Acute and chronic treatment with moclobemide, a reversible MAO-inhibitor, potentiates the antielectroshock activity of conventional antiepileptic drugs in mice.

BACKGROUND: Due to enhancing serotonergic and noradrenergic neurotransmission, moclobemide may influence seizure phenomena. In this study, we examined the effect of both acute and chronic treatment with moclobemide on seizures and the action of first-generation antiepileptic drugs: valproate, carbamazepine, phenobarbital and phenytoin. METHODS: The effect of moclobemide on seizures was assessed in the electroconvulsive threshold test, while its influence on antiepileptic drugs was estimated in the maximal electroshock test in mice. Undesired effects were evaluated in the chimney test (motor impairment) and step-through passive-avoidance task (long-term memory deficits). Finally, brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay. RESULTS: Given acutely, moclobemide at 62.5 and 75 mg/kg increased the electroconvulsive threshold. In contrast, chronic treatment with moclobemide up to 75 mg/kg did not influence this parameter. Acute moclobemide applied at subthreshold doses (up to 50 mg/kg) enhanced the antielectroshock effects of carbamazepine, valproate and phenobarbital. Chronic moclobemide (37.5-75 mg/kg) increased the action of all four antiepileptic drugs. All revealed interactions, except these between moclobemide and phenobarbital, seem to have pharmacokinetic nature, because the antidepressant drug, either in acute or in chronic treatment, increased the brain concentrations of respective antiepileptic drugs. In terms of undesired neurotoxic effects, acute and chronic moclobemide, antiepileptic drugs, and their combinations did not produce significant motor or long-term memory impairment. CONCLUSIONS: Acute and chronic therapy with moclobemide can increase the effectiveness of some antiepileptic drugs against the maximal electroshock test. In mice, this effect was, at least partially, due to pharmacokinetic interactions. So far as the results of experimental studies can be transferred to clinical conditions, moclobemide seems safe for the application in patients with epilepsy and depression. Possibly, in the case of certain antiepileptic drugs combined with moclobemide, their doses should be adjusted downwards.

Uncovering the potential risk of serotonin toxicity in Australian veterans using pharmaceutical claims data.

AIMS: We examined potential risk of serotonin toxicity in Australian veterans by quantifying the concomitant use of serotonergic medicine combinations from claims data collected by the Department of Veterans' Affairs (DVA). METHODS: This was a retrospective cohort study of 273 228 Australian veterans, war widows, widowers and dependents aged >or=55 years and holding full treatment entitlement for the period July 2000 to June 2004 or until death. The main outcome measure was potential concomitant use, estimated as the number of cohort members with an overlap in days of supply for serotonergic medicine combinations over the 4 year period for all medicine combinations and potentially life threatening combinations. RESULTS: From July 2000 to June 2004, 115 969 (42%) cohort members were dispensed at least one serotonergic medicine. 20 658 (8%) had at least one episode of potential concomitant use. We identified 1811 (0.7%) cohort members with at least one overlapping period of potentially life-threatening serotonergic medicine combinations, 937 of whom had the combinations dispensed within the recommended washout period. Three hundred and seventeen of these individuals were dispensed potentially life-threatening medicine combinations on the same day. The most common combinations were moclobemide with a selective serotonin reuptake inhibitor or tramadol. CONCLUSIONS: The individuals potentially at risk of mild to moderate serotonin toxicity were considerable and potentially life threatening combinations were not infrequent. While we were unable to determine how many individuals experienced serotonin toxicity this study indicates, for the first time, the potential size of the problem in a subgroup of elderly Australians. Clinicians and patients need to be vigilant regarding inadvertent concomitant use, especially that of moclobemide with a selective serotonin reuptake inhibitor or tramadol.

A comparative study of fluoxetine, moclobemide, and tianeptine in the treatment of posttraumatic stress disorder following an earthquake.

