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Biomedical subjects

M Versiani

Publications and source records attributed to M Versiani.

At least 19 recordsLinked to original sources

The role of noradrenaline and selective noradrenaline reuptake inhibition in depression.

Depression is a common disorder that impacts on all aspects of a person's life. For the past 10 years, clinicians have focused on serotonin in their treatment of depression. This is largely due to the growing acceptance of the efficacy and safety of the selective serotonin reuptake inhibitors (SSRIs) in comparison with older tricyclic antidepressants (TCAs). However, evidence for a role of noradrenaline in depression has been accumulating for some time, beginning with the discovery that drugs which either caused or alleviated depression acted to alter noradrenaline metabolism. Until recently, the role of noradrenaline in depression was predicted from clinical experience with noradrenergic TCAs (desipramine, nortriptyline and protriptyline) and selective serotonin and noradrenaline reuptake inhibitors (venlafaxine, milnacipran). The licensing of reboxetine, a selective noradrenaline reuptake inhibitor now allows the role of noradrenaline in depression to be investigated directly. This review presents key data from the literature that support a role for noradrenaline in depression taking into account neurophysiology, psychopharmacology and clinical trial data.

Adrenergic Uptake Inhibitors↗

The man with the purple nostrils: a case of rhinotrichotillomania secondary to body dysmorphic disorder.

OBJECTIVE: To describe a different type of self-injurious behavior that may be secondary to body dysmorphic disorder (BDD). METHOD: Single case report. RESULTS: We reported a case of an individual who have developed the self-destructive habit of pulling and severely scraping hairs and debris out of the mucous membrane of his nasal cavities. We have proposed the term rhinotrichotillomania to emphasize the phenomenological overlapping between trichotillomania (TTM) and rhinotillexomania (RTM) exhibited by this case. The main motivation behind the patient's actions was a distressing preoccupation with an imaginary defect in his appearance, which constitutes the core characteristic of BDD. The patient was successfully treated with imipramine. CONCLUSION: The case suggests that certain features of TTM, RTM, and BDD may overlap and produce serious clinical consequences. Patients with this condition may benefit from a trial of tricyclics when other effective medications, such as serotonin reuptake inhibitors, are not available for use.

Adrenergic Uptake Inhibitors↗

Respiratory panic disorder subtype and sensitivity to the carbon dioxide challenge test.

The aim of the present study was to verify the sensitivity to the carbon dioxide (CO2) challenge test of panic disorder (PD) patients with respiratory and nonrespiratory subtypes of the disorder. Our hypothesis is that the respiratory subtype is more sensitive to 35% CO2. Twenty-seven PD subjects with or without agoraphobia were classified into respiratory and nonrespiratory subtypes on the basis of the presence of respiratory symptoms during their panic attacks. The tests were carried out in a double-blind manner using two mixtures: 1) 35% CO2 and 65% O2, and 2) 100% atmospheric compressed air, 20 min apart. The tests were repeated after 2 weeks during which the participants in the study did not receive any psychotropic drugs. At least 15 of 16 (93.7%) respiratory PD subtype patients and 5 of 11 (43.4%) nonrespiratory PD patients had a panic attack during one of two CO2 challenges (P = 0.009, Fisher exact test). Respiratory PD subtype patients were more sensitive to the CO2 challenge test. There was agreement between the severity of PD measured by the Clinical Global Impression (CGI) Scale and the subtype of PD. Higher CGI scores in the respiratory PD subtype could reflect a greater sensitivity to the CO2 challenge due to a greater severity of PD. Carbon dioxide challenges in PD may define PD subtypes and their underlying mechanisms.

Adolescent↗

Double-blind, placebo-controlled study with reboxetine in inpatients with severe major depressive disorder.

