Inhibition of monkey brain semicarbazide-sensitive amine oxidase by various antidepressants

We examined whether the antidepressant drugs, such as the dicyclic drug zimeldine, the tricyclic drug imipramine, tetracyclic drug maprotiline, and the non-cyclic drug nomifensine, inhibit in vitro semicarbazide-sensitive amine oxidase (SSAO) activity in monkey brain. The deamination of 1 microM benzylamine was not inhibited at high concentrations of clorgyline or deprenyl, while it was highly sensitive for semicarbazide. When corresponding experiments were performed with 100 microM benzylamine, the opposite results were obtained. The most potent of inhibition of SSAO was observed by imipramine, followed by maprotiline, zimeldine and nomifensine. Inhibition of SSAO was not enhanced by varying the time of preincubation of the enzyme and various antidepressant drugs, indicating direct action on and reversible inhibition of SSAO. We found the tricyclic antidepressant drug to be the most selective inhibitors of SSAO activity in monkey brain, as compared with other type of antidepressant drugs.     

Do levels of dysfunctional attitudes predict recovery in major depression?

Thirty-seven patients who fulfilled DSM-lll-R criteria for Major Depressive Disorder were recruited for a double-blind controlled trial of desipramine and placebo for 6 weeks. Initial levels of dysfunctional attitudes in the placebo group, particularly those related to achievement, were found to predict changes in Hamilton Ratings for Depression between the initial Hamilton scores and those at week 6 (Hamilton change scores) with the initial level of depression controlled for. For subjects taking desipramine, levels of dysfunctional attitudes did not predict Hamilton change scores. The findings suggest that dysfunctional attitudes impair spontaneous recovery from depression and that the effects of antidepressant drug treatment may obscure this effect. Recovery from depression may include a complex mixture of biological and psychological pathways. © 1997 John Wiley & Sons, Ltd.     

Concomitant isocarboxazid/mianserin treatment of major depressive disorder

This paper reports combined antidepressant treatment with isocarboxazid /mianserin in 60 patients with endogenous depression/melancholia. The combination was used as the first drug treatment choice in 33 cases. Thirty-two patients obtained complete remission and one responded only incompletely. The depression improved after a few days' treatment, and full recovery was obtained after approximately 2 weeks. There were no serious side-effects or interactions, but weight gain was a common problem.     

A randomized, controlled trial of duloxetine alone vs. duloxetine plus a telephone intervention in the treatment of depression

OBJECTIVE: We hypothesized that combining antidepressant medication with a standardized telephone adherence support intervention would lead to superior outcomes in the treatment of depression compared with antidepressant medication alone. METHOD: Patients with depression were randomized to receive the antidepressant duloxetine alone (DLX), or duloxetine plus a standardized telephone intervention (DLX+TI), for 12 weeks of open-label treatment. The primary outcome measure was remission (HAMD 17 total score 90% at every visit) in both groups. CONCLUSIONS: A telephone intervention in combination with antidepressant medication (duloxetine) did not improve depression outcomes compared with antidepressant alone in this clinical trial, perhaps due to high drug adherence in both treatment groups. Addition of a telephone intervention was, however, associated with increased reporting of AEs.     

Right hemisphere abnormalities in major depression: Quantitative electroencephalographic findings before and after treatment

The quantitative EEGs of drug-free depressed patients were analyzed and compared to age and sex-matched controls, using spectral analysis. In addition, QEEGs of depressed patients after clinical improvement resulting from 6 weeks of antidepressant treatment were also analyzed. The subjects were 20 patients suffering from major depression (DSM-III-R). Scores on the Hamilton Rating Scale for Depression (HRSD) of all patients showed a reduction of more than 50% at the end of the 6th week. The results show: (1) delta and theta bipolar absolute powers of the right hemisphere increased in drug-free depressed patients, compared to controls. (2) No changes in all bands of QEEG were found after clinical improvement resulting from 6 weeks of treatment. These results suggest that the right hemisphere plays an important role in major depression, and that a reduction in symptoms is not necessarily indicative of an improvement in underlying major depression.     

