Anxiety Disorders: Goodwin G

Taylor MJ, Carney S, Geddes J, Goodwin G. · Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK, OX3 7JK. · Cochrane Database Syst Rev. · Pubmed #12804463 No free full text.

Abstract: BACKGROUND: There are a number of effective interventions for the treatment of depression. It is possible that the efficacy of these treatments will be improved further by the use of adjunctive therapies such as folate. OBJECTIVES: 1. To determine the effectiveness of folate in the treatment of depression 2. To determine the adverse effects and acceptability of treatment with folate. SEARCH STRATEGY: The Cochrane Controlled Trials Register (CCTR), and the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR) incorporating results of group searches of EMBASE, MEDLINE, LILACS, CINAHL, PSYNDEX and PsycLIT were searched. Reference lists of relevant papers and major textbooks of affective disorder were checked. Experts in the field and pharmaceutical companies were contacted regarding unpublished material. SELECTION CRITERIA: All randomised controlled trials that compared treatment with folic acid or 5'-methyltetrahydrofolic acid to an alternative treatment, whether another antidepressant medication or placebo, for patients with a diagnosis of depressive disorder (diagnosed according to explicit criteria). DATA COLLECTION AND ANALYSIS: Data were independently extracted from the original reports by two reviewers. Statistical analysis was conducted using Review Manager version 4.1. MAIN RESULTS: Three trials involving 247 people were included. Two studies involving 151 people assessed the use of folate in addition to other treatment, and found that adding folate reduced Hamilton Depression Rating Scale scores on average by a further 2.65 points (95% confidence interval 0.38 to 4.93). Fewer patients treated with folate experienced a reduction in their HDRS score of less than 50% at ten weeks (relative risk (RR) 0.47, 95% CI 0.24 to 0.92) The number needed to treat with folate for one additional person to experience a 50% reduction on this scale was 5 (95% confidence interval 4 to 33). One study involving 96 people assessed the use of folate instead of the antidepressant trazodone and did not find a significant benefit from the use of folate. The trials identified did not find evidence of any problems with the acceptability or safety of folate. REVIEWER'S CONCLUSIONS: 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.

Macritchie K, Geddes JR, Scott J, Haslam D, de Lima M, Goodwin G. · Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, OXON, UK, OX3 7JX. · Cochrane Database Syst Rev. · Pubmed #12535506 No free full text.

Abstract: BACKGROUND: Bipolar disorder is a common debilitating illness, characterised by acute affective episodes with full or partial inter-episode remission. Effective and acceptable treatment of acute episodes is required. Valproate has become a leading adjunctive and alternative mood stabilising treatment to lithium in bipolar disorder. OBJECTIVES: To determine the efficacy and acceptability of valproate in the treatment of acute episodes of bipolar disorder. SEARCH STRATEGY: The search included the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registrar (CCDANCTR), the Cochrane Controlled Clinical Trials Register (CCTR), reference lists of relevant papers and books, and contact with authors of trials, experts and pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials comparing valproate with placebo, other mood stabilisers and antipsychotic medication in the treatment of any bipolar affective episode. Participants were of both sexes, of all ages, with a diagnosis of bipolar affective disorder approximating to ICD 10 Code F31 and DSM IV 296. DATA COLLECTION AND ANALYSIS: Methodological quality was assessed independently by two reviewers blind to the authorship and source of papers. Ten randomised controlled trials were found comparing valproate with other interventions in mania. None was found examining its use in depression or mixed affective episodes. Data were extracted on the main outcome 'failure to respond by the end of the study' assessed by a less than 50% reduction in the Young Mania Rating Scale or the SADS-S mania scale. Three trials (316 participants) compared valproate with placebo. Three trials (158 participants) compared valproate with lithium. Two trials (363 participants) compared valproate with olanzapine. One trial (36 participants) compared valproate with haloperidol. Two trials (59 patients) compared valproate with carbamazepine. Acceptability of treatment was estimated using the outcome measure 'total number of subjects withdrawing from the study'. Three trials (321 patients) contributed to the comparison between valproate and placebo, two studies (144 patients) contributed to the comparison with lithium. One study (30 patients) provided data on this outcome in the comparison between valproate and carbamazepine. Pooled relative risks (with 95% confidence intervals) were calculated using fixed effect approaches. MAIN RESULTS: Valproate was more efficacious than placebo (RRR 38%; RR 0.62; 95% C.I. 0.51 to 0.77) in the treatment of mania. There was no significant difference between valproate and lithium (RRI 5%; RR 1.05; 95% C.I. 0.74-1.50) or between valproate and carbamazepine (RRR 34%; RR 0.66; 95% C.I. 0.38 to 1.16). Valproate was less effective than olanzapine (failure to achieve clinical response; RRI 25%; RR 1.25, 95% C.I. 1.01 to 1.54; average of 2.8 point less change on the Mania Rating Scale (95% CI 0.83 to 4.79). There were no significant differences in acceptability as measured by total number of subjects withdrawing from the study. There were significant differences in the side effect profiles of valproate and olanzapine, with more sedation and weight gain on olanzapine. REVIEWER'S CONCLUSIONS: There is consistent, if limited, evidence to suggest that valproate is an efficacious treatment for acute mania. Valproate may be less effective than olanzapine but may cause less sedation and weight gain. More well designed, randomised controlled trials investigating the relative efficacy and acceptability of valproate in the treatment of the full range of acute affective episodes occurring in bipolar disorder are required.