The efficacy and tolerability of reboxetine, a unique selective noradrenaline reuptake inhibitor, were compared with those of placebo in a 6-week, randomized, double-blind study of hospitalized patients with a DSM-III-R diagnosis of major depressive disorder. Fifty-two patients (25 in the placebo group, 27 in the reboxetine group) were included in the efficacy analysis. Sixteen (64%) of those in the placebo group and four (15%) in the reboxetine group were withdrawn during the study because of lack of efficacy. Improvement in the mean Hamilton Rating Scale for Depression (HAM-D) total score at last assessment was significantly greater in the reboxetine group than in the placebo group (p < 0.001). Similarly, the response rate to treatment, defined as > or =50% reduction in HAM-D total score, was 74% for patients who received reboxetine compared with 20% for those who received placebo (p < 0.001). A significantly greater response with reboxetine than with placebo was seen as early as day 10 of treatment (p = 0.006). The therapeutic efficacy of reboxetine was substantiated by improvement in mean scores on the Zung Self-Rating Scale and on the Clinical Global Impression Severity of Illness and Global Improvement scales. Reboxetine was well tolerated, and only one patient in each group withdrew because of adverse events. Dry mouth, insomnia, blurred vision, sweating, and constipation were recorded more frequently in the reboxetine group than in the placebo group. There was a tendency toward orthostatic changes in the systolic blood pressure, but this was not clinically significant. This study demonstrated that reboxetine is significantly more effective than placebo in the treatment of hospitalized patients with severe major depressive disorder and is well tolerated.

Adolescent↗

Neuropsychological sequelae in Kleine-Levin syndrome: case report.

Kleine-Levin syndrome is characterized by periodic hypersomnia, hyperphagia, sexual disinhibitions and behavioral disturbances. The prognosis is generally benign, with normal cognitive and social functions after the episodes. We describe a typical case of Kleine-Levin syndrome associated with apparent academic decline, neuropsychological sequelae and personality alterations after the second episode of the illness. Further research in the natural history of Kleine-Levin syndrome is needed, for example, to determine whether early intervention would improve long-term prognosis.

Adolescent↗

[Quantitative electroencephalography in obsessive-compulsive disorder: preliminary results].

The predictive value of quantitative electroencephalography (EEGq) was investigated with regard to the pharmacological treatment of 10 non-medicated obsessive-compulsive disorder (OCD) patients diagnosed according to DSM-IV criteria. The following variables were selected: bipolar relative power in alpha band for Cz-C3, Cz-C4, T3-T5, T4-T6, T3-F7 and T4-F8; bipolar relative power in theta band for Cz-C3, Cz-C4, T3-T5, T4-T6, T3-F7 and T4-F8; and monopolar relative power in theta band for Fp1, Fp2, F7, F3, Fz, F4 and F8. There was statistically significant deviations in five patients with regard to bipolar relative power in alpha band for central regions when compared to normative data bank (control group). This group of patients had a significantly lower age of OCD onset and worse response to pharmacotherapy with serotonin reuptake inhibitors.

Adolescent↗

A review of 19 double-blind placebo-controlled studies in social anxiety disorder (social phobia).

Nineteen double-blind placebo-controlled studies on the treatment of Social Anxiety Disorder (Social Phobia) are reviewed. Initial trials yielded a high degree of efficacy for phenelzine, a large difference between drug and placebo and a low rate of placebo response. Controlled studies with RIMAs (moclobemide and brofaromine) yielded more moderate levels of efficacy and more pronounced placebo effects. Results of the Liebowitz Social Anxiety Scale (LSAS) permit a comparison of the outcomes of the different controlled trials. Overall, the reduction in the mean total score with various drugs is inferior to 50%, probably because the chronic nature of the disorder is not amenable to drastic changes in short-term trials. Results with the LSAS and other scales justify a ranking of the efficacy of the drugs: Classical MAOIs > SRIs > RIMAs. Two controlled studies with benzodiazepines (clonazepam and bromazepam) would position them together with the SRIs relative to efficacy but with problems associated with unwanted effects and dependence. Controlled studies with SRIs (paroxetine and fluvoxamine) demonstrated very significant differences from placebo. Paroxetine is the SRI most extensively studied in Social Anxiety Disorder with positive therapeutic results.

Calcium Channel Blockers↗

Social functioning in depression: a review.

