moclobemide in reducing both depressive and anxiety symptoms.     

Efficacy of citalopram and moclobemide in patients with social phobia: some preliminary findings

The efficacy of irreversible and reversible monoamine oxidase inhibitors (MAOIs) in the treatment of social phobia (SP) is well established. Recently, selective serotonin reuptake inhibitors (SSRIs) have been used more frequently. In the present study, the efficacy and side-effect profile of citalopram, an SSRI, and moclobemide, the only MAOI used in Turkey, were compared. The 71 patients diagnosed with SP according to DSM-III-R were randomly assigned to two subgroups; citalopram (n = 36) or moclobemide (n = 35). The study was an 8-week, randomized, open-label, rater-blinded, parallel-group trial. All patients were assessed by Hamilton anxiety rating (HAM-A), Liebowitz social anxiety (LSAS), clinical global impression-severity of illness (CGI-SI) and clinical global impression-improvement (CGI-I) scales. There was a similar percentage of responders (citalopram 75%, n = 27 and moclobemide 74.3%, n = 26), with a >50% or greater reduction in LSAS total score and ratings of "very much" or "much improved" on the CGI-I. None of the patients withdrew from the study. The results of the present study suggest that citalopram has shown promising results in patients with SP.     

The effects of moclobemide on the pharmacokinetics of the 5-HT1B/1D agonist rizatriptan in healthy volunteers

AIMS: The new 5-HT1B/1D agonist rizatriptan (MK-0462) has recently been registered for the treatment of migraine. Its primary route of metabolism is via monoamine oxidase-A (MAO-A). Antidepressants such as the MAO-A inhibitor moclobemide may be used in patients with chronic headache syndromes. Hence, this study aimed to investigate the interactions between rizatriptan and moclobemide. METHODS: In a double-blind, randomized, placebo-controlled, two-period cross-over study 12 healthy, young volunteers (six males, six females) were treated with moclobemide (150 mg twice daily) or placebo for 4 days. On the fourth day, a single dose of rizatriptan (10 mg) was administered, and subsequently blood and urine samples were collected for assay of rizatripan and N-monodesmethyl rizatriptan. Plasma concentrates of 3,4-dihydroxyphenylglycol (DHPG), a marker of MAO-A inhibition, were also assessed. Supine and standing blood pressure were measured regularly. RESULTS: Both treatments were well tolerated. During moclobemide, the increase in supine diastolic blood pressure following rizatriptan administration was augmented. Inhibition of MAO by moclobemide was inferred from a persistent decrease in DHPG level (43% on average). When rizatriptan was coadministered with moclobemide, the area under the plasma drug concentration-time profiles for rizatriptan and its N-monodesmethyl metabolite increased 2.2-fold (90% CI, 1.93-2.47) and 5.3-fold (90% CI, 4.81-5.91), respectively, when compared with placebo. Peak plasma drug concentrations for rizatriptan and its n-monodesmethyl metabolite increased 1.4-fold (90% CI, 1.11-1.80) and 2.6-fold (90% CI, 2.23-3.14), respectively, and half-lives of both were prolonged. CONCLUSIONS: Moclobemide inhibited the metabolism of rizatriptan and its active N-monodesmethyl metabolite through inhibition of MAO-A. Thus, moclobemide may considerably potentiate rizatriptan action. Concurrent administration of moclobemide and rizatriptan is not recommended.     

Combined SSRI-RIMA treatment in refractory depression safety data and efficacy

Eighteen patients with refractory depression (dysthymia with superimposed major depression) were treated with a combination of fluvoxamine and moclobemide for 6 weeks and compared with 18 patients treated with fluvoxamine only. Both groups had improved only slightly after 8 weeks of TCA treatment and 6 weeks of SSRI treatment. Two main observations can be made concerning safety and efficacy. Firstly, side effects in the SSRI-RIMA group were minimal. Secondly, the SSRI-RIMA combination treatment significantly improved depression in refractory depressed patients, with a decrease in depression of about 40%. The SSRI mono-therapy group also significantly improved, though only by about 20%, indicating that positive effects of SSRI treatment may still develop even after 12 weeks of treatment. In conclusion, the study gives further support to the hypothesis that SSRI-RIMA combinations may be safe and well tolerated. This treatment may also offer some therapeutic advantages in at least some patients who have not responded to conventional pharmacological treatment.     

Inhibition of monoamine oxidase by moclobemide: effects on monoamine metabolism and secretion of anterior pituitary hormones and cortisol in healthy volunteers.

1. Single oral doses (100, 200 and 300 mg) of moclobemide, a reversible inhibitor of monoamine oxidase (MAO) with predominant effects on the A-type of the enzyme, were administered to eight young, healthy male volunteers in a double-blind, random-order, placebo-controlled study. The investigation was thereafter continued in an open fashion by administering a single 10 mg dose of the MAO-B inhibitor deprenyl to the same subjects. 2. Deamination of catecholamines was powerfully and dose-dependently inhibited by moclobemide, as evidenced by up to 40% decreases in the urinary excretion of deaminated catecholamine metabolites, corresponding increases in the excretion of non-deaminated, methylated metabolites, and up to 79% average decreases in the plasma concentration of 3,4-dihydroxyphenylglycol (DHPG), a deaminated metabolite of noradrenaline (NA), and up to 75% average decreases in the plasma concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC), a deaminated metabolite of dopamine. The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) was only slightly reduced. In contrast, deprenyl, in a dose which almost totally inhibited MAO-B activity in blood platelets, did not appreciably affect the plasma concentrations of DHPG or DOPAC. 3. Due to the rapid, reversible, dose-dependent and MAO-A specific effect of moclobemide on plasma concentrations of DHPG, it is suggested that DHPG in plasma may be a useful indicator of the magnitude and duration of MAO-A inhibition in man. 4. Sympatho-adrenal function at rest was not significantly altered by moclobemide, as judged by unchanged plasma catecholamine concentrations and stable blood pressure and heart rate recordings. 5. Monoamine oxidase type B activity in blood platelets was slightly (less than 30%) and transiently inhibited after moclobemide. 6. The secretion of prolactin was dose-dependently stimulated by moclobemide, whereas the plasma concentrations of growth hormone (hGH) and cortisol remained unchanged.