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Biomedical subjects

D Bakish

Publications and source records attributed to D Bakish.

54 records · Page 3Linked to original sources

Reduction in suicidal ideation with SSRIs: a review of 459 depressed patients.

This paper is a review of 459 outpatients treated in double-blind clinical drug trials using similar protocols which compared the clinical responses to specific serotonin reuptake inhibitors, norepinephrine reuptake inhibitors, mixed norepinephrine serotonin reuptake inhibitors, serotonin-2 antagonists and placebo. Although improvements in the total score on the Hamilton Rating Scale for Depression did not differ significantly among the groups, there were differences in the profile of response based on analysis of the items of the scale. The most striking difference was the significantly more rapid and effective improvement in depressed mood and the lessening of suicidal ideation among the patients treated with specific serotonin reuptake inhibitors.

Adolescent↗

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

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

Adult↗

A double-blind placebo-controlled comparison of moclobemide and amitriptyline in the treatment of depression.

The objective of this study was to determine if moclobemide is an effective treatment for depression and if it is well tolerated by patients. A randomized, double-blind placebo-controlled trial was conducted in a tertiary ambulatory clinic which treats depression. Fifty-five patients participated. They fit the DSM-III-R criteria for major depressive episode, scored at least 18 on the 17 item Hamilton Rating Scale for Depression (HRSD), were between the ages of 18 and 65, and were not suffering from a major medical illness. After a one week washout period, patients were randomly selected to receive placebo, amitriptyline or moclobemide for up to six weeks. Moclobemide is a well-tolerated medication at therapeutic doses; it is globally as effective as amitriptyline in the treatment of major depression.

Adult↗

A dose-finding study with remoxipride in the acute treatment of schizophrenic patients.

Two hundred and forty-two patients with acute schizophrenia were enrolled in a double-blind, comparative, dose-finding study of a novel antipsychotic, remoxipride. Remoxipride was evaluated in a low (30 to 90 mg), medium (120 to 240 mg) and a high (300 to 600 mg) dose range and compared with a haloperidol (15 to 45 mg), which was administered to a similar group of patients. The results support the antipsychotic effect of remoxipride, with maximum efficacy occurring at daily doses between 120 mg and 600 mg. Side-effects were more frequent at doses of remoxipride over 300 mg. In all groups, remoxipride caused consistently fewer extrapyramidal side-effects than haloperidol. The antipsychotic effect of remoxipride may be derived from specific blockade of dopamine D2 receptors in the mesolimbic tract. The findings also suggest that remoxipride may have a therapeutic effect on negative symptoms of schizophrenia.

Dose-Response Relationship, Drug↗

Event-related potentials and selective attention in major depressive illness.

Depressive episodes have been frequently characterized by deficits in information processing efficiency which are particularly evident when required to sustain or focus attention. As cerebral event-related potentials (ERPs) have been shown to reflect various aspects of selective attention and attentional dysfunction, this study attempted to examine ERPs in depressed patients performing a selective auditory attention task. Twenty-nine patients with a diagnosis of major depressive disorder (DSM-III) and 15 normal, non-psychiatric controls served as experimental subjects. Auditory potentials were recorded from the vertex of subjects who listened selectively to a series of tone pips in one ear and ignored concurrent tone pips to the other ear. Tone pips were delivered at short (320-500 ms) interstimulus intervals and subjects were required to detect, within the attended ear, rare 'target' tones of a different pitch than the more frequent 'standard' tones. In addition to behavioral indices of 'hits' and 'false alarms', ERP-derived measures included N1 amplitudes to attended and ignored stimuli, 'coefficients of attention' as calculated from N1 amplitude ratios and the latency onset and amplitude of the 'negative difference' (Nd) wave resulting from the subtraction of attended and ignored waveforms. Behavioral measures indicated that depressed patients were as efficient as controls in task performance and in fact they exhibited a significant left ear advantage in the additional task. Although a significant 'N1 effect' was observed with attended tones eliciting larger amplitudes than unattended tones, ERP measures of selective attention did not tend to differentiate the two groups.

Adult↗

Preparatory brain potentials in major depressive disorder.

1. Psychomotor slowing in depression is frequently reflected by delayed reaction times (RT). 2. The role of central arousal mechanisms in response slowing was examined by comparing scalp-recorded slow negative potentials of depressed patients with normal controls in two separate studies. 3. Varying fore-warned RT conditions elicited contingent negative variation (CNV) waveforms and the resultant mid-point amplitudes of these waveforms together with orienting (O-wave), expectancy (E-wave) and post-imperative negative variation (PINV) component amplitudes and sensory evoked responses (N1, P2) were compared between groups. 4. RTs were significantly slowed in depressed patients and the patient group exhibited consistently larger PINV amplitudes. Depending on the RT condition, patients also exhibited larger mid-point CNV amplitudes and smaller N1 and P2 amplitudes.

Adult↗

Fluoxetine potentiation by buspirone: three case histories.

The potentiation of fluoxetine by buspirone is described in three cases of treatment-resistant depression. All three patients improved markedly with very few side-effects from the medication. The possibility of synergy between drugs that affect serotonin reuptake inhibition, 5HT1A receptors and 5HT2 receptors is discussed.

Adult↗

Prediction of steady-state plasma levels of doxepin and imipramine from single dose levels in depressed outpatients.

