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Biomedical subjects

John R Geddes

Publications and source records attributed to John R Geddes.

At least 19 recordsLinked to original sources
PubMed2006

Early onset of selective serotonin reuptake inhibitor antidepressant action: systematic review and meta-analysis.

CONTEXT: Selective serotonin reuptake inhibitors (SSRIs) are often described as having a delayed onset of effect in the treatment of depression. However, some trials have reported clinical improvement as early as the first week of treatment. OBJECTIVE: To test the alternative hypotheses of delayed vs early onset of antidepressant action with SSRIs in patients with unipolar depression. DATA SOURCES: Trials identified by searching CENTRAL, The Cochrane Collaboration database of controlled trials (2005), and the reference lists of identified trials and other systematic reviews. STUDY SELECTION: Randomized controlled trials of SSRIs vs placebo for the treatment of unipolar depression in adults that reported outcomes for at least 2 time points in the first 4 weeks of treatment (50 trials from >500 citations identified). Trials were excluded if limited to participants older than 65 years or specific comorbidities. DATA EXTRACTION: Data were extracted on trial design, participant characteristics, and outcomes by a single reviewer. DATA SYNTHESIS: Pooled estimates of treatment effect on depressive symptom rating scales were calculated for weeks 1 through 6 of treatment. In the primary analysis, the pattern of response seen was tested against alternative models of onset of response. The primary analysis incorporated data from 28 randomized controlled trials (n=5872). A model of early treatment response best fit the experimental data. Treatment with SSRIs rather than placebo was associated with clinical improvement by the end of the first week of use. A secondary analysis indicated an increased chance of achieving a 50% reduction in Hamilton Depression Rating Scale scores by 1 week (relative risk, 1.64; 95% confidence interval, 1.2-2.25) with SSRI treatment compared with placebo. CONCLUSIONS: Treatment with SSRIs is associated with symptomatic improvement in depression by the end of the first week of use, and the improvement continues at a decreasing rate for at least 6 weeks.

Adult↗
PubMed2006

Pharmacological treatment for unipolar psychotic depression: Systematic review and meta-analysis.

BACKGROUND: The optimal pharmacological treatment of unipolar psychotic depression is uncertain. AIMS: To compare the clinical effectiveness of pharmacological treatments for patients with unipolar psychotic depression. METHOD: Systematic review and meta-analysis of randomised controlled trials. RESULTS: Ten trials were included in the review. We found no evidence that the combination of an antidepressant with an antipsychotic is more effective than an antidepressant alone. This combination was statistically more effective than an antipsychotic alone. CONCLUSIONS: Antidepressant monotherapy and adding an antipsychotic if the patient does not respond, or starting with the combination of an antidepressant and an antipsychotic, both appear to be appropriate options for patients with unipolar psychotic depression. However, clinically the balance between risks and benefits may suggest the first option should be preferred for many patients. Starting with an antipsychotic alone appears to be inadequate.

Affective Disorders, Psychotic↗
PubMed2006

Are all antidepressants really the same? The case of fluoxetine: a systematic review.

OBJECTIVE: To systematically review the efficacy and tolerability of fluoxetine, the most widely studied of newer antidepressants, in comparison with all other antidepressants in the acute treatment of depression in patients aged more than 18 years. DATA SOURCES: Studies were identified through electronic searches of the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to March 2004. The terms FLUOXETIN* OR adofen or docutrix or erocap or fluctin or fluctine or fluoxeren or fontex or ladose or lorien or lovan or mutan or prozac or prozyn or reneuron or sanzur or saurat or zactin were used. MEDLINE (1966-2004) and EMBASE (1974-2004) were searched using fluoxetine and randomized controlled trial or random allocation or double-blind method. No language restrictions were applied. Reference lists of relevant papers and previous systematic reviews were hand-searched for published reports up to March 2004. STUDY SELECTION: Only randomized controlled trials (either blind or nonblind) were included. DATA SYNTHESIS: 131 randomized controlled trials were eligible. A p value less than .01 was chosen to test the null hypothesis, and a 99% confidence interval was calculated to detect statistically significant differences with a high degree of confidence. Fixed- and random-effects relative risks, odds ratios (ORs), and Peto ORs were routinely calculated for each outcome measure. In terms of efficacy, we found a statistically significant difference favoring sertraline and venlafaxine over fluoxetine. In terms of tolerability, patients allocated to fluoxetine were less likely to leave the study early only in comparison with those allocated to amitriptyline and pramipexole. CONCLUSIONS: This systematic review highlighted that there are differences between fluoxetine and specific comparator antidepressants. Several of the differences met a prespecified criterion for clinical significance. The statistical approach adopted in this systematic review could represent a useful tool for putting clinical trial data into practice.

Adult↗
PubMed2005

Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials.