OBJECTIVE: This article reviews the available data on social functioning in depression and provides clinical guidelines and opinion on this important and expanding field. DATA SOURCES: A MEDLINE search was conducted to identify all English-language articles (1988-1999) using the search terms depression and social functioning, depression and social adjustment, depression and psychosocial functioning, and social functioning and antidepressant. Further articles were obtained from the bibliographies of relevant articles. DATA SYNTHESIS: Depressive disorders are frequently associated with significant and pervasive impairments in social functioning, often substantially worse than those experienced by patients with other chronic medical conditions. The enormous personal, social, and economic impact of depression, due in no small part to the associated impairments in social functioning, is often underappreciated. Both pharmacologic and psychotherapeutic approaches can improve social impairments, although there is a lack of extended, randomized controlled trials in this area using consistent assessment criteria. CONCLUSION: Despite this lack, it is becoming clear that not all treatments are equally effective in relieving the impaired social functioning associated with depressive disorders. Furthermore, efficacy in relieving the core symptoms of depression does not necessarily guarantee efficacy in relieving impaired social functioning.

Adaptation, Psychological↗

Reboxetine versus imipramine in the treatment of elderly patients with depressive disorders: a double-blind randomised trial.

BACKGROUND: Depression in older people is often unrecognised and untreated or under-treated. Antidepressant treatment may itself exacerbate a pre-existing illness, interact with concomitant medications or produce undesirable cognitive and sedative side effects. Newer antidepressants may offer advantages in terms of a lesser burden of adverse effects. METHODS: The comparative tolerability of the unique selective noradrenaline reuptake inhibitor (selective NRI) reboxetine (4-6 mg/day; n = 176) and that of imipramine (50-100 mg/day; n = 171) was assessed in an elderly ( > 65 years) cohort of depressed or dysthymic patients in an 8-week, double-blind, multicentre trial. Comparative efficacy was also assessed. RESULTS: Overall, 68% of patients in the reboxetine group experienced adverse events compared with 71% in the imipramine group. Reboxetine-treated patients were less likely to develop hypotension and related symptoms (7% vs. imipramine 16%) or cardiovascular disorders (12.5% vs. imipramine 21.1%), while those treated with imipramine were less likely to experience insomnia (6.3% vs. 2.9%). Adverse events were more often assessed as related to treatment (43%) and moderate to severe in intensity (73%) with imipramine than with reboxetine (33% and 65%, respectively). Furthermore, there were fewer serious adverse events in the reboxetine-treated group (P = 0.019). The reduction in the Hamilton Rating Scale for Depression (HAM-D) was comparable between the treatment groups in the total population. At the last assessment, the majority of patients in both treatment groups were assessed as normal to borderline or mildly ill using the Clinical Global Impression (CGI) scale. In a subanalysis of the dysthymic patients a modest but significant difference in favour of imipramine was observed for both HAM-D and CGI assessments. This may have been a reflection of a trend towards more severe depressive symptoms at baseline in the reboxetine group. CONCLUSIONS: Reboxetine is as effective as imipramine in the treatment of depression in elderly patients but is at least as well tolerated with a lower risk of hypotension and related symptoms, fewer serious adverse events, adverse event-related withdrawals and treatment-related adverse events.

Aged↗

Fluoxetine versus amitriptyline in the treatment of major depression with associated anxiety (anxious depression): a double-blind comparison.

Although common in clinical settings, major depressive disorder with associated anxious symptoms ('anxious depression') has not been well studied in antidepressant clinical trials. The aim of this study was to compare the effects of fluoxetine versus amitriptyline in this group of patients. After a single-blind placebo run-in period of 2 weeks, patients were treated on a double-blind basis with fluoxetine or amitriptyline for 8 weeks. Assessment instruments included: 21-item Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Clinical Global Impressions, Raskin Depression Scale and Covi Anxiety Scale. A total of 157 patients were randomized to either fluoxetine or amitriptyline. Fluoxetine was given at a fixed dose of 20 mg/day and amitriptyline was given in a range of 50-250 mg/day (mean of 138.1 mg/day). Fluoxetine was comparable to amitriptyline in all efficacy measures except the HAMD sleep factor. Unwanted effects were more frequent and more severe in the amitriptyline-treated patients. Fluoxetine was comparably efficacious to amitriptyline in the treatment of major depression with associated anxiety. Since fluoxetine was far better tolerated, it is a promising alternative for this frequent and disabling condition.