We have investigated the predictive value of single dose levels for steady state levels of two commonly used antidepressants, doxepin (DOX) and imipramine (IMI) in a population of 40 outpatients with unipolar depression. After a wash-out period, patients were given 75 mg of either doxepin or imipramine and blood samples were drawn 16 h after the dose. Treatment was continued for 2 weeks on a fixed 100 mg/day dose and after that the dose was adjusted according to patients' response. Drugs and their demethylated metabolites were determined weekly using a GC technique. There was a large (more than 5-fold) inter-individual variation in both the single dose and steady-state levels of the two drugs. However, a significant correlation was found between the single-dose levels and initial steady-state levels for both. The respective linear regression equations were: DOX (parent drug & demethylated metabolite): y = 1.4x + 16.8; r = 0.75, p less than 0.001; IMI (parent drug & demethylated metabolite): y = 3.1x + 4.9; r = 0.85; p less than 0.001. These results confirm, in a population of depressed outpatients, previous findings of a significant correlation between single dose and steady state plasma levels of imipramine, and indicate for the first time that such a correlation also exists for another commonly used tricyclic antidepressant, doxepin. From this relationship, dose requirement can be estimated for individual patients to achieve a desired steady-state concentration of total tricyclics (parent drug & metabolite).

Adolescent↗

Cis- and trans-isomers of doxepin and desmethyldoxepin in the plasma of depressed patients treated with doxepin.

Plasma levels of doxepin and desmethyldoxepin were measured in split samples of 20 depressed patients treated with doxepin by using a conventional extraction and gas chromatography method on a packed column (method 1) and derivation of secondary amine and gas chromatography on a capillary column, allowing the separation and simultaneous quantitation of the cis- and trans-isomers of the two compounds (method 2). We have found that significantly higher levels of desmethyldoxepin and of total drug are detected in plasma when the two isomers are separated and measured by method 2. We concluded that the plasma levels of doxepin reported in most previous studies were underestimated since the cis- and trans-isomers were not separated and included in the total drug concentration. Because the activity of the two isomers is different and their proportion varies in individual patients, we suggest that in future studies correlating plasma levels and the clinical effects of doxepin, both the cis- and the trans-isomers of doxepin and desmethyldoxepin be determined.

Chromatography, Gas↗

A controlled dose-ranging study of remoxipride and haloperidol in schizophrenia--a Canadian multicentre trial.

The efficacy and side-effect profile for three dose ranges of remoxipride were compared with haloperidol in 242 schizophrenic inpatients in 13 centres. All patients were in a productive phase of schizophrenia according to DSM-III criteria. Relative efficacy of low dose (30-90 mg daily) vs middle dose (120-240 mg daily) vs high dose (300-600 mg daily) was compared with the standard dose of haloperidol (15-45 mg daily), as were the side effects. It was concluded that the therapeutic efficacy of remoxipride was comparable to that of haloperidol for acute episodes of schizophrenia; that the low dose range was significantly less effective than the higher ranges; that there was a clear advantage of remoxipride over haloperidol with respect to incidence and severity of extrapyramidal symptoms. The general safety profile of remoxipride as assessed from clinical chemistry, haematology, and cardiovascular variables suggests that remoxipride in the dose ranges studied can be used safely for the treatment of schizophrenic patients.

Acute Disease↗

Antidepressant plasma levels and clinical response in depressed patients treated with oxaprotiline and doxepin.

Relationship between plasma levels of a new tetracyclic antidepressant oxaprotiline and a tricyclic antidepressant doxepin, the clinical response and side-effects was studied in 30 patients with primary endogenous depression. Patients were treated following a placebo wash-out period with gradually increasing doses (75, 150, 225 mg/day) of either drug for 4 weeks. The clinical outcome (percentage of responders and of decrease in HAMD scores) was similar in groups of patients treated with the two drugs. No significant relationship was found between the plasma levels of the parent drugs (oxaprotiline or doxepin) and a measure of clinical response (HAMD scores). However, in patients treated with doxepin, there was a significant relationship between the therapeutic response and plasma levels of the drug's metabolite, desmethyldoxepin. In addition, side-effects were more frequently observed in patients with higher plasma levels of both drugs. Incidences of anticholinergic side-effects was significantly higher in patients treated with doxepin.

Adult↗

Disulfiram and bipolar affective disorder: a case report.

The authors describe a case of bipolar affective disorder associated with disulfiram therapy and its interaction with ethanol. They recommend caution when prescribing disulfiram for patients with personal and familial antecedents of affective illness.

Bipolar Disorder↗

Platelet 3H imipramine binding: a possible predictor of response to antidepressant treatment.

No significant difference in the density (Bmax) of platelet 3H imipramine recognition sites were found between the group of 20 unmedicated depressed patients and 10 healthy volunteers. The mean KD value was significantly higher in the population of depressives than in controls. Non-responders (after 2 weeks of treatment with antidepressants) had significantly lower initial Bmax values than responders or control subjects. Density of platelet 3H imipramine site may thus be a predictor of early response to antidepressant therapy. No significant sex differences were found in KD or Bmax values in the depressed group or in control subjects. There was, however, a seasonal variation in Bmax but not in KD values of platelet 3H imipramine binding.

Adult↗

Relaxation-induced EEG alterations in panic disorder patients.

Based on previous reports of relaxation-induced panic attacks in panic disorder patients, quantitative electroencephalographic (EEG) profiles and subjective anxiety ratings were assessed in panic disorder patients and normal controls listening to neutral and relaxation audiotapes. Regardless of tape condition, patients exhibited a greater frequency and severity of panic-related symptoms. Relaxation failed to alter panic-related symptom ratings or anxiety ratings in patients and controls. Theta and alpha increments were observed during relaxation, but only in normal controls. High frequency beta activity was less evident in patients, regardless of tape conditions. Results are discussed in relation to arousal and treatment issues in panic disorder.

Adult↗