John Tiller

Efficacy and cognitive effects of right unilateral electroconvulsive therapy

The efficacy, memory, and cognitive effects of right unilateral (RUL) electroconvulsive therapy (ECT) at 2.5 times threshold in 32 inpatients with moderate to severe major depressive disorder were evaluated at baseline, during the course of treatment, and 1 month after treatment. Neuropsychological assessment included the Randt Memory Test, Personal Memory Test, short-version Wechsler Adult Intelligence Scale–Revised, and Self-Rating Scale of Memory Functions. At the treatment end point, although the Hamilton Depression Rating Scale mean score was decreased by 54.2%, the response rate of 2.5 times threshold RUL ECT using stringent criteria was only 31.2%. Treatment was associated with significant anterograde memory impairment in the short term. Mean total scores of the Randt Memory Test and Personal Memory Test were decreased from baseline by 14.8% and 32.5%, respectively, after six sessions of ECT. These memory deficits were significantly improved by the 1 month follow-up examination. Subjective memory scores increased consistently during treatment, correlating with improvements in mood. No adverse effects on nonmemory cognition were found. Although RUL ECT at 2.5 times threshold is not associated with marked or persistent cognitive disturbances, its efficacy may be insufficient in clinical practice.

The identification and treatment of depression by General Practitioners

Objective: To assess the level of recognition and knowledge about treatment of depression by General Practitioners (GPs). Method: Analysis of questionnaires completed by participants commencing a series of workshops aimed at improving their knowledge of the diagnosis and treatment of depression. Of the 3289 GPs involved in the program 2500 (76%% respondent rate) completed the questionnaires in a group situation. There was no difference between respondents and nonrespondents in terms of age, gender and year of graduation. Results: The majority of GPs believe they have a satisfactory competence in the recognition and treatment of depression, although a sizeable minority based their diagnosis predominantly on somatic symptoms. The GPs felt confident about their knowledge and skills in counselling and the use of antidepressant medication, but not in dealing with children and suicidal or pregnant patients. The most common symptoms used to identify ‘depression’ were sleep disorders and only 54%% listed depressed mood as a symptom on which the diagnosis is based. Only 28%% reported sufficient symptoms to meet criteria for DSM-IV major depressive disorder, which supports views that these criteria are inappropriate for general practice. Fifty-seven percent of doctors used medicine together with nonpharmacological treatment in the majority of patients, and medications doses were almost all within the range recommended in the product information. Conclusions: There is a need to improve GPs knowledge in diagnosing depression, in child psychiatry and in dealing with pregnant and suicidal patients.

The dexamethasone suppression test: Importance of dexamethasone concentrations

Plasma dexamethasone concentrations and cortisol response to dexamethasone were measured in 29 normal healthy volunteers, 23 depressed patients, and 10 patients with anorexia nervosa at 4:00 PM postdexamethasone. In each of the 3 groups, nonsuppressors had lower dexamethasone concentrations than suppressors. Of the subjects with plasma dexamethasone at or below 0.7 ng/ml, a significantly higher proportion (48%) were nonsuppressors compared to the proportion above 0.7 ng/ml (14%), all of whom were patients. Plasma dexamethasone concentrations in a subgroup of depressed nonsuppressors were high (mean 1.35 ng/ml), whereas the remainder were low (0.42 ng/ml) and were similar to the normal nonsuppressors (0.35 ng/ml), suggesting different mechanisms for nonsuppression in the subgroups. Plasma dexamethasone concentrations were similar in nonendogenous and endogenous depressives, in men and women, and in medicated and drug-free patients. None of the variables of age, weight, history of weight loss, Hamilton depression rating score, predexamethasone cortisol, or postdexamethasone cortisol were significantly correlated with plasma dexamethasone, except for body weight and a history of weight loss in the depressed group only. Mean plasma dexamethasone concentrations increased significantly from week 1 to week 2 in 7 depressed patients, whereas plasma cortisol decreased; however, the relationship between dexamethasone and cortisol varied considerably for individual patients.

MOCLOBEMIDE AND FLUOXETINE FOR PANIC DISORDER

Abstract An international, multicentre, double blind parallel group study compared the tolerability and efficacy of moclobemide with the selective serotonin reuptake inhibitor (SSRI) fluoxetine for panic disorder. SSRIs have been shown effective for panic. The target dose of moclobemide was 450 mg and of fluoxetine was 20 mg. There were two consecutive studies. An eight week study of acute adverse events, tolerability and efficacy was followed by a long-term extension study to 1 year. The efficacy data showed no significant difference between moclobemide and fluoxetine. Both had acute efficacy, with 63 % moclobemide and 70 % fluoxetine patients (ns) panic free at 8 weeks. Both agents were well tolerated to 8 weeks, but noclobemide had fewer severe adverse events (5) that fluoxetine (9). There were no severe adverse events in the extension phase with either drug, and almost all patients completing 1 year extension treatment (moclobemide 61 patients, fluoxetine 65) were much or very much improved. These data suggest moclobemide and fluoxetine are tolerated and effective for both acute panic treatment and maintenance therapy.

Is diazepam an antidepressant

In double-blind sequential study, diazepam was compared with the proven antidepressant moclobemide, in patients with atypical depression. Both agents significantly improved depression ratings over eight weeks of treatment. Diazepam was a significantly better antidepressant than moclobemide at four week, although not at eight weeks. All patients ceased diazepam within one year and none reported withdrawal reactions. These data suggest the need to reconsider that benzodiazepines may be antidepressants and to study their possible antidepressant actions.

