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Biomedical subjects

R T Joffe

Publications and source records attributed to R T Joffe.

At least 91 records · Page 5Linked to original sources

Thyroid hormones, the brain, and affective disorders.

Clinical thyroid disorders are frequently associated with psychiatric symptomatology, thus supporting a role for thyroid hormones in the biological basis of psychiatric disorders, particularly mood disorders. Despite extensive literature documenting various abnormalities of thyroid function tests in primary major depression, the role of thyroid hormones in the pathophysiology of affective disorders remains to be clarified. In this review, we describe the various abnormalities of thyroid hormone levels reported in primary affective illness. We also review the competing hypothesis to explain the abnormalities of thyroid function observed. Although neither model can fully explain the role of thyroid hormones in depressive illness, they provide working hypotheses for further study. Additional research is required to clarify the regulation of thyroid hormones by mature brain and the role of these hormones in the biological basis of affective illness.

Brain↗

Combined SSRI-moclobemide treatment of psychiatric illness.

BACKGROUND: To determine the efficacy and safety of a serotonin selective reuptake inhibitor (SSRI) combined with moclobemide in the treatment of 11 patients with various DSM-III-R diagnoses. METHOD: Subjects received moclobemide in doses of 150 to 800 mg/day together with sertraline (N = 5) in doses of 25 to 200 mg/day or fluvoxamine (N = 6) in doses of 50 to 200 mg/day. Patients were carefully monitored for side effects and for clinical response at the end of the trial, which lasted a minimum of 5 weeks. RESULTS: The combination was tolerated extremely well. Insomnia was the most common side effect, occurring in 5 of 11 subjects. A marked or complete therapeutic response was noted in 8 of 11 subjects. CONCLUSION: This open clinical trial suggests that combined SSRI-moclobemide treatment appears to be safe and well tolerated. It may also have therapeutic effects in treatment-refractory patients.

1-Naphthylamine↗

A placebo-controlled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression.

OBJECTIVE: To directly compare the efficacy of lithium carbonate and liothyronine sodium (triiodothyronine) in the augmentation of therapeutic response in antidepressant nonresponders. DESIGN: A randomized, double-blind, placebo-controlled study of 2 weeks' duration. SETTING: The Mood Disorders Program, Clarke Institute of Psychiatry and the University of Toronto, Ontario. PATIENTS: Fifty outpatients, males and females, with unipolar, nonpsychotic major depression who had failed to respond to treatment with desipramine hydrochloride or imipramine hydrochloride. RESULTS: Both liothyronine and lithium were more effective than placebo in reducing scores on the Hamilton Rating Scale for Depression. However, the antidepressant augmenting effect of these two compounds did not differ from each other. When response was defined as a 50% or more reduction in the Hamilton Rating Scale for Depression scores and a final score less than 10, we found that 10 of 17 subjects responded to liothyronine, nine of 17 responded to lithium and three of 16 responded to placebo. CONCLUSIONS: Our study suggests that both lithium and liothyronine may be considered as alternatives in augmenting antidepressant response in patients who do not respond to treatment with a tricyclic antidepressant.

Adult↗

Anxiety disorders and anxiety symptoms in a clinic sample of seasonal and non-seasonal depressives.

Thirty-eight patients with seasonal affective disorder (SAD) were compared with 33 non-seasonal recurrent major depressives (non-SAD) who presented during the winter months for differences in the prevalence of concurrent anxiety disorders and the impact of anxiety on treatment response. SAD patients received light therapy, whereas non-SAD patients received antidepressant medications. There was no differences in the prevalence of any anxiety disorder, or on scores of anxiety on the Hamilton Rating Scale for Depression between the SAD and non-SAD groups. The presence of any anxiety disorder was associated with a better response rate in SAD patients, and an inferior response rate in non-SAD patients. The findings refute previous suggestions that anxiety is more common in SAD than in non-SAD, but suggest that the presence of anxiety may be associated with differential treatment response rates.

Adult↗

Anxious and non-anxious bipolar disorder.

Eighty-one outpatients with bipolar disorder (BD) were grouped by SADS anxiety symptom scores (high vs. low) or diagnosis of generalized anxiety disorder, and/or panic disorder. BD patients with high anxiety scores were more likely to have suicidal behaviour (44% vs. 19%), alcohol abuse (28% vs. 6%), cyclothymia (44% vs. 21%) and an anxiety disorder (56% vs. 25%) with a trend toward lithium non-responsiveness. Diagnosis of an anxiety disorder was related only to high anxiety and lower GAS scores. Thus, anxiety may have similar clinical relevance in BD as it does in unipolar patients.

Adult↗

Light visor treatment for seasonal affective disorder: a multicenter study.

The effectiveness of light therapy in seasonal affective disorder (SAD) was evaluated in 105 subjects across five centers. Three intensities of light (60 lux, 600 lux, and 3500 lux) were used in a 2-week randomized, parallel design. There was no significant difference in antidepressant efficacy of the three intensities of light. All three intensities produced a similar frequency of antidepressant response to each other and to that reported in previous studies. There were site differences in the severity of depression during light treatment, but diagnosis and medication status did not affect antidepressant response. These findings suggest that light therapy has an antidepressant action by a nonspecific effect or that light is biologically active in the treatment of SAD across a wide range of intensities.

Adult↗

Inhibition by fluoxetine of cytochrome P450 2D6 activity.

