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Biomedical subjects

Guy M Goodwin

Publications and source records attributed to Guy M Goodwin.

At least 37 records · Page 2Linked to original sources

Long-term lithium therapy for bipolar disorder: systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The authors sought to determine the efficacy and acceptability of lithium for relapse prevention in bipolar disorder. METHOD: A systematic review and meta-analysis of randomized controlled trials comparing lithium with placebo in the long-term treatment of bipolar disorders was conducted. Data were obtained from searching the registers of the Cochrane Collaboration; reviewing reference lists, journals, and conference abstracts; and contacting authors, experts, and pharmaceutical companies. Outcomes investigated included risk of relapse (manic, depressive, and total) as well as risk of specific adverse effects and total withdrawal rates. RESULTS: Five randomized controlled trials (770 participants) were included. Lithium was more effective than placebo in preventing all relapses (random effects relative risk=0.65, 95% CI=0.50 to 0.84) and manic relapses (relative risk=0.62, 95% CI=0.40 to 0.95). The protective effect of lithium on depressive relapses was smaller and was less robust (relative risk=0.72, 95% CI=0.49 to 1.07). CONCLUSIONS: Lithium treatment reduces the risk of relapse in bipolar disorder. The preventive effect is clear for manic episodes, although it is equivocal for depressive episodes.

Antimanic Agents↗

Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition.

OBJECTIVE: Antidepressants that inhibit the reuptake of serotonin (SSRIs) or norepinephrine (SNRIs) are effective in the treatment of disorders such as depression and anxiety. Cognitive psychological theories emphasize the importance of correcting negative biases of information processing in the nonpharmacological treatment of these disorders, but it is not known whether antidepressant drugs can directly modulate the neural processing of affective information. The present study therefore assessed the actions of repeated antidepressant administration on perception and memory for positive and negative emotional information in healthy volunteers. METHOD: Forty-two male and female volunteers were randomly assigned to 7 days of double-blind intervention with the SSRI citalopram (20 mg/day), the SNRI reboxetine (8 mg/day), or placebo. On the final day, facial expression recognition, emotion-potentiated startle response, and memory for affect-laden words were assessed. Questionnaires monitoring mood, hostility, and anxiety were given before and after treatment. RESULTS: In the facial expression recognition task, citalopram and reboxetine reduced the identification of the negative facial expressions of anger and fear. Citalopram also abolished the increased startle response found in the context of negative affective images. Both antidepressants increased the relative recall of positive (versus negative) emotional material. These changes in emotional processing occurred in the absence of significant differences in ratings of mood and anxiety. However, reboxetine decreased subjective ratings of hostility and elevated energy. CONCLUSIONS: Short-term administration of two different antidepressant types had similar effects on emotion-related tasks in healthy volunteers, reducing the processing of negative relative to positive emotional material. Such effects of antidepressants may ameliorate the negative biases in information processing that characterize mood and anxiety disorders. They also suggest a mechanism of action potentially compatible with cognitive theories of anxiety and depression.

Adrenergic Uptake Inhibitors↗

Antidepressants for bipolar depression: a systematic review of randomized, controlled trials.

OBJECTIVE: This study reviewed the evidence from randomized, controlled trials on the efficacy and safety of antidepressants in the short-term treatment of bipolar depression. METHOD: The authors performed a systematic review and meta-analysis of randomized, controlled trials. They searched the Cochrane Collaboration Depression, Anxiety, and Neurosis Controlled Trials Register, incorporating results of searches of MEDLINE, EMBASE, CINAHL, PsycLIT, PSYNDEX, and LILACS. The main outcome measures were the proportion of patients who clinically responded to treatment and the rate of switching to mania. RESULTS: Twelve randomized trials were included, with a total of 1,088 randomly assigned patients. Five trials compared one or more antidepressants with placebo: 75% of these patients were receiving a concurrent mood stabilizer or an atypical antipsychotic. Antidepressants were more effective than placebo. Antidepressants did not induce more switching to mania (the event rate for antidepressants was 3.8% and for placebo, it was 4.7%). Six trials allowed comparison between two antidepressants. The rate of switching for tricyclic antidepressants was 10%, and for all other antidepressants combined, it was 3.2%. CONCLUSIONS: Antidepressants are effective in the short-term treatment of bipolar depression. The trial data do not suggest that switching is a common early complication of treatment with antidepressants. It may be prudent to use a selective serotonin reuptake inhibitor or a monoamine oxidase inhibitor rather than a tricyclic antidepressant as first-line treatment. Given the limited evidence, there is a compelling need for further studies with longer follow-up periods and careful definition and follow-up of emerging mania and partial remission.