PURPOSE: Although antidepressant drugs have been proven as an effective treatment for posttraumatic stress disorder (PTSD), there are few comparative studies of antidepressants that are acting on different neurotransmitters. The main aim of this study is to compare the efficacy of different class of antidepressant drugs on the PTSD. SUBJECTS/MATERIALS AND METHODS: In this open label study, the patients who met DSM-IV criteria for PTSD were randomly assigned to flexible doses of fluoxetine, moclobemide, or tianeptine. After the first assessment, consecutive assessments were performed at the end of weeks 2, 4, 8, and 12 using clinician administered PTSD scale (CAPS) and Clinical Global Impression of Severity (CGI-S). Changes in the total score of CAPS and sub-scale scores of symptom clusters (re-experience, avoidance, and hyperarousal) were the main output of efficacy. All statistics were based on intention-to-treat and last-observation-carried-forward (LOCF) principles. RESULTS: Thirty-eight patients were assigned to fluoxetine, 35 patients were assigned to moclobemide, and 30 patients were assigned to tianeptine group. Gender distributions and mean ages of the treatment groups were not significantly different. Drop-out rates due to an adverse events or unknown reasons were not significantly different among fluoxetine (18.4%), moclobemide (14.3%), and tianeptine (20.0%) groups. All three treatments has led to a significant improvement in PTSD severity assessed with CAPS total score (ANOVA P < 0.001). Similarly, total scores of re-experiencing, avoidance, and hyperarousal clusters that are subscales of CAPS were significantly reduced by all three treatments (with ANOVA all P values < 0.001). There was not significant difference in terms of treatment effect between three groups. DISCUSSION: Treatment groups showed very similar improvement on all ratings scales. The findings support that fluoxetine, moclobemide, and tianeptine are all effective in the treatment of PTSD. Different mechanisms of action for these antidepressant drugs might result in the same common neurochemical end point. However, further studies using different classes of antidepressant drugs are needed.

Combined treatment with corticosteroids and moclobemide favors normalization of hypothalamo-pituitary-adrenal axis dysregulation in relapsing-remitting multiple sclerosis: a randomized, double blind trial.

Hyperresponsiveness of the hypothalamo-pituitary-adrenal (HPA) axis in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system, is presumably due to diminished corticosteroid receptor function. It probably influences the immune response, but its clinical significance is not clear. Similar HPA dysregulation occurs in depression and is reversible with successful antidepressant treatment. We conducted a double blind, placebo-controlled trial to evaluate the neuroendocrine effect of cotreatment with the antidepressant moclobemide as an adjunct to oral corticosteroids in MS. Twenty-one patients with definite relapsing-remitting MS (11 females, aged 33.9 +/- 2.0 yr; Expanded Disability Status Scale score of neurological impairment, 2.0--6.5) in acute relapse were treated with placebo (n = 13) or 300 mg moclobemide (reversible monoamine oxidase A inhibitor; n = 8) for 75 days. All received oral fluocortolone from day 7 on, and the dose was tapered until day 29. Effects were evaluated using the combined dexamethasone-CRH test and clinically on days 1, 30, and 75. At baseline, the HPA axis was mildly activated, comparably for treatment groups [area under the curve for cortisol (AUC-Cort), 213.8 +/- 76.8 arbitrary units in the moclobemide group vs. 225.8 +/- 65.1 in the steroid alone group; mean +/- SEM]. In a group of healthy controls with comparable demographic characteristics, the AUC-Cort was 107.4 +/- 14.1. Moclobemide cotreatment resulted in normalization of the HPA axis response, whereas the HPA system hyperresponse was maintained with steroids alone (AUC-Cort on day 30, 85.9 +/- 22.8 vs.177.1 +/- 68.5; on day 75, 111.0 +/- 46.0 vs. 199.2 +/- 64.6). The change in Expanded Disability Status Scale was comparable for both groups. Although corticosteroids alone had no effect on the HPA response using the dexamethasone-CRH test, treatment with moclobemide combined with corticosteroids favors normalization of the HPA response in relapsing-remitting MS.

Antidepressant-related erectile dysfunction: management via avoidance, switching antidepressants, antidotes, and adaptation.

The ideal antidepressant would control depression with no adverse effect on sexual function. Erectile dysfunction and other sexual dysfunction associated with antidepressant medication treatment are problems with many antidepressants and can lead to patient dissatisfaction and decreased compliance with treatment. A computerized MEDLINE search (English language, 1966-2003) was performed using the terms antidepressive agents, erectile dysfunction, and sexual dysfunction. Emphasis was placed on studies with specific sexual function measurements taken before and after treatment and placebo control. Mixed mediator, nonserotonergic antidepressants that block postsynaptic serotonin type 2 receptors (nefazodone, mirtazapine) or that primarily increase dopamine or norepinephrine levels (bupropion) were thought to be good choices for avoiding antidepressant-associated sexual dysfunction or for switching patients in whom antidepressant-associated sexual dysfunction emerged. Comparisons with serotonin reuptake inhibitors (SRIs) have revealed less desire and orgasm dysfunction with nonserotonergic bupropion, less orgasm dysfunction with nefazodone, and superior overall satisfaction with sexual functioning with bupropion or nefazodone. However, most of these studies have design flaws that make evidence-based claims of efficacy difficult to substantiate. Agents proposed for antidote use in antidepressant-associated sexual dysfunction have either not been studied in men or not proved efficacious in randomized placebo-controlled trials. Switching to and augmentation with bupropion or nefazodone have also not clearly shown efficacy in controlled trials and require care and monitoring to avoid SRI discontinuation symptoms and loss of antidepressant efficacy. Few proposed treatment options, apart from avoidance, have proved effective for antidepressant-associated sexual dysfunction, which can have negative consequences on depression management.