The effects of antidepressant treatment on serum cytokines and nutritional status in hemodialysis patients

The aim of this study was to investigate the effects of antidepressant treatment on serum cytokines and nutritional status in hemodialysis patients. Twenty-eight hemodialysis patients with a depressed mood were given 20 mg of fluoxetine for 8 weeks. The degree of depressive symptoms, the serum levels of interleukin-1beta, interleukin-2, interleukin-6, tumor necrosis factor-alpha, c-reactive protein, and markers of nutritional status were assessed at baseline and after treatment. The outcome was assessed in terms of response to treatment (>50% reduction in the score of the Hamilton depression rating scale). Antidepressant treatment decreased the serum level of interleukin-beta1 in both response and nonresponse groups, and increased the serum level of interleukin-6 only in the response group. At baseline, the level of interleukin-6 in the response group was lower than in the nonresponse group. Antidepressant treatment also increased fat distribution significantly in the response group which might have slightly improved the nutritional status. This study suggests that antidepressant treatment improve depressive symptoms and may affect immunological functions and nutritional status in chronic hemodialysis patients with depression.     

Does somatosensory amplification decrease with antidepressant treatment?

Somatosensory amplification refers to a tendency to experience somatic and visceral sensations as unusually intense, noxious, and disturbing. The authors wanted to determine whether somatosensory amplification is a stable construct or whether it might change with antidepressant therapy. Fifteen patients with fibromyalgia and 17 patients with major depressive disorder received antidepressant treatment and were assessed after 6 and 12 weeks of treatment. Amplification scores responded to antidepressant treatment in patients with major depression but not in patients with fibromyalgia, despite a decrease in the levels of depression in both groups. When change in depression and anxiety scores was partialled out from change in somatosensory amplification scores, the amplification scores did not change significantly in either the depressed or the fibromyalgia groups. Given the small numbers and the marginal significance of the results, the authors are unable to say definitely just how independent of depression somatosensory amplification is. Whether somatosensory amplification is a measure of depression per se should be tested in a more definitive and larger future study.     

Fluoxetine and norfluoxetine plasma concentrations during relapse-prevention treatment

BACKGROUND: Virtually no attention has been given to the relationship between antidepressant plasma drug concentrations and relapse-prevention during maintenance therapy. The purpose of this study was to investigate the relationship between steady-state plasma drug concentrations and outcome during relapse-prevention therapy with fluoxetine. METHODS: The patients studied had responded to acute fluoxetine treatment for major depression (defined by DSM-III-R). Patients who met criteria for remission after 10-12 weeks of open-label acute fluoxetine therapy (N=395 of 839 patients), were randomly assigned to one of four treatment arms (50 weeks of fluoxetine, 38 weeks of fluoxetine followed by 12 weeks of placebo, 14 weeks of fluoxetine followed by 36 weeks of placebo and 50 weeks of placebo). Plasma fluoxetine and norfluoxetine concentrations were measured (1) after 4 and 8 weeks of open-label treatment and (2) at the beginning and after 14 weeks of double-blind, relapse-prevention therapy. RESULTS: Mean drug plasma levels were stable throughout the study. There was no significant difference in steady state plasma levels for the patients who relapsed compared to those who completed fluoxetine therapy without relapsing after 14, 38 or 50 weeks of fluoxetine relapse-prevention treatment. In addition, time-to-relapse was not related to steady-state drug plasma levels. Finally, after dividing patients into two groups based on their drug plasma levels, no significant differences were seen in the cumulative proportions of patients staying well during relapse-prevention therapy. DISCUSSION: Plasma concentrations of fluoxetine and/or its metabolite norfluoxetine, are not correlated with relapse in patients treated with a fixed dose of 20 mg/day fluoxetine. Fluoxetine plasma levels cannot be used to guide relapse-prevention treatment.     