Potent inhibition of cytochrome P450 2D6 (CYP2D6) in human liver microsomes by fluoxetine and its major metabolite norfluoxetine was confirmed (apparent inhibition constant values, 0.2 mumol/L). Several other serotonergic agents were also found to be competitive inhibitors of this genetically polymorphic enzyme. The O-demethylation ratio of dextromethorphan that expressed CYP2D6 activity in 19 patients receiving fluoxetine fell in the region of the antimode separating the O-demethylation ratio values observed in 208 extensive metabolizers from 15 poor metabolizers of a control group of healthy subjects. Inhibition of CYP2D6 activity in patients undergoing treatment with fluoxetine or other serotonin uptake inhibitors could contribute to toxicity or attenuated response from concurrent medications that are substrates of this enzyme. Other in vitro studies indicated that CYP2D6 catalyzes the O-demethylation of oxycodone to form oxymorphone. This reaction was inhibited by fluoxetine and its normetabolite in liver microsomes from both extensive and poor metabolizer individuals, indicating that these compounds are not selective inhibitors of CYP2D6 activity.

Adult↗

Clinical features of situational and nonsituational major depression.

Clinical lore has long supported the subtype of situational or reactive depression. To date, however, there has been limited empirical research support for this subtype of major depression. We examined demographic, clinical and personality features of situational and nonsituational depression in 89 outpatients with unipolar nonpsychotic major depressive disorder. Situational depressives had a less recurrent course of illness and appeared to respond more completely to the antidepressant used for their current episode. Demographic and personality measures did not distinguish situational and nonsituational depression.

Adult↗

Side effects of light therapy in seasonal affective disorder.

The authors report the frequency of side effects of light therapy in 105 patients with seasonal affective disorder treated with three intensities of light. Common symptoms to emerge during treatment were headache (19%), eyestrain (17%), and feeling "wired" (14%). There was no relationship between side effects and intensity of light used.

Female↗

The Tridimensional Personality Questionnaire in major depression.

The authors examined Tridimensional Personality Questionnaire scores in 40 patients with unipolar nonpsychotic major depression before and after antidepressant treatment. They found that scores on the novelty seeking and reward dependence dimensions were not affected by depressed state or by treatment response status. However, scores on the harm avoidance dimension were significantly lower in antidepressant responders and were altered by depressed state.

Adult↗

Anxious and nonanxious depression.

The authors used the anxiety summary score described by Clayton and associates to assess anxious and nonanxious subtypes of depression in a group of 134 outpatients with major depression. Patients with anxious depression were only slightly less likely to respond to their first tricyclic antidepressant than patients with nonanxious depression. When functional severity or symptom severity was controlled for, this differential treatment response did not hold.

Adult↗

Predictors of response to lithium and triiodothyronine augmentation of antidepressants in tricyclic non-responders.

Although both lithium and triiodothyronine (T3) augmentation strategies may be rapid, safe, and effective ways of treating patients who fail to respond to tricyclics, little is known about the clinical or biochemical correlates of response. We examined clinical and endocrine variables which distinguished T3 and lithium responders from each other and from non-responders in a post-hoc analysis of two studies involving 51 subjects who had received these augmentation strategies under double-blind conditions. Lithium non-responders were more severely depressed and had more insomnia and weight loss than responders. T3 responders could be distinguished from lithium responders by greater weight loss. There were no reliable clinical differences between T3 responders and non-responders. Thyroid function tests did not differ between any of the treatment or response groups. Our findings suggest that clinical but not endocrine variables may distinguish responders to these two augmentation strategies.

Adult↗

Valproate in bipolar disorder: the Canadian perspective.

Lithium is the primary treatment for bipolar disorder. However, a substantial proportion of patients are either lithium-resistant or develop side-effects which limit the effectiveness of treatment. The anticonvulsants, particularly valproate and carbamazepine, are alternatives to lithium in the treatment of bipolar disorder. The data on the efficacy of these compounds are reviewed. Clinical issues relating to their use as an alternative to lithium and potentially as a first-line treatment are discussed. The role of anticonvulsants in the broad range of treatment options available for bipolar patients are evaluated.

Anticonvulsants↗

An open study of buspirone augmentation of serotonin reuptake inhibitors in refractory depression.

BACKGROUND: We evaluated the efficacy of buspirone in the augmentation of antidepressant response to the serotonin reuptake inhibitors. METHOD: Twenty-five patients with major depressive disorder who had failed several previous treatments for their current depressive episode were included. After failing a trial of fluoxetine or fluvoxamine, they received buspirone in addition to the serotonin reuptake inhibitor for 3 weeks in an open clinical trial. RESULTS: Seventeen of 25 patients had a marked or complete antidepressant response. CONCLUSION: These data provide clinical evidence suggesting that buspirone augmentation may be useful clinical alternative in depressed patients who fail to respond to a serotonin reuptake inhibitor.

Adult↗

Diagnostic specificity of the dependent and self-critical personality dimensions in major depression.

Validational studies of self-critical and dependent personality dimensions as vulnerability factors for depression have been tested primarily with depressed samples, employing research designs devised to address state vs. trait and trait-situational congruity issues. In this study we examined the diagnostic specificity to depression of these two personality dimensions, comparing Self-Criticism and Dependency scores as measured by the Depressive Experiences Questionnaire (DEQ) in two samples of outpatients: (1) panic disorder with agoraphobia; and (2) non-psychotic, unipolar major depression. As hypothesized, the two groups differed on Self-Criticism, with the depressed group scoring higher, but no differences were found for Dependency. These findings were similar even when depressed mood was partialed out. These results complement a growing body of research associating Self-Criticism, as specifically measured by the DEQ, with depression.

Adult↗