Antidepressant-induced sexual dysfunction during treatment with moclobemide, paroxetine, sertraline, and venlafaxine.

BACKGROUND: Recent reports suggest that adverse effects on sexual function occur in up to 50% of patients who are treated with selective serotonin reuptake inhibitor (SSRI) antidepressants. Previously cited low rates were more likely a function of underreporting than underoccurrence. There is less evidence about rates of dysfunction with serotonin-norepinephrine reuptake inhibitor (SNRI) and reversible inhibitor of monoamine oxidase A (RIMA) antidepressants. The purpose of this report is to evaluate disturbances in sexual drive/desire and arousal/orgasm in 107 patients who met criteria for major depressive disorder and received treatment with either moclobemide, paroxetine, sertraline, or venlafaxine. METHOD: All consenting eligible patients who met DSM-IV criteria for major depressive disorder completed the Sexual Functioning Questionnaire, version 1 (SFQ) and were assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D) prior to and after 8 or 14 weeks of antidepressant therapy. Analyses were carried out to examine the effect of gender, drug type, pretreatment level of sexual dysfunction, and drug response on reported sexual dysfunction. RESULTS: Compared with women, men experienced a significantly greater level of drug-related impairment in drive/desire (p < .05), whereas there were no statistically significant differences in levels of arousal/orgasm impairment between men and women. The reported impairment in drive/desire items for men ranged from 38% to 50% and from 26% to 32% for women. No differences were found across the 4 antidepressants in men, whereas in women, rates of dysfunction were generally higher with sertraline and paroxetine, but only significantly so in comparison with moclobemide on some measures (p < .03). Rates of sexual dysfunction with venlafaxine tended to fall between those of SSRIs and the RIMA agent. An unexpected relationship was found between favorable drug response and a decreased level of drug-induced sexual dysfunction. CONCLUSION: Antidepressant-induced sexual dysfunction occurs in approximately 30% to 70% of patients who are treated with sertraline or paroxetine. Lower rates are reported with moclobemide and venlafaxine. Clinicians should evaluate the various aspects of sexual dysfunction before and during antidepressant therapy.

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.

Effects of antidepressant treatments on polymorphonuclear elastase levels in patients with depression.

BACKGROUND: We have previously reported that severe depression is associated with immunological and inflammatory alterations and these alterations may be showed easily by polymorphonuclear elastase (PMNE) measurements. The purpose of the present study is to show how PMN elastase levels change before and after antidepressant treatment. METHODS: Fifty-five patients with depression (40 with major depression [MD], 15 with dysthymic disorder [DD]) were included in the study. Blood samples were drawn prior to drug treatment, and 3 months after the treatment. Severity of depression was measured by 24-item Hamilton depression rating scale (HDRS). RESULTS: There was a positive correlation between Delta PMNE levels and Delta HDRS in patients with MD, but not in patients with DD. Twenty-eight patients were given moclobemide, and 27 patients were given imipramine. It was seen that PMN elastase levels were significantly reduced after 3-month antidepressant treatment period only in patients with MD. CONCLUSION: These findings suggest that PMNE activity is a state dependent parameter and improvement of depressive symptoms due to antidepressant treatment may lead to decrement of PMNE levels. CLINICAL IMPLICATION AND LIMITATIONS: PMN elastase measurements may be used as a sensitive biological marker to follow the time-course of the disease activity in patients with major depression.

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.

Moclobemide discontinuation syndrome predominantly presenting with influenza-like symptoms.

A case of moclobemide discontinuation syndrome who predominantly presented with influenza-like symptoms is presented. Sertraline treatment did not modify the symptoms, which may suggest different mechanisms with regard to different antidepressant drug discontinuation syndromes. Implications for clinical care are reviewed.

Efficacy and tolerability of moclobemide in bulimia nervosa: a placebo-controlled trial.