The benefit from whole body acupuncture in major depression

BACKGROUND: In a single-blind placebo-controlled study design we investigated the efficacy of acupuncture additionally applied to drug treatment in major depression. METHODS: We randomly included 70 inpatients with a major depressive episode in three different treatment groups: verum acupuncture, placebo acupuncture and a control group. All three groups were pharmacologically treated with the antidepressant mianserin. The verum group received acupuncture at specific points considered effective in the treatment of depression. The placebo group was treated with acupuncture at non-specific locations and the control group received pharmacological treatment plus clinical management. Acupuncture was applied three times a week over a period of 4 weeks. Psychopathology was rated by judges blind to verum/placebo conditions twice a week over 8 weeks. RESULTS: Patients who experienced acupuncture improved slightly more than patients treated with mianserin alone. CONCLUSIONS: Additionally applied acupuncture improved the course of depression more than pharmacological treatment with mianserin alone. However, we could not detect any differences between placebo and verum acupuncture.     

Graduate mental health worker case management of depression in UK primary care: a pilot study.

BACKGROUND: Based on data from large multicentre US trials, the National Institute for Health and Clinical Excellence (NICE) is advocating a stepped-care model for the management of depression, with 'case management' or 'collaborative care' for selected patients in primary care. AIM: To conduct a pilot study examining the use of graduate mental health workers case managing depressed primary care NHS patients. DESIGN OF STUDY: A randomised controlled trial comparing usual GP care with or without case management over 16 weeks of acute antidepressant drug treatment. SETTING: Three primary care practices in the North East of England. METHOD: Patients with depression, aged 18-65 years, who had failed to adequately respond to antidepressant treatment, were randomised to the two treatments. Assessments were made at baseline, 12, and 24 weeks using a combination of observer and self ratings. RESULTS: Randomisation of 62 patients required screening of 1073 potential patients. There was little difference in outcome between the two treatment arms but a gradual improvement in symptoms over time was seen. Client satisfaction was assessed as high across both treatments. CONCLUSION: While this pilot study confirmed the integrity of the study protocol and the suitability of the outcome measures and randomisation procedure, it raises questions regarding the practicality of recruitment and feasibility of the intervention. It would be crucial to address these issues prior to the implementation of a large multi-centre randomised controlled trial.     

Six months of desipramine for dysthymia: can dysthymic patients achieve normal social functioning?

BACKGROUND: There is evidence that antidepressant medication improves social dysfunction during acute treatment in dysthymic patients but it is unknown if the gain in social functioning persists or progresses with longer-term antidepressant treatment. We examine the effect of 6 months of desipramine treatment on social functioning in dysthymic patients. METHODS: Forty-six subjects with DSM-III-R dysthymia (70% with superimposed major depression) who had responded to 10 weeks of open-label desipramine (DMI) treatment received 16 additional weeks of continuation DMI. Social functioning was measured at weeks 0, 10 and 26 with the Social Adjustment Scale-Self Report. RESULTS: Euthymia was maintained and a marginally significant trend for further improvement in overall social functioning appeared during continuation treatment. Only 24% of subjects achieved normative level of social adjustment after 6 months of DMI treatment. LIMITATIONS: The main limitation was the lack of a placebo control group. CONCLUSION: Acute improvement in social functioning persists during continuation treatment. However, most dysthymic patients did not achieve a community level of social adjustment. Significant social dysfunction persists in dysthymic patients with low levels of depressive symptomatology after 6 months of intense DMI treatment.     

A double-blind, placebo-controlled, efficacy, safety, and pharmacokinetic study of INN 00835, a novel antidepressant peptide, in the treatment of major depression

