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 comorbidity, (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.