A 6-week double-blind placebo-controlled trial was carried out to examine the efficacy and tolerability of moclobemide, a monoamine oxidase type A selective and reversible inhibitor, in the treatment of bulimia nervosa. Patients were admitted to the study even if they were unable to adhere to a tyramine-free diet. Fifty-two normal-weight women (age range 18-40 years) suffering from bulimia nervosa (DSM-IV criteria) completed the trial. Particular emphasis was placed on evaluating the incidence of hypertension and other side-effects in chronically treated patients. At the usual antidepressant dose of 600 mg, moclobemide was not significantly superior to placebo in the reducing the weekly number of binge eating episodes or in improving several measures of eating attitudes and behaviour (BITE, EDI, TFEQ) in normal-weight bulimia nervosa. The dropout rate was relatively low (29%), and the side-effects were limited and equally distributed between the two treatment groups. No patient experienced a hypertensive crisis during the study and no serious side-effect was detected. The study indicates that moclobemide 600 mg pro die is not efficacious in bulimia nervosa, but it can be safely administered, even to young subjects, at a very high risk of consuming large amounts of tyramine-rich foods without dietary restrictions.

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.

Newer antidepressants: a comparison of tolerability in general practice.

BACKGROUND: An increasing number of antidepressants have been released on the United Kingdom market in recent years, and these are being prescribed more frequently in general practice. Clinical trials suggest that such agents have similar efficacy and the choice of drug is probably based on tolerability, toxicity in overdose, and cost. AIM: To compare the tolerability and safety profile of six, newly marketed antidepressants used in general practice. METHOD: Studies have been conducted for six antidepressants: fluoxetine, sertraline, paroxetine, moclobemide, venlafaxine, and nefazodone, using the technique of prescription-event monitoring. Patients were identified using incident dispensed prescription data. Questionnaires were sent to patients' general practitioners six months after the date of first prescription. Questionnaires asked for date of birth, sex, indication for prescribing each drug, and all events entered in the patients' records after the date of first prescription. RESULTS: Each cohort exceeded 10,000 patients. Nausea/vomiting was the most frequently reported event for all drugs. The difference in incidence rates for drowsiness/sedation, male sexual dysfunction, and hypertension is shown. Mortality data are also reported. CONCLUSION: Frequently reported events were similar for all six drugs but there were clinically and statistically significant differences for less frequently reported events. The adjusted mortality rate was identical between the six drugs. This study provides valuable comparative data for six, widely used antidepressants in general practice.

[Biological treatment of depression in the elderly]. / Thérapeutiques biologiques de la dépression du sujet âgé.

Depression has a high prevalence and a poor outcome in the aged. However, it is often under diagnosed and under treated although treatment with antidepressants at optimal dose and duration can be effective on full remission. Numerous antidepressants are effective but most of them produce side effects. The choice of antidepressants must take into account the effect of age on side-effects and pharmacokinetics. IRSS or moclobemide are recommended as first-choice antidepressants because of a presumed side effect better profile. A dimensional approach based on neurobiological hypothesis of depression, specific clinical features of late life depression (e.g. psychomotor retardation) and biological target of the antidepressants should promote treatment efficacy.

Lack of efficacy of moclobemide or imipramine in the treatment of recurrent brief depression: results from an exploratory randomized, double-blind, placebo-controlled treatment study.

'Recurrent brief depression' (RBD) is a common, distressing and impairing depressive disorder for which there is no current proven pharmacological or psychological treatment. This multicentre, randomized, fixed-dose, parallel-group, placebo-controlled study of the reversible inhibitor of monoamine oxidase moclobemide (450 mg/day) and the tricyclic antidepressant imipramine (150 mg/day) evaluated the potential efficacy of active medication, when compared with placebo, in patients with recurrent brief depression, recruited in the mid-1990s. After a 2-4-week single-blind placebo run-in period, a total of 35 patients were randomized to receive double-blind medication for 4 months, but only 16 completed the active treatment period. An intention-to-treat analysis of the 34 evaluable patients found no evidence for the efficacy of moclobemide or imipramine, when compared with placebo, in significantly reducing the severity, duration or frequency of depressive episodes. A total of 28 patients experienced at least one adverse event, and four patients engaged in nonfatal self-harm. Limitations of the study include the small sample size and the high rate of participant withdrawal. The lack of efficacy of these antidepressant drugs and the previous finding of the lack of efficacy of the selective serotonin reuptake inhibitor fluoxetine together indicate that medications other than antidepressant drugs should be investigated as potential treatments for what remains a common, distressing and potentially hazardous condition.