BACKGROUND: INN 00835 is a synthetic pentapeptide with a potential for rapid onset of action as an antidepressant. Its efficacy was investigated in a pilot study in patients diagnosed with major depression. METHODS: Fifty two patients received either active drug - INN 00835 (26 patients) - or placebo (26 patients), subcutaneously at 0.2 mg/kg for 5 consecutive days. The patients were evaluated for an additional 4 weeks after treatment. Efficacy was evaluated by the following psychiatric rating scales: HAMD, MADRS, CSRS, CGI, and VAS. The effect of treatment was also evaluated by using a biochemical marker: changes in blood platelet serotonin (5HT) uptake rates in drug-treated patients compared to those in the placebo group. Plasma concentrations of INN 00835 were measured by LC/MS. RESULTS: Statistical analysis indicated a strong pharmacodynamic correlation between plasma drug concentrations at 1 h after dosing and the reduction in the severity of depression as measured by the psychiatric rating scales. A minimum effective plasma concentration (MEC) of INN 00835 was 5 ng/ml. Statistically significant differences in response to treatment (P<0.05) were found between patients with plasma concentrations above MEC and those in the placebo group, as well as between subjects with plasma concentrations above and below the MEC. The peak effect was observed after the 5-day treatment and the response to treatment persisted during the 4-week follow-up period. The change of 5HT uptake rates after treatment was significantly larger in the drug-treated group than in the placebo group. Limitations: This was a pilot study conducted in a relatively small population (52 patients) and the limited number of blood sampling times did not allow a comprehensive pharmacokinetic analysis. There was a relatively large placebo response. The results have to be confirmed in future, large scale studies. CONCLUSIONS: INN 00835 appears to be a promising drug for the treatment of major depression.     

米氮平与马普替林治疗抑郁症对照研究

目的 评价米氮平与马普替林治疗抑郁症的疗效和不良反应.方法 将符合CCMD-3诊断标准的60例抑郁症住院和门诊患者,随机平分为两组,分别给予米氮平和马普替林治疗,疗程6周.用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)和副反应量表(TESS)评定疗效和不良反应.结果 米氮平与马普替林治疗抑郁症的疗效接近,但前者起效更快,不良反应少于后者.结论 米氮平是一种安全、有效的新一代抗抑郁药,可以作为治疗抑郁症的第一线抗抑郁药使用.     

Randomized, double-blind pilot trial comparing lamotrigine versus citalopram for the treatment of bipolar depression

BACKGROUND: Uncertainty exists regarding the best approach for treating bipolar depression among patients already receiving a first-line mood stabilizer. The aim of this pilot study was to compare adding a second mood stabilizer or an antidepressant at this treatment decision point. METHODS: Twelve-week, randomized, double-blind pilot trial comparing the addition of lamotrigine or citalopram for bipolar depressed patients on mood stabilizer medication. Change in depressive symptoms and risk of switch were examined. RESULTS: Twenty subjects were randomized. Each treatment group experienced a significant mean reduction in total MADRS scores (citalopram Delta - 14.2, p=0.002; lamotrigine Delta - 13.3, p= 0.001), and there was no significant difference between treatment groups (p=0.78). Total response rates increased from 31.6% at week 6 to 52.6% at week 12. One out of ten patients in each group experienced a switch to hypomania. LIMITATIONS: Small sample size. Lack of a placebo arm. CONCLUSIONS: Results of this small trial suggest that both lamotrigine and citalopram appear to be reasonable choices as add-on acute treatment for bipolar depression, with response rates continuing to rise considerably past 6 weeks of treatment.     

Effects on sleep: a double-blind study comparing trimipramine to imipramine in depressed insomniac patients

Trimipramine, a sedating tricyclic antidepressant, and imipramine were compared on polysomnographic parameters during a 4-week double-blind trial in depressed patients with insomnia and anxiety. Trimipramine eliminated objective evidence of sleep disturbance. This was not the case with imipramine, although depression improved similarly in both groups. Subjects' sleep appeared unchanged or more disturbed at the end of the treatment with imipramine. For trimipramine, the major changes in sleep parameters occurred during the first week of drug administration and did not parallel the gradual changes seen in the measures of depression. Additionally, trimipramine did not suppress REM sleep even in a subgroup of six trimipramine patients who had short rapid-eye-movement (REM) sleep latencies during the placebo baseline period, even though their depression was alleviated. The data demonstrate that (a) antidepressants may vary in their effects on sleep, even though they have similar effects on depression; (b) REM sleep suppression does not necessarily accompany improvement in depression; and (c) reports of improved sleep by patients undergoing antidepressant therapy may not reflect improvement on objective measures of sleep. The different sleep effects suggest the possibility of different antidepressant pathways.     