Moclobemide for anxiety disorders: a focus on moclobemide for panic disorder

Moclobemide is a reversible selective inhibitor of monoamine oxidase A. It has proven efficacy in a wide range of depressive disorders, including agitated anxious depression. In an international, multicentre, double-blind parallel-group study, the tolerability and efficacy of moclobemide were compared with that of the selective serotonin reuptake inhibitor fluoxctine. The target dose of moclobemide was 450 mg/day in the dose range of 300–600 mg/day, while the target dose for fluoxetine was 20 nig/day in the dose range of 10–30 mg/day. There were two consecutive studies. The first was an 8-week short-term study of acute adverse events, tolerabilily and efficacy. The efficacy data showed no significant difference between moclobemide and fluoxetine. Evaluation of the tolerability in a long-term study of up to 1 year is still in progress. A review of the moclobemide safety database for panic disorder with 624 patients showed a marginal increase in events with moclobemide compared with placebo for insomnia (11.2%), dizziness (4.5%) and dry mouth (3.7%), with rates for headaches and nausea lower for moclobemide than placebo.These data suggest moclobemide is a well tolerated and effective treatment for panic disorder.

A consensus statement for safety monitoring guidelines of treatments for major depressive disorder

Objective: This paper aims to present an overview of screening and safety considerations for the treatment of clinical depressive disorders and make recommendations for safety monitoring. Method: Data were sourced by a literature search using MEDLINE and a manual search of scientific journals to identify relevant articles. Draft guidelines were prepared and serially revised in an iterative manner until all co-authors gave final approval of content. Results: Screening and monitoring can detect medical causes of depression. Specific adverse effects associated with antidepressant treatments may be reduced or identified earlier by baseline screening and agent-specific monitoring after commencing treatment. Conclusion: The adoption of safety monitoring guidelines when treating clinical depression is likely to improve overall physical health status and treatment outcome. It is important to implement these guidelines in the routine management of clinical depression.

The dexamethasone suppression test: A study in a normal population

One hundred healthy, non-depressed volunteers were given a standard dexamethasone suppression test (DST) to determine the appropriate criterion values of plasma cortisol to define suppression or nonsuppression. By radioimmunoassay (RIA) of cortisol, the criterion value for 5% nonsuppression was plasma cortisol greater than 187 nmol/l, and for suppression less than 153 nmol/l, with an indeterminate range between these values. Use of the widely accepted pre-determined criterion value of 138 nmol/l gave a significantly greater frequency of nonsuppression. Values of cortisol measured by two RIAs in a subset of 43 volunteers were not equivalent. With the experimentally determined criterion value, no significant differences between nonsuppressors and suppressors were found for any measured physical or psychological parameters. Women taking oral contraceptives had significantly higher plasma cortisol pre-dexamethasone and post-dexamethasone. Their exclusion did not alter the calculated criterion value for the remainder, but their separately estimated criterion value was significantly higher. Caution should be exercised when classifying the DST status of women on oral contraceptives, particularly when values are at the lower end of the nonsuppressor range. Determination of a separate normal range for them may be warranted.

Dual action antidepressants and some important considerations

Objective: To review controlled studies of long-term treatment and their side-effects with newer dual action antidepressants following an acute episode of major depression. Method: A literature review (MedLine) was undertaken and references were selected for their relevance and methodology in describing their contribution to the examination of our objective. Result and Conclusion: Three dual action antidepressants are identified: venlafaxine, mirtazapine and milnacipran. These are more effective and better tolerated than the older tricyclic antidepressants in the treatment of an acute episode of depression and in the prevention of relapse. They also offer advantages in that they lack autonomic side-effects of the tricyclics. However, sedation, nausea and sexual side-effects may occur with venlafaxine, and weight gain with mirtazapine.

Effects of asenapine in bipolar I patients meeting proxy criteria for moderate-to-severe mixed major depressive episodes: a post hoc analysis.

OBJECTIVE Depression is the predominant psychosocial and suicide burden in bipolar disorder, yet there is a paucity of evidence-based treatments for bipolar depression. METHODS This post hoc subgroup analysis of data pooled from two 3-week, randomized, placebo- and olanzapine-controlled trials (December 2004-April 2006, N = 489 and November 2004-April 2006, N = 488) examined a subgroup of patients meeting criteria for moderate-to-severe mixed major depressive episodes, defined using DSM-IV-TR criteria for mixed episodes (mania and major depression simultaneously) with a baseline Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥ 20. RESULTS Decreases in MADRS scores (least squares mean [SE]), the a priori primary outcome, were significantly greater in the asenapine group than in the placebo group from baseline to day 7 (-11.02 [1.82] vs -4.78 [1.89]; P = .0195), day 21 (-14.03 [2.01] vs -7.43 [2.09]; P = .0264), and endpoint (-10.71 [1.76] vs -5.19 [1.98]; P = .039). Decreases in MADRS scores with asenapine were significantly greater than with olanzapine from baseline to day 7 (-6.26 [1.47]; P = .0436). Decreases in Young Mania Rating Scale mean total score were greater with asenapine than with placebo or olanzapine at all time points assessed. A significantly greater reduction from baseline to day 21 in the Short Form-36 mental component summary score was observed with asenapine, but not olanzapine, compared with placebo (16.57 vs 5.97; P = .0093). Asenapine was generally well tolerated. CONCLUSIONS These data provide support for the potential efficacy of asenapine in mixed major depressive episodes; however, these data cannot be linearly extrapolated to nonmixed major depression.