1. Predictors of good and poor response in GAD
shorter duration of symptoms (venlafaxine, fluoxetine)1, 2
co-morbid dysthymia (venlafaxine)1, psychiatric co-morbidity3
history of depression, panic disorder (venlafaxine)4
severity of psychosocial impairment (TAU) 3
lower symptom severity (escitalopram) 5
history of benzodiazepine use (venlafaxine) 4
longer duration of untreated illness (SSRI, venlafaxine) 6
1. Perugi G et al. Neuropsychobiol 2002; 46:
2. Simon NM et al. Depress Anx 2006; 23:
3. Rodriguez BF et al. J Nerv Ment Dis 2006; 194: 91-97
4. Pollack M et al. J Clin Psychopharmacol 2003; 23:
5. Stein DJ et al. J Clin Psychiatry 2006; 67:
6. Altamura CA et al. CNS Spectrums 2008; 13:

2. Duration of treatment after response

3. Low probability of remission in GAD
The Harvard-Brown Anxiety Research Program (a prospective, observational, longitudinal study) was designed to investigate variables that influenced the clinical course of GAD in 167 patients aged 18 years of age
Patients were assessed at study enrolment and re-examined at 6–12-month intervals using the Longitudinal Interval Follow-up Evaluation, which generates a 6-point psychiatric status rating (PSR); a PSR score of 6 indicates full DSM-III-R criteria for GAD
Full remission was defined as occasional or no symptoms (PSR of 1 or 2) for 8 consecutive weeks
Treatment was not controlled over the course of the study, although most patients were taking treatment at some time
The probability of full remission over 5 years was low (0.38)
Full remission was least likely to occur in patients with poor relationships with their spouse and those with personality disorders
Reference
Yonkers KA, et al. Br J Psychiatry. 2000; 176: 544–549.
*Full remission: Psychiatric Status Rating <3 for 8 weeks following index episode.
Adapted from Yonkers KA, et al. Br J Psychiatry. 2000; 176: 544–549.
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4. Placebo-controlled relapse prevention studies
*** p < vs. placebo
***
***
***
***
***
n=170
n=168
n=278
n=288
n=187
n=188
n=211
n=213
n=216
n=216
Pregabalin
24 wks
Paroxetine
24 wks
Escitalopram
24-72 wks
Duloxetine
24 wks
Quetiapine
52 wks
Feltner et al. Int Clin Psychopharmacol 2008; 23: 18-28; Stocchi et al. J Clin Psychiatry 2003; 64: ;
Allgulander et al. Int J Neuropsychopharmacol 2006; 9: 495–505; Davidson et al. Eur Neuropsychopharmacol 2008; 18: ; accessed 10/11/08

5. Management after initial non-response

6. Possible treatment options after pharmacological RX non-response
increase in dose ? (no clear evidence)
switch to alternative treatment
pregabalin
Buspirone
SNRI
Benzodiazepines
agomelatine
Quetiapine
CBT
augmentation with pregabalin, olanzapine, quetiapine or risperidone or pindolol
Combination of 2 evidence based drug treatments when no contraindication (risk of serotonin syndrome in SSRI/SNRI or Mirtazapine combinations)
combination drug and psychological treatment?
use of complementary approaches

7. Possible treatment options after psychological RX non-response
augmentation with SSRI’s

8. Combining CBT and drug treatment in GAD
due to lack of data, not currently possible to draw conclusions for GAD
continuing need for large RCT of CBT vs SSRI vs [CBT+SSRI]
Bandelow B et al. World J Biol Psychiatr 2007; 8:

9. Summary: Treatment of GAD
Aims of treatment in GAD are to reduce symptoms of anxiety; to minimise disruption to day-to-day functioning, with minimal adverse effects
Effective treatments for GAD include psychological therapy, pharmacological therapy and self-help1
Numerous effective pharmacological therapies exist, including selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), Pregabalin, Benzodiazepines, Azapirones…2
Current treatments may have limitations
GAD is often inappropriately treated1
Pharmacotherapy is the cornerstone of GAD treatment2
Numerous effective pharmacological therapies exist, including benzodiazepines, tricyclic antidepressants, selective serotonin re-uptake inhibitors, serotonin-noradrenaline re-uptake inhibitors, azapirones and pregabalin1
References
Montgomery S, et al. Expert Opin Pharmacother. 2006; 7: 2139–2154.
National Institute for Health and Clinical Excellence. CG22 Anxiety: Algorithm (management of Generalised Anxiety Disorder). Available at Accessed: March, 2008.
National Institute for Health and Clinical Excellence. CG22 Anxiety: Algorithm (management of Generalised Anxiety Disorder). Available at Accessed: March, 2008.
Montgomery SA. Expert Opin Pharmacother. 2006; 7: 2139–2154.
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