Adult↗

Reboxetine, a unique selective NRI, prevents relapse and recurrence in long-term treatment of major depressive disorder.

BACKGROUND: The long-term efficacy and tolerability of the antidepressant reboxetine, a unique selective norepinephrine reuptake inhibitor (selective NRI), were assessed in an international study. METHOD: Two hundred eighty-three patients with recurrent DSM-III-R major depression who responded to 6 weeks of reboxetine treatment (> or =50% decrease in Hamilton Rating Scale for Depression [HAM-D] total score) were randomly assigned to receive reboxetine or placebo for 46 weeks in a double-blind phase. Relapse (> or =50% increase in HAM-D total score and/or a HAM-D total score > or =18) rate was the principal assessment criterion and included patients who experienced relapse or recurrence. Only patients who remained relapse-free at the end of the first 6-month treatment period were included in the relapse rate assessment at the end of the second 6-month treatment period. RESULTS: Reboxetine was associated with a markedly lower relapse rate than placebo (22% vs. 56%; p<.001) and a greater cumulative probability of a maintained response (p = .0001) during long-term treatment. Patients in remission (HAM-D total score < or =10) at the time of random assignment were less likely to relapse (16% reboxetine, 48% placebo; p<.001). The proportion of patients who were relapse-free and therefore remained in the study was significantly (p< or =.001) higher among those on reboxetine treatment than on placebo at the end of the first (61% vs. 40%) and second (88% vs. 59%) 6 months of treatment. Additional efficacy measures supported these findings. The incidence of adverse events with reboxetine was low and comparable with that for placebo. Discontinuation due to adverse events occurred infrequently. CONCLUSION: Reboxetine treatment over 1 year is more effective than placebo in the prevention of relapse in patients with recurrent depression. The low relapse rates at the end of the second 6 months of treatment further suggest that reboxetine effectively prevents recurrence of depressive symptoms following episode resolution. Reboxetine is well tolerated in long-term treatment of depression, a finding that bodes well for long-term patient compliance.

Adrenergic Uptake Inhibitors↗

Pharmacotherapy of dysthymic and chronic depressive disorders: overview with focus on moclobemide.

Chronic depression was once considered untreatable pharmacologically. Open studies conducted around 1980 demonstrated efficacious results with tricyclics, classical MAOIs and lithium in 45% of cases. The subsequent delineation of dysthymia in DSM-III and its future editions as well as ICD.10, facilitated controlled trials in subjects with "pure dysthymia" and those with superimposed major depression (so-called "double-depression"). TCAs, SSRIs, RIMA, and benzamides have all proven effective in an average of 65% vs. an average of 25% with placebo. Well tolerated compounds--e.g. moclobemide, sertraline and desipramine--may permit the long-term clinical management of this spectrum of dysthymic and related conditions. Patients with "lifetime pure dysthymia" tend to respond more slowly to antidepressants than those with concurrent major depression ("double-depression") or those with "pure dysthymia" but with history of major depressive episodes. Chronicity is now well established: indeed discontinuation of antidepressants in a 4-year maintenance study has resulted in 89% rate of relapse. Dysthymia is a disabling condition and high doses of antidepressants are needed to achieve full recovery.

Antidepressive Agents↗

Moclobemide and imipramine in chronic depression (dysthymia): an international double-blind, placebo-controlled trial. International Collaborative Study Group.