Adult↗

Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials.

The objective of this review was to determine the effectiveness, adverse effects and acceptability of folate in the treatment of depression. Electronic databases (Cochrane Controlled Trials Register and the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register) and reference lists were searched, and authors, experts and pharmaceutical companies contacted to identify randomized controlled trials that compared treatment with folic acid or 5'-methyltetrahydrofolic acid to an alternative treatment, for patients with a diagnosis of depressive disorder. Three randomized trials (247 participants) were included. Two studies assessed the use of folate in addition to other treatment, and found that adding folate reduced Hamilton Depression Rating Scale (HDRS) scores on average by a further 2.65 points [95% confidence interval (CI) 0.38-4.93]. Fewer patients treated with folate experienced a reduction in their HDRS score of less than 50% at 10 weeks (relative risk 0.47, 95% CI 0.24-0.92). The remaining study found no statistically significant difference when folate alone was compared with trazodone. The identified trials did not find evidence of any problems with the acceptability or safety of folate. The limited available evidence suggests folate may have a potential role as a supplement to other treatment for depression. It is currently unclear if this is the case both for people with normal folate levels, and for those with folate deficiency.

Administration, Oral↗

A pooled analysis of 2 placebo-controlled 18-month trials of lamotrigine and lithium maintenance in bipolar I disorder.

BACKGROUND: Two clinical trials, prospectively designed for combined analysis, compared placebo, lithium, and lamotrigine for treatment of bipolar I disorder in recently depressed or manic patients. METHOD: 1315 bipolar I patients (DSM-IV) enrolled in the initial open-label phase, and 638 were stabilized and randomly assigned to 18 months of double-blind monotherapy with lamotrigine (N = 280; 50-400 mg/day fixed dose or 100-400 mg/day flexible dose), lithium (N = 167; serum level of 0.8-1.1 mEq/L), or placebo (N = 191). The primary endpoint was time from randomization to intervention for a mood episode. Data were gathered from August 1997 to August 2001. RESULTS: Lamotrigine and lithium were superior to placebo for time to intervention for any mood episode (median survival: placebo, 86 days [95% CI = 58 to 121]; lithium, 184 days [95% CI = 119 to not calculable]; lamotrigine, 197 days [95% CI = 144 to 388]). Lamotrigine was superior to placebo for time to intervention for depression (median survival: placebo, 270 days [95% CI = 138 to not calculable]; lithium, median not calculable; lamotrigine, median not calculable). Lithium and lamotrigine were superior to placebo for time to intervention for mania (median survival not calculable for any group). Results of additional analyses adjusted for index mood were similar; however, only lithium was superior to placebo for intervention for mania. There was no evidence that either active treatment caused affective switch. Adverse event analysis indicated more diarrhea (19% vs. 7%, p <.05) and tremor (15% vs. 4%, p <.05) in lithium-treated patients compared with lamotrigine-treated patients. CONCLUSIONS: Lamotrigine and lithium stabilized mood by delaying the time to treatment for a mood episode. Lamotrigine was effective against depression and mania, with more robust activity against depression. Lithium was effective against mania.

Adult↗

The role of the anterior cingulate cortex in the counting Stroop task.

The role of the anterior cingulate in the counting Stroop task was examined using transcranial magnetic stimulation (TMS). TMS was given over sites targeting more dorsal and more ventral anterior cingulate cortex and a control area of parietal cortex whilst subjects reported the number of words presented on the screen using a key press. The Stroop interference effect was abolished by TMS over both anterior cingulate sites. These findings support functional neuroimaging research which suggests that cingulate cortex is central to the processes underlying the Stroop task.

Adult↗

Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review.

