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Generalised Anxiety Disorder Generalised Anxiety Disorder The evolution of the evidence Chris Gale Revised for Psychiatry Trainees, June 2011 Hypotheses GAD is a not uncommon cause of disability, but GAD is commonly missed. Most studies are of patients without co- morbidity, (which are the minority). Evidence base analysis is dependent on the studies used. The data set for this group of patients is now reasonably rich, however, the application of this data set is problematic. Hypothesis one. Generalized anxiety disorder has a community 12 month prevelence in the range 1-4%. GAD is a significant cause of disability. However, it is highly co-morbid in 75-80% cases. It is therefore frequently diagnosed. Definition Ongoing anxiety, multiple events, disproportionate. Somatic symptoms. Causing subjective stress. 12-month prevalence Generalized Anxiety Disorder, National Surveys. Survey Diagnostic Total Male Female system. (95%CI) (95% CI) (95% CI) Te Rau DSM-IV 2.0 (1.7—2.3) 1.4 (1.1 – 1.8) 2.6 (2.2 –3.1) Hinegaro Germany DSM-IV 1.5 (1.2 – 1.9) 1.0 (0.6 – 1.5) 2.1 (1.5 – 2.8) Australia DSM-IV 2.7 (2.2-- 2.3) 2.0 (1.3 – 2.6) 3.5 (2.7 – 4.3) GAD or MDE have the equivalent effect on disability as ageing 12 years . Profiles of mean Medical Outcomes Study Short Form 36 (SF–36) sub-scale scores according to the absence dark) or presence (light) of prevalent mood disorders (adjusted for age, gender and presence of any chronic medical conditions), sub-scales are: PF=Physical Functioning; RP, Role Physical; BP, Bodily Pain; GH, General Health; V, Vitality; SF, Social Functioning; RE, Role Emotional; MH, Mental Health. From Surtees. British Journal of Psychiatry (2003) 183: 299-303 Outcome. One review long term studies: − 25% achieve remission by 2 years followup. − 38% in remission at 5 years follow-up. Harvard/Brown (HARP) project − has reported 5 year outcome of step-wise protocol treatment combining medication and cognitive. 38% fully remit. 47% partial remission. 27% of those who achieve full remission relapse. 39% with partial remission relapse. Summary GAD occurs in about 2% population. It is more common in women. GAD causes significant distress, time out of role, and perceived poor mental health. GAD (when co morbid) increases health care usage. Hypothesis two. Four of five patients with GAD will be co- morbid. One in four to one in five will have “pure” GAD in clinical settings. Almost all RCTs, however, are based on the pure population. Methods of reporting results. P values. Mean difference, 95% confidence interval. Risk reduction, (risk ratio) Numbers needed to treat Effect size. P values Generated from a statistical test. − Dependant on appropriate use of test. − Statistical significance does not always mean clinical signficance. Risk reduction Measure of statistical significance Needs categorical data. Ratio of proportion of events. Generally reported with 95% CI. Common in EBM, meta analysis. Mean difference Continuous outcomes. Difference between changes in scale over treatment period. Reported with 95% CI Used Cochrane. Effect size Cohen's d (1988) Hedges's g − the difference − is an inferential between the measure. means, M1 - M2, It is normally divided by standard computed by using deviation, s, of the square root of either group. the Mean Square Error − Cohen defined can be computed effect sizes as from the value of "small, d = .2," the t test of the differences between "medium, d = .5," the two groups "large, d = .8", Comparison of various methods describing effect size Hypothesis four. The data set for clinical efficacy is rich. − Issue for many questions is analysis of meta- analysis. The number of effectiveness studies is less. − Methods of unpacking effects of comorbidity are in development. − Most EBM protocols downgrade this data. Data set is weaker at extremes of age. Psychotherapy techniques. Cognitive therapy. Anxiety management training − Almost all analytical psychotherapies are not in data set. − Data set tends to short term studies, but longer term data is available for CBT. Medications. Benzodiazepines. Apiprazoles − Buspirone, Abecarnil, Opipramol Antidepressants. − Tricyclics, SSRIs − Venlafaxine Hyoscine, Trifluoperazine, Risperidone (augmentation). Mood stabilisers Kava. Quetiapine monotherapy versus placebo for generalised anxiety disorder, outcome: 1.1 Response - as defined by original studies. Quetiapine monotherapy versus placebo for generalised anxiety disorder, outcome: 1.2 Remission - as defined by original studies. Risperidone versus placebo added to antidepressants for generalised anxiety disorder, outcome: 7.1 Response - as defined by original study. Summary treatment. Best evidence for cognitive therapy, less anxiety management training. Reasonable evidence for antidepressants, azapirones, benzodiazepines, atypical antipsychotics. Side effect profile suggests reserving Benzodiazepines and azapirone to second line, and atypicals for treatment resistent. Use of EBM Fair number of effectiveness studies: now number of meta-analyses. − Most efficacy studies. − Applicability to patients seen an issue. It may be efficacy studies needed before effectiveness. Issue of applicability findings. − Access to CBT/other practitioners. − CBT practitioners access to supervision, and other support (e.g. manuals). GAD GAD is not uncommon, however pure GAD is fairly rare. − GAD is often missed clinically. − Most published data is efficacy, and (thus) persons with comorbidity excluded. − Need for effectiveness trials, including patients with comorbidity. HARP study. Clinical Audits. .
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