An international, multicenter, placebo-controlled study was undertaken to determine the safety and antidepressant efficacy of moclobemide, a new reversible inhibitor of monoamine oxidase A, and imipramine in the treatment of dysthymia (DSM-III-R). A total of 315 patients were enrolled and randomly assigned to an 8-week treatment in one of three groups (moclobemide, imipramine and placebo). Patients were male or female outpatients aged between 18 and 65 years meeting DSM-III-R criteria for dysthymia, primary type, with late or early onset. Of the patients in each group 85% completed the 8-week treatment period. The percentage of patients who no longer fulfilled DSM-III-R symptom criteria at treatment endpoint was significantly higher in the moclobemide (60%) and imipramine (49%) treatment groups than in the placebo group (22%). Differences to placebo were also statistically significant both for moclobemide and for imipramine on the other efficacy variables (i.e. Hamilton Rating Scale for Depression, final overall efficacy assessment, Clinical Global Impression and symptom check list self-rating). A significant superiority of moclobemide and imipramine over placebo was found in pure dysthymia and in double-depression, as well as in early and late onset subgroups. In early onset cases, moclobemide was significantly more effective than was imipramine on the Hamilton Rating Scale for Depression. Anticholinergic symptoms and sleepiness were significantly more frequent side effects on imipramine than on moclobemide or on placebo, and the investigators' final overall assessment of tolerability significantly favoured moclobemide over imipramine. This study demonstrates the efficacy of high dose moclobemide (mean dose 675 mg/day) and high dose imipramine (220 mg/day) against placebo in the treatment of dysthymia. Moclobemide was better tolerated than was imipramine.

Adolescent↗

Social phobia: long-term treatment outcome and prediction of response--a moclobemide study.

In this open, prospective, structured, naturalistic study of the efficacy of long-term treatment in social phobia 93 consecutive outpatients suffering from severe generalized or circumscribed social phobia (median Liebowitz Social Anxiety Scale score 83) and a high degree of concomitant psychiatric disease were administered treatment with moclobemide (712 +/- 75 mg/day at steady state). Fifty-nine patients who responded (Clinical Global Impression for Change: very much/much improved) completed 2 years of treatment. Patients then entered a drug-free period of at least 1 month during which 88% of the patients deteriorated. In a further 2-year treatment period with moclobemide those patients who had deteriorated became responders again. Symptoms recurred in a substantial number of the patients at the end of the study when the dose was reduced and then discontinued. Post-study follow up at 6-24 months after study completion found that 63.2% of patients were almost asymptomatic or had only mild symptoms, 15.8% were off all treatment, 28.1% were back on moclobemide, 10.6% were taking another psychotropic drug and 8.8% were in psychotherapy. All previous non-responders to moclobemide and mostly alcohol abusers (36.9%), had moderate or severe social phobia and were off all treatment (13.3%), on psychotherapy (15.9%) or on another psychotropic drug (8.8%). Discriminant analysis correctly predicted outcome in 93.5% of all patients. Alcohol abuse was by far the strongest predictor of negative outcome. Coexisting generalized anxiety disorder and dysthymia were less potent in this regard, whereas high baseline Hamilton anxiety or depression scale scores, circumscribed social phobia, or social phobia unassociated with avoidant personality disorder were predictors of a positive outcome. In conclusion, severe social phobia can be successfully treated in the long-term but many patients may need medication or psychotherapy for many years. Treatment should start as early as possible because complications such as alcohol abuse make treatment difficult.

Adolescent↗

The long-term treatment of social phobia with moclobemide.

Patients meeting the social phobia criteria of the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) on the DSM-III-R Structured Clinical Interview (n = 101) entered a long-term moclobemide treatment study. These patients were treated for 2 years with moclobemide (phase I) followed by drug withdrawal, in most cases abruptly (phase II). Those who relapsed entered phase III for a further period of 2 years of treatment. During phase I 40 patients (39.6%) withdrew due to inefficacy or relapse. Two patients were removed from the study because of other diagnoses (borderline or schizophreniform). At the end of phase I the remaining patients (58.4%) were rated as not ill (45.5%) or minimally ill (11.9%). Effort was taken to achieve the maximum dose of moclobemide (750 mg/day) and the mean (+/-SD) dose was 723.3 +/- 67.7 mg/day (month 21). A marked decrease in symptoms in the patients who responded was recorded on the Liebowitz Scale for Social Phobia, Clinical Global Impressions. Hamilton Anxiety Scale and Hamilton Depression Scale. Non-response was mainly associated with co-morbidity, especially alcohol abuse, axis II disorders, and a history of major depression or secondary dysthymia. The drug was well tolerated; the more frequent side effects were mild and occurred mainly in the first 2 months of phase I, including nausea, headaches or insomnia. In phase II there was a relapse rate of 88% and 51 patients entered phase III; these patients are still being treated.

Adolescent↗