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Biomedical subjects

Sidney Kennedy

Publications and source records attributed to Sidney Kennedy.

5 recordsLinked to original sources

EEG correlates of acute and chronic paroxetine treatment in depression.

Single dose administration of efficacious antidepressant agents elicit characteristic pharmaco-electroencephalographic (EEG) profiles in healthy volunteers but acute and chronic pharmaco-EEG profiling of antidepressant action in depressed patients has been relatively lacking. This study sought to examine the quantitative topographic EEGs of depressed patients in response to paroxetine treatment. Thirty male patients, meeting DSM-IV criteria for major depression, were examined before and after a single 20 mg dose. These, and an additional 40 patients, were also assessed following 6 weeks of treatment. Eyes-closed resting EEG, collected from 21 scalp sites, was spectrally analyzed to yield regional measures of absolute/relative power and mean frequency in delta, theta, alpha, beta and total spectrum frequency bands. Chronic treatment resulted in a significant reduction in scores on the Hamilton Rating Scale for Depression (HAM-D), with 80% of treatment completers exhibiting a >50% reduction in depression ratings at the end of the 6th week. Acute paroxetine did not alter EEG in patients but chronic treatment was associated with significant alterations as shown by diffuse decreases in alpha power and increases in slow (delta and theta) and anterior fast (beta) wave power, Mean theta and alpha (occipital) frequency were slowed while mean total frequency was accelerated at frontal sites and decreased at occipital sites. The chronic pharmaco-EEG response pattern reflects both sedating and activating actions in regional specific areas which are relevant to the pathophysiology and the pharmacotherapeutic treatment of depression.

Adult↗

Assessing full remission.

The 17-item Hamilton Rating Scale for Depression (HAM-D17) has been used for 4 decades as the "gold standard" instrument to assess the severity of depression and response to therapy in clinical research. The clinical utility of the HAM-D17 is hampered, in part, by the length of time required to administer the interview and by concern about a lack of inter-rater reliability. Several groups have developed shorter versions of the HAM-D17 for use in clinical practice. However, despite extensive research highlighting the importance of achieving full remission in minimizing the risk of relapse and recurrence, these shortened questionnaires have not been validated for the task of distinguishing between remission and response. A shortened form of the HAM-D17 with cut-off scores for full remission would offer a useful tool that physicians could readily employ in clinical practice. On the basis of the responses of a sample of 292 patients with major depression who received standard clinical treatment at a tertiary university affiliated hospital (Depression Clinic, Centre for Addiction and Mental Health, Toronto Ont.) we derived a shortened version of the HAM-D. Seven items with the greatest frequency of occurrence and sensitivity to change with treatment were identified and designated as the Toronto HAM-D7. A score of 3 or less on the Toronto HAM-D7 was found to correlate with the 17-item HAM-D definition of full remission (i.e., score of 7 or less).

Adult↗

Prevalence and outcome of partial remission in depression.

The goal of treatment of major depression should be full remission. Many patients, however, fail to achieve or maintain symptom-free status. Residual depressive symptoms are common, even where there has been a robust response to antidepressant therapy. In clinical studies, approximately one-third of patients achieve a full remission, one-third experience a response and one-third are nonresponders. Partial remission is characterized by the presence of poorly defined residual symptoms. These symptoms typically include depressed mood, psychic anxiety, sleep disturbance, fatigue and diminished interest or pleasure. It is currently unclear which factors predict partial remission. However, it is clear that residual symptoms are powerful predictors of relapse, with relapse rates 3-6 times higher in patients with residual symptoms than in those who experience full remission. Residual symptoms are also associated with more medical and psychiatric visits, increased public assistance, disability benefits, thoughts of and attempts at suicide and chronicity. The risk of stroke and coronary events is also higher in patients with residual depressive symptoms. The substantial proportion of patients who achieve only partial remission has traditionally been neglected in antidepressant trials. Given that residual symptoms may relate, in part, to an incompatibility between patient and treatment, further research is needed to predict a better match. These symptoms are a clinically relevant state of illness, and the correct choice of initial antidepressant treatment should offer the greatest chance of achieving full remission.

Adult↗

Pharmacotherapy to sustain the fully remitted state.

Full remission should be the goal of antidepressant therapy; anything less leaves the patient with residual symptoms and an increased risk of relapse and recurrence. Most antidepressant agents offer similar rates of response, but there are some differences in the ability of different agents to promote a full remission. The greatest chance of achieving full remission occurs early in the course of treatment; thus, initial antidepressant strategies should be those that have the greatest therapeutic potential. Other strategies that may help improve the chances of achieving full remission include optimizing drug dosages and using combination and augmentation strategies. Failure to achieve full remission and early discontinuation of antidepressant therapy have been associated with a greater incidence of relapse and recurrence. Continued antidepressant therapy has clearly been shown to effectively reduce the probability of relapse and recurrence by about half compared with placebo. Therefore, once a patient achieves remission, it is important to continue the same antidepressant therapy for at least 6-12 months and, for many patients, considerably longer. Medication should continue at the dose that was initially effective because using low-dose maintenance therapy appears to decrease the protective benefits.

Antidepressive Agents↗