Antidepressive treatment with monoamine oxidase inhibitors and the occurrence of intraoperative hemodynamic events: a retrospective observational cohort study.

OBJECTIVE: To investigate the occurrence of intraoperative hemodynamic events when antidepressive treatment with monoamine oxidase inhibitors (MAOIs) was continued during anesthesia. METHOD: A retrospective observational cohort study was conducted among patients who were admitted for elective surgery requiring anesthesia in 8 Dutch hospitals (2004-2010). The index group included current users of irreversible (tranylcypromine) and reversible (moclobemide) MAOIs. The reference group included a sample of nonusers matched to the index group on hospital, type and period of surgery, and type of anesthesia (ratio 1:3). The outcome of interest was the occurrence of the following intraoperative hemodynamic events: hypotension or hypertension and tachycardia or bradycardia. RESULTS: Approximately 280,000 surgical procedures were performed in the participating hospitals in the total observational period of 33 years. The index group included 26 and 25 users of tranylcypromine and moclobemide, respectively. The reference groups included 149 nonusers. Intraoperative hypotension occurred less frequently in users of tranylcypromine (46%) than in nonusers (73%) (P = .01). The occurrence of hypertension, bradycardia, and tachycardia during anesthesia was not different between users of tranylcypromine (27%, 50%, and 12%, respectively) and those in the reference group (35%, 61%, and 26%, respectively). The occurrence of hypotension, hypertension, bradycardia, and tachycardia was not different between users of moclobemide and the reference group. CONCLUSIONS: Severe adverse hemodynamic events, such as hypertension and tachycardia, did not occur more frequently in users of both the irreversible MAOI tranylcypromine and the reversible MAO-A inhibitor moclobemide compared to nonusers. These findings suggest that there is no longer much justification to discontinue these MAOIs before surgery, with the considerable risk of compromising patients' psychiatric status.

Hypothermia in a combined intoxication with doxepin and moclobemide in an adolescent.

OBJECTIVE: Intoxication with antidepressants, frequently encountered in pediatric emergency medicine, can often lead to life threatening situations. While hyperthermia, hypertonicity and rigidity are symptoms indicative of a serotonin syndrome triggered by an intoxication with serotonin reuptake inhibitors or monoamine oxidase inhibitors, cardiotoxicity, coma and ECG changes are typical of an intoxication with tricyclic antidepressants. CASE REPORT: Hypothermia (instead of the expected hyperthermia) is described for the first time as a persistent symptom during the course of a combined moclobemide-doxepin intoxication in an attempted suicide of a 16-year-old adolescent. DISCUSSION: The administration of serotonin reuptake inhibitors alone or in combination with other medication which increases the level of 5-hydroxytryptamine, i.e. serotonin, in the synaptic cleft mainly leads to hyperthermia. According to a recent study, however, the application of a selective 5-HT(1a) agonist to transgenic mice with a prominent overexpression of the 5-HT(1a) receptor lead to immobility and hypothermia. These findings might help to explain the hypothermia observed in the case of the intoxicated 16-year-old. CONCLUSION: Intoxication with antidepressants should not be excluded a priori in a hypothermic patient who displays other clinical signs of the said intoxication.

Serotonin toxicity caused by moclobemide too soon after paroxetine-selegiline.

Serotonin toxicity is an iatrogenic complication of serotonergic drug therapy. It is due to an overstimulation of central and peripheral serotonin receptors that lead to neuromuscular, mental and autonomic changes. Moclobemide is a reversible inhibitor of monoamine oxidase (MAO)-A, selegiline is an irreversible selective inhibitor of MAO-B, and paroxetine is a selective serotonin reuptake inhibitor. Combined use of these agents is known to cause serotonin toxicity. A 53-year-old woman had been treated with paroxetine and selegiline. After moclobemide was prescribed in place of paroxetine without a washout period, she quickly developed confusion, agitation, ataxia, diaphoresis, tremor, mydriasis, ocular clonus, hyperreflexia, tachycardia, moderately elevated blood pressure and high fever, symptoms that were consistent with serotonin toxicity. Discontinuation of the drugs, hydration and supportive care were followed by remarkable improvement of baseline status within 3 days. This case demonstrates that serotonin toxicity may occur even with small doses of paroxetine, selegiline and moclobemide in combination. Physicians managing patients with depression must be aware of the potential for serotonin toxicity and should be able to recognize and treat or, ideally, anticipate and avoid this pharmacodynamically-mediated interaction that may occur between prescribed drugs.