Burgess S, Geddes J, Hawton K, Townsend E, Jamison K, Goodwin G. · Department of Psychiatry, University of Oxford, Oxford, UK, OX3 7JX. · Cochrane Database Syst Rev. · Pubmed #11687035 No free full text.

Abstract: BACKGROUND: Mood disorders are common, disabling and tend to be recurrent. They carry a high risk of suicide. Maintenance treatment, aimed at the prevention of relapse, is therefore of vital importance. Lithium has been used for some years as the mainstay of maintenance treatment in bipolar affective disorder, and to a lesser extent in unipolar disorder. However, the efficacy and effectiveness of prophylactic lithium therapy has been disputed. Low suicide rates in lithium-treated patients have led to claims that lithium has a specific anti-suicidal effect. If so, this is of considerable importance as treatments for mental disorders in general have not been shown convincingly to be effective in suicide prevention. OBJECTIVES: 1. To investigate the efficacy of lithium treatment in the prevention of relapse in recurrent mood disorders. 2. To examine the effect of lithium treatment on consumers' general health and social functioning, its acceptability to consumers, and the side-effects of treatment. 3. To investigate the hypothesis that lithium has a specific effect in reducing the incidence of suicide and deliberate self-harm in persons with mood disorders. SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR) and The Cochrane Controlled Clinical Trials Register (CCTR) were searched. Reference lists of relevant papers and major text books of mood disorder were examined. Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable trials, published or unpublished. Specialist journals concerning lithium were hand searched. SELECTION CRITERIA: Randomised controlled trials comparing lithium with placebo, where the stated intent of treatment was maintenance or prophylaxis. Participants were males and females of all ages with diagnoses of mood disorder. Discontinuation studies (in which all participants had been stable on lithium for some time before being randomised to either continued lithium treatment or placebo substitution) were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted from the original reports independently by two reviewers. The main outcomes studied were related to the objectives stated above. Data were analysed for all diagnoses of mood disorder and for bipolar and unipolar disorder separately. Data were analysed using Review Manager version 4.0. MAIN RESULTS: Nine studies were included in the review, reporting on 825 participants randomly allocated to lithium or placebo. Lithium was found to be more effective than placebo in preventing relapse in mood disorder overall, and in bipolar disorder. The most consistent effect was found in bipolar disorder (random effects OR 0.29; 95% CI 0.09 to 0.93 ). In unipolar disorder, the direction of effect was in favour of lithium, but the result (when heterogeneity between studies was allowed for) did not reach statistical significance. Considerable heterogeneity was found between studies in all groups of patients. The direction of effect was the same in all studies; no study found a negative effect for lithium. Heterogeneity may have been due to differences in selection of participants, and to differing exposures to lithium in the pre-study phase resulting in variable influence of a discontinuation effect. There was little reported data on overall health and social functioning of participants under the different treatment conditions, or on the participants' own views of their treatment. Descriptive analysis showed that assessments of general health and social functioning generally favoured lithium. Small absolute numbers of deaths and suicides, and the absence of data on non-fatal suicidal behaviours, made it impossible to draw meaningful conclusions about the place of lithium therapy in suicide prevention. REVIEWER'S CONCLUSIONS: This systematic review indicates that lithium is an efficacious maintenance treatment for bipolar disorder. In unipolar disorder the evidence of efficacy is less robust. This review does not cover the relative efficacy of lithium compared with other maintenance treatments, which is at present unclear. There is no definitive evidence from this review as to whether or not lithium has an anti-suicidal effect. Systematic reviews and large scale randomised studies comparing lithium with other maintenance treatments (e.g. anti-convulsants, antidepressants) are necessary. Outcomes relating to death and suicidal behaviour should be included in all future maintenance studies of mood disorder.