The role of metabolite-specific antibodies in nomifensine-dependent immune hemolytic anemia

Nomifensine is an antidepressant drug (widely used in Europe, but not yet available in the United States), which has been linked to intravascular hemolysis. We studied 19 patients (18 women and 1 man) with acute intravascular hemolysis due to nomifensine-dependent antibodies. Transitory renal insufficiency developed in at least seven patients, and four required temporary dialysis. To investigate the antibodies, we used nomifensine, its three main metabolites, and its ex vivo antigens (urine samples from a volunteer collected 1.5 to 16 hours after the ingestion of 100 mg of nomifensine). We found an extraordinary heterogeneity of antibody response. Only five antibodies appeared to be primarily reactive with nomifensine. The remaining antibodies reacted either optimally or exclusively in the presence of one or more of the metabolites. Three of the metabolite-specific antibodies were positive only in the presence of ex vivo antigens, indicating specificity for as-yet-unidentified early and late metabolites of nomifensine. All the antibodies were capable of activating complement and belonged to the IgG or IgM class or both. Two serum samples also contained weak IgA antibodies. In addition to a variable degree of cross-reactivity of the antibodies, at least one serum sample had two drug-dependent red-cell antibodies (IgG against nomifensine and IgM against metabolites), and one sample had a drug-dependent IgM red-cell antibody and an IgG platelet antibody. Despite their serologic heterogeneity, all the antibodies were strongly reactive with ex vivo antigens. We recommend the use of ex vivo antigens as the technique of choice for the detection of nomifensine-dependent (and probably other drug-dependent) antibodies.     

Alpha-1-acid glycoprotein in major depressive disorder. Relationships to severity, response to treatment and imipramine plasma levels

BACKGROUND: Increased plasma levels of alpha-1-acid glycoprotein (AGP) were reported in major depressive disorder. However, the relationship between AGP levels, severity of depression, treatment response and antidepressant levels are still unclear. METHODS: Plasma AGP levels were measured in 36 subjects with major depressive disorder before and after a 6-week treatment with imipramine and in 30 controls. Free imipramine plasma levels of depressed patients were measured at 6 weeks. Comparative analysis between depressed patients and controls, between non-responders (N = 12) and responders (N = 24), and between severely depressed patients (N = 14) and moderately depressed patients (N = 22) were made. RESULTS: Depressed patients had significantly higher mean values of AGP than control subjects. Imipramine non-responders and specially severely depressed patients had significantly greater increases of AGP levels during treatment than other depressed subgroups. There was no correlation between baseline AGP levels and severity of depression or free imipramine levels. LIMITATIONS: The most significant limitations of this study are the small sample size and the fact that all the subjects were out-patients. Results should not be generalized to in-patient populations. CONCLUSIONS: Depressed patients showed high baseline concentrations of AGP. AGP levels did not predict either free imipramine plasma levels or differential response after 6 weeks of treatment with imipramine. A greater increase of AGP during treatment was associated with severity of depression and treatment non-response. Clinical implications: The relationship between high plasma levels of AGP, severity of depression and lack of treatment response is clarified. The influence of imipramine levels is minimized.     

A cluster randomized trial comparing two interventions to improve treatment of major depression in primary care

BACKGROUND: Many patients with major depression are non-adherent to antidepressant medication and do not receive care according to current guidelines. There is increasing evidence that treatment of depression in primary care can be improved. Comparison between effective interventions may help to establish the active ingredients of such interventions. METHOD: In a randomized trial two interventions to improve treatment of major depression in primary care were compared (1) a depression care programme, targeting general practitioners (GPs), patients, and systematic follow-up, and (2) a systematic follow-up programme. Thirty GPs were randomized and 211 primary-care patients with current major depression were included. All patients were prescribed a selective serotonin reuptake inhibitor. Outcome measures included adherence to antidepressant medication, and depression outcome. RESULTS: No significant differences in adherence rates and treatment outcome measures were demonstrated between interventions at week 10 or week 26. Adherence rates were high and treatment outcome was favourable. CONCLUSIONS: The depression care programme was not superior to the systematic follow-up programme. Systematic follow-up in depression treatment in primary care seems to be an intervention per se, having the potential to improve adherence and treatment outcome.