OBJECTIVE: Observational studies suggest that long-term lithium treatment has a strong antisuicidal effect in mood disorders, but it is uncertain whether this association is a genuine therapeutic effect or is due to confounding factors in nonrandomized studies. The authors conducted a systematic review and meta-analysis of randomized trials to investigate the effect of lithium, compared to placebo and other active treatments, on the risk of suicide, deliberate self-harm, and all-cause mortality in patients with mood disorder. METHOD: The data source was the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register, incorporating results of searches of MEDLINE (1966-June 2002), EMBASE (1980-June 2002), CINAHL (1982-March 2001), PsycLIT (1974-June 2002), PSYNDEX (1977-October 1999), and LILACS (1982-March 2001). The Cochrane Central Register of Controlled Trials (CENTRAL) was searched with the term "lithium" for new records entered into the database from 1999 to 2003. Studies selected included randomized, controlled trials comparing lithium with placebo or all other compounds used in long-term treatment for mood disorders (unipolar depression, bipolar disorder, schizoaffective disorder, dysthymia, and rapid cycling, diagnosed according to DSM or ICD criteria). Of 727 references identified in the search, 52 articles were marked as possibly relevant on the basis of the abstract, and 32 randomized, controlled trials were eligible for inclusion in the review. Two independent reviewers extracted the data, and disagreements were resolved by consensus with a third reviewer. Methodological quality was assessed according to the criteria of the Cochrane Collaboration. When the outcomes of interest were not reported, an attempt was made to obtain the required data from the original authors. RESULTS: In 32 trials, 1,389 patients were randomly assigned to receive lithium and 2,069 to receive other compounds. Patients who received lithium were less likely to die by suicide (data from seven trials; two versus 11 suicides; odds ratio=0.26; 95% confidence interval [CI]=0.09-0.77). The composite measure of suicide plus deliberate self-harm was also lower in patients who received lithium (odds ratio=0.21; 95% CI=0.08-0.50). There were fewer deaths overall in patients who received lithium (data from 11 trials; nine versus 22 deaths; odds ratio=0.42, 95% CI=0.21-0.87). CONCLUSIONS: Lithium is effective in the prevention of suicide, deliberate self-harm, and death from all causes in patients with mood disorders.

Cause of Death↗
PubMed2004

Developing the BALANCE trail--the role of the pilot study and start-up phase.

OBJECTIVES: The initial design of the BALANCE (Bipolar Affective disorder: Lithium / ANtiConvulsant Comparative Evaluation) Trial of maintenance treatment for bipolar disorder was based on the experience of previous trials in bipolar disorder and psychiatry and on the methods developed for large randomized trials in other areas of medicine. This report describes the adaptations to the initial design and trial procedures following the initial phases of the study. The rationale for the trial and full protocol have been published elsewhere. METHODS: A pilot study and start-up phase were used to check the tolerability of the interventions, refine the trial design and develop trial procedures that are acceptable to both clinicians and patients. RESULTS: Changes to the procedures included: the dropping of masking of allocated treatment from clinicians and participants; introduction of the use of postal delivery to supply medication; and dispensing with the proposed schedule of regular follow up appointments. In addition, support was made available to participating psychiatrists who often had limited experience of participating in randomized trials. CONCLUSIONS: Pilot studies and start-up phases are essential to refine clinical trial design and allow development of procedures that are both methodologically rigorous and flexible and robust enough to promote recruitment and follow up. BALANCE is now actively recruiting in the UK and USA.

Anticonvulsants↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2003

Meta-analysis of brain weight in schizophrenia.

Brain weight is often said to be decreased in schizophrenia, but a reduction has only been found in a minority of studies. We have therefore carried out a meta-analysis to answer this basic neuropathological question. Data were identified from literature searches and from contacting researchers in the field who were invited to submit unpublished data. Inclusion criteria were: an operational diagnosis of schizophrenia, or comparison subjects with no neurological or psychiatric history, aged 18 or over, for whom brain weight, age and sex were known. Exclusion criteria were: a history of head injury, epilepsy, substance dependence or leucotomy; neuropathological evidence of neurodegenerative disorder or focal brain lesion. Results were analysed by multilevel modelling. Brain weight was, as expected, related to age and sex (both p<0.0001). After control for these factors, there was an effect of diagnosis, with brains from the 540 schizophrenia subjects being 2% lighter than from the 794 controls (weighted mean difference=24 g [95% confidence interval, 1-47 g]; p=0.04). The difference was similar in male and female patients. There was no correlation with duration of illness. In conclusion, brain weight is slightly but significantly reduced in schizophrenia, consistent in direction and magnitude with MRI volumetric findings. The result encourages a continuing search for the histological and molecular correlates of schizophrenia.

Adolescent↗
PubMed2003

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↗
PubMed2003

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↗