BACKGROUND: Antidepressant drugs can promote remission from acute depressive episodes. Our aim was to establish how long such treatments should be continued to prevent relapse. METHOD: We did a systematic overview of evidence from randomised trials of continuing treatment with antidepressants in patients with depressive disorders who have responded to acute treatment. Medline, Embase, Cinahl, PsycLIT, Psyndex, and Lilacs were searched. FINDINGS: Data were pooled from 31 randomised trials (4410 participants). Continuing treatment with antidepressants reduced the odds of relapse by 70% (95% CI 62-78; 2p<0.00001) compared with treatment discontinuation. The average rate of relapse on placebo was 41% compared with 18% on active treatment. The treatment effect seemed to persist for up to 36 months, although most trials were of 12 months' duration, and so the evidence on longer-term treatment requires confirmation. Significantly more participants allocated antidepressants withdrew from the trials than did those allocated to placebo (18% vs 15%, respectively; odds ratio 1.30, 95% CI 1.07-1.59): the treatment effect could be even greater in adherent patients. The two-thirds reduction in risk of depressive relapse seemed to be largely independent of the underlying risk of relapse, the duration of treatment before randomisation, or the duration of the randomly allocated therapy. INTERPRETATION: Antidepressants reduce the risk of relapse in depressive disorder, and continued treatment with antidepressants would benefit many patients with recurrent depressive disorder. The treatment benefit for an individual patient will depend on their absolute risk of relapse with greater absolute benefits in those at higher risk. Further trials are needed to establish the optimum length of therapy and should include patients who were not well represented in these trials, including those at low risk of relapse.

Antidepressive Agents↗

Latest maintenance data on lithium in bipolar disorder.

Although lithium is generally considered to be the gold standard for maintenance therapy in bipolar disorder, evidence of its efficacy has rested on only a small number of adequately designed studies. Results from the lamotrigine bipolar trials, which included lithium as an active comparator, will substantially increase confidence in long-term lithium treatment. In a meta-analysis of these data, lithium was significantly more effective than placebo in preventing relapse in patients with bipolar disorder (relative risk [RR] 0.65; 95% confidence interval [CI] 0.50, 0.84). Furthermore, lithium had significant efficacy against manic relapse (RR 0.61; 95% CI 0.39, 0.95), with a less substantial, not statistically significant, effect against depressive relapse (RR 0.72; 95% CI 0.49, 1.07). Factors such as disease subtype, likelihood of adherence to treatment regimen, tolerability, and dose uncertainty should be considered in the selection of lithium maintenance therapy.

Bipolar Disorder↗

Toward a neuropsychological theory of antidepressant drug action: increase in positive emotional bias after potentiation of norepinephrine activity.

OBJECTIVE: Antidepressants that increase serotonin or norepinephrine in the brain are effective in treating depression, but there is no neuropsychological account of how these changes relieve depressive states. Cognitive theories suggest that biases in information processing lead depressed patients to make unrealistically negative judgments about themselves and the world. METHOD: A single dose of the noradrenergic antidepressant reboxetine or placebo was administered to 24 healthy volunteers. Effects on emotional processing were assessed through facial expression recognition, emotional categorization, and emotional memory. RESULTS: On the three measures, reboxetine biased perception toward positive, rather than negative, information in the absence of changes in nonemotional performance or mood. CONCLUSIONS: These results suggest that a single dose of an antidepressant can increase the processing of positively valenced material in nondepressed volunteers. Antidepressants may therefore work in a manner similar to that of psychological treatments that aim to redress negative biases in information processing.

Adrenergic Uptake Inhibitors↗

The British Association for Psychopharmacology guidelines for treatment of bipolar disorder: a summary.

The BAP has provided a review of the research evidence and clinical experience in the treatment of bipolar disorder. It has produced guidelines that give very real practical advice to clinicians in the day-to-day management of this difficult condition. Its recommended enhancement of routine care may well increase adherence to treatment, especially if the patient is involved in choice of medicine, leading to lower overall morbidity. It is timely since awareness of the specific needs of bipolar patients is growing and there is an increased choice of effective treatments for all phases of the illness.

Antidepressive Agents↗

Acute administration of citalopram facilitates memory consolidation in healthy volunteers.

OBJECTIVES: Decreasing serotonergic neurotransmission in humans has been found to impair memory consolidation. Such effects may be relevant to the memory deficits seen in major depression and the cognitive actions of antidepressant drugs used to treat them. However, the improvement in cognitive function often found following successful pharmacological treatment in depression may be confounded by symptom improvement. RATIONALE: The present study assessed the effects of an acute challenge with the selective serotonergic re-uptake inhibitor citalopram in healthy (non-depressed) females. METHODS: Immediate and delayed recall/recognition was assessed using the auditory verbal learning test following 10 mg (intravenous) citalopram or placebo in a double-blind between groups design. RESULTS: Immediate recall on the verbal memory test was unaffected by citalopram administration. However, volunteers receiving citalopram showed enhanced long-term memory performance in terms of delayed recall and recognition relative to those receiving placebo. Sustained attention performance was also comparable in the two groups of subjects suggesting that non-specific increases in information processing are not responsible for this effect. CONCLUSIONS: These results indicate that augmentation of serotonergic neurotransmission is associated with increased memory consolidation, which may be relevant to its therapeutic and cognitive actions in acutely depressed patients.