Burgess S, Geddes J, Hawton K, Townsend E, Jamison K, Goodwin G. · Department of Psychiatry, University of Oxford, Oxford, UK, OX3 7JX. · Cochrane Database Syst Rev. · Pubmed #11406061 No free full text.

Abstract: BACKGROUND: Mood disorders are common, disabling and tend to be recurrent. They carry a high risk of suicide. Maintenance treatment, aimed at the prevention of relapse, is therefore of vital importance. Lithium has been used for some years as the mainstay of maintenance treatment in bipolar affective disorder, and to a lesser extent in unipolar disorder. However, the efficacy and effectiveness of prophylactic lithium therapy has been disputed. Low suicide rates in lithium-treated patients have led to claims that lithium has a specific anti-suicidal effect. If so, this is of considerable importance as treatments for mental disorders in general have not been shown convincingly to be effective in suicide prevention. OBJECTIVES: 1. To investigate the efficacy of lithium treatment in the prevention of relapse in recurrent mood disorders. 2. To examine the effect of lithium treatment on consumers' general health and social functioning, its acceptability to consumers, and the side-effects of treatment. 3. To investigate the hypothesis that lithium has a specific effect in reducing the incidence of suicide and deliberate self-harm in persons with mood disorders. SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR) and The Cochrane Controlled Clinical Trials Register (CCTR) were searched. Reference lists of relevant papers and major text books of mood disorder were examined. Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable trials, published or unpublished. Specialist journals concerning lithium were hand searched. SELECTION CRITERIA: Randomised controlled trials comparing lithium with placebo, where the stated intent of treatment was maintenance or prophylaxis. Participants were males and females of all ages with diagnoses of mood disorder. Discontinuation studies (in which all participants had been stable on lithium for some time before being randomised to either continued lithium treatment or placebo substitution) were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted from the original reports independently by two reviewers. The main outcomes studied were related to the objectives stated above. Data were analysed for all diagnoses of mood disorder and for bipolar and unipolar disorder separately. Data were analysed using Review Manager version 4.0. MAIN RESULTS: Nine studies were included in the review, reporting on 825 participants randomly allocated to lithium or placebo. Lithium was found to be more effective than placebo in preventing relapse in mood disorder overall, and in bipolar disorder. The most consistent effect was found in bipolar disorder (random effects OR 0.29; 95% CI 0.09 to 0.93 ). In unipolar disorder, the direction of effect was in favour of lithium, but the result (when heterogeneity between studies was allowed for) did not reach statistical significance. Considerable heterogeneity was found between studies in all groups of patients. The direction of effect was the same in all studies; no study found a negative effect for lithium. Heterogeneity may have been due to differences in selection of participants, and to differing exposures to lithium in the pre-study phase resulting in variable influence of a discontinuation effect. There was little reported data on overall health and social functioning of participants under the different treatment conditions, or on the participants' own views of their treatment. Descriptive analysis showed that assessments of general health and social functioning generally favoured lithium. Small absolute numbers of deaths and suicides, and the absence of data on non-fatal suicidal behaviours, made it impossible to draw meaningful conclusions about the place of lithium therapy in suicide prevention. REVIEWER'S CONCLUSIONS: This systematic review indicates that lithium is an efficacious maintenance treatment for bipolar disorder. In unipolar disorder the evidence of efficacy is less robust. This review does not cover the relative efficacy of lithium compared with other maintenance treatments, which is at present unclear. There is no definitive evidence from this review as to whether or not lithium has an anti-suicidal effect. Systematic reviews and large scale randomised studies comparing lithium with other maintenance treatments (e.g. anti-convulsants, antidepressants) are necessary. Outcomes relating to death and suicidal behaviour should be included in all future maintenance studies of mood disorder.