Adult↗

Enhanced recognition of disgust in bipolar illness.

BACKGROUND: Bipolar disorder is associated with functional and structural abnormalities in the brain circuits involved in processing emotional stimuli. Although impairments of cognitive function have been found to persist in bipolar patients during periods of euthymic mood, it is not known whether abnormalities in emotional processing also occur during these periods of recovery. METHODS: The present investigation assessed the ability of euthymic patients with bipolar disorder to recognize different facial expressions of emotion, compared with matched controls. A nonemotional facial categorization task was used to control for possible nonspecific differences in perception or attention. RESULTS: In contrast to the small impairments seen in the nonemotional categorization task, patients with bipolar disorder showed a robust facilitation in the discrimination of disgusted facial expressions. The recognition of other basic negative and positive emotions was unchanged. CONCLUSIONS: The present results suggest a selective facilitation of the processes involved in recognizing facial expressions of disgust in patients with bipolar disorder. This difference in perception may be relevant to the decreased self-esteem and social functioning that have been associated with the euthymic phase of this disorder.

Adult↗

A dose-finding study on the effects of branch chain amino acids on surrogate markers of brain dopamine function.

RATIONALE: We have previously shown in healthy volunteers that an amino acid mixture lacking tyrosine and phenylalanine reduces tyrosine availability to the brain and produces cognitive and neuroendocrine effects consistent with reduced dopamine function. This could provide a potential nutritional approach to disorders such as mania and schizophrenia, which are characterised by overactivity of dopamine pathways. The amino acid mixture we tested previously is unpalatable, whereas mixtures containing only branch chain amino acids can be made more palatable. However, the effects of such mixtures on dopamine function in humans have not been studied. OBJECTIVE: To assess the tolerability of different doses of branch chain amino acids and to measure their effects on neuroendocrine and cognitive measures sensitive to changes in dopamine function. METHODS: We used a randomised, double-blind, cross-over design in 12 healthy volunteers to assess the effect of single oral doses of 10 g, 30 g and 60 g branch chain amino acids on plasma prolactin and a test of spatial recognition memory RESULTS: The branch chain amino acids were well tolerated. The availability of tyrosine for brain catecholamine synthesis decreased in a dose-related manner. As hypothesised, the drink increased both the plasma prolactin and the latency to respond on the spatial recognition memory task. CONCLUSIONS: A drink containing branch chain amino acids is well tolerated in healthy volunteers and produces effects consistent with lowered dopamine function.

Adult↗

Sustained attention deficit in bipolar disorder is not a working memory impairment in disguise.

Euthymic patients with bipolar disorder have been reported to show persistent deficits in sustained attention. However, the sustained attention task which was used also placed demands on working memory. Bipolar disorder patients in the euthymic state were therefore compared with healthy controls on two measures of sustained attention with and without a working memory component. Signal detection methodology was applied to the results. Euthymic patients with bipolar disorder were particularly impaired at detecting targets in the sustained attention task without a working memory component. This deficit was still apparent in a sub-group of patients who were not currently receiving lithium medication. By contrast, performance in the sustained attention task involving working memory task was not significantly different in the two groups. Sustained attention deficits apparent during the euthymic period of bipolar disorder cannot be explained in terms of working memory impairment and represents a reduced inherent capacity rather than a change in response bias. Deficits in sustaining attention may help explain the difficulties in psychological and occupational functioning in bipolar disorder patients during remission.

Adult↗

Sustained attention deficit in bipolar disorder.

BACKGROUND: Recovery in bipolar disorder is central to its definition but is rarely complete. Previous work has suggested that neuropsychological impairment persists during the euthymic state but has been confounded partly by mild affective symptoms in remitted patients. AIMS: To characterise neuropsychological functioning in the euthymic phase of bipolar disorder with an emphasis on tasks of executive functioning. METHOD: Thirty euthymic patients with bipolar disorder were compared with thirty healthy controls on neuropsychological tasks differentially sensitive to damage within prefrontal cortex. RESULTS: Bipolar I patients were impaired on tasks of attentional set shifting, verbal memory and sustained attention. Only sustained attention deficit survived controlling for mild affective symptoms. This deficit was related to progression of illness, but was none the less present in a subgroup of patients near illness onset. CONCLUSIONS: Sustained attention deficit may represent a neuropsychological vulnerability marker for bipolar disorder, providing a focus for further understanding of the phenotype and analysis of the neuronal networks involved.

Adolescent↗